Abstract: The present invention relates generally to the control of body weight of animals including mammals and humans, and more particularly to materials identified herein as modulators of body weight, and to diagnostic and therapeutic uses of such modulators. In its broadest aspect, the present invention relates to nucleotide sequences corresponding to the murine and human OB gene, and two isoforms thereof, and proteins expressed by such nucleotides or degenerate variations thereof, that demonstrate the ability to participate in the control of mammalian body weight and that have been postulated to play a critical role in the regulation of body weight and adiposity. The present invention further provides nucleic acid molecules for use as molecular probes or as primers for polymerase chain reaction (PCR) amplification. In further aspects, the present invention provides cloning vectors and mammalian expression vectors comprising the nucleic acid molecules of the invention.

Abstract: Novel methods for use in identifying or assaying compounds which can simulate the ability of amylin to cause hyperlactemia and hyperglycemia in in vivo biological models, or for use in evaluating the potency of compounds known or suspected to simulate these actions of amylin, which involve introducing test samples into in vivo test systems and determining the presence or amount of a rise in lactate, or determining the presence or amount of a rise in lactate and a rise in glucose, following test sample administration.

Abstract: The present invention relates to a process for producing a therapeutic powder formulation, comprising (a) providing an acidic aqueous solution comprising an insulin or analoguc or derivative thereof and an enhancer; (b) adjusting the pH to a pH in the range of 4.5 to 7.4; (c) precipitating a product comprising the insulin or analogue or derivative thereof and the enhancer, wherein the precipitation is performed essentially without evaporation of the solution; and (d) removing the water.

Abstract: An herbal composition for the treatment of diabetes, comprising 15 percent by weight of dried, powdered seeds of Trigonella foenum-graecum; 23 percent by weight of dried, powdered seeds of Nigella sativa; 10 percent by weight of dried, powdered leaves of Origanum vulgare; 10 percent by weight of dried, powdered sap of Rosmarinus officinalis; 15 percent by weight of dried, powdered beans of Lupinus termis; 12 percent by weight of dried, powdered black leaves of Lawsonia inermis; and 15 percent by weight of dried, powdered seeds of Foeniculum vulgare. The herbal composition may be administered in non-encapsulated powder form or in capsule form.

Abstract: The present invention is directed to a microsphere for the controlled release of a biologically active molecule which comprises a biologically active molecule and an ester of hyaluronic acid or mixtures of said esters of hyaluronic acids, and wherein said biologically active molecule is surrounded by or adhered to said ester of hyaluronic acid, and wherein said microsphere has a diameter of between 1 .mu.m to 100 .mu.m.

Abstract: Methods are provided for treating or alleviating the symptoms of subjects with psychological disorders, metabolic disorders, chronic stress-related disorders, sleep disorders, conditions associated with sexual senescence, aging, or premature aging by treating such subjects with IGF or mutant IGF either alone or complexed with IGFBP-3. Methods for increasing the levels of DHEA or DHEAS and treating or alleviating the symptoms of subjects with disorders characterized by low levels of DHEA or DHEAS by administering effective amounts of IGF or mutant IGF alone or complexed with IGFBP-3 are also provided. Methods for increasing the level of T4 and treating or alleviating the symptoms of subjects with disorders characterized by low levels of T3 or T4 by administering effective amounts of IGF or mutant IGF alone or complexed with IGFBP-3 are additionally provided.

Abstract: The present invention generally relates to novel encapsulation compositions and methods. In particular, the invention relates to stabilized microcapsule compositions which comprise a layer of a crosslinked, mixed functionality, polymer matrix, and methods for their preparation. The encapsulated compositions may comprise the crosslinked polymer matrix layer as an inner layer, an outer layer, or an intermediate layer of an overall encapsulated composition. The compositions will generally also comprise a biological material, e.g., cells, proteins, and the like, encapsulated within the composition. The compositions and methods of the invention are useful in a variety of applications, including cell culturing and transplant therapy.

Abstract: The present invention relates to a compound of general formula I ##STR1## for treating medical disorders related to binding to human somatostatin receptor subtypes.

Abstract: The present invention relates to protracted human insulin derivatives in which the A21 and the B3 amino acid residues are, independently, any amino acid residue which can be coded for by the genetic code except Lys, Arg and Cys; Phe.sup.B1 may be deleted; the B30 amino acid residue is (a) a non-codable, lipophilic amino acid having from 10 to 24 carbon atoms, in which case an acyl group of a carboxylic acid with up to 5 carbon atoms is bound to the .epsilon.-amino group of Lys.sup.B29 ; or (b) the B30 amino acid residue is deleted or is any amino acid residue which can be coded for by the genetic code except Lys, Arg and Cys, in any of which cases the .epsilon.-amino group of Lys.sup.B29 has a lipophilic substituent; and any Zn.sup.2+ complexes thereof with the proviso that when B30 is Thr or Ala and A21 and B3 are both Asn, and Phe.sup.B1 is present, then the insulin derivative is always present as a Zn.sup.2+ complex.

