Tests for the rapid evaluation of ischemic states and kits

The present invention relates to rapid methods for the detection of ischemic states and to kits for use in such methods. Provided for is a rapid method of testing for and quantifying ischemia based upon methods of detecting and quantifying the existence of an alteration of the serum protein albumin which occurs following an ischemic event; methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of circulating albumin, analysis and measurement of the ability of serum albumin to bind exogenous cobalt, detection and measurement of the presence of endogenous copper in a purified albumin sample and use of an immunological assay specific to the altered form of serum albumin which occurs following an ischemic event. Also taught by the present invention is the detection and measurement of an ischemic event by measuring albumin N-terminal derivatives that arise following an ischemic event, including truncated albumin species lacking one ...

Determination of fertility potential from the oxidation-reduction potential of a biological sample

Methods and systems for measuring and using the oxidation-reduction potential (ORP) of a biological sample are provided. The system generally includes a test strip and a readout device for determining the ORP. The measured ORP is then used to determine characteristics relating to the fertility of the sample or the subject from which the sample was derived. Some characteristics that can be determined include the quality of a sperm sample, an oocyte or a fertilized egg. The measured ORP value can also be used to determine the specific characteristics of a spermatozoa sample, such as the morphology of the spermatozoa, the motility of the spermatozoa, the number of cells in the sample and the concentration of the cells in the sample. Knowledge of such characteristics and fertility potential can be used to identify individuals that might benefit from specific fertility treatments.

Treatment of T-cell mediated diseases

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions.

METHOD FOR TREATMENT OF DISEASES

The invention provides a method of inhibiting vascular hyperpermeability in an animal in need thereof. The method comprises administering a vascular-hyperpermeability-inhibiting amount of a danazol compound to the animal. The invention also provides a method of modulating the cytoskeleton of an endothelial cell in an animal. The method comprises administering an effective amount of a danazol compound to the animal.

Treatment of Comorbid Premature Ejaculation and Erectile Dysfunction

The invention provides a method of treating comorbid premature ejaculation and erectile dysfunction. In particular, the method comprises administering an effective amount of a tramadol material and an effective amount of a phosphodiesterase inhibitor. The invention also provides a pharmaceutical composition comprising a pharmaceutically-acceptable carrier, a tramadol material and a phosphodiesterase inhibitor. The invention further provides a kit comprising a tramadol material and a phosphodiesterase inhibitor.

METAL-BINDING COMPOUNDS AND USES THEREFOR

The invention provides a method of reducing the damage done by reactive oxygen species (ROS) in an animal. The invention also provides a method of reducing the concentration of a metal in an animal. These methods comprise administering to the animal an effective amount of a metal-binding compound as further described in the application. The invention further provides a method of reducing the damage done by ROS to a cell, a tissue or an organ that has been removed from an animal. This method comprising contacting the cell, tissue or organ with a solution or medium containing an effective amount of a metal-binding compound of the invention. The invention further provides novel metal-binding compounds, pharmaceutical compositions comprising the metal-binding compounds, and kits comprising a container holding a metal-binding compound of the invention.

MEASUREMENT AND USES OF OXIDATIVE STRESS

The present invention provides a method of determining the overall oxidative status of a body fluid or a tissue of a patient by measuring the oxidation-reduction potential (ORP) of the body fluid or tissue. The method has been found to be useful in the diagnosis, evaluation and monitoring of patients who have suffered a trauma (such as a head injury), patients suspected of being critically-ill or who are critically ill, patients who have an infection, and patients suspected of having a myocardial infarction (MI) or who have had an MI. The method has also been found useful in monitoring and evaluating exercise performance in patients. In addition, the method has been found useful in monitoring and evaluating stored blood products and patients who will receive such a product.

METHOD OF USING DIKETOPIPERAZINES AND COMPOSITION CONTAINING THEM

The invention provides a method of inhibiting the effects of platelet activating factor (PAF). For instance, a disease or condition mediated by PAF (particularly inflammation) can be treated or platelet aggregation can be inhibited. The invention also provides a method of inhibiting the production and/or release of interleukin 8 (IL-8) by cells. The effects of PAF and the production and/or release of IL-8 are inhibited according to the invention by a compound of the formula: 2. The method of wherein Ris —CHCOOH.3. The method of wherein Ris the side chain of alanine.4. The method of wherein Ris the side chain of alanine.528.-. (canceled)29. The method of claim 1 , wherein the compound is administered as a pharmaceutical formulation.30. The method of claim 29 , wherein the pharmaceutical formation is a topical formulation.31. The method of claim 30 , wherein the topical formulation is an ointment claim 30 , a paste claim 30 , a cream claim 30 , a gel claim 30 , a lotion claim 30 , a powder or a spray.32. A method of treating psoriasis comprising topically applying to an animal in need thereof claim 30 , a pharmaceutical composition wherein the pharmaceutical composition comprises 3-methyl-2 claim 30 ,5-diketopiperazine-6-acetic acid and is formulated for topical administration. This application is a continuation of U.S. application Ser. No. 13/252,377, filed Oct. 4, 2011, which is a continuation of U.S. application Ser. No. 10/397,964, filed Mar. 25, 2003, now U.S. Pat. No. 8,455,517, which is a continuation of issued U.S. Pat. No. 6,555,543, filed Aug. 2, 2001 and issued Apr. 29, 2003, which claims benefit of provisional application 60/222,849, filed Aug. 4, 2000. The entire disclosure of the prior applications, are hereby incorporated by reference.This invention relates to methods of inhibiting the effects of platelet activating is factor using certain diketopiperazines. The invention also relates to methods of inhibiting the production and/or release of interleukin ...

TREATMENT OF T-CELL MEDIATED DISEASES

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions.

Marker useful for detection and measurement of free radical damage and method

The present invention teaches a marker useful for detection and measurement of free radical damage. Specifically, the invention takes advantage of alterations which occur to the N-terminus of the albumin molecule, a circulating protein in human blood, in the presence of free radicals. These alterations effect the ability of the N-terminus of the albumin molecule to bind metals. Methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of an albumin containing sample, analysis and measurement of the ability of albumin to bind exogenous cobalt, detection and measurement of the presence of copper in a purified albumin sample and use of an immunological assay specific to the altered form of serum albumin which occurs following free radical damage. Also taught by the present invention is the use of the compound Asp-Ala-His-Lys-R, wherein R is any chemical group capable of being detected when bound to any compound capable of binding to ...

Metal-binding compounds and uses therefor

Method of using diketopiperazines and composition containing them

The invention provides a method of inhibiting the effects of platelet activating factor (PAF). For instance, a disease or condition mediated by PAF (particularly inflammation) can be treated or platelet aggregation can be inhibited. The invention also provides a method of inhibiting the production and/or release of interleukin 8 (IL-8) by cells. The effects of PAF and the production and/or release of IL-8 are inhibited according to the invention by a compound of the formula: wherein R 1 and R 2 are defined in the application, or a physiologically-acceptable salt thereof. The invention also provides pharmaceutical compositions comprising these compounds.

Metal-binding compounds and uses therefor

The invention provides a method of reducing the damage done by reactive oxygen species (ROS) in an animal. The invention also provides a method of reducing the concentration of a metal in an animal. These methods comprise administering to the animal an effective amount of a metal-binding compound as further described in the application. The invention further provides a method of reducing the damage done by ROS to a cell, a tissue or an organ that has been removed from an animal. This method comprising contacting the cell, tissue or organ with a solution or medium containing an effective amount of a metal-binding compound of the invention. The invention further provides novel metal-binding compounds, pharmaceutical compositions comprising the metal-binding compounds, and kits comprising a container holding a metal-binding compound of the invention.

Marker useful for detection and measurement of free radical damage and method

The present invention teaches a marker useful for detection and measurement of free radical damage. Specifically, the invention takes advantage of alterations which occur to the N-terminus of the albumin molecule, a circulating protein in human blood, in the presence of free radicals. These alterations affect the ability of the N-terminus of the albumin molecule to bind metals. Methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of an albumin containing sample, analysis and measurement of the ability of albumin to bind exogenous cobalt, detection and measurement of the presence of copper in a purified albumin sample and use of an immunological assay specific to the altered form of serum albumin which occurs following free radical damage. Also taught by the present invention is the use of the compound Asp-Ala-His-Lys-R (SEQ ID NO:1), wherein R is any chemical group capable of being detected when bound to any compound capable ...

Implantable medical devices with increased immune tolerance, and methods for making and implanting

The present invention relates to the contacting of one or more surfaces of an implantable medical device with one or more diketopiperazines (DKPs).

METHOD FOR TREATMENT OF DISEASES

The invention provides a method of inhibiting vascular hyperpermeability in an animal in need thereof. The method comprises administering a vascular-hyperpermeability-inhibiting amount of a danazol compound to the animal. The invention also provides a method of modulating the cytoskeleton of an endothelial cell in an animal. The method comprises administering an effective amount of a danazol compound to the animal.

TREATMENT OF T-CELL MEDIATED DISEASES

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions. 191-. (canceled)92. A pharmaceutical composition comprising albumin and an aspartic acid-alanine diketopiperazine (DA-DKP) or a physiologically-acceptable salt thereof , wherein the composition is formulated for topical or transdermal administration.93. The composition of claim 92 , wherein the composition is formulated for topical administration.94. The composition of claim 93 , wherein the composition is an ointment claim 93 , a paste claim 93 , a cream claim 93 , a lotion claim 93 , or a gel.95. The composition of claim 92 , wherein the composition is formulated for transdermal administration.96. The composition of claim 95 , wherein in the composition is in a transdermal patch.97. The composition of claim 92 , wherein the composition is formulated for slow or controlled release.98. The composition of claim 92 , wherein the composition is administered to a subject having a T-cell mediated disease.99. A method to treat a subject having a T-cell mediated disease comprising administering a composition comprising albumin and DA-DKP or a physiologically-acceptable salt thereof topically to the subject.100. The method of claim 99 , wherein the T-cell mediated disease is a T-cell mediated autoimmune disease.101. The method of claim 100 , wherein the T-cell mediated autoimmune disease is selected from the group consisting of psoriasis claim 100 , rheumatoid arthritis claim 100 , neuritis and scleroderma.102. A method to treat a ...

Tests for the rapid evaluation of ischemic states and kits

Test for the rapid evaluation of ischemic states and kit

TREATMENT OF DISEASES AND CONDITIONS MEDIATED BY INCREASED PHOSPHORYLATION

The invention provides methods for the treatment of diseases and conditions mediated by increased phosphorylation, such as inflammation and cancer. The invention also provides methods for the inhibition of increased phosphorylation in cells, tissues and organs. The methods utilize a phosphate acceptor compound (PAC). The invention also provides products comprising a PAC.

METHODS OF TREATMENT OF DISEASES

The invention provides a method of inhibiting vascular hyperpermeability in an animal in need thereof. The method comprises administering a vascular-hyperpermeability-inhibiting amount of a danazol compound to the animal. The method comprises administering an effective amount of a danazol compound to the animal accounting for the body fat content of the animal. The invention also provides a method of modulating the cytoskeleton of an endothelial cell in an animal. 1. A method of treating nephropathy in an animal in need thereof comprising:a. determining the body fat content of the animal; andb. administering to the animal a vascular-hyperpermeability-inhibiting amount of a danazol compound corresponding to the body fat content of the animal.2. The method of claim 1 , wherein the step of determining comprises calculating the body mass index (BMI) of the animal.3. The method of wherein the danazol compound is administered orally.4. The method of claim 2 , wherein the danazol compound is administered in an amount between about 0.5 mg/BMI unit/day to about 1.0 mg/BMI unit/day.5. The method of claim 1 , wherein the danazol compound is administered twice daily.6. The method of claim 2 , wherein the amount of the danazol compound is between about 2 mg/day and about 15 mg/day when the BMI of the animal is less than 26.7. The method of claim 6 , wherein the amount of the danazol compound is about 5 mg/day when the BMI of the animal is less than 26.8. The method of claim 2 , wherein the amount of the danazol compound is between about 2 mg/day and about 15 mg/day when the BMI of the animal is between 26 and 35.9. The method of claim 8 , wherein the amount of the danazol compound is about 10 mg/day when the BMI of the animal is between 26 and 35.10. The method of claim 2 , wherein the amount of the danazol compound is between about 5 mg/day and about 45 mg/day when the BMI of the animal is greater than 35.11. The method of claim 10 , wherein the amount of the danazol compound ...

Metal-binding compounds and uses therefor

Methylphenidate derivatives and uses of them

The present invention provides methods of using compounds of formula I: and salts and prodrugs thereof, wherein n, R1 and R2 are defined herein. The invention also provides certain novel compounds of formula I and pharmaceutical compositions comprising them.

Implantable medical devices with increased immune tolerance, and methods for making and implanting

The present invention relates to the contacting of one or more surfaces of an implantable medical device with one or more diketopiperazines (DKPs).

Metal-binding compounds and uses therefor

The invention provides a method of reducing the damage done by reactive oxygen species (ROS) in an animal. The invention also provides a method of reducing the concentration of a metal in an animal. These methods comprise administering to the animal an effective amount of a metal-binding compound as further described in the application. The invention further provides a method of reducing the damage done by ROS to a cell, a tissue or an organ that has been removed from an animal. This method comprising contacting the cell, tissue or organ with a solution or medium containing an effective amount of a metal-binding compound of the invention. The invention further provides novel metal-binding compounds, pharmaceutical compositions comprising the metal-binding compounds, and kits comprising a container holding a metal-binding compound of the invention.

Treatment of diseases

The invention provides (i) a method of treating metabolic syndrome in an animal, (ii) a method of suppressing the appetite of an animal, (iii) a method of treating obesity in an animal, (iv) a method of reducing the weight of an animal in need thereof, (v) a method of reducing a blood lipid level in an animal in need thereof, (vi) a method of treating non-alcoholic steatohepatitis in an animal, and (vii) a method of inhibiting adipogenesis. The methods comprise administering an effective amount of an active ingredient, wherein the active ingredient comprises a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-acceptable salt of either of them to the animal. The invention also provides a kit comprising a container holding a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-acceptable salt of either of them; and instructions for administration. The diketopiperazines have the formula given in the application.

TREATMENT OF T-CELL MEDIATED DISEASES

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions. 191-. (canceled)92. A pharmaceutical composition comprising a diketopiperazine (DKP)-containing fraction of a solution of a protein or peptide , wherein the DKP-containing fraction is produced by separating a protein or peptide selected from the group consisting of albumin , immunoglobulin and erythropoietin from the solution of a protein or peptide , wherein the DKP is selected from the group consisting of YE-DKP , MR-DKP and DA-DKP.93. The composition of wherein the DKP-containing fraction contains components having molecular weights less than 3000.94. The composition of wherein the protein or peptide is a human protein or peptide.95. The composition of wherein the protein or peptide is a human albumin.96. The composition of wherein the protein or peptide is a human protein or peptide.97. The composition of wherein the protein or peptide is a human albumin.98. The composition of claim 92 , wherein the DKP-containing fraction is separated from the solution of the protein or peptide by a separation method selected from the group consisting of size exclusion chromatography claim 92 , affinity chromatography claim 92 , anion exchange chromatography claim 92 , cation exchange chromatography and filtration.99. A DKP-containing fraction produced by separating a protein or peptide from a solution of a protein or peptide selected from the group consisting of albumin claim 92 , immunoglobulin and erythropoietin claim 92 , wherein the ...

Treatment of degenerative joint disease

The invention provides a method of treating a degenerative joint disease. The method comprises administering an effective amount of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP). The invention also provides a pharmaceutical product as well as a kit comprising DA-DKP.

Uses of methylphenidate derivatives

The present invention provides methods of using compounds of formula I: and salts and prodrugs thereof, wherein n, R 1 and R 2 are defined herein.

Method and apparatus for measuring oxidation-reduction potential

Methods and systems for measuring the oxidation-reduction potential of a fluid sample are provided. The system includes a test strip with a sample chamber adapted to receive a fluid sample. The sample chamber can be associated with a filter membrane. The test strip also includes a reference cell. The oxidation-reduction potential of a fluid sample placed in the sample chamber can be read by a readout device interconnected to a test lead that is in electrical contact with the sample chamber, and a reference lead that is in electrical contact with the reference cell. Electrical contact between a fluid sample placed in the sample chamber and the reference cell can be established by a bridge. The oxidation-reduction potential may be read as an electrical potential between the test lead and the reference lead of the test strip.

TREATMENT OF DEGENERATIVE JOINT DISEASE

The invention provides a method of treating a degenerative joint disease. The method comprises administering an effective amount of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP). The invention also provides a pharmaceutical product as well as a kit comprising DA-DKP. 1. A method of treating hip pain in a human comprising administering to a hip of the human an intra-articular injection of an effective amount of a pharmaceutical composition comprising DA-DKP prepared by removing albumin from a solution of a human serum albumin composition.2. (canceled)3. The method of wherein the composition is administered no more frequently than once every six months claim 1 , once every 5 months claim 1 , once every 4 months claim 1 , once every 3 months claim 1 , or once every 2 months.4. (canceled)5. (canceled)6. The method claim 1 , wherein the composition administered by intra-articular injection is a composition having a concentration of DA-DKP from about 50 μM to about 350 μM.7. The method of claim 1 , wherein the composition further comprises N-acetyl-tryptophan (NAT) claim 1 , caprylic acid claim 1 , caprylate or combinations thereof.8. The method of claim 7 , wherein the composition is a composition having a concentration of NAT claim 7 , caprylic acid claim 7 , caprylate or combinations thereof from about 4 mM to about 20 mM.9. (canceled)10. The method of claim 1 , wherein the step of removing the albumin comprises treating the human serum albumin composition by a separation method selected from the group consisting of ultrafiltration claim 1 , sucrose gradient centrifugation claim 1 , chromatography claim 1 , salt precipitation claim 1 , and sonication.11. The method of claim 10 , wherein the step of removing comprises passing the human serum albumin composition over an ultrafiltration membrane with a molecular weight cut off that retains the albumin claim 10 , and wherein the resulting ...

Treatment of diseases and conditions mediated by increased phosphorylation

The invention provides methods for the treatment of diseases and conditions mediated by increased phosphorylation, such as inflammation and cancer. The invention also provides methods for the inhibition of increased phosphorylation in cells, tissues and organs. The methods utilize a phosphate acceptor compound (PAC). The invention also provides products comprising a PAC.

