WO2001028532A3 - Methods and compositions for predicting, diagnosing and treating lipodystrophy - Google Patents

Methods and compositions for predicting, diagnosing and treating lipodystrophy Download PDF

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Publication number
WO2001028532A3
WO2001028532A3 PCT/CA2000/001208 CA0001208W WO0128532A3 WO 2001028532 A3 WO2001028532 A3 WO 2001028532A3 CA 0001208 W CA0001208 W CA 0001208W WO 0128532 A3 WO0128532 A3 WO 0128532A3
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WO
WIPO (PCT)
Prior art keywords
lipodystrophy
levels
therapy
antiretroviral
protease inhibitor
Prior art date
Application number
PCT/CA2000/001208
Other languages
French (fr)
Other versions
WO2001028532A2 (en
Inventor
Kevin C Kain
Lena Serghides
Original Assignee
Kevin C Kain
Lena Serghides
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from CA002289365A external-priority patent/CA2289365A1/en
Application filed by Kevin C Kain, Lena Serghides filed Critical Kevin C Kain
Priority to EP00969122A priority Critical patent/EP1223983A2/en
Priority to CA002387919A priority patent/CA2387919A1/en
Priority to AU78949/00A priority patent/AU7894900A/en
Publication of WO2001028532A2 publication Critical patent/WO2001028532A2/en
Publication of WO2001028532A3 publication Critical patent/WO2001028532A3/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/07—Retinol compounds, e.g. vitamin A
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/203—Retinoic acids ; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/193—Colony stimulating factors [CSF]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/20—Interleukins [IL]
    • A61K38/2026—IL-4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56983—Viruses
    • G01N33/56988—HIV or HTLV
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/70596—Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value

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  • Pharmacology & Pharmacy (AREA)
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  • Engineering & Computer Science (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
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  • Marine Sciences & Fisheries (AREA)
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  • AIDS & HIV (AREA)
  • Food Science & Technology (AREA)
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  • Tropical Medicine & Parasitology (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

This invention relates to a method of predicting those individuals at risk of developing lipodystrophy associated with antiretroviral therapy is disclosed. The method includes the steps of: (a) measuring CD36 levels in the patient prior to protease inhibitor or antiretroviral therapy; (b) measuring CD36 levels in the patient after initiating protease inhibitor or antiretroviral therapy; (c) determining whether CD36 levels after antiretroviral or protease inhibitor therapy are changed after therapy, a change in CD36 levels being predictive of the subsequent development of lipodystrophy. The invention also includes a composition for treating or preventing lipodystrophy associated with PI or antiretroviral therapy. The composition includes PPARη-RXR agonist to up-regulate CD36 in admixture with a pharmaceutically acceptable carrier, excipient, or diluent. The composition can be used in a method to prevent or treat lipodystrophy. The invention also includes a method of determining whether a test compound causes lipodystrophy in a mammal.
PCT/CA2000/001208 1999-10-19 2000-10-18 Methods and compositions for predicting, diagnosing and treating lipodystrophy WO2001028532A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP00969122A EP1223983A2 (en) 1999-10-19 2000-10-18 Methods and compositions for predicting, diagnosing and treating lipodystrophy
CA002387919A CA2387919A1 (en) 1999-10-19 2000-10-18 Methods and compositions for predicting, diagnosing and treating lipodystrophy
AU78949/00A AU7894900A (en) 1999-10-19 2000-10-18 Methods and compositions for predicting, diagnosing and treating lipodystrophy

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US16034699P 1999-10-19 1999-10-19
US60/160,346 1999-10-19
CA2,289,365 1999-11-12
CA002289365A CA2289365A1 (en) 1999-10-19 1999-11-12 Methods and compositions for predicting, diagnosing and treating lipodystrophy

Publications (2)

Publication Number Publication Date
WO2001028532A2 WO2001028532A2 (en) 2001-04-26
WO2001028532A3 true WO2001028532A3 (en) 2002-01-03

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CA2000/001208 WO2001028532A2 (en) 1999-10-19 2000-10-18 Methods and compositions for predicting, diagnosing and treating lipodystrophy

Country Status (3)