Abstract: Combinations of a glitazone antidiabetic agent and a biguanide antidiabetic agent, and optionally a sulfonylurea antidiabetic agent, are useful for treating diabetes mellitus and improving glycemic control.

Abstract: The invention relates to methods and compositions for the treatment of autoimmune disease. Specifically, compositions comprising heat shock proteins, including gp96, hsp90, and hsp70, are disclosed. Immunotherapeutic methods for administering the hsp-containing compositions are disclosed. Furthermore, methods for preventing rejection of organs transplanted to treat autoimmune disease are disclosed. The disclosed methods are useful for treating a variety of autoimmune diseases, including insulin dependent diabetes mellitus.

Abstract: A process for the long term modification and regulation of lipid and carbohydrate metabolism--generally to reduce obesity, insulin resistance, and hyperinsulinemia or hyperglycemia, or both (these are the hallmarks of noninsulin dependent, or Type II diabetes)--by administration (i.e., by oral, sublingual or parenternal administration) to a vertebrate, animal or human, of a dopamine agonist, e.g., bromocriptine. Administration of the bromocriptine is made over a limited period at a time of day dependent on the normal circadian rhythm of insulin resistant and insulin sensitive members of a similar species. Insulin resistance, and hyperinsulinemia and hyperglycemia, or both, can be controlled in humans on a long term basis by such treatment inasmuch as the short term daily administration resets hormonal timing in the neural centers of the brain to produce long term effects.

Abstract: Human growth hormone variants are disclosed having enhanced affinity for the growth hormone receptor. Also disclosed are human growth hormone variants conjugated to one or more chemical groups, such as poly(ethylene glycol), which is believed to prolong the in vivo half-life of the variants.

Abstract: The invention relates to inositolglycans having insulin-like action. Specific compounds are provided having the formula IA--Z--R (I)where A is the radical H--P(O)(OH)--, H--P(S)(OH)--, HO--P(S)(OH)--, HS--P(S)(OH)--, (C.sub.1 -C.sub.4)-alkyl-P(O)(OH)--, (C.sub.1 -C.sub.4)-alkyl-P(S)(OH)--, S(O).sub.2 (OR.sup.1)--, S(O)(OR.sup.1)--, NH.sub.2 --C(O)--, R.sup.1 R.sup.2 N--, R.sup.1 R.sup.2 N--C(O)--NH--, R.sup.1 O--SO.sub.2 --NH--, (C.sub.1 -C.sub.4)-alkyl-SO.sub.2 --, (C.sub.1 -C.sub.4)-alkyl-S(O)-- or R.sup.1 --S--, Z is 2 to 6 substituted or unsubstituted sugar radicals and R is substituted or unsubstituted inositol. The inventive compounds are suitable for the treatment of diabetes mellitus or noninsulin-dependent diabetes.

Abstract: Compounds of the formula ##STR1## where T is ##STR2## and R(A), R(B), R(C), R(D), R(E), R(F), x and y have the meanings indicated in the claims, and their pharmaceutically acceptable salts are effective inhibitors of the cellular sodium-proton antiporter (Na.sup.+ /H.sup.+ exchanger). These compounds are therefore outstandingly suitable for treatment of all illnesses which are to be attributed to increased Na.sup.+ /H.sup.+ exchange.

Abstract: Tissue-destructive conditions related to excess proteinase activity in a biological system are treated or prevented by administering to the system a composition which combines a tetracycline and a bisphosphonate in synergistic proteinase inhibiting amounts.

Abstract: Systemic delivery of insulin to a mammalian host is accomplished by inhalation of a dry powder of insulin. It has been found that dry insulin powders are rapidly absorbed through the alveolar regions of the lungs.

Abstract: The present invention relates to the use of creatine compounds for treating or preventing a metabolic disorder related to body weight control such as obesity, and it's associated diseases in a patient experiencing said disorder. The creatine compounds which can be used in the present method include (1) analogues of creatine which can act as substrates or substrate analogues for the enzyme creatine kinase; (2) compounds which can act as inhibitors of creatine kinase; (3) compounds which can modulate the creatine transporter (4) N-phosphocreatine analogues bearing transferable or non-transferable moieties which mimic the N-phosphoryl group. (5) compounds which modify the association of creatine kinase with other cellular components.