METHODS AND SYSTEMS FOR MEASURING AND USING THE OXIDATION-REDUCTION POTENTIAL OF A BIOLOGICAL SAMPLE

Methods and systems for measuring and using the oxidation-reduction characteristics of a biological sample are provided. The system generally includes a test strip and a readout device. A fluid sample is placed in the test strip, and the test strip is in turn operatively connected to the readout device. The readout device provides a controlled current that is sent across the fluid in the sample chamber. In addition, the readout device identifies an inflection point or transition time at which the voltage between contacts of the test strip is changing at the highest rate. The oxidation-reduction capacity of the sample is taken as the integral of the current profile from the time at which current begins to be supplied to the sample to the identified transition time. 1. A system for identifying an oxidative capacity of a fluid , comprising:a fluid sample; a reference cell;', 'a sample chamber;', 'a counter electrode, wherein a first portion of the counter electrode extends into the sample chamber;', 'a working electrode, wherein a first portion of the working electrode extends into the sample chamber;', 'a reference electrode, wherein the reference electrode is in electrical contact with the reference cell;, 'a test strip, including a first contact;', 'a second contact;', 'a third contact;', 'a test signal power supply, wherein a first terminal of the test signal power supply is electrically connected to the first contact, and wherein a second terminal of the test signal power supply is electrically connected to the second contact;', 'an electrometer, wherein a first input of the electrometer is electrically connected to the second contact, and wherein a second input of the electrometer is electrically connected to the third contact;', 'memory;', 'a processor, wherein with the first contact electrically connected to the counter electrode, the second contact electrically connected to the working electrode, and the third contact electrically connected to the reference ...

METAL-BINDING COMPOUNDS AND USES THEREFOR

The invention provides a method of reducing the damage done by reactive oxygen species (ROS) in an animal. The invention also provides a method of reducing the concentration of a metal in an animal. These methods comprise administering to the animal an effective amount of a metal-binding compound as further described in the application. The invention further provides a method of reducing the damage done by ROS to a cell, a tissue or an organ that has been removed from an animal. This method comprising contacting the cell, tissue or organ with a solution or medium containing an effective amount of a metal-binding compound of the invention. The invention further provides novel metal-binding compounds, pharmaceutical compositions comprising the metal-binding compounds, and kits comprising a container holding a metal-binding compound of the invention.

TREATMENT OF DEGENERATIVE JOINT DISEASE

The invention provides a method of treating a degenerative joint disease. The method comprises administering an effective amount of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP). The invention also provides a pharmaceutical product as well as a kit comprising DA-DKP. 1. A method of treating a degenerative joint disease comprising administering to an animal in need thereof an effective amount of a pharmaceutical composition comprising DA-DKP.2. The method of claim 1 , wherein the degenerative joint disease is osteoarthritis.3. The method of wherein the composition is administered no more frequently than once every six months claim 1 , once every 5 months claim 1 , once every 4 months claim 1 , once every 3 months claim 1 , or once every 2 months.4. The method of claim 1 , wherein the composition is administered by an administration route selected from the group consisting of local administration claim 1 , topical administration claim 1 , and injection.5. The method of claim 4 , wherein administration by injection is by intra-articular injection.6. The method of claim 5 , wherein the composition administered by intra-articular injection is a composition having a concentration of DA-DKP from about 50 μM to about 350 μM.7. The method of claim 1 , wherein the composition further comprises N-acetyl-tryptophan (NAT) claim 1 , caprylic acid claim 1 , caprylate or combinations thereof.8. The method of claim 7 , wherein the composition is a composition having a concentration of NAT claim 7 , caprylic acid claim 7 , caprylate or combinations thereof from about 4 mM to about 20 mM.9. The method of claim 1 , wherein the DA-DKP is in a composition prepared by removing albumin from a solution of a human serum albumin composition.10. The method of claim 9 , wherein the step of removing the albumin comprises treating the human serum albumin composition by a separation method selected from the group ...

METHOD AND APPARATUS FOR MEASURING OXIDATION-REDUCTION POTENTIAL

Methods and systems for measuring the oxidation-reduction potential of a fluid sample are provided. The system includes a test strip with a sample chamber adapted to receive a fluid sample. The sample chamber can be associated with a filter membrane. The test strip also includes a reference cell. The oxidation-reduction potential of a fluid sample placed in the sample chamber can be read by a readout device interconnected to a test lead that is in electrical contact with the sample chamber, and a reference lead that is in electrical contact with the reference cell. Electrical contact between a fluid sample placed in the sample chamber and the reference cell can be established by a bridge. The bridge may comprise filter element such as a piece of filter paper that is wetted, for example by the fluid sample, or an electrolytic gel. The oxidation-reduction potential may be read as an electrical potential between the test lead and the reference lead of the test strip. 1. An oxidation-reduction potential test device , comprising:a substrate;a sample chamber; a first area extending into the sample chamber;', 'a second area extending from the sample chamber;, 'a first test lead supported by the substrate, the first test lead including a first area extending into the sample chamber;', 'a second area extending from the sample chamber;, 'a second test lead supported by the substrate, the second test lead includinga reference cell; a first area in electrical contact with the reference cell;', 'a second area extending from the reference cell;, 'a reference lead, including;'}a filter, wherein the filter extends from at least a portion of the sample chamber to an area adjacent the reference cell.2. The device of claim 1 , further comprising:an overlay, wherein at least a portion of each of the first test lead, the second test lead, the reference cell, the reference lead, and the filter are located between the substrate and the overlay when the overlay is interconnected to the ...

Therapeutic methods and compounds

The invention provides diketopiperazines of formula I. The invention also provides pharmaceutical compositions comprising the diketopiperazines, or pharmaceutically-acceptable salts or prodrugs thereof, as the active ingredient. The invention further provides therapeutic treatments that utilize the diketopiperazines of formula I, including inhibition of a proliferative disease or condition, inhibition of angiogenesis, treatment of an angiogenic disease or condition, treatment of cancer and precancerous conditions, treatment of a fibrotic disorder, treatment of a viral infection, treatment of an Akt-mediated disease or condition, inhibition of the production, release or both of matrix metalloproteinase-9, and inhibition of Akt activation.

Metal-binding compounds and uses therefor

The invention provides a method of reducing the damage done by reactive oxygen species (ROS) in an animal. The invention also provides a method of reducing the concentration of a metal in an animal. These methods comprise administering to the animal an effective amount of a metal-binding compound as further described in the application. The invention further provides a method of reducing the damage done by ROS to a cell, a tissue or an organ that has been removed from an animal. This method comprising contacting the cell, tissue or organ with a solution or medium containing an effective amount of a metal-binding compound of the invention. The invention further provides novel metal-binding compounds, pharmaceutical compositions comprising the metal-binding compounds, and kits comprising a container holding a metal-binding compound of the invention.

Method of delaying ejaculation

The invention provides a method of delaying ejaculation. The method comprises administering an effective amount of a tramadol material to a human male prior to sexual intercourse. The method is particularly useful for treating premature ejaculation.

Metal-binding compounds and uses therefor

The invention provides a method of reducing the damage done by reactive oxygen species (ROS) in an animal. The invention also provides a method of reducing the concentration of a metal in an animal. These methods comprise administering to the animal an effective amount of a metal-binding compound as further described in the application. The invention further provides a method of reducing the damage done by ROS to a cell, a tissue or an organ that has been removed from an animal. This method comprising contacting the cell, tissue or organ with a solution or medium containing an effective amount of a metal-binding compound of the invention. The invention further provides novel metal-binding compounds, pharmaceutical compositions comprising the metal-binding compounds, and kits comprising a container holding a metal-binding compound of the invention.

METHODS FOR TREATING DISEASES ASSOCIATED WITH RESPIRATORY VIRUSES

The present disclosure provides a method of treating a disease associated with a respiratory virus. The method comprises administering an effective amount of a pharmaceutical composition prepared by removing albumin from a solution of a human serum albumin composition and/or comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP), such as a low molecular weight fraction of human serum albumin. The present disclosure also provides a pharmaceutical product as well as a kit comprising DA-DKP.

METHODS OF TREATMENT OF DISEASES

The invention provides a method of inhibiting vascular hyperpermeability in an animal in need thereof. The method comprises administering a vascular-hyperpermeability-inhibiting amount of a danazol compound to the animal. The method comprises administering an effective amount of a danazol compound to the animal accounting for the body fat content of the animal. The invention also provides a method of modulating the cytoskeleton of an endothelial cell in an animal. 1. A method of inhibiting vascular hyperpermeability in an animal in need thereof comprising:a. determining the body fat content of the animal; andb. administering to the animal a vascular-hyperpermeability-inhibiting amount of a danazol compound corresponding to the body fat content of the animal.2. The method of claim 1 , wherein the step of determining comprises calculating the body mass index (BMI) of the animal.3. The method of wherein the danazol compound is administered orally.4. The method of claim 2 , wherein the danazol compound is administered in an amount between about 0.5 mg/BMI unit/day to about 1.0 mg/BMI unit/day.5. The method of claim 1 , wherein the danazol compound is administered twice daily.6. The method of claim 2 , wherein the amount of the danazol compound is between about 2 mg/day and about 15 mg/day when the BMI of the animal is less than 26.7. The method of claim 6 , wherein the amount of the danazol compound is about mg/day when the BMI of the animal is less than 26.8. The method of claim 2 , wherein the amount of the danazol compound is between about 2 mg/day and about 15 mg/day when the BMI of the animal is between 26 and 35.9. The method of claim 8 , wherein the amount of the danazol compound is about 10 mg/day when the BMI of the animal is between 26 and 35.10. The method of claim 2 , wherein the amount of the danazol compound is between about 5 mg/day and about 45 mg/day when the BMI of the animal is greater than 35.11. The method of claim 10 , wherein the amount of the ...

Treatment of T-cell mediated diseases

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions.

Method of using diketopiperazines and composition containing them

The invention provides a method of inhibiting the effects of platelet activating factor (PAF). For instance, a disease or condition mediated by PAF (particularly inflammation) can be treated or platelet aggregation can be inhibited. The invention also provides a method of inhibiting the production and/or release of interleukin 8 (IL-8) by cells. The effects of PAF and the production and/or release of IL-8 are inhibited according to the invention by a compound of the formula: wherein R1and R2are defined in the application, or a physiologically-acceptable salt thereof. The invention also provides pharmaceutical compositions comprising these compounds.

MULTIPLE LAYER GEL

A multiple layer gel and method for forming a multiple layer gel are provided. The multiple layer gel includes an isolation layer and an electrolyte layer. The isolation layer provides a molecular weight screen, to prevent proteins or other molecules from contacting a reference cell covered by the isolation layer. The electrolyte layer covers the isolation layer, and provides a source of ions that place the reference cell in ionic and/or electrical contact with a fluid sample. The multiple layer gel can be used to maintain a reliable reference voltage from an associated reference cell while an electrical potential or other electrical characteristic of a sample fluid is being determined. 1. An oxidation-reduction potential test device , comprising:a substrate;a spacer layer interconnected to at least a portion of the substrate, wherein the spacer layer defines a sample chamber;a test strip overlay, wherein the test strip overlay is interconnected to at least a portion of the spacer layer; a first area extending into the sample chamber;', 'a second area extending from the sample chamber to a readout region;, 'a first test lead supported by the substrate, the first test lead including a first area extending into the sample chamber;', 'a second area extending from the sample chamber to a readout region;, 'a second test lead supported by the substrate, the second test lead includinga reference cell; a first area in electrical contact with the reference cell;', 'a second area extending from the reference cell to a readout region;, 'a reference lead, including;'}a filter, wherein at least a portion of the filter overlaps at least a portion of each of the first area of the first test lead, the first area of the second test lead, and the first area of the reference lead; anda gel volume, wherein the gel volume includes a first layer in contact with the reference cell and a second layer over the first layer, and wherein the first layer differs in composition from the second ...

Treatment of T-cell mediated diseases

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions.

Therapeutic methods and compounds

The invention provides diketopiperazines of formula I. The invention also provides pharmaceutical compositions comprising the diketopiperazines, or pharmaceutically-acceptable salts or prodrugs thereof, as the active ingredient. The invention further provides therapeutic treatments that utilize the diketopiperazines of formula I, including inhibition of a proliferative disease or condition, inhibition of angiogenesis, treatment of an angiogenic disease or condition, treatment of cancer and precancerous conditions, treatment of a fibrotic disorder, treatment of a viral infection, treatment of an Akt-mediated disease or condition, inhibition of the production, release or both of matrix metalloproteinase-9, and inhibition of Akt activation.

TREATMENT OF DEGENERATIVE JOINT DISEASE

The invention provides a method of treating a degenerative joint disease. The method comprises administering an effective amount of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP). The invention also provides a pharmaceutical product as well as a kit comprising DA-DKP.

Method and apparatus for measuring oxidation-reduction potential

Methods and systems for measuring the oxidation-reduction potential of a fluid sample are provided. The system includes a test strip with a sample chamber adapted to receive a fluid sample. The sample chamber can be associated with a filter membrane. The test strip also includes a reference cell. The oxidation-reduction potential of a fluid sample placed in the sample chamber can be read by a readout device interconnected to a test lead that is in electrical contact with the sample chamber, and a reference lead that is in electrical contact with the reference cell. Electrical contact between a fluid sample placed in the sample chamber and the reference cell can be established by a bridge. The oxidation-reduction potential may be read as an electrical potential between the test lead and the reference lead of the test strip.

Method of using diketopiperazines and composition containing them

The invention provides a method of inhibiting the effects of platelet activating factor (PAF). For instance, a disease or condition mediated by PAF (particularly inflammation) can be treated or platelet aggregation can be inhibited. The invention also provides a method of inhibiting the production and/or release of interleukin 8 (IL-8) by cells. The effects of PAF and the production and/or release of IL-8 are inhibited according to the invention by a compound of the formula: wherein R1and R2are defined in the application, or a physiologically-acceptable salt thereof. The invention also provides pharmaceutical compositions comprising these compounds.

MEASUREMENT AND USES OF OXIDATIVE STRESS

The present invention provides a method of determining the overall oxidative status of a body fluid or a tissue of a patient by measuring the oxidation-reduction potential (ORP) of the body fluid or tissue. The method has been found to be useful in the diagnosis, evaluation and monitoring of patients who have suffered a trauma (such as a head injury), patients suspected of being critically-ill or who are critically ill, patients who have an infection, and patients suspected of having a myocardial infarction (MI) or who have had an MI. The method has also been found useful in monitoring and evaluating exercise performance in patients. In addition, the method has been found useful in monitoring and evaluating stored blood products and patients who will receive such a product.

Use of copper chelators to inhibit the inactivation of protein C

The present invention is based on the unexpected discovery that activated protein C (APC) is inactivated by copper. Accordingly, the invention provides improved methods of treating diseases and conditions treatable with APC which utilize a copper chelator to inhibit the inactivation of APC by copper.

Treatment of disease with n-acetyl kynurenine

The invention provides a method, composition and kit for treating T-cell mediated diseases, degenerative joint diseases or diseases mediated by platelet activating factor (PAF) comprising administering to an animal in need thereof, an effective amount a pharmaceutical composition containing N-acetyl-kynurenine (NAK) or pharmaceutically acceptable salts thereof as the active ingredient.

Methods and products for treatment of diseases

The present invention relates to the treatment of diseases and conditions with an effective amount of a steroid having those formulas given in the specification, or a pharmacologically-acceptable salt or ester thereof. The disease or conditions treatable according to the invention include angiogenic diseases and conditions of the eye, angiogenic diseases and conditions of the brain, inflammatory diseases and conditions of the eye, inflammatory diseases and conditions of the brain and neurodegenerative diseases.

Methods and products for treatment of diseases

The present invention relates to the treatment of diseases and conditions with an effective amount of a steroid having those formulas given in the specification, or a pharmacologically-acceptable salt or ester thereof. The disease or conditions treatable according to the invention include angiogenic diseases and conditions of the eye, angiogenic diseases and conditions of the brain, inflammatory diseases and conditions of the eye, inflammatory diseases and conditions of the brain and neurodegenerative diseases.

TREATMENT OF JOINT CONDITIONS

The invention provides a method of treating a joint condition. The method comprises administering a multi-dose regimen of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP). The invention also provides a method of treating osteoarthritis with multiple doses of a low-molecular weight fraction of human serum albumin. 1. A method of treating a joint condition comprising administering to an animal in need thereof an effective amount of a pharmaceutical composition comprising DA-DKP in a multi-dose regimen.2. The method of claim 1 , wherein the joint condition is a joint disease.3. The method of claim 2 , wherein the joint disease is a degenerative joint disease.4. The method of claim 3 , wherein the degenerative joint disease is osteoarthritis.5. The method of claim 1 , wherein the joint condition is a joint injury.6. The method of claim 5 , wherein the joint injury is at least one of a traumatic injury and a post-operative injury.7. The method of claim 5 , wherein the joint injury is a repetitive strain injury.8. The method of claim 1 , wherein the joint condition is inflammation.9. The method of claim 1 , wherein the composition is administered by an administration route selected from the group consisting of local administration claim 1 , topical administration claim 1 , and injection.10. The method of claim 9 , wherein administration by injection is by intra-articular injection.11. The method of claim 10 , wherein the composition administered by intra-articular injection is a composition having a concentration of DA-DKP from about 50 μM to about 350 μM.12. The method of claim 1 , wherein the composition further comprises N-acetyl-tryptophan (NAT) claim 1 , caprylic acid claim 1 , caprylate or combinations thereof.13. The method of claim 10 , wherein the composition is a composition having a concentration of NAT claim 10 , caprylic acid claim 10 , caprylate or combinations thereof from about 4 ...

DETERMINATION OF FERTILITY POTENTIAL FROM THE OXIDATION-REDUCTION POTENTIAL OF A BIOLOGICAL SAMPLE

Methods and systems for measuring and using the oxidation-reduction potential (ORP) of a biological sample are provided. The system generally includes a test strip and a readout device for determining the ORP. The measured ORP is then used to determine characteristics relating to the fertility of the sample or the subject from which the sample was derived. Some characteristics that can be determined include the quality of a sperm sample, an oocyte or a fertilized egg. The measured ORP value can also be used to determine the specific characteristics of a spermatozoa sample, such as the morphology of the spermatozoa, the motility of the spermatozoa, the number of cells in the sample and the concentration of the cells in the sample. Knowledge of such characteristics and fertility potential can be used to identify individuals that might benefit from specific fertility treatments.

