Abstract: The present invention is directed to the treatment of multiple sclerosis by periodically administering a high dose of methotrexate at a level sufficiently high to cross the blood brain barrier. The methotrexate administration is accompanied by leucovorin rescue of the periphery. The high dose methotrexate is preferably administered at 1 to 4 month intervals. The periodic high dose methotrexate treatment may be used in conjunction with interim treatments using a therapeutic agent that is effective in treating MS, but does not cross the BBB in cytotoxic amounts. It is contemplated that the method of the present invention may be employed to treat other non-infectious, non-neoplastic inflammatory conditions of the CNS.

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 PGI2-mimetic, a thromboxane (TXA2) inhibitor, a compound possessing TXA2-agonistic and TXA2-inhibiting properties, a compound possessing TXA2-antagonistic and PGI2-memetic activities, and a TXA2 antagonist.

Abstract: The invention relates to a method for removing bile salts from a patient in need thereof and compositions useful in the method. The method comprises administering to the patient a therapeutically effective amount of a salt of an alkylated and crosslinked polymer. The alkylated and crosslinked polymer salt comprises the reaction product of crosslinked polymers, or salts and copolymers thereof having amine containing repeat units, with at least one aliphatic alkylating agent.

Abstract: The inhibition of the formation and development of amyloidoses, as well as the dissolution of amyloidoses in organisms is claimed. Methods for the diagnosis of amyloidoses using aromatic and heteroaromatic compounds having at least one electron-withdrawing groups are claimed.

Abstract: A method prevents or treats diseases associated with high plasma cholesterol levels. In addition, this method reduces plasma cholesterol levels. The method comprises administering a lipase inhibitor, e.g. orlistat, and a pharmaceutically acceptable bile acid sequestrant.

Abstract: A pharmaceutical composition contains a nitric oxide donor and advantageously an optional corticosteroid and/or topical anesthetic. The composition is useful in a method for treating anal disorders such as anal fissure, anal ulcer, hemorrhoidal disease, levator spasm, and so forth, by topical application to or proximate the affected area.

Abstract: The present invention provides methods for treating female sexual dysfunctions by administering to a female individual a therapeutically effective amount of at least one compound that donates, transfers or releases nitrogen monoxide, that induces the production of endogenous endothelium-derived relaxing factor, that stimulates endogenous synthesis of nitrogen monoxide, or that is a substrate for nitric oxide synthase. The methods may further comprise administering a therapeutically effective amount of a phosphodiesterase inhibitor and/or a nitrosated and/or nitrosylated phosphodiesterase inhibitor.

Abstract: Patients with pathologic conditions involving constriction or proliferation of smooth muscle or disease associated with cysteine containing proteins, or who are at risk for such, are administered a therapeutically effective amount of a nitric oxide (NO) donor which is insufficient to acutely lower mean arterial blood pressure or pulmonary artery pressure by more than 10%. In one subgenus, NO donor is administered to modify red blood cell membrane receptors to prevent red blood cells from causing vasoconstriction. A related method which allows increased dosage of NO donor without acutely lowering mean arterial blood pressure comprises administering the NO donor into an artery of the patient. In another method, patients having a cardiovascular syndrome, or who are at risk for such, are administered a therapeutically effective amount of thiol which does not acutely affect blood pressure to a significant degree.

Abstract: A method of treating cells that carry at least one APOE4 allele comprises increasing nitric oxide levels in the cells (e.g., by administering an exogenous source of nitric oxide to the cells) by an amount sufficient to combat the decrease of nitric oxide level associated with the presence of the APOE4 allele. Also disclosed is a method of increasing nitric oxide levels in cells in need thereof which comprises administering APOE to the cells in an amount sufficient to increase nitric oxide levels in the cells.

Abstract: The invention provides methods of treating diseases of the central and peripheral nervous systems that are associated with abnormal calcifications within the nervous system, such as Fahr disease. These methods involve administration of bisphosphonates, such as disodium etidronate, to patients.