Abstract: Agonist analogues of amylin and related pharmaceutical compositions, and methods of treatment of diabetes and other insulin-requiring states, as well as methods of treatment of hypoglycemia, are provided.

Abstract: This invention relates to the use of aldose reductase inhibitors in the treatment, prevention or reversal of diabetic cardiomyopathy in a human subject.

Abstract: The present invention relates to methods and pharmaceutical compositions for decreasing the production of interferon-gamma inducing factor (IGIF). The invention also relates to methods and pharmaceutical compositions for decreasing the production of interferon-gamma (IFN-.gamma.). The compositions comprise a therapeutically effective amount of a compound which inhibits interleukin-1.beta. converting enzyme (ICE) and a pharmaceutically acceptable carrier. The methods comprise the step of administering the above compositions to a subject. The present invention also relates to methods for treating or reducing the advancement, severity or effects of an IGIF- or IFN-.gamma.-mediated inflammatory, infectious or autoimmune condition.

Abstract: A method of treatment for diabetic neuropathy using combined administration of a formulation including as an active ingredient a prostaglandin I derivative, especially a prostaglandin I.sub.2 derivative with an anti-diabetic agent is applied to hypofunction of motor nerve and sensory nerve to which conventional anti-diabetic agents do not provide sufficient treatments, with nerve conduction velocities improved.

Abstract: The present invention provides novel complexes consisting of certain GLP-1 molecules associated with a divalent metal cation that is capable of co-precipitating with a GLP-1 molecule. Pharmaceutical compositions and methods of using such complexes for enhancing the expression of insulin in B-type islet cells is claimed, as is a method for treating maturity onset diabetes mellitus in mammals, particularly humans.

Abstract: Combinations of a sulfonylurea antidiabetic agent and a glitazone antidiabetic agent are useful for treating diabetes mellitus and improving glycemic control.

Abstract: Pharmaceutical agents for treating diabetus mellitus which contain a compound of formula I ##STR1## as the active substance, in which A, B, A' and W have the meanings stated in the claims, new compounds of formula I as well as processes for their production.

Abstract: Preeclampsia and preterm labor in a pregnant female mammal are treated by administering thereto a combination of a progestin and a nitric oxide synthase substrate, a nitric oxide donor or both, optionally in further combination with one or more of a cyclooxygenase inhibitor, a PGI.sub.2 -mimetic, a thromboxane (TXA.sub.2) inhibitor, a compound possessing TXA.sub.2 -agonistic and TXA.sub.2 -inhibiting properties, a compound possessing TXA.sub.2 -antagonistic and PGI.sub.2 -memetic activities, and a TXA.sub.2 antagonist.

Abstract: Composition and method of using the same for preventing or treating microalbuminuria in a warm blooded animal in which the composition contains effective amounts of vitamin E, folic acid, a magnesium-releasing compound, a chromium-releasing compound and vitamin B-12.

Abstract: Dysmenorrhea, disfunctional uterine bleeding, preterm labor and postpartum labor in female mammals are treated by inhibiting uterine contractility by administering thereto a nitric oxide synthase substrate, a nitric oxide donor or both, optionally in combination with one or more of a prostaglandin inhibitor, a prostacyclin-mimetic, a progestin, an oxytocin antagonist or a .beta.-agonist in an amount effective to ameliorate the symptoms thereof; and inadequate menses treated and induction of abortion or stimulation of labor in a pregnant female is achieved by uterine contractility stimulation by administering thereto a nitric oxide inhibitor, either alone or optionally in a combination of progesterone antagonist, an oxytocin or oxytocin analogue antagonist or a prostaglandin.

Abstract: Derivatives of glucagon-like peptide I (GLP-1) and especially GLP-1(7-36) have been found to have insulinotropic activity. The invention pertains to the use of GLP-1(7-36) for the treatment of type II diabetes mellitus.

Abstract: The invention relates to the use of R-(+)-.alpha.-lipoic acid, R-(-)-dihydrolipoic acid or their metabolites, salts, esters and amides for the synthesis of drugs for the treatment of diabetes mellitus of types I and II, compensated and decompensated insulin resistance and sequelae or late complications of diabetes mellitus, such as cataracts, polyneuropathy, nephropathy, as well as sequelae or late complications of insulin resistance.