Metal-binding compounds and uses therefor

The invention provides a method of reducing the damage done by reactive oxygen species (ROS) in an animal. The invention also provides a method of reducing the concentration of a metal in an animal. These methods comprise administering to the animal an effective amount of a metal-binding compound as further described in the application. The invention further provides a method of reducing the damage done by ROS to a cell, a tissue or an organ that has been removed from an animal. This method comprising contacting the cell, tissue or organ with a solution or medium containing an effective amount of a metal-binding compound of the invention. The invention further provides novel metal-binding compounds, pharmaceutical compositions comprising the metal-binding compounds, and kits comprising a container holding a metal-binding compound of the invention.

Method of using diketopiperazines and composition containing them

The invention provides a method of inhibiting the effects of platelet activating factor (PAF). For instance, a disease or condition mediated by PAF (particularly inflammation) can be treated or platelet aggregation can be inhibited. The invention also provides a method of inhibiting the production and/or release of interleukin 8 (IL-8) by cells. The effects of PAF and the production and/or release of IL-8 are inhibited according to the invention by a compound of the formula: wherein R1 and R2 are defined in the application, or a physiologically-acceptable salt thereof. The invention also provides pharmaceutical compositions comprising these compounds.

Treatment of degenerative joint disease

The invention provides a method of treating a degenerative joint disease. The method comprises administering an effective amount of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP). The invention also provides a pharmaceutical product as well as a kit comprising DA-DKP.

Determination of fertility potential from the oxidation-reduction potential of a biological sample

Methods and systems for measuring and using the oxidation-reduction potential (ORP) of a biological sample are provided. The system generally includes a test strip and a readout device for determining the ORP. The measured ORP is then used to determine characteristics relating to the fertility of the sample or the subject from which the sample was derived. Some characteristics that can be determined include the quality of a sperm sample, an oocyte or a fertilized egg. The measured ORP value can also be used to determine the specific characteristics of a spermatozoa sample, such as the morphology of the spermatozoa, the motility of the spermatozoa, the number of cells in the sample and the concentration of the cells in the sample. Knowledge of such characteristics and fertility potential can be used to identify individuals that might benefit from specific fertility treatments.

Measurement and uses of oxidative status

The present invention provides a method of determining the overall oxidative status of a body fluid or a tissue of a patient by measuring the oxidation-reduction potential (ORP) of the body fluid or tissue. The method has been found to be useful in the diagnosis, evaluation and monitoring of patients who have suffered a trauma (such as a head injury), patients suspected of being critically-ill, patients who have a viral infection, and patients suspected of having a myocardial infarction. The method has also been found useful in monitoring and evaluating exercise performance in patients. In addition, the method has been found useful in monitoring and evaluating stored blood products and patients who will receive such a product.

TREATMENT OF DISEASES

The invention provides (i) a method of treating metabolic syndrome in an animal, (ii) a method of suppressing the appetite of an animal, (iii) a method of treating obesity in an animal, (iv) a method of reducing the weight of an animal in need thereof, (v) a method of reducing a blood lipid level in an animal in need thereof, (vi) a method of treating non-alcoholic steatohepatitis in an animal, and (vii) a method of inhibiting adipogenesis. The methods comprise administering an effective amount of an active ingredient, wherein the active ingredient comprises a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-acceptable salt of either of them to the animal. The invention also provides a kit comprising a container holding a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-acceptable salt of either of them; and instructions for administration. The diketopiperazines have the formula given in the application. 877. The method of any one of - wherein Rand R , which may be the same or different , each is (x) a side chain of an amino acid , wherein the amino acid is glycine , alanine , valine , norvaline , α-aminoisobutyric acid , 2 ,4-diaminobutyric acid , 2 ,3-diaminobutyric acid , leucine , isoleucine , norleucine , serine , homoserine , threonine , aspartic acid , asparagine , glutamic acid , glutamine , lysine , hydroxylysine , arginine , homoarginine , citrulline , phenylalanine , p-aminophenylalanine , tyrosine , tryptophan , thyroxine , cysteine , homocysteine , methionine , penicillamine or ornithine , or (y) a derivative of a side chain of one of these amino acids , wherein the derivatives are those recited in -.977. The method of any one of - wherein Rand R , which may be the same or different , each is (x) a side chain of an amino acid , wherein the amino acid is glycine , alanine , valine , norvaline , α-aminoisobutyric acid , 2 ,4-diaminobutyric acid , 2 ,3-diaminobutyric acid , leucine , isoleucine , norleucine , ...

METHOD AND APPARATUS FOR MEASURING OXIDATION-REDUCTION POTENTIAL

Methods and systems for measuring the oxidation-reduction potential of a fluid sample are provided. The system includes a test strip with a sample chamber adapted to receive a fluid sample. The sample chamber can be associated with a filter membrane. The test strip also includes a reference cell. The oxidation-reduction potential of a fluid sample placed in the sample chamber can be read by a readout device interconnected to a test lead that is in electrical contact with the sample chamber, and a reference lead that is in electrical contact with the reference cell. Electrical contact between a fluid sample placed in the sample chamber and the reference cell can be established by a bridge. The oxidation-reduction potential may be read as an electrical potential between the test lead and the reference lead of the test strip. 1. An oxidation-reduction potential test device , comprising:a substrate;a sample chamber; a first area extending into the sample chamber;', 'a second area extending from the sample chamber;, 'a first test lead supported by the substrate, the first test lead includinga reference cell; a first area in electrical contact with the reference cell;', 'a second area extending from the reference cell;, 'a reference lead, including;'}a bridge, wherein a fluid sample in the sample chamber is placed in electrical contact with the reference cell by the bridge.2. The device of claim 1 , further comprising:an overlay, wherein at least a portion of the first test lead, the reference cell, at least a portion of the reference lead, and the bridge are held between the substrate and the overlay when the overlay is interconnected to the substrate.3. The device of claim 2 , wherein the overlay includes an aperture claim 2 , and wherein the aperture corresponds to at least a portion of the sample chamber when the overlay is interconnected to the substrate.4. The device of claim 3 , further comprising:a filter element, wherein the filter element at least one of extends ...

IMPLANTABLE MEDICAL DEVICES WITH INCREASED IMMUNE TOLERANCE, AND METHODS FOR MAKING AND IMPLANTING

The present invention relates to the contacting of one or more surfaces of an implantable medical device with one or more diketopiperazines (DKPs).

Measurement and uses of oxidative stress

The present invention provides a method of determining the overall oxidative status of a body fluid or a tissue of a patient by measuring the oxidation-reduction potential (ORP) of the body fluid or tissue. The method has been found to be useful in the diagnosis, evaluation and monitoring of patients who have suffered a trauma (such as a head injury), patients suspected of being critically-ill, patients who have a viral infection, and patients suspected of having a myocardial infarction. The method has also been found useful in monitoring and evaluating exercise performance in patients. In addition, the method has been found useful in monitoring and evaluating stored blood products and patients who will receive such a product.

Therapeutic methods and compounds

The invention provides diketopiperazines of formula I. The invention also provides pharmaceutical compositions comprising the diketopiperazines, or pharmaceutically-acceptable salts or prodrugs thereof, as the active ingredient. The invention further provides therapeutic treatments that utilize the diketopiperazines of formula I, including inhibition of a proliferative disease or condition, inhibition of angiogenesis, treatment of an angiogenic disease or condition, treatment of cancer and precancerous conditions, treatment of a fibrotic disorder, treatment of a viral infection, treatment of an Akt-mediated disease or condition, inhibition of the production, release or both of matrix metalloproteinase-9, and inhibition of Akt activation.

Methods and systems for measuring and using the oxidation-reduction potential of a biological sample

Methods and systems for measuring and using the oxidation-reduction characteristics of a biological sample are provided. The system generally includes a test strip and a readout device. A fluid sample is placed in the test strip, and the test strip is in turn operatively connected to the readout device. The readout device provides a controlled current that is sent across the fluid in the sample chamber. In addition, the readout device identifies an inflection point or transition time at which the voltage between contacts of the test strip is changing at the highest rate. The oxidation-reduction capacity of the sample is taken as the integral of the current profile from the time at which current begins to be supplied to the sample to the identified transition time.

IMPLANTABLE MEDICAL DEVICES WITH INCREASED IMMUNE TOLERANCE, AND METHODS FOR MAKING AND IMPLANTING

The present invention relates to the contacting of one or more surfaces of an implantable medical device with one or more diketopiperazines (DKPs). 161.-. (canceled)62. An implantable medical device , wherein a surface of the device comprises components of a filtrate of human serum albumin , wherein one of the components is DA-DKP.6377.-. (canceled)78. The device of claim 62 , wherein the implantable medical device is selected from the group consisting of a graft claim 62 , catheter claim 62 , stent claim 62 , prosthetic claim 62 , breast implant claim 62 , pump claim 62 , tube claim 62 , pin claim 62 , rod claim 62 , screw claim 62 , brace claim 62 , plate and pace maker.79. The device of claim 62 , wherein the implantable medical device is composed of a material selected from the group consisting of metal claim 62 , steel claim 62 , titanium claim 62 , glass claim 62 , polymers claim 62 , plastics claim 62 , and ceramics.80. The device of claim 62 , wherein the components are adhered to the surface of the device.81. The device of claim 62 , wherein the components are impregnated into the surface of the device.82. The device of claim 62 , wherein the components are coated onto the surface of the device.83. The device of claim 62 , produced by contacting the device with a filtrate of human serum albumin claim 62 , wherein the solution adheres to the device.84. The device of claim 62 , wherein the DA-DKP is in the filtrate at a concentration of about 1 μM to about 500 μM.85. The device of claim 62 , wherein the DA-DKP is in the filtrate at a concentration of about 50 μM to about 100 μM.86. The device of claim 62 , wherein the concentration of the DKP on a surface of the implantable medical device exposed to the body is about 1 ng/cmto about 200 ng/cm.87. The device of claim 62 , wherein the concentration of the DA-DKP on a surface of the implantable medical device exposed to the body is about 50 ng/cm.88. A method to prepare the implantable medical device of for ...

METHOD AND APPARATUS FOR MEASURING OXIDATION-REDUCTION POTENTIAL

Methods and systems for measuring the oxidation-reduction potential of a fluid sample are provided. The system includes a test strip with a sample chamber adapted to receive a fluid sample. The sample chamber can be associated with a filter membrane. The test strip also includes a reference cell. The oxidation-reduction potential of a fluid sample placed in the sample chamber can be read by a readout device interconnected to a test lead that is in electrical contact with the sample chamber, and a reference lead that is in electrical contact with the reference cell. Electrical contact between a fluid sample placed in the sample chamber and the reference cell can be established by a bridge. The oxidation-reduction potential may be read as an electrical potential between the test lead and the reference lead of the test strip.

METHODS AND SYSTEMS FOR MEASURING AND USING THE OXIDATION-REDUCTION POTENTIAL OF A BIOLOGICAL SAMPLE

Methods and systems for measuring and using the oxidation-reduction characteristics of a biological sample are provided. The system generally includes a test strip and a readout device. A fluid sample is placed in the test strip, and the test strip is in turn operatively connected to the readout device. The readout device provides a controlled current that is sent across the fluid in the sample chamber. In addition, the readout device identifies an inflection point or transition time at which the voltage between contacts of the test strip is changing at the highest rate. The oxidation-reduction capacity of the sample is taken as the integral of the current profile from the time at which current begins to be supplied to the sample to the identified transition time. 1. A method of evaluating a subject in a medical facility for treatment of a disease or condition prior to discharge from the medical facility to determine whether the subject is at risk of readmission to the medical facility for the disease or condition , or complications thereof , if the patient were to be discharged from the medical facility , comprising:a. measuring the static oxidation-reduction potential (sORP) and/or the capacity oxidation-reduction potential (cORP) of the subject;b. comparing the measured sORP and/or cORP to a reference value to determine the discharge status of the subject; andc. making a discharge decision for the subject based on the discharge status of the subject.211.-. (canceled)12. A method for diagnosing , evaluating or monitoring a subject for diabetes , comprising:a. measuring the static oxidation-reduction potential (sORP) and/or the capacity oxidation-reduction potential (cORP) of the subject;b. comparing the measured sORP and/or cORP to a reference value to determine the diabetes status of the subject; andc. treating the subject based on the diabetes status of the subject.1322.-. (canceled)23. A method for diagnosing , evaluating or monitoring a subject for sepsis , ...

Methods for treating diseases associated with respiratory viruses

The present disclosure provides a method of treating a disease associated with a respiratory virus. The method comprises administering an effective amount of a pharmaceutical composition prepared by removing albumin from a solution of a human serum albumin composition and/or comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP), such as a low molecular weight fraction of human serum albumin. The present disclosure also provides a pharmaceutical product as well as a kit comprising DA-DKP.

METHOD FOR TREATMENT OF DISEASES

The invention provides a method of inhibiting vascular hyperpermeability in an animal in need thereof. The method comprises administering a vascular-hyperpermeability-inhibiting amount of a danazol compound to the animal. The invention also provides a method of modulating the cytoskeleton of an endothelial cell in an animal. The method comprises administering an effective amount of a danazol compound to the animal.

Treatment of Comorbid Premature Ejaculation and Erectile Dysfunction

The invention provides a method of treating comorbid premature ejaculation and erectile dysfunction. In particular, the method comprises administering an effective amount of a tramadol material and an effective amount of a phosphodiesterase inhibitor. The invention also provides a pharmaceutical composition comprising a pharmaceutically-acceptable carrier, a tramadol material and a phosphodiesterase inhibitor. The invention further provides a kit comprising a tramadol material and a phosphodiesterase inhibitor. 16-. (canceled)7. A pharmaceutical composition consisting of one or more pharmaceutically-acceptable carriers , a tramadol material and a phosphodiesterase (PDE) inhibitor.8. The composition of wherein the tramadol material is tramadol or a pharmaceutically-acceptable form thereof claim 7 , and the PDE inhibitor is a PDE3 claim 7 , PDE4 or PDE5 inhibitor.9. The composition of wherein the PDE inhibitor is a PDE5 inhibitor.10. The composition of wherein the tramadol material is (±)cis-tramadol or a pharmaceutically-acceptable salt thereof claim 9 , and the PDE5 inhibitor is sildenafil or a pharmaceutically-acceptable form thereof claim 9 , vardenafil or a pharmaceutically-acceptable form thereof claim 9 , tadalafil or a pharmaceutically-acceptable form thereof claim 9 , or a combination of two or more of the foregoing PDE5 inhibitors.11. The composition of wherein the tramadol material is (±)cis-tramadol hydrochloride claim 10 , and the PDE5 inhibitor is sildenafil citrate claim 10 , vardenafil hydrochloride claim 10 , tadalafil or a combination of two or more of the foregoing PDE5 inhibitors.12. The composition of wherein the PDE5 inhibitor is sildenafil citrate.1319-. (canceled) This application is a divisional application of U.S. application Ser. No. 12/029,783, filed Feb. 12, 2008, which claims priority from U.S. Provisional Patent Application No. 60/889,369 filed February 12, 2007. The entire disclosures of the prior applications are considered to be part ...

Methylphenidate derivatives and uses of them

The present invention provides methods of using compounds of formula I: and salts and prodrugs thereof, wherein n, R1and R2are defined herein. The invention also provides certain novel compounds of formula I and pharmaceutical compositions comprising them.

Methods of treatment of diseases

The invention provides a method of inhibiting vascular hyperpermeability in an animal in need thereof. The method comprises administering a vascular-hyperpermeability-inhibiting amount of a danazol compound to the animal. The method comprises administering an effective amount of a danazol compound to the animal accounting for the body fat content of the animal. The invention also provides a method of modulating the cytoskeleton of an endothelial cell in an animal.

Treatment of Comorbid Premature Ejaculation and Erectile Dysfunction

The invention provides a method of treating comorbid premature ejaculation and erectile dysfunction. In particular, the method comprises administering an effective amount of a tramadol material and an effective amount of a phosphodiesterase inhibitor. The invention also provides a pharmaceutical composition comprising a pharmaceutically-acceptable carrier, a tramadol material and a phosphodiesterase inhibitor. The invention further provides a kit comprising a tramadol material and a phosphodiesterase inhibitor. 112-. (canceled)13. A kit comprising:(a) a container holding a tramadol material and a phosphodiesterase (PDE) inhibitor; or(b) a first container holding a tramadol material and a second container holding a phosphodiesterase (PDE) inhibitor.14. The kit of wherein the tramadol material is tramadol or a pharmaceutically-acceptable form thereof claim 13 , and the PDE inhibitor is a PDE3 claim 13 , PDE4 or PDE5 inhibitor.15. The kit of wherein the PDE inhibitor is a PDE5 inhibitor.16. The kit of wherein the tramadol material is (±)cis-tramadol or a pharmaceutically-acceptable salt thereof claim 15 , and the PDE5 inhibitor is sildenafil or a pharmaceutically-acceptable form thereof claim 15 , vardenafil or a pharmaceutically-acceptable form thereof claim 15 , tadalafil or a pharmaceutically-acceptable form thereof claim 15 , or a combination of two or more of the foregoing PDE5 inhibitors.17. The kit of wherein the tramadol material is (±)cis-tramadol hydrochloride claim 16 , and the PDE5 inhibitor is sildenafil citrate claim 16 , vardenafil hydrochloride claim 16 , tadalafil or a combination of two or more of the foregoing PDE5 inhibitors.18. The kit of wherein the PDE5 inhibitor is sildenafil citrate.19. The kit of further comprising instructions for using the tramadol material and the PDE inhibitor to treat comorbid premature ejaculation and erectile dysfunction in a male. This application is a divisional application of U.S. application Ser. No. 12/029,783, ...