Abstract: The invention relates to a method for removing bile salts from a patient in need thereof and compositions useful in the method. The method comprises administering to the patient a therapeutically effective amount of a salt of an alkylated and crosslinked polymer. The alkylated and crosslinked polymer salt comprises the reaction product of crosslinked polymers, or salts and copolymers thereof having amine containing repeat units, with at least one aliphatic alkylating agent.

Abstract: Nitric oxide synthase and nitric-oxide-related bioactivity are shown to be necessary and sufficient for activation of an oocyte during the process of fertilization. Methods are provided for the modulation of oocyte activation through modulation of nitric oxide levels. Oocyte activation is enhanced by the addition of nitric oxide synthase, nitric oxide synthase activators, nitric oxide donors, or other compounds that increase the nitric oxide levels of the oocyte during fertilization. The administration of NOS inhibitors is used to block oocyte activation, where contraception is desired.

Abstract: The invention relates to a method for removing bile salts from a patient in need thereof and compositions useful in the method. The method comprises administering to the patient a therapeutically effective amount of a salt of an alkylated and crosslinked polymer. The alkylated and crosslinked polymer salt comprises the reaction product of crosslinked polymers, or salts and copolymers thereof having amine containing repeat units, with at least one aliphatic alkylating agent.

Abstract: The present invention provides a method to control parasitic and saprophagous mites on beneficial insects such as honeybees via the application of a parasiticidally or saprophagouscidally effective amount of a mitochondrial electron transport inhibitor or a pyrimidine compound of formula I.

Abstract: A pharmaceutical composition contains a nitric oxide donor and advantageously an optional corticosteroid and/or topical anesthetic. The composition is useful in a method for treating anal disorders such as anal fissure, anal ulcer, hemorrhoidal disease, levator spasm, and so forth, by topical application to or proximate the affected area.

Abstract: The present invention describes a novel treatment for movement disorders, including tardive dyskinesia, tic disorders, Tourette's syndrome, and blepharospasm, and other focal dystonias. The treatment of the present invention utilizes agents that simultaneously act as NMDA-type glutamate receptor antagonists and GABA-A receptor agonists. Preferably these two activities are characteristic of a single agent, for example acamprosate. Alternatively, separate agents having these activities can be combined and administered together. The invention also provides a third agent that acts as a non-competitive NMDA-receptor blocking agent or ion channel blocker that augments the effect of the primary treatment. A particularly preferred ion channel blocking agent is magnesium. Alternatively, magnesium can be administered alone for prevention and treatment of movement disorders.

Abstract: Compositions and methods of the topical treatment of equine laminitis are disclosed. In particular, combinations of a fast acting nitric oxide (NO) donor, a sustained acting NO donor and an NSAID mixed in a lipid-based carrier are described. The application of such combinations to the affected areas, e.g., the hoofs and surrounding tissues, of an equine afflicted with laminitis provides relief from the debilitating effects of this painful, often life-threatening condition.

Abstract: Nitric oxide generating compounds or compounds which induce in situ synthesis of nitric oxide can be used to inhibit rhinovirus infection. Nitric oxide has the ability to inhibit both viral replication as well as the synthesis of cytokines, in particular the proinflammatory cytokines. Thus the symptoms of rhinovirus infections can be ameliorated by treatments to increase nitric oxide in the respiratory tract.

Abstract: The invention relates to a method for removing bile salts from a patient in need thereof and compositions use full in the method. The method comprises administering to the patient a therapeutically effective amount of a salt of an alkylated and crosslinked polymer. The alkylated and crosslinked polymer salt comprises the reaction product of polymers, or salts and copolymers thereof having amine containing repeat units, with at least one aliphatic alkylating agent and a crosslinking agent.

Abstract: Primary and secondary osteoporosis in a female or a male mammal is treated by administering thereto a nitric oxide synthase substrate, a nitric oxide donor or both, optionally; in further combination with one or more of an estrogen, a progestin, an anabolic steroid. Nitric oxide substrate or donor also can be combined with one or more of other medications acting on bone, such as bisphosphonate, calcitonin, fluoride, androgen and other novel therapeutic agents. Either nitric oxide donor or substrate by itself or combination with other medications as described above can be used in both women and men, (preferably human) for prevention and treatment of osteoporosis and other metabolic bone disorders.