Abstract: Insulin preparations of superior physical stability, comprising dissolved and/or precipitated human insulin or an analogue or derivative thereof, and a water-soluble reduced or non-reducing carbohydrate containing at least 4 carbon atoms in the main carbohydrate structure, or a water-soluble non-reducing ester and/or ether derivative of a carbohydrate or reduced carbohydrate containing at least 4 carbon atoms in the main carbohydrate structure, or mixtures thereof are disclosed.

Abstract: The subject invention concerns novel materials and methods for the treatment and/or prevention of autoimmune disease. In a specific embodiment, elevated production of prostaglandin synthase-2 (PGS-2) is correlated with autoimmune dysfunction.

Abstract: A combination of a mucosally administrable bystander antigen and an orally, enterally, or parenterally administrable methotrexate is employed to make a pharmaceutical formulation and to treat or prevent autoimmune disease.

Abstract: The present invention provides a method for treatin hypertension in insulin resistant patients comprising the administration of an insulin sensitizing agent, particularly ciglitazone or pioglitazone.

Abstract: Novel 1,4,5-substituted imidazole compounds and compositions for use in therapy.

Abstract: A method for treating diabetes in a mammal by moderately controlling blood glucose concentration in the mammal together with administering to the mammal an amount of a tetracycline compound effective to reduce complications associated with diabetic hyperglycemia. The method enables long term management of diabetes by avoiding the problems associated with tight control of blood glucose concentrations, i.e., hypoglycemia tolerance and seizures, while simultaneously avoiding the problems associated with conventional moderate control of blood glucose concentrations, i.e., pathological complications associated with hyperglycemia, such as nephropathy, retinopathy, etc. Blood glucose concentration can be controlled by moderate administration (e.g.

Abstract: Novel cryptolepine analogs useful as hypoglycemic agents and methods for their use as hypoglycemic agents, for example, in the treatment of diabetes, and a method for their synthesis are described. As hypoglycemic agents, the novel cryptolepine analogs are useful for the treatment of insulin-dependent diabetes mellitus (IDDM or Type I) and non-insulin dependent diabetes mellitus (NIDDM or Type II).

Abstract: The present invention is directed to a method for the prophylactic and therapeutic treatment of diabetic retinopathy. The method involves the administration of an inhibitor of the protein tyrosine kinase pathway to an animal, such as a mammal, in particular a human, in an amount sufficient to treat the retina for diabetic retinopathy prophylactically or therapeutically. The inhibitor of the protein tyrosine kinase pathway is preferably genistein or an analogue or prodrug thereof or a pharmaceutically acceptable salt of any of the foregoing.

Abstract: A herbal anti-diabetic therapeutic product comprising from about 89.5-98.5% of powdered inner seed of Dolichos biflorus and from about 10.5-1.5% of powdered fibrous outer shell of the seed of Dolichos biflorus wherein the product is subjected to radiation for a period of 10-20 minutes.

Abstract: The present invention generally relates to novel encapsulation compositions and methods. In particular, the invention relates to stabilized microcapsule compositions which comprise a layer of a crosslinked, mixed functionality, polymer matrix, and methods for their preparation. The encapsulated compositions may comprise the crosslinked polymer matrix layer as an inner layer, an outer layer, or an intermediate layer of an overall encapsulated composition. The compositions will generally also comprise a biological material, e.g., cells, proteins, and the like, encapsulated within the composition. The compositions and methods of the invention are useful in a variety of applications, including cell culturing and transplant therapy.

Abstract: The invention covers a method of implanting a living donor cell into a host animal without inflammatory response or rejection of the donor cell by the host animal, by obtaining an uncoated particle of a biocompatible, temperature-independent gel that encapsulates the living donor cell, wherein the uncoated particle provides a molecular weight cutoff that prevents host animal immune cells from entering the particle, yet does not have to prevent entry of host animal IgG and complement into the particle, and implanting the uncoated particle into the host animal.

Abstract: A highly effective pure, natural, ingestible antidiabetic may be made from Shilianhua (Echevaria glauca, Sinocrassula berger, Crassulaceae) by washing leaves and/or stems of the Shilianhua plant, crushing them in a grinder, breaking the cell walls to form a filterable material, filtering the material to produce a filtrate, and decompressing and concentrating the filtrate to produce a concentrated solution. The cell walls may be broken using medical alcohol, quick freezing and thawing, or ultrasonic mixing. The concentrated solution is then made into a powder, or concentrated powder, by baking, crushing, and passage through a 60 mesh screen; using a silica gel column; using a Saphadex column; or by treatment with a CH.sub.3 COOC.sub.2 H.sub.5 solution. Treatment of, or to prevent, diabetes by lowering blood sugar at least 10% (e. g.