Method of using diketopiperazines and composition containing them

The invention provides a method of inhibiting the effects of platelet activating factor (PAF). For instance, a disease or condition mediated by PAF (particularly inflammation) can be treated or platelet aggregation can be inhibited. The invention also provides a method of inhibiting the production and/or release of interleukin 8 (IL-8) by cells. The effects of PAF and the production and/or release of IL-8 are inhibited according to the invention by a compound of the formula: wherein R1 and R2 are defined in the application, or a physiologically-acceptable salt thereof. The invention also provides pharmaceutical compositions comprising these compounds.

"METHODS AND PRODUCTS FOR TREATMENT OF DISEASES"

The present invention relates to the treatment of diseases and conditions with an effective amount of a steroid having those formulas given in the specification, or a pharmacologically-acceptable salt or ester thereof. The disease or conditions treatable according to the invention include angiogenic diseases and conditions of the eye, angiogenic diseases and conditions of the brain, inflammatory diseases and conditions of the eye, inflammatory diseases and conditions of the brain and neurodegenerative diseases.

Measurement and Uses of Oxidative Status

The present invention provides a method of determining the overall oxidative status of a body fluid or a tissue of a patient by measuring the oxidation-reduction potential (ORP) of the body fluid or tissue. The method has been found to be useful in the diagnosis, evaluation and monitoring of patients who have suffered a trauma (such as a head injury), patients suspected of being critically-ill or who are critically ill, patients who have an infection, and patients suspected of having a myocardial infarction (MI) or who have had an MI. The method has also been found useful in monitoring and evaluating exercise performance in patients. In addition, the method has been found useful in monitoring and evaluating stored blood products and patients who will receive such a product. 132-. (canceled)33. A method of evaluating the suitability of a stored blood product for transfusing an individual , comprising:a. measuring the oxidation-reduction potential (ORP) of a stored blood product; and,b. comparing the ORP of the stored blood product with the ORP of a corresponding blood product immediately after it was obtained from a donor (fresh blood product);wherein if the ORP of the stored blood product is significantly different than the ORP of the fresh blood product, discarding the stored blood product.34. The method of claim 33 , wherein the stored blood product has been stored for one or more days.35. The method of claim 33 , wherein the blood product is whole blood.36. The method of claim 33 , wherein the blood product is packed red blood cells.37. The method of claim 33 , wherein the ORP of the stored blood product is measured one per day during storage.38. The method of claim 33 , wherein the ORP value is measured by contacting the stored blood product with an electrode connected to a machine that provides a readout of the ORP.39. A method of reducing side effects due to transfusion of a stored blood product claim 33 , comprising:a. measuring the oxidation-reduction ...

Tests for the rapid evaluation of ischemic states and kits

The present invention relates to rapid methods for the detection of ischemic states and to kits for use in such methods. Provided for is a rapid method of testing for and quantifying ischemia based upon methods of detecting and quantifying the existence of an alteration of the serum protein albumin which occurs following an ischemic event; methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of circulating albumin, analysis and measurement of the ability of serum albumin to bind exogenous cobalt, detection and measurement of the presence of endogenous copper in a purified albumin sample and use of an immunological assay specific to the altered form of serum albumin which occurs following an ischemic event. Also taught by the present invention is the detection and measurement of an ischemic event by measuring albumin N-terminal derivatives that arise following an ischemic event, including truncated albumin species lacking one ...

TREATMENT OF T-CELL MEDIATED DISEASES

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions. 191-. (canceled)92. A method of treating inflammation or an inflammatory disease involving , caused by or exacerbated by T-cells , comprising administering to an animal in need thereof an effective amount of a pharmaceutical composition comprising a filtrate of a solution of a protein or peptide , wherein the filtrate is produced by passing the solution of a protein or peptide over an ultrafiltration membrane with a molecular weight cutoff that retains a protein selected from the group consisting of albumin , immunoglobulin and erythropoietin , and wherein the filtrate comprises: a diketopiperazine selected from the group consisting of YE-DKP , MR-DKP and DA-DKP.93. The method of wherein the filtrate contains components having molecular weights less than 3000.94. The method of wherein the protein or peptide is a human protein or peptide.95. The method of wherein the protein or peptide is a human albumin.96. The method of wherein the protein or peptide is a human protein or peptide.97. The method of wherein the protein or peptide is a human albumin.98. The method of wherein the animal is a human.99. A method of reducing the symptoms claim 92 , severity or both of a T-cell mediated disease claim 92 , comprising administering to an animal in need thereof an effective amount of a pharmaceutical composition comprising a filtrate of a solution of a protein or peptide claim 92 , wherein the filtrate is produced by passing the ...

TREATMENT OF T-CELL MEDIATED DISEASES

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions. 191-. (canceled)92. A method of treating a T-cell mediated pulmonary disease , comprising:administering a pharmaceutical composition comprising an alanine-aspartic acid diketopiperazine (DA-DKP)-containing fraction of a solution of human albumin, caprylic acid, and N-acetyl tryptophan to an animal in need thereof by inhalation or insufflation, wherein:the DA-DKP-containing fraction is produced by passing a solution of albumin over an ultrafiltration membrane with a molecular weight cutoff that retains the human albumin; andthe pulmonary disease is selected from the group consisting of sarcoidosis, acute interstitial pneumonitis, alveolitis, and pulmonary fibrosis.93. The method of claim 92 , wherein the pharmaceutical composition is formulated as a powder claim 92 , a spray claim 92 , or a solution.94. The method of claim 92 , wherein the pharmaceutical composition is administered to the upper or lower respiratory tract.95. The method of claim 92 , wherein the pharmaceutical composition is administered by inhalation.96. The method of claim 92 , wherein the pharmaceutical composition is an aerosol spray.97. The method of claim 96 , wherein the aerosol spray is administered by an insufflator claim 96 , a nebulizer claim 96 , or a pressurized pack.98. The method of claim 97 , wherein the aerosol spray is administered by a nebulizer.99. A method of treating inflammatory lung damage claim 97 , comprising:administering a ...

METHOD OF USING DIKETOPIPERAZINES AND COMPOSITION CONTAINING THEM

The invention provides a method of inhibiting the effects of platelet activating factor (PAF). For instance, a disease or condition mediated by PAF (particularly inflammation) can be treated or platelet aggregation can be inhibited. The invention also provides a method of inhibiting the production and/or release of interleukin 8 (IL-8) by cells. The effects of PAF and the production and/or release of IL-8 are inhibited according to the invention by a compound of the formula: wherein R1 and R2 are defined in the application, or a physiologically-acceptable salt thereof. The invention also provides pharmaceutical compositions comprising these compounds.

Treatment of degenerative joint disease

The invention provides a method of treating a degenerative joint disease. The method comprises administering an effective amount of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP). The invention also provides a pharmaceutical product as well as a kit comprising DA-DKP.

TREATMENT OF T-CELL MEDIATED DISEASES

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions. 191.-. (canceled)92. A pharmaceutical composition comprising a filtrate containing a diketopiperazine derived from a protein or peptide , the filtrate having been produced by chromatography of a solution of the protein or peptide containing the diketopiperazine.93. The composition of wherein the chromatography is size-exclusion chromatography.94. The composition of wherein the filtrate contains components having molecular weights less than 3000.95. The composition of wherein the protein is an albumin claim 92 , an immunoglobulin or an erythropoietin.96. The composition of wherein the protein or peptide is a human protein or peptide.97. The composition of wherein the protein or peptide is a human albumin.98. The composition of wherein the protein is an albumin claim 93 , an immunoglobulin or an erythropoietin.99. The composition of wherein the protein or peptide is a human protein or peptide.100. The composition of wherein the protein or peptide is a human albumin.101. The composition of wherein the protein is an albumin claim 94 , an immunoglobulin or an erythropoietin.102. The composition of wherein the protein or peptide is a human protein or peptide.103. The composition of wherein the protein or peptide is a human albumin.104. A filtrate containing a diketopiperazine derived from a protein or peptide claim 94 , the filtrate having been produced by chromatography of a solution of the protein or peptide containing the ...

Methylphenidate derivatives and uses of them

The present invention provides methods of using compounds of formula I: and salts and prodrugs thereof, wherein n, R1 and R2 are defined herein. The invention also provides certain novel compounds of formula I and pharmaceutical compositions comprising them.

METAL-BINDING COMPOUNDS AND USES THEREFOR

The invention provides a method of reducing the damage done by reactive oxygen species (ROS) in an animal. The invention also provides a method of reducing the concentration of a metal in an animal. These methods comprise administering to the animal an effective amount of a metal-binding compound as further described in the application. The invention further provides a method of reducing the damage done by ROS to a cell, a tissue or an organ that has been removed from an animal. This method comprising contacting the cell, tissue or organ with a solution or medium containing an effective amount of a metal-binding compound of the invention. The invention further provides novel metal-binding compounds, pharmaceutical compositions comprising the metal-binding compounds, and kits comprising a container holding a metal-binding compound of the invention.

Treatment of T-cell mediated diseases

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions.

Test for the rapid evaluation of ischemic states and kits

The present invention relates to rapid methods for the detection of ischemic states and to kits for use in such methods. Provided for is a rapid method of testing for and quantifying ischemia based upon methods of detecting and quantifying the existence of an alteration of the serum protein albumin which occurs following an ischemic event; methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of circulating albumin, analysis and measurement of the ability of serum albumin to bind exogenous cobalt, detection and measurement of the presence of endogenous copper in a purified albumin sample and use of an immunological assay specific to the altered form of serum albumin which occurs following an ischemic event. Also taught by the present invention is the detection and measurement of an ischemic event by measuring albumin N-terminal derivatives that arise following an ischemic event, including truncated albumin species lacking one ...

METHODS AND SYSTEMS FOR MEASURING AND USING THE OXIDATION-REDUCTION POTENTIAL OF A BIOLOGICAL SAMPLE

Methods and systems for measuring and using the oxidation-reduction characteristics of a biological sample are provided. The system generally includes a test strip and a readout device. A fluid sample is placed in the test strip, and the test strip is in turn operatively connected to the readout device. The readout device provides a controlled current that is sent across the fluid in the sample chamber. In addition, the readout device identifies an inflection point or transition time at which the voltage between contacts of the test strip is changing at the highest rate. The oxidation-reduction capacity of the sample is taken as the integral of the current profile from the time at which current begins to be supplied to the sample to the identified transition time. 1110.-. (canceled)111. A method for evaluating or monitoring the quality of a banked blood product , comprising:a. measuring the static oxidation-reduction potential (sORP) and/or the capacity oxidation-reduction potential (cORP) of the banked blood product;b. comparing the measured sORP and/or cORP to a reference value to determine the status of the banked blood product; andc. treating the banked blood product based on the status of the banked blood product.112. The method of claim 111 , wherein the step of measuring is measuring the sORP.113. The method of claim 111 , wherein the step of measuring is measuring the cORP.114. The method of claim 111 , wherein the step of measuring is measuring the sORP and the cORP.115. The method of claim 111 , wherein the reference value is a normal quality banked blood product reference value.116. The method of claim 111 , wherein the reference value is low quality banked blood product reference value.117. The method of claim 111 , wherein the reference value is a reference value obtained from the same banked blood product at an earlier time.118. The method of claim 111 , wherein the quality of the banked blood product is that the product is of low quality.119. The ...

TREATMENT OF DISEASES

The invention provides a method of inhibiting vascular hyperpermeability in an animal in need thereof. The method comprises administering an effective amount of a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-acceptable salt of either of them to the animal, wherein the diketopiperazine has the formula set forth in the specification. 2. The method of wherein the animal is in need of the diketopiperazine claim 1 , prodrug or salt because of the presence of a disease or condition mediated by vascular hyperpermeability.3. The method of wherein administration of the diketopiperazine claim 2 , prodrug or salt is commenced immediately upon diagnosis of the disease or condition.4. The method of wherein the disease or condition is a vascular complication of diabetes.5. The method of wherein the vascular complication is edema claim 4 , accumulation of low density lipoproteins in subendothelial space claim 4 , accelerated atherosclerosis claim 4 , accelerated aging of vessel walls in the brain claim 4 , myocardial edema claim 4 , myocardial fibrosis claim 4 , diastolic dysfunction claim 4 , diabetic cardiomyopathy claim 4 , retardation of lung development in the fetuses of diabetic mothers claim 4 , alterations of one or more pulmonary physiological parameters claim 4 , increased susceptibility to infections claim 4 , vascular hyperplasy in the mesentery claim 4 , diabetic neuropathy claim 4 , diabetic macular edema claim 4 , diabetic nephropathy claim 4 , diabetic retinopathy claim 4 , or redness claim 4 , discoloration claim 4 , dryness and ulcerations of the skin.6. The method of wherein the vascular complication is edema.7. The method of wherein the vascular complication is diabetic cardiomyopathy.8. The method of wherein the vascular complication is diabetic neuropathy.9. The method of wherein the vascular complication is diabetic macular edema.10. The method of wherein the vascular complication is diabetic retinopathy.11. The method of wherein ...

Marker useful for detection and measurement of free radical damage and method

The present invention teaches a marker useful for detection and measurement of free radical damage. Specifically, the invention takes advantage of alterations which occur to the N-terminus of the albumin molecule, a circulating protein in human blood, in the presence of free radicals. These alterations effect the ability of the N-terminus of the albumin molecule to bind metals. Methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of an albumin-containing sample, analysis and measurement of the ability of albumin to bind exogenous cobalt, detection and measurement of the presence of copper in a purified albumin sample and use of an immunological assay specific to the altered form of serum albumin which occurs following free radical damage. Also taught by the present invention is the use of the peptide Asp Ala His Lys and the compound Asp-Ala-His-Lys-R, wherein R is any chemical group capable of producing a detectable signal ...

Treatment of T-cell mediated diseases

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions.

Treatment of T-cell mediated diseases

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions.

Methylphenidate Derivatives and Uses of Them

The present invention provides methods of using compounds of formula I: and salts and prodrugs thereof, wherein n, R1 and R2 are defined herein. The invention also provides certain novel compounds of formula I and pharmaceutical compositions comprising them.

Treatment of T-cell mediated diseases

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions.

Use of low molecular weight fractions of human serum albumin in treating diseases

The present invention provides a method of modulating various aspects of the immune system. In particular, the present invention teaches the use of diketopiperazines (DKPs) to modulate various aspects of the immune system such as, for example, inflammation, T-cells and various cytokines.

TREATMENT OF DISEASES AND CONDITIONS MEDIATED BY INCREASED PHOSPHORYLATION

The invention provides methods for the treatment of diseases and conditions mediated by increased phosphorylation, such as inflammation and cancer. The invention also provides methods for the inhibition of increased phosphorylation in cells, tissues and organs. The methods utilize a phosphate acceptor compound (PAC). The invention also provides products comprising a PAC.

Multiple layer gel

A multiple layer gel and method for forming a multiple layer gel are provided. The multiple layer gel includes an isolation layer and an electrolyte layer. The isolation layer provides a molecular weight screen, to prevent proteins or other molecules from contacting a reference cell covered by the isolation layer. The electrolyte layer covers the isolation layer, and provides a source of ions that place the reference cell in ionic and/or electrical contact with a fluid sample. The multiple layer gel can be used to maintain a reliable reference voltage from an associated reference cell while an electrical potential or other electrical characteristic of a sample fluid is being determined.

METHOD OF USING DIKETOPIPERAZINES AND COMPOSITION CONTAINING THEM

The invention provides a method of inhibiting the effects of platelet activating factor (PAF). For instance, a disease or condition mediated by PAF (particularly inflammation) can be treated or platelet aggregation can be inhibited. The invention also provides a method of inhibiting the production and/or release of interleukin 8 (IL-8) by cells. The effects of PAF and the production and/or release of IL-8 are inhibited according to the invention by a compound of the formula: 128-. (canceled)30. The composition of wherein Ris the side chain of an amino acid selected from the group consisting of alanine claim 29 , valine claim 29 , leucine claim 29 , isoleucine claim 29 , serine claim 29 , threonine claim 29 , aspartic acid claim 29 , asparagine claim 29 , glutamic acid claim 29 , glutamine claim 29 , hydroxylysine claim 29 , histidine claim 29 , tyrosine claim 29 , thyroxine and norvaline.31. The composition of wherein Ris the side chain of an amino acid selected from the group consisting of alanine claim 30 , valine claim 30 , leucine claim 30 , isoleucine claim 30 , serine claim 30 , threonine claim 30 , aspartic acid claim 30 , asparagine claim 30 , glutamic acid claim 30 , glutamine claim 30 , hydroxylysine claim 30 , tyrosine claim 30 , thyroxine and norvaline.32. The composition of wherein Ris the side chain of an amino acid selected from the group consisting of alanine claim 29 , valine claim 29 , leucine claim 29 , isoleucine claim 29 , phenylalanine claim 29 , and norvaline.33. The composition of wherein Ris the side chain of an amino acid selected from the group consisting of alanine claim 32 , valine claim 32 , leucine claim 32 , isoleucine and norvaline.34. The composition of wherein Ris the side chain of alanine.35. The composition of wherein Ris —ORand Ris a lower alkyl.36. The composition of wherein Ris —ORand Ris a lower alkyl.37. The composition of wherein Ris —NH.38. The composition of wherein Ris —NH.39. The composition of wherein Ris —OH.40. The ...

METHOD OF USING DIKETOPIPERAZINES AND COMPOSITION CONTAINING THEM

The invention provides a method of inhibiting the effects of platelet activating factor (PAF). For instance, a disease or condition mediated by PAF (particularly inflammation) can be treated or platelet aggregation can be inhibited. The invention also provides a method of inhibiting the production and/or release of interleukin 8 (IL-8) by cells. The effects of PAF and the production and/or release of IL-8 are inhibited according to the invention by a compound of the formula: 128-. (canceled)30. The composition of wherein Ris the side chain of alanine claim 29 , valine claim 29 , leucine claim 29 , isoleucine or norvaline.31. The composition of wherein Ris the side chain of alanine.32. The composition of wherein Ris the side chain of serine or threonine.33. The composition of wherein Ris the side chain of aspartic acid claim 29 , asparagine claim 29 , glutamic acid or glutamine.34. The composition of wherein Ris —NHand Ris —CHCONH.35. The composition of wherein Ris —NHand Ris —CHCONH.37. The composition of wherein Ris the side chain of an amino acid selected from the group consisting of alanine claim 36 , valine claim 36 , leucine claim 36 , isoleucine claim 36 , serine claim 36 , threonine claim 36 , aspartic acid claim 36 , asparagine claim 36 , glutamic acid claim 36 , glutamine claim 36 , hydroxylysine claim 36 , tyrosine claim 36 , thyroxine and norvaline.38. The composition of wherein Ris the side chain of alanine claim 36 , valine claim 36 , leucine claim 36 , isoleucine or norvaline.39. The composition of wherein Ris the side chain of alanine.40. The composition of wherein Ris the side chain of serine or threonine.41. The composition of wherein Ris the side chain of aspartic acid claim 36 , asparagine claim 36 , glutamic acid or glutamine.42. The composition of wherein Ris the side chain of lysine claim 36 , hydroxylysine or ornithine.43. The composition of wherein Ris —OH and Ris —CHCOOH.44. The composition of wherein Ris —OH and Ris —CHCOOH.46. The ...