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EP (1) EP1223983A2 (en)
AU (1) AU7894900A (en)
WO (1) WO2001028532A2 (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2824332A1 (en) * 2001-05-04 2002-11-08 Inst Nat Sante Rech Med NUCLEIC ACID CODING POLYPEPTIDE CGL1 AND APPLICATION OF THIS NUCLEIC ACID AND POLYPEPTIDE CGL1 IN DIAGNOSIS AND THERAPEUTICS
FR2854078B1 (en) * 2003-04-28 2008-01-11 Univ Toulouse PROCESS FOR PRODUCING AN IMMUNO-STIMULATING THERAPEUTIC COMPOSITION
WO2005037189A2 (en) * 2003-08-13 2005-04-28 The Burnham Institute Cytoplasmic activity of retinoid x receptor and its regulation by ligands and dimerization
US20050239889A1 (en) * 2004-04-26 2005-10-27 Jean Gosselin In vivo release of endogenous anti-microbial mediators by leukotriene B4 (LTB4) administration
EP1656934A1 (en) * 2004-11-12 2006-05-17 Cognis IP Management GmbH Use of physiologically active fatty acids for treating lipodystrophy

Citations (4)

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Publication number Priority date Publication date Assignee Title
WO1997041831A1 (en) * 1996-05-07 1997-11-13 Cornell Research Foundation, Inc. Stimulation of immune response with low doses of il-2
WO2000000194A1 (en) * 1998-06-27 2000-01-06 Photogenesis, Inc. Ophthalmic uses of ppargamma agonists and ppargamma antagonists
CA2257804A1 (en) * 1998-12-28 2000-07-05 Applied Research Systems Ars Holding N.V. Treatment of hiv-associated dysmorphia/dysmetabolic syndrome
WO2000042211A1 (en) * 1999-01-19 2000-07-20 Glaxo Group Limited Methods of screening protease inhibitors, of inducing mice susceptible to hiv protease inhibitor-induced dyslipidemia, and genes associated therewith

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997041831A1 (en) * 1996-05-07 1997-11-13 Cornell Research Foundation, Inc. Stimulation of immune response with low doses of il-2
WO2000000194A1 (en) * 1998-06-27 2000-01-06 Photogenesis, Inc. Ophthalmic uses of ppargamma agonists and ppargamma antagonists
CA2257804A1 (en) * 1998-12-28 2000-07-05 Applied Research Systems Ars Holding N.V. Treatment of hiv-associated dysmorphia/dysmetabolic syndrome
WO2000042211A1 (en) * 1999-01-19 2000-07-20 Glaxo Group Limited Methods of screening protease inhibitors, of inducing mice susceptible to hiv protease inhibitor-induced dyslipidemia, and genes associated therewith

Non-Patent Citations (7)

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Title
CONF RETROVIRUSES OPPORTUNISTIC INFECT, JAN 31-FEB 4 1999, 6TH P193 (ABSTRACT NO. 665) *
DATABASE AIDSLINE [online] US NATIONAL LIBRARY OF MEDICINE (NLM),BETHESDA, MD, US; LENHARD JM ET AL: "Indinavir enhances retinoic acid signaling: nelfinavir, saquinavir, and ritonavir inhibit retinoid effects in vitro", XP002165993, retrieved from DIALOG Database accession no. 00205308 *
DATABASE BIOSIS BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1992, KLEIN ET AL: "GENERALIZED LIPODYSTROPHY IN-VIVO EVIDENCE FOR HYPERMETABOLISM AND INSULIN-RESISTANT LIPID GLUCOSE AND AMINO ACID KINETICS", XP002165955 *
FENG ET AL: "Expression of CD36 is dependent on PKC and PPARgamma.", FASEB JOURNAL, vol. 13, 12 March 1999 (1999-03-12), pages A200, XP000994810 *
FISCHER ET AL: "Benign symmetrische lipomatose (peripheral lipodystrophy) bei antiretroviraler Therapie der HIV Infektion.", DEUTSCHE MEDIZINISCHE WOCHENSCHRIFT, vol. 123, 1998, pages 1512 - 16, XP000995512 *
METABOLISM CLINICAL AND EXPERIMENTAL, vol. 41, 1992, pages 893 - 6 *
MICHELET ET AL: "Safety and efficacy of ritonavir and saquinavir in combination with zidovudine and lamivudine", CLINICAL PHARMACOLOGY & THERAPEUTICS, vol. 65, 1999, pages 661 - 71, XP000995156 *

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AU7894900A (en) 2001-04-30
EP1223983A2 (en) 2002-07-24
WO2001028532A2 (en) 2001-04-26

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