Abstract: This invention concerns compositions and methods utilizing a compound of the formula: ##STR1## for reducing or controlling inflammation and treating pathological conditions mediated by intercellular adhesion. More particularly, the present invention concerns compositions and methods for blocking or modulating the function of the Beta.sub.2 Integrin family of cell adhesion molecules.

Abstract: The present invention provides a new composition, food product and uses for a known compound. More particularly, the present invention provides a new pharmaceutical composition containing 3-guanidinopropionic acid and a method of using 3-guanidinopropionic acid to prevent or treat obesity in non-insulin dependent diabetic (NIDDM) patients that is caused by treatment with anti-diabetic drugs, such as an insulin sensitizing drug or an insulin secretion stimulating drug. Examples of insulin sensitizing drugs are pioglitazone and pioglitazone hydrochloride. Examples of insulin secretion stimulating drugs are glyburide and glimepiride. The present invention also provides a new food product containing 3-guanidinopropionic acid and a method of using 3-guanidinopropionic acid to increase endurance, stamina and exercise capacity.

Abstract: An edible composition comprising a mixture of at least two herbs selected from the group consisting of Syzygium cumini, Gymnema sylvestre, Momordica charantia and Solanum melongena. Preferably, the composition comprises a mixture of Syzygium cumini and Momordica charantia. A mixture of Syzygium cumini, Gymnema sylvestre and Momordica charantia is particularly preferred. The herbal mixtures are useful as dietary supplements and are especially useful for lowering the glucose level of the blood in mammals, particularly humans suffering from diabetes mellitus.

Abstract: The need for the delivery of insulin by injection can be reduced or eliminated by a method whereby an aerosolized insulin formulation is delivered to a patient's lungs and the rate at which the insulin is absorbed into the blood is increased by the use of monomeric insulin and/or an inhale-exhale breathing maneuver. Particles of insulin and in particular monomeric insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The rate of absorption is enhanced by the monomeric form of insulin and by instructing the patient to inhale maximally and thereafter exhale maximally. This maneuver causes a spike in the rate at which insulin enters the circulatory system thereby increasing the rate at which glucose is removed from the circulatory system. The insulin or insulin analog may be a dry powder but is preferably in a liquid formulation delivered to the patient from a hand-held, self-contained device which automatically releases an aerosolized burst of formulation.

Abstract: A medicinal composition is provided for treatment of diabetes in a human subject. The medicinal composition of the invention induces a significant reduction in serum glucose due to the regeneration of pancreatic islet cells. A medicinal composition according to the invention necessarily includes a pharmacologically significant quantity of (-)epicatechin augmented with a comparable amount of gymnemic acid. For best results smaller quantities of cinnamomum tamala, syzygium cumini, trigonella foenum graceum, azardichta indica, ficus racemosa, and tinospora cordifolia are also included in the composition. One to two grams of the medicinal composition of the invention are administered to a diabetic human subject three times a day before meals. The unique combination of components in the medicinal composition leads to a regeneration of the pancreas cells which then start producing insulin on their own.

Abstract: The invention relates to active substance combinations which consist of at least one polypeptide with the biological action of fibroblast growth factors and of at least one cationic polyelectrolyte. These combinations permit improved dosage of the FGF activity. The invention also relates to a method of treating wounds, burns, skin ulcers, diabetic gangrene, mucosal ulcers and lesions, skin donation and transplantation sites, or surgical wounds by administering a peptide having FGF activity with an amount of cationic polyelectrolyte which is effective to decrease non-specific binding of the peptide having FGF activity.

Abstract: A method for treating diabetes mellitus by administering composition providing a gastrin/CCK receptor ligand, e.g. a gastrin, and an EGF receptor ligand, e.g. TGF.alpha., in an amount sufficient to effect differentiation of pancreatic islet precursor cells to mature insulin-secreting cells. The composition can be administered systemically or expressed in situ by cells transgenically supplemented with one or both of a gastrin/CCK receptor ligand gene, e.g. a preprogastrin peptide precursor gene and an EGF receptor ligand gene, e.g. a TGF.alpha. gene.

Abstract: This invention provides an interdigitation-fusion liposome comprising an arachidonic acid metabolite, a lipid bilayer comprising a lipid and an aqueous compartment comprising a release-inhibiting buffer. Preferred arachidonic acid metabolites are the prostaglandins, particularly PGE.sub.1. The liposomal formulations can be used to treat animals, particularly humans, for diseases, disorders or conditions which can be ameliorated by prostaglandins, e.g., cell activation/adhesion disorders and inflammatory disorders.