Methylphenidate Derivatives and Uses of Them

The present invention provides methods of using compounds of formula I: and salts and prodrugs thereof, wherein n, R 1 and R 2 are defined herein. The invention also provides certain novel compounds of formula I and pharmaceutical compositions comprising them.

THERAPEUTIC METHODS AND COMPOUNDS

The invention provides diketopiperazines of formula I. The invention also provides pharmaceutical compositions comprising the diketopiperazines, or pharmaceutically-acceptable salts or prodrugs thereof, as the active ingredient. The invention further provides therapeutic treatments that utilize the diketopiperazines of formula I, including inhibition of a proliferative disease or condition, inhibition of angiogenesis, treatment of an angiogenic disease or condition, treatment of cancer and precancerous conditions, treatment of a fibrotic disorder, treatment of a viral infection, treatment of an Akt-mediated disease or condition, inhibition of the production, release or both of matrix metalloproteinase-9, and inhibition of Akt activation. 150.-. (canceled)52. The method of wherein Rof the diketopiperazine: (d) a side chain of an amino acid, wherein the amino acid is glycine, alanine, valine, norvaline, α-aminoisobutyric acid, 2,4-diaminobutyric acid, 2,3-diaminobutyric acid, leucine, isoleucine, norleucine, serine, homoserine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, hydroxylysine, histidine, arginine, homoarginine, citrulline, phenylalanine, p-aminophenylalanine, tyrosine, tryptophan, thyroxine or ornithine; or', {'claim-ref': {'@idref': 'CLM-00051', 'claim 51'}, '(e) a derivative of a side chain of an amino acid, wherein the amino acid is one of those recited in (d), and the derivative of the side chain is one of those recited in part (c) of ; and'}], 'is{'sup': '2', 'Rhas formula II or III.'}53. The method of wherein Rof the diketopiperazine is:(f) a side chain of an amino acid, wherein the amino acid is glycine, alanine, valine, norvaline, α-aminoisobutyric acid, 2,4-diaminobutyric acid, 2,3-diaminobutyric acid, leucine, isoleucine, norleucine, serine, homoserine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, hydroxylysine, arginine, homoarginine, citrulline or ornithine; or{'claim-ref': {'@idref': 'CLM- ...

Methods and products for treatment of diseases

The invention provides a method of treating a disease or condition mediated by vascular hyperpermeability in an animal. The method comprises administering an amount of a danazol compound effective to inhibit vascular hyperpermeability and an amount of a second drug effective to treat the disease or condition. The invention further provides a method of inhibiting vascular hyperpermeability when it is a side effect caused by administration of a drug to, or another treatment of, an animal. The method comprises administration of an amount of a danazol compound effective to inhibit the vascular hyperpermeability. The invention also provides a method of modulating the cytoskeleton of endothelial cells in an animal comprising administering an amount of a danazol compound and an amount of a second drug effective to modulate the cytoskeleton. The present invention also relates to pharmaceutical compositions and kits comprising a danazol compound and a second drug.

TREATMENT OF T-CELL MEDIATED DISEASES

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions. 191-. (canceled)92. A pharmaceutical composition comprising an alanine-aspartic acid diketopiperazine (DA-DKP) and a component selected from the group consisting of caprylic acid , N-acetyl tryptophan and combinations thereof.93. The composition of claim 92 , wherein the composition is produced by passing a solution of albumin over an ultrafiltration membrane with a molecular weight cutoff that retains albumin claim 92 , and wherein the filtrate comprises the DA-DKP.94. The composition of wherein the DA-DKP filtrate contains components having molecular weights less than 3000.95. The composition of wherein the albumin is a human albumin.96. The composition of claim 92 , wherein the composition is formulated for administration by an administration route selected from the group consisting of topical administration claim 92 , transdermal administration claim 92 , oral administration claim 92 , inhalation or insufflations claim 92 , and parenteral administration.97. The composition of claim 96 , wherein the composition formulated for parenteral administration is by injection.98. The composition of claim 96 , wherein the composition formulated for oral administration is in a form selected from the group consisting of capsules claim 96 , cachets claim 96 , pills claim 96 , tablets claim 96 , powders claim 96 , granules claim 96 , as a solution or a suspension in an aqueous or non-aqueous liquid claim 96 , or an oil-in-water or water- ...

TREATMENT OF T-CELL MEDIATED DISEASES

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions. 191-. (canceled)92. A container comprising a pharmaceutical formulation , wherein the formulation comprises a filtrate of a solution of a protein or peptide produced by passing the solution of a protein or peptide over an ultrafiltration membrane with a molecular weight cutoff that retains a protein selected from the group consisting of albumin , immunoglobulin and erythropoietin , and wherein the filtrate comprises a diketopiperazine selected from the group consisting of YE-DKP , MR-DKP and DA-DKP.93. The container of claim 92 , wherein the container comprises a unit dose of the pharmaceutical formulation.94. The container of claim 92 , wherein the container comprises multiple doses of the pharmaceutical formulation.95. The container of claim 92 , wherein the filtrate contains components having molecular weights less than 3000.96. The container of wherein the protein or peptide is a human protein or peptide.97. The container of wherein the protein or peptide is a human albumin.98. The container of wherein the protein or peptide is a human protein or peptide.99. The container of wherein the protein or peptide is a human albumin.100. The container of claim 92 , wherein the filtrate is lyophilized.101. The container of claim 100 , wherein in the filtrate is in a form selected from the group consisting of powders claim 100 , granules and tablets.102. The container of claim 100 , wherein a sterile liquid carrier is added to the ...

DIAGNOSIS AND MONITORING OF INFLAMMATION, ISCHEMIA AND APPENDICITIS

The invention provides methods and kits for diagnosing and monitoring inflammation and/or ischemia in an animal. The methods comprise determining the quantity of a post-translationally modified protein, other than phosphorylated tau, present in a body fluid from an animal. 161.-. (canceled)62. A method of diagnosing or monitoring cardiac ischemia in an animal comprising:(a) determining the quantity of phosphorylated troponin I present in a body fluid of the animal; and(b) determining if the quantity of phosphorylated troponin I is significantly altered compared to a normal quantity in the same body fluid to determine if ischemia is present.63. The method of wherein the body fluid is serum or plasma.6480.-. (canceled)81. The method of wherein the quantity of phosphorylated troponin I is determined by a binding-partner assay.82. The method of wherein the binding-partner assay is an immunoassay.83. The method of further comprising:obtaining one or more additional diagnostic parameters of cardiac ischemia; andusing the quantity of phosphorylated troponin I and the additional diagnostic parameter(s) to diagnose or monitor the ischemia.84. The method of wherein the additional diagnostic parameter is an electrocardiogram claim 83 , a cardiac troponin T level claim 83 , or combinations of the foregoing.85. The method of wherein the quantity of phosphorylated troponin I is determined by a binding-partner assay.86. The method of wherein the binding-partner assay is an immunoassay.87. A method for the early diagnosis of cardiac ischemia in an animal comprising performing the steps of the method of within the first 24 hours after the onset of symptoms indicative of cardiac ischemia.88. The method of wherein the steps of the method are performed within the first 12 hours after the onset of symptoms indicative of cardiac ischemia.89. The method of wherein the quantity of phosphorylated troponin I is determined by a binding-partner assay90. The method of wherein the binding- ...

Safety Stanchion and Belt Reel

A safety stanchion includes a support base having a vertically extending generally cylindrical post which in turn includes an upper end supporting a belt reel. Within the belt reel, a belt spool having a quantity of flexible belt wound thereon is supported for rotation and spring biased toward a belt rewound configuration. A connector is supported on the outer end of the belt facilitating the withdrawal of a belt portion against the spring force for connection to an adjacent cooperating safety stanchion. The belt reel further defines a plurality of slots each configured to receive corresponding connectors of adjacent safety stanchions to form a pathway or guide for persons within the area. The vertical post is formed of a clear material and a message sleeve bearing a visible message such as direction information or advertising is received within the post. 1. A safety stanchion comprising:a base;a hollow post formed of a light transmissive material having a first end joined to said base and extending vertically from said base, said post having second end defining an upper edge and an interior passage between said ends;a belt reel having a housing defining an interior, an open bottom end and a closed top end, said housing receiving said second end within said interior such that said upper edge is against said closed top end and a rotatably supported belt spool within said second end of said hollow post and said housing interior;a length of flexible belt defining a belt width and having a first end coupled to said belt spool, a portion wound upon said belt spool and a second end extending outwardly from said housing;a return spring within said housing coupled to said belt spool urging said belt spool toward winding said belt;a belt connector secured to said second end of said flexible belt; anda message element having visible indicia thereon said message element being supported within said interior passage such that said visible indicia are visible through said post.2. ...

MULTIPLE LAYER GEL

A multiple layer gel and method for forming a multiple layer gel are provided. The multiple layer gel includes an isolation layer and an electrolyte layer. The isolation layer provides a molecular weight screen, to prevent proteins or other molecules from contacting a reference cell covered by the isolation layer. The electrolyte layer covers the isolation layer, and provides a source of ions that place the reference cell in ionic and/or electrical contact with a fluid sample. The multiple layer gel can be used to maintain a reliable reference voltage from an associated reference cell while an electrical potential or other electrical characteristic of a sample fluid is being determined. 1. An oxidation-reduction potential test device , comprising:a substrate;a spacer layer interconnected to at least a portion of the substrate, wherein the spacer layer defines a sample chamber;a test strip overlay, wherein the test strip overlay is interconnected to at least a portion of the spacer layer; a first area extending into the sample chamber;', 'a second area extending from the sample chamber to a readout region;, 'a first test lead supported by the substrate, the first test lead including a first area extending into the sample chamber;', 'a second area extending from the sample chamber to a readout region;, 'a second test lead supported by the substrate, the second test lead includinga reference cell; a first area in electrical contact with the reference cell;', 'a second area extending from the reference cell to a readout region;, 'a reference lead, including;'}a filter, wherein at least a portion of the filter overlaps at least a portion of each of the first area of the first test lead, the first area of the second test lead, and the first area of the reference lead; anda gel volume, wherein the gel volume includes a first layer in contact with the reference cell and a second layer over the first layer, and wherein the first layer differs in composition from the second ...

TREATMENT OF DISEASES

The invention provides (i) a method of treating metabolic syndrome in an animal, (ii) a method of suppressing the appetite of an animal, (iii) a method of treating obesity in an animal, (iv) a method of reducing the weight of an animal in need thereof, (v) a method of reducing a blood lipid level in an animal in need thereof, (vi) a method of treating non-alcoholic steatohepatitis in an animal, and (vii) a method of inhibiting adipogenesis. The methods comprise administering an effective amount of an active ingredient, wherein the active ingredient comprises a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-acceptable salt of either of them to the animal. The invention also provides a kit comprising a container holding a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-acceptable salt of either of them; and instructions for administration of the diketopiperazine, the prodrug or the pharmaceutically-acceptable salt according to a method of the invention. The diketopiperazines have the formula given in the application. 15-. (canceled)7. (canceled)8. The method of wherein Rand R , which may be the same or different , each is (x) a side chain of an amino acid , wherein the amino acid is glycine , alanine , valine , norvaline , α-aminoisobutyric acid , 2 ,4-diaminobutyric acid , 2 ,3-diaminobutyric acid , leucine , isoleucine , norleucine , serine , homoserine , threonine , aspartic acid , asparagine , glutamic acid , glutamine , lysine , hydroxylysine , arginine , homoarginine , citrulline , phenylalanine , p-aminophenylalanine , tyrosine , tryptophan , thyroxine , cysteine , homocysteine , methionine , penicillamine or ornithine , or (y) a derivative of a side chain of one of these amino acids , wherein the derivatives are those recited in .9. The method of wherein Rand R , which may be the same or different , each is (x) a side chain of an amino acid , wherein the amino acid is glycine , alanine , valine , norvaline , α- ...

REDUCING SIDE EFFECTS OF TRAMADOL

The invention provides methods of reducing the side effects of tramadol. Accordingly, in one embodiment, the invention provides a method of reducing the incidence of newly-discovered side effects related to sexual function in human males taking a tramadol material. The method comprises administering a phosphodiesterase inhibitor to a male taking the tramadol material. The invention also provides pharmaceutical compositions. In one embodiment, the composition comprises a tramadol material and a phosphodiesterase inhibitor. The invention further provides kits. In one embodiment, the kit comprises a tramadol material and a phosphodiesterase inhibitor. 1. A method of reducing the incidence of a side effect related to sexual function in a human male taking a tramadol material , wherein the side effect is caused by the tramadol material , and wherein the side effect is erectile dysfunction , anorgasmia , penile hypoesthesia , decreased libido , decreased orgasmic sensation or a combination of two or more of the foregoing , the method comprising administering an effective amount of one or more phosphodiesterase type V (PDE5) inhibitors in a total amount from 25 mg to 100 mg to the male in addition to the tramadol material.2. (canceled)3. The method of wherein the side effect is erectile dysfunction.4. An improved method of treating a disease or condition in a human male for which a tramadol material is an effective treatment claim 1 , the improvement comprising administering an effective amount of one or more phosphodiesterase type V (PDE5) inhibitors in a total amount from 25 mg to 100 mg to the male in addition to the tramadol material to reduce the incidence of a side effect related to sexual function caused by the tramadol material claim 1 , wherein the side effect is erectile dysfunction claim 1 , anorgasmia claim 1 , penile hypoesthesia claim 1 , decreased libido claim 1 , decreased orgasmic sensation or a combination of two or more of the foregoing.5. The method of ...

METHOD OF USING DIKETOPIPERAZINES AND COMPOSITION CONTAINING THEM

The invention provides a method of inhibiting the effects of platelet activating factor (PAF). For instance, a disease or condition mediated by PAF (particularly inflammation) can be treated or platelet aggregation can be inhibited. The invention also provides a method of inhibiting the production and/or release of interleukin 8 (IL-8) by cells. The effects of PAF and the production and/or release of IL-8 are inhibited according to the invention by a compound of the formula: 128-. (canceled)30. The composition of wherein Ris —OH or —OR.31. The composition of wherein Ris —OH.32. The composition of wherein Ris —CHCOOH.33. The composition of claim 29 , wherein Ris the side chain of an amino acid selected from the group consisting of glycine claim 29 , alanine claim 29 , valine claim 29 , leucine claim 29 , isoleucine claim 29 , phenylalanine claim 29 , and norvaline.34. The composition of claim 33 , wherein Ris the side chain of alanine.35. The composition of claim 30 , wherein Ris the side chain of an amino acid selected from the group consisting of glycine claim 30 , alanine claim 30 , valine claim 30 , leucine claim 30 , isoleucine claim 30 , phenylalanine claim 30 , and norvaline.36. The composition of claim 35 , wherein Ris the side chain of alanine.37. The composition of claim 31 , wherein Ris the side chain of an amino acid selected from the group consisting of glycine claim 31 , alanine claim 31 , valine claim 31 , leucine claim 31 , isoleucine claim 31 , phenylalanine claim 31 , and norvaline.38. The composition of claim 37 , wherein Ris the side chain of alanine.39. The composition of claim 32 , wherein Ris the side chain of an amino acid selected from the group consisting of glycine claim 32 , alanine claim 32 , valine claim 32 , leucine claim 32 , isoleucine claim 32 , phenylalanine claim 32 , and norvaline.40. The composition of claim 39 , wherein Ris the side chain of alanine.41. A pharmaceutical composition for inhibiting inflammation comprising a ...

MEASUREMENT AND USES OF OXIDATIVE STATUS

The present invention provides a method of determining the overall oxidative status of a body fluid or a tissue of a patient by measuring the oxidation-reduction potential (ORP) of the body fluid or tissue. The method has been found to be useful in the diagnosis, evaluation and monitoring of patients who have suffered a trauma (such as a head injury), patients suspected of being critically-ill, patients who have a viral infection, and patients suspected of having a myocardial infarction. The method has also been found useful in monitoring and evaluating exercise performance in patients. In addition, the method has been found useful in monitoring and evaluating stored blood products and patients who will receive such a product. 132-. (canceled)33. A method of evaluating a patient having a broken bone to assess the patient comprising:a) contacting a body fluid of the patient with an electrode to measure the oxidation-reduction potential (ORP) of the body fluid;b) comparing the ORP of the body fluid with the ORP of a normal to assess the severity of patient's injury.34. The method of claim 33 , further comprising selecting the patient for no hospital admission if the ORP of the body fluid is statistically the same as claim 33 , or lower than claim 33 , the ORP of a normal.35. The method of claim 33 , wherein the patient is a hospital patient and further comprising selecting the patient for discharge from the hospital if the ORP of the body fluid is statistically the same as claim 33 , or lower than claim 33 , the ORP of a normal.36. The method of claim 33 , further comprising selecting the patient for hospital admission if the ORP of the body fluid is statistically greater than the ORP of a normal.37. The method of claim 33 , wherein the ORP correlates to an Injury Severity Score (ISS) of about 30.38. The method of wherein the ORP is measured once per day or a plurality of times per day.39. The method of wherein the ORP is measured in plasma from the patient.40. The ...