Abstract: The use of certain heterocyclic derivatives for treating parasitic protozoa infections in mammals, in particular bovine trichomoniasis and giardiasis, is disclosed.

Abstract: Disclosed is a method for decreasing NMDA receptor-mediated neuronal damage in a mammal by administering to the mammal a nitroso-compound that generates nitric-oxide or related redox species, in a concentration effective to effect neuroprotection. Also disclosed is a method for decreasing NMDA receptor-mediated neuronal damage in a mammal by administering to the mammal a nitroso-compound that generates nitric oxide (or a related redox species such as NO.sup.- or NO.sup.+ equivalent), or a physiologically concentration effective to cause such neuroprotection.

Abstract: The invention relates to a method for removing bile salts from a patient in need thereof and compositions useful in the method. The method comprises administering to the patient a therapeutically effective amount of an alkylated and crosslinked polymer. The alkylated and crosslinked polymer comprises the reaction product of polymers, or salts and copolymers thereof having amine containing repeat units, with at least one aliphatic alkylating agent and a crosslinking agent.

Abstract: The invention relates to a drug, which contains one or more inhibitors for the cGMP-stimulated phosphodiesterase (PDE II) together with conventional substrates and/or diluents. Preferably the drug contains erythro-9-(2-hydroxy-3-nonyl)-adenine or 2-o-propoxyphenyl-8-azapurine-6-one, optionally together with one or more activators of guanyl cyclase. The invention also relates to the application of inhibitors of cGMP-stimulated phosphodiesterase (PDE II) for the control and prophylaxis of cardiovascular diseases and for the manufacture of drugs for cardiovascular diseases. Preferably erythro-9-(2-hydroxy-3-nonyl)-adenine or 2-o-propoxyphenyl-8-azapurine-6-one is used, optionally together with one or more activators of guanyl cyclase.

Abstract: A method for removing bile salts from a patient by ion exchange by administering to the patient a therapeutically effective amount of one or more highly crosslinked polymers characterized by a repeat unit having the formula ##STR1## or copolymer thereof, where n is an integer; R.sup.1 is H or a C.sub.1 -C.sub.8 alkyl group; M is ##STR2## Z is O, NR.sup.3 R, S, or (CH.sub.2).sub.m ; m=0-10; R.sup.3 is H or a C.sub.1 -C.sub.8 alkyl group; and R.sup.2 is ##STR3## where p=0-10, and each R.sup.4, R.sup.5, and R.sup.6, independently, is H, C.sub.1 -C.sub.8 alkyl group, or an aryl group.

Abstract: Compositions and methods of the topical treatment of equine laminitis are disclosed. In particular, combinations of a fast acting nitric oxide (NO) donor, a sustained acting NO donor and an NSAID mixed in a lipid-based carrier are described. The application of such combinations to the affected areas, e.g., the hoofs and surrounding tissues, of an equine afflicted with laminitis provides relief from the debilitating effects of this painful, often life-threatening condition.

Abstract: The present invention relates to a class of dihydrophenanthrene which are isolated from Calanthe discolor Lindl. and derivatives thereof.

Abstract: The present invention describes the use of nitric-oxide-liberating or transferring compounds, stimulators of endogenous NO formation, as well as stimulators of guanylate cyclase, for prevention, treatment and elimination of endothelial dysfunctions and the diseases accompanying these dysfunctions or caused by them, as well as the use of said compounds to produce pharmaceutical products for the cited areas of application.

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: 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: 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: Lipophilic active substance composition and its use in a new method of treating erectile dysfunction by administration thereof, optionally together with a hydrophilic vehicle and optionally an antibacterial agent into the urethra.