TREATMENT OF JOINT CONDITIONS

The invention provides a method of treating a joint condition. The method comprises administering a multi-dose regimen of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP). The invention also provides a method of treating osteoarthritis with multiple doses of a low-molecular weight fraction of human serum albumin. 133.-. (canceled)34. A method of treating a joint disease comprising administering to an animal in need thereof an effective amount of a pharmaceutical composition comprising DA-DKP prepared by removing albumin from a solution of a human serum albumin composition in a multi-dose regimen , wherein the composition is administered once every three months and wherein the number of doses is from 2 to 10 doses.35. The method of claim 34 , wherein the joint disease is a degenerative joint disease.36. The method of claim 35 , wherein the degenerative joint disease is osteoarthritis.37. The method of claim 34 , wherein the composition administered by intra-articular injection is a composition having a concentration of DA-DKP from about 50 μM to about 350 μM.38. The method of claim 34 , wherein the composition further comprises N-acetyl-tryptophan (NAT) claim 34 , caprylic acid claim 34 , caprylate or combinations thereof.39. The method of claim 38 , wherein the composition is a composition having a concentration of NAT claim 38 , caprylic acid claim 38 , caprylate or combinations thereof from about 4 mM to about 20 mM.40. The method of claim 34 , wherein the step of removing the albumin comprises treating the human serum albumin composition by a separation method selected from the group consisting of ultrafiltration claim 34 , sucrose gradient centrifugation claim 34 , chromatography claim 34 , salt precipitation claim 34 , and sonication.41. The method of claim 40 , wherein the step of removing comprises passing the human serum albumin composition over an ultrafiltration membrane with a ...

METHODS FOR TREATING DISEASES ASSOCIATED WITH RESPIRATORY VIRUSES

The present disclosure provides a method of treating a disease associated with a respiratory virus. The method comprises administering an effective amount of a pharmaceutical composition prepared by removing albumin from a solution of a human serum albumin composition and/or comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP), such as a low molecular weight fraction of human serum albumin. The present disclosure also provides a pharmaceutical product as well as a kit comprising DA-DKP. 120-. (canceled)21. A method of treating one or more symptoms of a SARS-Coronavirus-2 (SARS-CoV-2) infection in a patient , comprising administering to the patient a pharmaceutical composition comprising DA-DKP.22. The method of claim 21 , wherein the one or more symptoms are selected from the group consisting of acute respiratory distress syndrome (ARDS) claim 21 , acute lung injury (ALI) claim 21 , interstitial lung disease claim 21 , pulmonary fibrosis claim 21 , pneumonia claim 21 , reactive airway disease syndrome claim 21 , respiratory distress requiring supplemental oxygen claim 21 , long COVID and combinations thereof.23. The method of claim 21 , wherein the one or more symptoms are selected from the group consisting of fatigue claim 21 , shortness of breath or difficulty breathing claim 21 , low exercise tolerance claim 21 , low blood oxygen saturation claim 21 , cough claim 21 , sore throat claim 21 , stuffy or runny nose claim 21 , joint pain claim 21 , chest pain claim 21 , tightness or discomfort claim 21 , muscle pain claim 21 , muscle weakness claim 21 , fever claim 21 , heart palpitations claim 21 , difficulty thinking and/or concentrating claim 21 , depression and combinations thereof.24. The method of claim 23 , wherein the patient has experienced the one or more symptoms for at least four weeks claim 23 , at least one month claim 23 , at least two months claim 23 , or at least three months.25. The method of claim 21 , ...

TREATMENT OF T-CELL MEDIATED DISEASES

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions.

TREATMENT OF DISEASES

The invention provides a method of inhibiting vascular hyperpermeability in an animal in need thereof. The method comprises administering an effective amount of a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-acceptable salt of either of them to the animal, wherein the diketopiperazine has the formula set forth in the specification. 2. The method of wherein the animal is in need of the diketopiperazine claim 1 , prodrug or salt because of the presence of a disease or condition mediated by vascular hyperpermeability.3. The method of wherein administration of the diketopiperazine claim 2 , prodrug or salt is commenced immediately upon diagnosis of the disease or condition.4. The method of wherein the disease or condition is a vascular complication of diabetes.5. The method of wherein the vascular complication is edema claim 4 , accumulation of low density lipoproteins in subendothelial space claim 4 , accelerated atherosclerosis claim 4 , accelerated aging of vessel walls in the brain claim 4 , myocardial edema claim 4 , myocardial fibrosis claim 4 , diastolic dysfunction claim 4 , diabetic cardiomyopathy claim 4 , retardation of lung development in the fetuses of diabetic mothers claim 4 , alterations of one or more pulmonary physiological parameters claim 4 , increased susceptibility to infections claim 4 , vascular hyperplasy in the mesentery claim 4 , diabetic neuropathy claim 4 , diabetic macular edema claim 4 , diabetic nephropathy claim 4 , diabetic retinopathy claim 4 , or redness claim 4 , discoloration claim 4 , dryness and ulcerations of the skin.6. The method of wherein the vascular complication is edema.7. The method of wherein the vascular complication is diabetic cardiomyopathy.8. The method of wherein the vascular complication is diabetic neuropathy.9. The method of wherein the vascular complication is diabetic macular edema.10. The method of wherein the vascular complication is diabetic retinopathy.11. The method of wherein ...

TREATMENT OF JOINT CONDITIONS

The invention provides a method of treating a joint condition. The method comprises administering a multi-dose regimen of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP). The invention also provides a method of treating osteoarthritis with multiple doses of a low-molecular weight fraction of human serum albumin. 1. A method of treating a joint condition comprising administering to an animal with a Kellgren-Lawrence Grade 4 pain score an effective amount of a pharmaceutical composition comprising DA-DKP prepared by removing albumin from a solution of a human serum albumin composition in a multi-dose regimen , wherein the number of doses in the multi-dose regimen is between 2 and 6 doses per 52 weeks.2. The method of claim 1 , wherein the joint condition is a joint disease.3. The method of claim 2 , wherein the joint disease is a degenerative joint disease.4. The method of claim 3 , wherein the degenerative joint disease is osteoarthritis.5. The method of claim 1 , wherein the joint condition is a joint injury.6. The method of claim 5 , wherein the joint injury is at least one of a traumatic injury and a post-operative injury.7. The method of claim 5 , wherein the joint injury is a repetitive strain injury.8. The method of claim 1 , wherein the joint condition is inflammation.9. The method of claim 1 , wherein the composition is administered by an administration route selected from the group consisting of local administration claim 1 , topical administration claim 1 , and injection.10. The method of claim 9 , wherein administration by injection is by intra-articular injection.11. The method of claim 10 , wherein the composition administered by intra-articular injection is a composition having a concentration of DA-DKP from about 50 μM to about 350 μM.12. The method of claim 1 , wherein the composition further comprises N-acetyl-tryptophan (NAT) claim 1 , caprylic acid claim 1 , caprylate or ...

METHOD AND APPARATUS FOR MEASURING OXIDATION-REDUCTION POTENTIAL

Methods and systems for measuring the oxidation-reduction potential of a fluid sample are provided. The system includes a test strip with a sample chamber adapted to receive a fluid sample. The sample chamber can be associated with a filter membrane. The test strip also includes a reference cell. The oxidation-reduction potential of a fluid sample placed in the sample chamber can be read by a readout device interconnected to a test lead that is in electrical contact with the sample chamber, and a reference lead that is in electrical contact with the reference cell. Electrical contact between a fluid sample placed in the sample chamber and the reference cell can be established by a bridge. The oxidation-reduction potential may be read as an electrical potential between the test lead and the reference lead of the test strip. 1. An oxidation-reduction potential test device , comprising:a substrate;a sample chamber;a filter, wherein the filter occupies at least a portion of the sample chamber; a first area extending into the sample chamber;', 'a second area extending from the sample chamber;, 'a first test lead supported by the substrate, the first test lead including a first area extending into the sample chamber;', 'a second area extending from the sample chamber;, 'a second test lead supported by the substrate, the second test lead includinga reference cell; a first area in electrical contact with the reference cell;', 'a second area extending from the reference cell;, 'a reference lead, including;'}a bridge, wherein the bridge includes at least a portion of the filter, and wherein a fluid sample in the sample chamber is placed in electrical contact with the reference cell by the bridge.2. The device of claim 1 , further comprising:an overlay, wherein at least a portion of the first test lead, the second test lead, the reference cell, at least a portion of the reference lead, and the bridge are held between the substrate and the overlay when the overlay is ...

TREAMENT OF T-CELL MEDIATED DISEASES

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions. 191-. (canceled)92. A method of manufacturing a pharmaceutical composition comprising passing a solution of albumin over an ultrafiltration membrane with a molecular weight cutoff that retains albumin to produce a filtrate , wherein the filtrate comprises an alanine-aspartic acid diketopiperazine (DA-DKP) and a component selected from the group consisting of caprylic acid , N-acetyl tryptophan and combinations thereof , wherein the composition is an isotonic aqueous solution.93. The method of wherein the filtrate contains components having molecular weights less than 3000.94. The method of wherein the albumin is a human albumin.95. The method of claim 92 , further comprising placing the filtrate into a plastic bottle having a shaped closure adapted to deliver liquid contents dropwise. This application is a continuation of U.S. application Ser. No. 12/753,671, filed Apr. 2, 2010, which is a continuation of U.S. application Ser. No. 10/846,482, filed May 14, 2004, now U.S. Pat. No. 7,732,403 which claims benefit of provisional application Ser. Nos. 60/471,017, filed May 15, 2003; 60/489,270, filed Jul. 21, 2003; 60/514,930, filed Oct. 27, 2003; and 60/517,338, filed Nov. 4, 2003, the complete disclosures of which are incorporated herein by reference.This invention relates to the treatment of T-cell mediated diseases and to the inhibition of the activation of T-cells using certain diketopiperazines. The invention also relates to ...

THERAPEUTIC METHODS AND COMPOUNDS

The invention provides diketopiperazines of formula I. The invention also provides pharmaceutical compositions comprising the diketopiperazines, or pharmaceutically-acceptable salts or prodrugs thereof, as the active ingredient. The invention further provides therapeutic treatments that utilize the diketopiperazines of formula I, including inhibition of a proliferative disease or condition, inhibition of angiogenesis, treatment of an angiogenic disease or condition, treatment of cancer and precancerous conditions, treatment of a fibrotic disorder, treatment of a viral infection, treatment of an Akt-mediated disease or condition, inhibition of the production, release or both of matrix metalloproteinase-9, and inhibition of Akt activation. 150.-. (canceled)52. The method of wherein Rof the diketopiperazine: (d) a side chain of an amino acid, wherein the amino acid is glycine, alanine, valine, norvaline, α-aminoisobutyric acid, 2,4-diaminobutyric acid, 2,3-diaminobutyric acid, leucine, isoleucine, norleucine, serine, homoserine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, hydroxylysine, histidine, arginine, homoarginine, citrulline, phenylalanine, p-aminophenylalanine, tyrosine, tryptophan, thyroxine or ornithine; or', {'claim-ref': {'@idref': 'CLM-00051', 'claim 51'}, '(e) a derivative of a side chain of an amino acid, wherein the amino acid is one of those recited in (d), and the derivative of the side chain is one of those recited in part (c) of ; and'}], 'is{'sup': '2', 'Rhas formula II or III.'}53. The method of wherein Rof the diketopiperazine is:(f) a side chain of an amino acid, wherein the amino acid is glycine, alanine, valine, norvaline, α-aminoisobutyric acid, 2,4-diaminobutyric acid, 2,3-diaminobutyric acid, leucine, isoleucine, norleucine, serine, homoserine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, hydroxylysine, arginine, homoarginine, citrulline or ornithine; or{'claim-ref': {'@idref': 'CLM- ...

TREATMENT OF DISEASE WITH N-ACETYL KYNURENINE

The invention provides a method, composition and kit for treating T-cell mediated diseases, degenerative joint diseases or diseases mediated by platelet activating factor (PAF) comprising administering to an animal in need thereof, an effective amount a pharmaceutical composition containing N-acetyl-kynurenine (NAK) or pharmaceutically acceptable salts thereof as the active ingredient. 118-. (canceled)19. A dosage form , comprising:N-acetyl-kynurenine, or a pharmaceutically acceptable salt thereof;a second active agent; anda pharmaceutically-acceptable carrier.20. The dosage form of claim 19 , further comprising:one or more excipients; andone or more isotonic agents.21. The dosage form of claim 19 , wherein the amount of N-acetyl-kynurenine in the dosage form is selected from greater than about 50 μM claim 19 , about 60 μM claim 19 , about 70 μM claim 19 , about 80 μM claim 19 , about 90 μM and about 100 μM.22. The dosage form of claim 19 , wherein the amount of N-acetyl-kynurenine in the dosage form is selected from about 1 μM-about 200 μM and about 20 μM-about 100 μM.23. The dosage form of claim 19 , wherein the second active agent is selected from an analgesic claim 19 , an anti-inflammatory drug and combinations thereof.24. The dosage form of claim 19 , wherein the second active agent is N-acetyl tryptophan.25. The dosage form of claim 19 , wherein the pharmaceutically-acceptable carrier is propylene glycol claim 19 , water claim 19 , or both propylene glycol and water.26. The dosage form of claim 20 , wherein the one or more excipients are a vegetable oil claim 20 , a cellulose derivative claim 20 , or both a vegetable oil and a cellulose derivative.27. The dosage form of claim 20 , wherein the isotonic agent is sodium chloride.28. The dosage form of claim 19 , which is formulated as a powder claim 19 , an ointment claim 19 , a paste claim 19 , a cream claim 19 , a gel claim 19 , or a patch.29. The dosage form of claim 19 , which is formulated as a cream.30. A ...

IMPLANTABLE MEDICAL DEVICES WITH INCREASED IMMUNE TOLERANCE, AND METHODS FOR MAKING AND IMPLANTING

The present invention relates to the contacting of one or more surfaces of an implantable medical device with one or more diketopiperazines (DKPs). 1. A method to prepare an implantable medical device for implantation in a subject , comprising contacting the device with a diketopiperazine comprising the side chains of aspartic acid and alanine (DA-DKP).216.-. (canceled)17. The method of claim 1 , wherein the implantable medical device is selected from the group consisting of a graft claim 1 , catheter claim 1 , stent claim 1 , prosthetic claim 1 , breast implant claim 1 , pump claim 1 , tube claim 1 , pin claim 1 , rod claim 1 , screw claim 1 , brace claim 1 , plate and pace maker.1820.-. (canceled)21. The method of claim 1 , wherein the implantable medical device is composed of a material selected from the group consisting of metal claim 1 , steel claim 1 , titanium claim 1 , glass claim 1 , polymers claim 1 , plastics claim 1 , and ceramics.22. The method of claim 1 , wherein the DA-DKP is adhered to claim 1 , impregnated into claim 1 , or coated onto the surface of the implantable medical device.2324.-. (canceled)25. The method of claim 1 , wherein the implantable medical device is contacted with a solution comprising DA-DKP claim 1 , wherein the solution adheres to the implantable medical device.26. The method of claim 1 , wherein the DA-DKP is in an amount of about 1 μM to about 500 μM.27. The method of claim 1 , wherein the DA-DKP is in an amount of about 50 μM to about 100 μM.28. The method of claim 1 , wherein the concentration of the DA-DKP on a surface of the implantable medical device exposed to the body is about 1 ng/cmto about 200 ng/cm.29. The method of claim 1 , wherein the concentration of the DA-DKP on a surface of the implantable medical device exposed to the body is about 50 ng/cm.30. A method for implanting a medical device comprising implanting a medical device into a subject claim 1 , wherein a surface of the device comprises a diketopiperazine ...

TREATMENT OF DEGENERATIVE JOINT DISEASE

The invention provides a method of treating a degenerative joint disease. The method comprises administering an effective amount of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP). The invention also provides a pharmaceutical product as well as a kit comprising DA-DKP. 127-. (canceled)28. A method of treating hand pain in a human comprising administering to a hand of the human an intra-articular injection of an effective amount of a pharmaceutical composition comprising DA-DKP prepared by removing albumin from a solution of a human serum albumin composition. This application is a continuation of U.S. application Ser. No. 16/279,667, filed Feb. 19, 2019; which is a continuation of U.S. application Ser. No. 15/453,573, filed Mar. 8, 2017, now U.S. Pat. No. 10,251,930; which is a continuation of U.S. application Ser. No. 14/604,479, filed Jan. 23, 2015, now U.S. Pat. No. 9,623,072; which is a continuation of U.S. application Ser. No. 14/350,634, filed Apr. 9, 2014, now U.S. Pat. No. 8,980,834; which is a national stage application under 35 U.S.C. 371 and claims the benefit of PCT Application No. PCT/US2012/059455 having an international filing date of Oct. 10, 2012, which designated the United States, which PCT application claims the benefit of priority under 35 U.S.C. § 119(e) to U.S. Provisional Patent Application No. 61/545,474, filed Oct. 10, 2011 and U.S. Provisional Patent Application No. 61/561,221, filed Nov. 17, 2011, the entire disclosures of each of which are incorporated herein by reference.The invention relates to a method of treating a degenerative joint disease. The method comprises administering an effective amount of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP). The invention also provides a pharmaceutical product comprising DA-DKP.Osteoarthritis is the most common form of arthritis, affecting 25 ...

Method For Improving Animal Food Product Quality

The invention relates to food animal care and husbandry. Disclosed is a novel method of evaluating the production characteristics of a food animal or group of food animals, is provided. More specifically, the invention relates to a method of determining the overall oxidative status of a sample taken from a food animal by measuring the oxidation-reduction potential (ORP) of the sample. The measured ORP value of the sample is then used to review the animal's environment and, if necessary, adjust the environment of the animal. In order to improve the production characteristics of food products from the animal. Also provided is a method of using the ORP value of a food product to determine production characteristics of the food product. 1. A method for evaluating a production characteristic of a food animal comprising:measuring the oxidation-reduction potential (ORP) of a sample of the animal; and determining if the ORP is significantly different than a reference ORP value.2. The method of claim 1 , wherein the food animal is for a food selected from the group consisting of meat claim 1 , dairy claim 1 , eggs and combinations thereof.3. The method of claim 1 , wherein the food animal is selected from the group consisting of bovine claim 1 , camelids claim 1 , caprae claim 1 , lagomorphs claim 1 , ovis claim 1 , swine claim 1 , cervidae claim 1 , birds claim 1 , fish claim 1 , crustaceans claim 1 , mollusks claim 1 , reptiles claim 1 , chickens claim 1 , ducks claim 1 , geese claim 1 , pigeons claim 1 , doves claim 1 , pheasants claim 1 , partridge claim 1 , turkey claim 1 , emu claim 1 , swan claim 1 , ostrich claim 1 , bison claim 1 , carabao claim 1 , cattle claim 1 , buffalo claim 1 , yak claim 1 , llama claim 1 , camel claim 1 , goat claim 1 , rabbits claim 1 , sheep claim 1 , swine claim 1 , fish claim 1 , crustaceans claim 1 , mollusks claim 1 , reptiles and combinations thereof.4. The method of claim 1 , wherein the production characteristic is selected from the ...