Abstract: The invention relates to a method for removing bile salts from a patient in need thereof and compositions useful in the method. The method comprises administering to the patient a therapeutically effective amount of an alkylated and crosslinked polymer. The alkylated and crosslinked polymer comprises the reaction product of polymers, or salts and copolymers thereof having amine containing repeat units, with at least one aliphatic alkylating agent and a crosslinking agent.

Abstract: Primary and secondary osteoporosis in a female or a male mammal is treated by administering thereto a nitric oxide synthase substrate, a nitric oxide donor or both, optionally; in further combination with one or more of an estrogen, a progestin, an anabolic steroid. Nitric oxide substrate or donor also can be combined with one or more of other medications acting on bone, such as bisphosphonate, calcitonin, fluoride, androgen and other novel therapeutic agents. Either nitric oxide donor or substrate by itself or combination with other medications as described above can be used in both women and men, (preferably human) for prevention and treatment of osteoporosis and other metabolic bone disorders.

Abstract: Lipophilic active substance composition and its use in a new method of treating erectile dysfunction by administration of nitroglycerine together with a hydrophilic vehicle and optionally an antibacterial agent into the urethra.

Abstract: A method for removing bile salts from a patient by ion exchange by administering to the patient a therapeutically effective amount of one or more highly crosslinked polymers characterized by a repeat unit having the formula ##STR1## or copolymer thereof, where n is an integer; R.sup.1 is H or a C.sub.1 -C.sub.8 alkyl group: M is ##STR2## Z is O, NR.sup.3, S, or (CH.sub.2).sub.m ; m=0-10; R.sup.3 is H or a C.sub.1 -C.sub.8 alkyl group; and R.sup.2 is ##STR3## where p=0-10, and each R.sup.4, R.sup.5, and R.sup.6, independently, is H, a C.sub.1 -C.sub.8 alkyl group, or an aryl group.

Abstract: Disclosed is a method and patch for decreasing NMDA receptor-mediated neuronal damage in a mammal by administering to the mammal a nitroso-compound that generates nitric-oxide or related redox species, in a concentration effective to effect neuroprotection. Also disclosed is a method for decreasing NMDA receptor-mediated neuronal damage in a mammal by administering to the mammal a nitroso-compound that generates nitric oxide (or a related redox species such as NO.sup.- or NO.sup.+ equivalent), or a physiologically concentration effective to cause such neuroprotection.

Abstract: Disclosed is a method for decreasing NMDA receptor-mediated neuronal damage in a mammal by administering to the mammal a nitroso-compound that generates nitric-oxide or related redox species, in a concentration effective to effect neuroprotection. Also disclosed is a method for decreasing NMDA receptor-mediated neuronal damage in a mammal by administering to the mammal a nitroso-compound that generates nitric oxide (or a related redox species such as NO.sup.- or NO.sup.+ equivalent), or a physiologically concentration effective to cause such neuroprotection.

Abstract: A method is provided for nonoxidatively cleaving the phosphorus-oxygen linkage of nucleic acids and certain anticholinesterases such as insecticides using a macrocyclic copper(II) complex. A composition suited for such cleavage is also provided.

Abstract: A pharmaceutical composition contains a nitric oxide donor and advantageously an optional corticosteroid and/or topical anesthetic. The composition is useful in a method for treating anal disorders such as anal fissure, anal ulcer, hemorrhoidal disease, levator spasm, and so forth, by topical application to or proximate the affected area.

Abstract: The invention relates to alkylated amine polymers and a method for removing bile salts from a patient that includes administering to the patient a therapeutically effective amount of product produced by a process comprising alkylating one or more crosslinked amine polymers, salts or copolymers thereof with at least one alkylating agent. The reaction product is characterized in that: (i) at least some of the nitrogen atoms are unreacted with alkylating agent; and (ii) less than 10 mol % of the nitrogen atoms in the polymer react with the alkylating agent to form quaternary ammonium units.

Abstract: A method for removing bile salts from a patient that includes administering to the patient a therapeutically effective amount of product produced by a process comprising alkylating one or more crosslinked amine polymers, salts or copolymers thereof with at least one alkylating agent. The reaction product is characterized in that: (i) at least some of the nitrogen atoms are unreacted with alkylating agent; and (ii) less than 10 mol% of the nitrogen atoms in the polymer react with the alkylating agent to form quaternary ammonium units.