TREAMENT OF T-CELL MEDIATED DISEASES

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions. 191-. (canceled)92. A pharmaceutical composition comprising an alanine-aspartic acid diketopiperazine (DA-DKP)-containing fraction of a solution of human albumin , wherein the DA-DKP-containing fraction is produced by separating human albumin from the human albumin solution , and wherein the composition is formulated for topical or transdermal administration in a dosage form selected from the group consisting of powders , sprays , ointments , pastes , creams , lotions , gels , solutions , patches , drops and inhalants.93. The composition of claim 92 , wherein the DA-DKP-containing fraction is separated from the human albumin solution by passing the human albumin solution over an ultrafiltration membrane with a molecular weight cutoff that retains the DA-DKP-containing fraction.94. The composition of claim 93 , wherein the molecular weight cutoff is less than 3000.95. The composition of claim 92 , further comprising a component selected from the group consisting of caprylic acid claim 92 , N-acetyl tryptophan and combinations thereof.96. The composition of claim 92 , wherein the composition is formulated for topical or transdermal administration in a dosage form selected from the group consisting of ointments claim 92 , pastes claim 92 , creams claim 92 , lotions claim 92 , and gels.97. The composition of claim 92 , wherein the composition is formulated for topical or transdermal administration in a cream dosage form.98. A ...

TREATMENT OF T-CELL MEDIATED DISEASES

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions. 2. The method of wherein R claim 1 , Ror both is the side chain of aspartic acid claim 1 , the side chain of glutamic acid claim 1 , or a derivative of a side chain of aspartic acid or glutamic acid wherein the —COOH group is replaced by a —COORgroup or a —CON(R)group.3. The method of wherein Ris the side chain of aspartic acid or a derivative of the side chain of aspartic acid wherein the —COOH group is replaced by a —COORgroup or a —CON(R)group claim 2 , and Ris the side chain of alanine.4. The method of wherein Ris the side chain of aspartic acid or a derivative of the side chain of aspartic acid wherein the —COOH group is replaced by a —COORgroup or a —CON(R)group claim 2 , and Ris the side chain of tyrosine.5. The method of wherein Ris the side chain of glutamic acid or a derivative of the side chain of glutamic acid wherein the —COOH group is replaced by a —COORgroup or a —CON(R)group claim 2 , and Ris the side chain of alanine.6. The method of wherein Ris the side chain of glutamic acid or a derivative of the side chain of glutamic acid wherein the —COOH group is replaced by a —COORgroup or a —CON(R)group claim 2 , and Ris the side chain of tyrosine.7. The method of wherein Ris the side chain of aspartic acid or glutamic acid and Ris the side chain of alanine.8. The method of wherein Ris the side chain of aspartic acid or glutamic acid and Ris the side chain of tyrosine.9. The method of wherein Rand Rare both a ...

Methods and products for treatment of diseases

The invention provides a method of treating a disease or condition mediated by vascular hyperpermeability in an animal. The method comprises administering an amount of a danazol compound effective to inhibit vascular hyperpermeability and an amount of a second drug effective to treat the disease or condition. The invention further provides a method of inhibiting vascular hyperpermeability when it is a side effect caused by administration of a drug to, or another treatment of, an animal. The method comprises administration of an amount of a danazol compound effective to inhibit the vascular hyperpermeability. The invention also provides a method of modulating the cytoskeleton of endothelial cells in an animal comprising administering an amount of a danazol compound and an amount of a second drug effective to modulate the cytoskeleton. The present invention also relates to pharmaceutical compositions and kits comprising a danazol compound and a second drug.

Compositions for the mobilization, homing, expansion and differentiation of stem cells and methods of using the same

The invention provides compositions that increase the mobilization, homing, expansion, and/or differentiation of stem cells and methods of using the same for the treatment of mammals.

DETERMINATION OF FERTILITY POTENTIAL FROM THE OXIDATION-REDUCTION POTENTIAL OF A BIOLOGICAL SAMPLE

Methods and systems for measuring and using the oxidation-reduction potential (ORP) of a biological sample are provided. The system generally includes a test strip and a readout device for determining the ORP. The measured ORP is then used to determine characteristics relating to the fertility of the sample or the subject from which the sample was derived. Some characteristics that can be determined include the quality of a sperm sample, an oocyte or a fertilized egg. The measured ORP value can also be used to determine the specific characteristics of a spermatozoa sample, such as the morphology of the spermatozoa, the motility of the spermatozoa, the number of cells in the sample and the concentration of the cells in the sample. Knowledge of such characteristics and fertility potential can be used to identify individuals that might benefit from specific fertility treatments. 112-. (canceled)13. A method of evaluating the fertility potential of a successful implantation of a fertilized egg , comprising:a. measuring the static oxidation-reduction potential (sORP) and/or the capacity oxidation-reduction potential (cORP) of medium in which a fertilized egg is being cultured;b. comparing the measured sORP and/or cORP of a sample of the medium to a reference value, wherein if the ORP value of the medium being tested is significantly increased compared to the reference value identifies the fertilized egg cultured in the medium as being unlikely to establish and maintain a successful implantation; andc. treating the medium with an antioxidant if the ORP value of the medium being tested is significantly increased compared to the reference value.14. The method of claim 13 , wherein the fertilized egg being cultured is a zygote.15. The method of claim 13 , wherein the fertilized egg being culture is a blastocyst.16. The method of claim 13 , wherein the medium is compared every 30 minutes claim 13 , 1 hour claim 13 , 2 hours claim 13 , 3 hours claim 13 , 4 hours claim 13 , 5 ...

METHOD FOR TREATMENT OF DISEASES

The invention provides a method of inhibiting vascular hyperpermeability in an animal in need thereof. The method comprises administering a vascular-hyperpermeability-inhibiting amount of a danazol compound to the animal. The invention also provides a method of modulating the cytoskeleton of an endothelial cell in an animal. The method comprises administering an effective amount of a danazol compound to the animal. 1. A method of inhibiting vascular hyperpermeability in an animal in need thereof comprising administering to the animal a vascular-hyperpermeability-inhibiting amount of a danazol compound.2. The method of wherein the animal is in need of the danazol compound because of the presence of a disease or condition mediated by vascular hyperpermeability.3. The method of wherein administration of the danazol compound is commenced immediately upon diagnosis of the disease or condition.419.-. (canceled)20. The method of wherein the animal is in need of the danazol compound because of one or more early signs of claim 1 , or a predisposition to develop claim 1 , a disease or condition mediated by vascular hyperpermeability.21. (canceled)22. The method of wherein the vascular hyperpermeability is vascular hyperpermeability of a continuous endothelium found in claim 1 , or around claim 1 , a brain claim 1 , diaphragm claim 1 , duodenal musculature claim 1 , fat claim 1 , heart claim 1 , kidney claim 1 , large blood vessel claim 1 , lung claim 1 , mesentery claim 1 , nerve claim 1 , retina claim 1 , skeletal muscle claim 1 , skin or testis.23. The method of wherein the continuous endothelium is found in claim 22 , or around claim 22 , a brain claim 22 , heart claim 22 , lung claim 22 , nerve or retina.24. The method of wherein the vascular hyperpermeability is vascular hyperpermeability of a fenestrated endothelium found in claim 1 , or around claim 1 , a kidney claim 1 , a pancreas claim 1 , an adrenal claim 1 , an endocrine gland or an intestine.25. The method of ...

TREATMENT OF DEGENERATIVE JOINT DISEASE

The invention provides a method of treating a degenerative joint disease. The method comprises administering an effective amount of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP). The invention also provides a pharmaceutical product as well as a kit comprising DA-DKP.

Spectrum-splitting concentrator photovoltaic module with direct fluid cooling, and associated methods

A spectrum-splitting concentrator photovoltaic (CPV) module utilizes direct fluid cooling of photovoltaic cells in which an array of photovoltaic cells is fully immersed in a flowing heat transfer fluid. Specifically, at least a portion of both the front face and the rear face of each photovoltaic cell comes into direct contact with heat transfer fluid, thereby enhancing coupling of waste heat out of the photovoltaic cells and into the heat transfer fluid. The CPV module is designed to maximize transmission of infrared light not absorbed by the photovoltaic cells, and therefore may be combined with a thermal receiver that captures the transmitted infrared light as part of a hybrid concentrator photovoltaic-thermal system.

HYBRID RECEIVER FOR CONCENTRATED PHOTOVOLTAIC-THERMAL POWER SYSTEMS, AND ASSOCIATED METHODS

A hybrid receiver for a concentrator photovoltaic-thermal power system combines a concentrator photovoltaic (CPV) module and a thermal module that converts concentrated sunlight into electrical energy and thermal heat. Heat transfer fluid flowing through a cooling block removes waste heat generated by photovoltaic cells in the CPV module. The heat transfer fluid then flows through a helical tube illuminated by sunlight that misses the CPV module. Only one fluid system is used to both remove the photovoltaic-cell waste heat and capture high-temperature thermal energy from sunlight. Fluid leaving the hybrid receiver can have a temperature greater than 200° C., and therefore may be used as a source of process heat for a variety of commercial and industrial applications. The hybrid receiver can maintain the photovoltaic cells at temperatures below 110° C. while achieving overall energy conversion efficiencies exceeding 80%. 1. A hybrid receiver , comprising:a concentrator photovoltaic module having a heat transfer plate and an array of photovoltaic cells thermally coupled to the heat transfer plate; and (i) a cooling block forming an internal path through which heat transfer fluid can flow, a bottom face of the heat transfer plate being in direct thermal contact with a top face of the cooling block; and', '(ii) a helical tube surrounding the cooling block and connected to the cooling block such that the heat transfer fluid flows through the helical tube after flowing through the cooling block., 'a thermal module having2. The hybrid receiver of claim 1 , further comprising a reflective shroud surrounding the concentrator photovoltaic module and the thermal module claim 1 , and shaped to reflect thermal radiation and scattered light from the thermal module onto the helical tube.3. The hybrid receiver of claim 2 , the reflective shroud being made of aluminum.4. The hybrid receiver of claim 1 ,further comprising an inlet pipe connected to a rear face of the cooling block, ...

COMPOSITIONS FOR THE MOBILIZATION, HOMING, EXPANSION AND DIFFERENTIATION OF STEM CELLS AND METHODS OF USING THE SAME

The invention provides compositions that increase the mobilization, homing, expansion, and/or differentiation of stem cells and methods of using the same for the treatment of mammals. 1. A method to cause an effect selected from the group consisting of stem cell mobilization , stem cell homing , stem cell expansion , and stem cell differentiation in a subject , comprising administering DA-DKP to a subject in need thereof.2. The method of claim 1 , wherein the step of administering comprises administering a pharmaceutical composition comprising DA-DKP.3. The method of claim 2 , wherein the pharmaceutical composition further comprises N-acetyl tryptophan claim 2 , caprylate and/or caprylic acid.4. The method of claim 2 , wherein the pharmaceutical composition comprises a fraction of human serum albumin claim 2 , wherein substantially all of the albumin has been removed from the fraction.5. The method of claim 2 , wherein the pharmaceutical composition comprises a low molecular weight fraction of human serum albumin.6. The method of claim 4 , wherein the low molecular weight fraction of human serum albumin is a less than 5000 molecular weight fraction.7. The method of claim 4 , wherein the low molecular weight fraction of human serum albumin is produced by filtration.8. The method of claim 2 , wherein the pharmaceutical composition is prepared by a process comprising heating human serum albumin under conditions effective to cause the formation of DA-DKP.9. The method of claim 2 , wherein the pharmaceutical composition is prepared by a process comprising contacting human serum albumin with an enzyme that cleaves the two N-terminal amino acids of human albumin under conditions effective to produce DA-DKP.10. The method of claim 2 , wherein the DA-DKP is a synthetic DA-DKP.11. The method of claim 2 , wherein the DA-DKP is administered locally to the subject.12. The method of claim 10 , wherein the site of local administration is selected from the group consisting of a ...

Measurement and Uses of Oxidative Status

The present invention provides a method of determining the overall oxidative status of a body fluid or a tissue of a patient by measuring the oxidation-reduction potential (ORP) of the body fluid or tissue. The method has been found to be useful in the diagnosis, evaluation and monitoring of patients who have suffered a trauma (such as a head injury), patients suspected of being critically-ill or who are critically ill, patients who have an infection, and patients suspected of having a myocardial infarction (MI) or who have had an MI. The method has also been found useful in monitoring and evaluating exercise performance in patients. In addition, the method has been found useful in monitoring and evaluating stored blood products and patients who will receive such a product.

TREATMENT OF RHINITIS

The invention provides a method of treating rhinitis. The method comprises administering an effective amount of a danazol compound or a pharmaceutically acceptable salt thereof. The invention also provides a pharmaceutical product formulated for nasal administration. The product comprises a danazol compound or a pharmaceutically acceptable salt thereof. 1. A method of treating rhinitis comprising administering an effective amount of a danazol compound or a pharmaceutically acceptable salt thereof , to an animal in need thereof.2. The method of claim 1 , wherein the rhinitis is allergic rhinitis.3. The method of claim 1 , wherein the effective amount of the danazol compound or the pharmaceutically acceptable salt thereof is from about 100 μg to about 3000 μg per day.4. The method of claim 1 , wherein the effective amount of the danazol compound or the pharmaceutically acceptable salt thereof is from about 500 μg to about 1500 μg per day.5. The method of claim 1 , wherein administration of the danazol compound or a pharmaceutically acceptable salt thereof claim 1 , is commenced within 24 hours of diagnosis of rhinitis.6. The method of claim 1 , wherein administration of the danazol compound or a pharmaceutically acceptable salt thereof claim 1 , is commenced at the appearance of one or more early signs of claim 1 , or a predisposition to develop claim 1 , rhinitis.7. The method of claim 6 , wherein the one or more early signs of rhinitis are selected from the group consisting of rhinorrhea claim 6 , nasal congestion claim 6 , nasal itching and sneezing.8. The method of claim 1 , wherein the danazol compound is danazol.9. The method of claim 1 , wherein the danazol compound or a pharmaceutically acceptable salt thereof is administered in combination with a second drug suitable for treating rhinitis.10. The method of claim 9 , wherein the second drug suitable for treating rhinitis is selected from the group consisting of antihistamines claim 9 , decongestants claim 9 , ...

Treatment of rhinitis

The invention provides a method of treating rhinitis. The method comprises administering an effective amount of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP) formulated for nasal administration. The invention also provides a pharmaceutical product comprising a DA-DKP containing composition.

Method of using diketopiperazines and composition containing them

The invention provides a method of inhibiting the effects of platelet activating factor (PAF). For instance, a disease or condition mediated by PAF (particularly inflammation) can be treated or platelet aggregation can be inhibited. The invention also provides a method of inhibiting the production and/or release of interleukin 8 (IL-8) by cells. The effects of PAF and the production and/or release of IL-8 are inhibited according to the invention by a compound of the formula: wherein R 1 and R 2 are defined in the application, or a physiologically-acceptable salt thereof. The invention also provides pharmaceutical compositions comprising these compounds.

TREATMENT OF DISEASE WITH N-ACETYL KYNURENINE

The invention provides a method, composition and kit for treating T-cell mediated diseases, degenerative joint diseases or diseases mediated by platelet activating factor (PAF) comprising administering to an animal in need thereof, an effective amount a pharmaceutical composition containing N-acetyl-kynurenine (NAK) or pharmaceutically acceptable salts thereof as the active ingredient. 1. A method of treating a T-cell mediated disease , a degenerative joint disease , or a disease mediated by platelet activating factor , comprising administering to an animal in need thereof , an effective amount of a pharmaceutical composition consisting essentially of N-acetyl-kynurenine or a pharmaceutically acceptable salt thereof.2. A method of treating a T-cell mediated disease , a degenerative joint disease , or a disease mediated by platelet activating factor , comprising administering to an animal in need thereof , an effective amount of a pharmaceutical composition comprising (i) N-acetyl-kynurenine or a pharmaceutically acceptable salt thereof and (ii) a second active agent effective to treat the disease.3. The method of claim 2 , wherein the second active agent effective to treat the disease is selected from the group consisting of an analgesic claim 2 , an anti-inflammatory drug claim 2 , and combinations thereof.4. The method of claim 1 , wherein the N-acetyl-kynurenine or a pharmaceutically acceptable salt thereof is in a concentration greater than about 50 about 60 about 70 about 80 about 90 or about 100 μM.5. The method of claim 1 , wherein the T-cell mediated disease is selected from the group consisting of graft rejection claim 1 , graft versus host disease claim 1 , an unwanted delayed-type hypersensitivity reaction claim 1 , a T-cell mediated pulmonary disease and an autoimmune disease.6. The method of claim 1 , wherein the T-cell mediated disease is multiple sclerosis claim 1 , inclusion body myositis (IBM) claim 1 , amyotrophic lateral sclerosis (ALS) claim 1 , ...

IMPLANTABLE MEDICAL DEVICES WITH INCREASED IMMUNE TOLERANCE, AND METHODS FOR MAKING AND IMPLANTING

The present invention relates to the contacting of one or more surfaces of an implantable medical device with one or more diketopiperazines (DKPs). 1. A method to prepare an implantable medical device for implantation in a subject , comprising contacting the device with a diketopiperazine (DKP).3. The method of wherein R claim 2 , Ror both is the side chain of aspartic acid claim 2 , the side chain of glutamic acid claim 2 , or a derivative of a side chain of aspartic acid or glutamic acid wherein the —COOH group is replaced by a —COORgroup or a —CON(R)group.4. The method of wherein Ris the side chain of aspartic acid or a derivative of the side chain of aspartic acid wherein the —COOH group is replaced by a —COORgroup or a —CON(R)group claim 3 , and Ris the side chain of alanine.5. The method of wherein Ris the side chain of aspartic acid or a derivative of the side chain of aspartic acid wherein the —COOH group is replaced by a —COORgroup or a —CON(R)group claim 3 , and Ris the side chain of tyrosine.6. The method of wherein Ris the side chain of glutamic acid or a derivative of the side chain of glutamic acid wherein the —COOH group is replaced by a —COORgroup or a —CON(R)group claim 3 , and Ris the side chain of alanine.7. The method of wherein Ris the side chain of glutamic acid or a derivative of the side chain of glutamic acid wherein the —COOH group is replaced by a —COORgroup or a —CON(R)group claim 3 , and Ris the side chain of tyrosine.8. The method of wherein Ris the side chain of aspartic acid or glutamic acid and Ris the side chain of alanine9. The method of wherein Ris the side chain of aspartic acid or glutamic acid and Ris the side chain of tyrosine.10. The method of wherein Rand Rare both a hydrophobic side chain or a hydrophobic side chain derivative.11. The method of wherein:{'sup': 1', '2, '(a) Rand R, which may be the same or different, each is the side chain of glycine, alanine, valine, norvaline, α-aminobutyric acid, leucine, isoleucine, ...

TREATMENT OF DISEASES MEDIATED BY VASCULAR HYPERPERMEABILITY

The invention provides a method of inhibiting vascular hyperpermeability in an animal in need thereof. The method comprises administering an effective amount of a pharmaceutical composition prepared by removing albumin from a human serum albumin composition and one or more p38 MAPK inhibitors to the animal. 1. A method of inhibiting vascular hyperpermeability in an animal in need thereof comprising administering to the animal an effective amount of(i) a pharmaceutical composition prepared by removing albumin from a human serum albumin composition; and(ii) one or more p38 MAPK inhibitors.2. The method of wherein the one or more p38 MAPK inhibitors is selected from the group consisting of SB 203580 claim 1 , SB 203580 hydrochloride claim 1 , SB 202190 claim 1 , SB 239063 claim 1 , SB 706504 claim 1 , AL 8697 claim 1 , AMG 548 claim 1 , CMPD-1 claim 1 , DBM 1285 dihydrochloride claim 1 , EO 1428 claim 1 , JX 401 claim 1 , ML 3403 claim 1 , RWJ 67657 claim 1 , SCIO 469 hydrochloride claim 1 , SKF 86002 dihydrochloride claim 1 , SX 011 claim 1 , TA 01 claim 1 , TA 02 claim 1 , TAK 715 claim 1 , VX 702 claim 1 , VX 745 claim 1 , p38 MAPK Inhibitor TOCRISET™ claim 1 , and combinations thereof.3. The method of wherein the animal has a disease or condition mediated by vascular hyperpermeability.4. The method of wherein administration of the pharmaceutical composition and the one or more p38 MAPK inhibitors is commenced immediately upon diagnosis of the disease or condition.5. The method of claim 3 , wherein the disease or condition is an ocular disease.6. The method of wherein the disease or condition is a vascular complication of diabetes.7. The method of wherein the vascular complication is edema claim 6 , accumulation of low density lipoproteins in subendothelial space claim 6 , accelerated atherosclerosis claim 6 , accelerated aging of vessel walls in the brain claim 6 , myocardial edema claim 6 , myocardial fibrosis claim 6 , diastolic dysfunction claim 6 , diabetic ...

METHODS AND SYSTEMS FOR MEASURING AND USING THE OXIDATION-REDUCTION POTENTIAL OF A BIOLOGICAL SAMPLE

Methods and systems for measuring and using the oxidation-reduction characteristics of a biological sample are provided. The system generally includes a test strip and a readout device. A fluid sample is placed in the test strip, and the test strip is in turn operatively connected to the readout device. The readout device provides a controlled current that is sent across the fluid in the sample chamber. In addition, the readout device identifies an inflection point or transition time at which the voltage between contacts of the test strip is changing at the highest rate. The oxidation-reduction capacity of the sample is taken as the integral of the current profile from the time at which current begins to be supplied to the sample to the identified transition time. 1. A readout device , comprising:a plurality of readout contacts; a current supply;', 'an electrometer,, 'an analog front end, includingwherein the current supply is operable to provide a current to first and second contacts of the plurality of readout contacts, and wherein the electrometer is operable to read a voltage potential between the second contact and a third contact of the readout contacts.2. The device of claim 1 , further comprising:a controller;an analog to digital converter, wherein the analog to digital converter connects the electrometer to the controller;a digital to analog converter, wherein the digital to analog converter connects the controller to the current supply.3. The device of claim 2 , wherein the controller is operable to determine an inflection point in the voltage potential claim 2 , and is further operable to determine a quantity of the charge supplied between a first time and the inflection point.4. The device of claim 3 , further comprising:a user interface, wherein the user interface includes a user output, and wherein the user output provides a cORP value derived from the determined quantity of the charge supplied between the first time and the inflection point.5. The ...

Use of orp for characterizing stroke patients

Methods and systems for measuring and using the oxidation-reduction potential (ORP) of a biological sample are provided. Also provided are methods of characterizing an individual who has suffered a stroke by measuring the ORP of a biological sample. The disclosed methods can be used to characterize the individual with regard to their likelihood of survival, severity of the stroke and their estimated length of stay in a medical facility.

TREATMENT OF DEGENERATIVE JOINT DISEASE

The invention provides a method of treating a degenerative joint disease. The method comprises administering an effective amount of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP). The invention also provides a pharmaceutical product as well as a kit comprising DA-DKP. 127.-. (canceled)28. A method of treating joint pain in a human comprising administering to a joint of the human selected from the group consisting of a shoulder joint , a hand joint and a spinal joint , an intra-articular injection of an effective amount of a pharmaceutical composition comprising DA-DKP prepared by removing albumin from a solution of a human serum albumin composition.29. The method of wherein the composition is administered at a frequency selected from the group consisting of:a. no more frequently than once every six months,b. no more frequently than once every 5 months,c. no more frequently than once every 4 months,d. no more frequently than once every 3 months, ande. no more frequently than once every 2 months.30. The method of claim 28 , wherein the composition administered by intra-articular injection is a composition having a concentration of DA-DKP from 50 μM to 350 μM.31. The method of claim 28 , wherein the composition further comprises N-acetyl-tryptophan (NAT) claim 28 , caprylic acid claim 28 , caprylate or combinations thereof.32. The method of claim 31 , wherein the composition is a composition having a concentration of NAT claim 31 , caprylic acid claim 31 , caprylate or combinations thereof from 4 mM to 20 mM.33. The method of claim 28 , wherein the step of removing the albumin comprises treating the human serum albumin composition by a separation method selected from the group consisting of ultrafiltration claim 28 , sucrose gradient centrifugation claim 28 , chromatography claim 28 , salt precipitation claim 28 , and sonication.34. The method of claim 33 , wherein the step of removing ...

METHODS FOR PRODUCING DIKETOPIPERAZINES AND COMPOSITIONS CONTAINING DIKETOPIPERAZINES

Methods of making increased amounts of diketopiperazines (DKP) such as DA-DKP in pharmaceutical compositions of proteins and peptides are disclosed. The disclosure further provides methods of making a DKP, including (1) contacting albumin with an enzyme (such as a dipeptidyl peptidase N (DPP-IV)) that cleaves a pair of N-terminal amino acids from the albumin, and (2 heating the albumin under conditions effective to cause the formation of the DKP. Further, treatment of DKP- and albumin-containing streams to produce improved, higher value, DKP compositions and purified albumin compositions for therapeutic uses is also disclosed. In addition to a first therapeutic DKP composition comprising a low albumin content, a second valuable therapeutic composition is also produced characterized by a high albumin concentration. 1. A method for treating a feed stream comprising albumin and aspartic acid-alanine diketopiperazine (DA-DKP) to produce compositions , the method comprising:processing the feed stream to produce a first albumin-lean stream and a first albumin-rich stream, wherein the first albumin-lean stream comprises a first portion of the DA-DKP present in the feed stream, and the first albumin-rich stream comprises a second portion of the DA-DKP present in the feed stream;reacting the first albumin-rich stream in order to produce DA-DKP resulting in a reaction stream comprising albumin and DA-DKP; andprocessing the reaction stream to produce a second albumin-lean stream and a second albumin-rich stream, wherein the second albumin-lean stream comprises a portion of the DA-DKP present in the reaction stream, and the second albumin-rich stream comprises a second portion of the DA-DKP present in the reaction stream.2. The method of claim 1 , wherein at least one of the first and second albumin-lean streams possess therapeutic value.3. The method of claim 1 , wherein at least one of the first and second albumin-rich streams possess therapeutic value.4. The method of claim ...

USE OF LOW MOLECULAR WEIGHT FRACTIONS OF HUMAN SERUM ALBUMIN IN TREATING DISEASES

The present invention provides a method of modulating various aspects of the immune system. In particular, the present invention teaches the use of diketopiperazines (DKPs) to modulate various aspects of the immune system such as, for example, inflammation, T-cells and various cytokines. 1. A method of inhibiting inflammation , the method comprising administering to an individual in need thereof an effective amount of a pharmaceutical composition comprising a low molecular weight fraction (LMWF) of human serum albumin (HSA) , wherein the individual is not administered a cyclooxygenase-2 (COX-2) antagonist within the period of time ranging from about one hour before to about 6 hours after administration of the pharmaceutical composition.2. The method of claim 1 , wherein the LMWF of HSA contains components having a molecular weight of less than 5000.3. The method of claim 1 , wherein the LMWF of HSA contains components having a molecular weight less than 3000.4. The method of claim 1 , wherein at least one of the components in the LMWF of HSA comprises DA-DKP.5. The method of claim 1 , wherein the LMWF of HSA comprises one or more compounds selected from the group consisting of N-acetyl tryptophan and caprylic acid.6. The method of claim 1 , wherein the individual receiving the pharmaceutical composition is not administered a COX-2 antagonist within a time period selected from the group consisting of at least about one hour claim 1 , at least about 12 hours claim 1 , at least about one day claim 1 , at least about two days claim 1 , at least about three days claim 1 , at least about four days claim 1 , at least about five days claim 1 , at least about six days claim 1 , at least about seven days claim 1 , at least about eight days or at least about nine days and 10 days claim 1 , prior to administration of the pharmaceutical composition.7. The method of claim 1 , wherein the individual receiving the pharmaceutical composition is not administered a COX-2 antagonist ...

Method and system for optically performing an assay to determine a medical condition

A method and system are disclosed for detecting a medical condition wherein a blood or plasma sample is combined with a metal such as cobalt and optically analyzed for an optical distinction that identifies the medical condition. The invention is useful for diagnosing medical conditions such as ischemia. Moreover, the diagnoses of patient samples according to the invention may be enhanced by developing a mathematical model based on signal processing techniques such as principal component analysis on the data obtained in patient studies.

Method for treatment of diseases

Diagnosis and monitoring of inflammation, ischemia and appendicitis

The invention provides methods and kits for diagnosing and monitoring inflammation and/or ischemia in an animal. The methods comprise determining the quantity of a post-translationally modified protein, other than phosphorylated tau, present in a body fluid from an animal. The invention also provides an improved method and kits for diagnosing appendicitis in an animal. The method comprises determining the quantities of orthohydroxyhippuric acid and of a marker of general inflammation, such as a post-translationally modified protein, present in one or more body fluids of the animal.

Method for treatment of diseases

The present invention relates to a vascular-hyperpermeability-inhibiting amount of a compound selected from danazol and pharmaceutically acceptable salts of danazol, for use in treating a disease or condition mediated by vascular hyperpermeability in an animal in need thereof, wherein the disease or condition is atherosclerosis.

Method for treatment of diseases

The invention provides a method of inhibiting vascular hyperpermeability in an animal in need thereof. The method comprises administering a vascular- hyperpermeability-inhibiting amount of a danazol compound to the animal. The invention also provides a method of modulating the cytoskeleton of an endothelial cell in an animal. The method comprises administering an effective amount of a danazol compound to the animal.

Treatment of comorbid premature ejaculation and erectile dysfunction using tramadol and a phosphodiesterase (pde) inhibitor

Disclosed is the use of a tramadol material and a phosphodiesterase (PDE) inhibitor in the manufacture of a composition for treating comorbid premature ejaculation and erectile dysfunction, wherein the PDE inhibitor is a PDE5 inhibitor, or a combination of two or more of the foregoing PDE5 inhibitors.

Use of diketopiperazines for inhibiting vascular hyperpermeability

The invention provides a method of inhibiting vascular hyperpermeability in an animal in need thereof. The method comprises administering an effective amount of a diketopiperazme, a prodrug of a diketopiperazme or a pharmaceutically-acceptable salt of either of them to the animal, wherein the diketopiperazme has the formula set forth in the specification. The invention also provides a method of modulating the cytoskeleton of an endothelial cell in an animal. The method comprises administering an effective amount of a diketopiperazme, a prodrug of a diketopiperazme or a pharmaceutically-acceptable salt of either of them to the animal, wherein the diketopiperazme has the formula set forth in the specification. The invention further provides a kit. The kit comprises a diketopiperazme, a prodrug of a diketopiperazme or a pharmaceutically-acceptable salt of either of them to the animal, wherein the diketopiperazme has the formula set forth in the specification.

Oral care methods and products

The invention provides methods, oral care products and kits for treating mouth tissues of an animal. In particular, the invention provides methods, oral care products and kits which use or comprise a non-peptide polyamine chelating agent, most preferably trientine, or a physiologically-acceptable salt thereof, which can inhibit the release of pro- inflammatory cytokines, particularly interleukin 8, from cells located in tissues of the mouth and can reduce the damage done by reactive oxygen species (ROS) to such tissues.

Metal-binding compounds and uses therefor

The invention provides a method of reducing the damage done by reactive oxygen species (ROS) in an animal. The invention also provides a method of reducing the concentration of a metal in an animal. These methods comprise administering to the animal an effective amount of a metal-binding compound as further described in the application. The invention further provides a method of reducing the damage done by ROS in a tissue or an organ that has been removed from an animal. This method comprising contacting the tissue or organ with a solution containing an effective amount of a metal-binding compound of the invention. The invention further provides novel metal-binding compounds, pharmaceutical compositions comprising the metal-binding compounds, and kits comprising a container holding a metal-binding compound of the invention.

Danazol for inhibiting vascular hyperpermeability or modulating cytoskeletons of endothelial cells, and pharmaceutical compositions or drugs containing said danazol

【課題】血管透過性亢進を抑制するための又は内皮細胞の細胞骨格を調整するための製薬組成物又は医薬品を提供すること。【解決手段】血管透過性亢進を抑制するための製薬組成物は、血管透過性亢進を抑制する量のダナゾール又はその薬学的に許容可能な塩を含む。更に、内皮細胞の細胞骨格を調整するための医薬品は、内皮細胞の細胞骨格を調整するのに有効な量のダナゾール又はその薬学的に許容可能な塩を含む。【選択図】 図１

Pharmaceutical dosage forms and compositions comprising danazol

The invention provides a method of inhibiting vascular hyperpermeability in an animal in need thereof. The method comprises administering a vascular- hyperpermeability-inhibiting amount of a danazol compound to the animal. The invention also provides a method of modulating the cytoskeleton of an endothelial cell in an animal. The method comprises administering an effective amount of a danazol compound to the animal.

Compositions for the mobilization, homing, expansion and differentiation of stem cells and methods of using the same

The invention provides compositions that increase the mobilization, homing, expansion, and/or differentiation of stem cells and methods of using the same for the treatment of mammals.

Method of delaying ejaculation

The invention provides a method of delaying ejaculation. The method comprises administering an effective amount of a tramadol material to a human male prior to sexual intercourse. The method is particularly useful for treating premature ejaculation.

Methods and products for treatment of diseases

Therapeutic methods and compounds

Treatment of joint conditions

【課題】関節病態を治療する方法を提供する。【解決手段】アスパラギン酸およびアラニンのアミノ酸側鎖を有するジケトピペラジン（ＤＡ－ＤＫＰ）を含む医薬組成物の複数回投与レジメンを投与することを含む。また、ヒト血清アルブミンの低分子量画分の複数回投与を用いて変形性関節症を治療する方法を提供する。【選択図】なし

Reducing side effects of tramadol

The invention provides methods of reducing the side effects of tramadol. Accordingly, in one embodiment, the invention provides a method of reducing the incidence of newly-discovered side effects related to sexual function in human males taking a tramadol material. The method comprises administering a phosphodiesterase inhibitor to a male taking the tramadol material. The invention also provides pharmaceutical compositions. In one embodiment, the composition comprises a tramadol material and a phosphodiesterase inhibitor. The invention further provides kits. In one embodiment, the kit comprises a tramadol material and a phosphodiesterase inhibitor.

Method for treatment of diseases

The present invention relates to a vascular-hyperpermeability-inhibiting amount of a compound selected from danazol and pharmaceutically acceptable salts of danazol, for use in treating a disease or condition mediated by vascular hyperpermeability in an animal in need thereof, wherein the disease or condition is diabetes.

Oral care methods and products

Treatment of comorbid premature ejaculation and erectile dysfunction

The invention provides a method of treating comorbid premature ejaculation and erectile dysfunction. In particular, the method comprises administering an effective amount of a tramadol material and an effective amount of a phosphodiesterase inhibitor. The invention also provides a pharmaceutical composition comprising a pharmaceutically-acceptable carrier, a tramadol material and a phosphodiesterase inhibitor. The invention further provides a kit comprising a tramadol material and a phosphodiesterase inhibitor.

Treatment of t-cell mediated diseases

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention ftirther provides methods of making improve d pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions.

Method of using diketopiperazines and composition containing them

The invention provides a method of inhibiting the effects of platelet activating factor (PAF). For instance, a disease or condition mediated by PAF (particularly inflammation) can be treated or platelet aggregation can be inhibited. The invention also provides a method of inhibiting the production and/or release of interleukin 8 (IL-8) by cells. The effects of PAF and the production and/or release of IL-8 are inhibited according to the invention by a compound of formula (1) wherein R1 and R2 are defined in the application, or a physiologically-acceptable salt thereof. The invention also provides pharmaceutical compositions comprising these compounds.

Treatment of T-cell mediated diseases