Abstract: The stimulation of ovulation in a female may be achieved by administering a nitric oxide source, optionally in further combination with one or more of clomiphene, a gonadotropin, and an LH-RH agonist.

Abstract: A medical preparation for treating anal disorders comprises an effective amount of a nitric oxide donor, preferably an organic nitrate. The preparation may be in the form of an ointment that is applied to affected tissue at least once daily.

Abstract: This invention relates to a method for administering systemically active agents through the skin or mucosal membranes of humans and animals and into the bloodstream in a transdermal device or formulation comprising topically administrating with said systemic agent an effective amount of a membrane penetration enhancer having the structural formula ##STR1## or the pharmaceutically acceptable salt thereof wherein W represents oxygen, sulfur or two hydrogen radicals; Z represents --CH.sub.2 --; R represents alkyl optionally substituted with one to three double or triple bonds, --SR"', --OR"', --NHR"', or --COOR.sub.1 ; R"' represents alkyl, alkylthioalkyl, alkoxyalkyl, amino alkyl, optionally substituted with a phenyl, or benzoyl; R' represents hydrogen, alkyl, alkoxy, acyloxy, alkylthio, hydroxy or --(CH.sub.2).sub.y COOR.sub.1 ; R" represents hydrogen or --(CH.sub.2).sub.y COOR.sub.1 ; R.sub.

Abstract: Disclosed is a method for decreasing NMDA receptor-mediated neuronal damage in a mammal by administering to the mammal a nitroso-compound that generates nitric-oxide or related redox species, in a concentration effective to effect neuroprotection. Also disclosed is a method for decreasing NMDA receptor-mediated neuronal damage in a mammal by administering to the mammal a nitroso-compound that generates nitric oxide (or a related redox species such as NO.sup.31 or NO.sup.+ equivalent), or a physiologically concentration effective to cause such neuroprotection.

Abstract: An aromatic compound of the formula: ##STR1## wherein R.sup.1 is a C.sub.3 -C.sub.8 alkyl group, a C.sub.3 -C.sub.8 alkoxy group, an alkoxyalkyl group having 3 to 8 carbon atoms, a C.sub.3 -C.sub.8 alkenyl group, a C.sub.3 -C.sub.8 alkenyloxy group, an alkenyloxyalkyl group having 3 to 8 carbon atoms, a C.sub.3 -C.sub.8 haloalkyl group, a C.sub.3 -C.sub.8 alkoxy group, a haloalkoxyalkyl group having 3 to 8 carbon atoms, a C.sub.3 -C.sub.8 haloalkenyl group, a C.sub.3 -C.sub.8 haloalkenyloxy group, a haloalkenyloxyalkyl group having 3 to 8 carbon atoms or a C.sub.3 -C.sub.8 alkynyloxy group; R.sup.2 is a halogen atom; R.sup.3 is, the same or different, a hydrogen atom, a halogen atom or a methyl group; R.sup.4 is a hydrogen atom or a methyl group R.sup.5 is, the same or different, a hydrogen atom, a halogen atom, a C.sub.1 -C.sub.4 alkyl group, a C.sub.1 -C.sub.4 haloalkyl group, a C.sub.1 -C.sub.4 alkoxy group, a C.sub.1 -C.sub.4 haloalkoxy group, a C.sub.1 -C.sub.4 alkylthio group, a C.sub.1 -C.sub.

Abstract: This invention relates to a method for administering systemically active agents including therapeutic agents through the skin or mucosal membranes of humans and animals and into the blood stream in a transdermal device or formulation comprising topically administering with said systemic agent an effective amount of a membrane penetration enhancer being a carboxylic acid derivative or a salt thereof represented in one embodiment by the general formula ##STR1## wherein W represents oxygen, sulfur, or two hydrogen radicals; wherein Z represents oxygen, sulfur, or --CH.sub.2 --;wherein R represents alkyl optionally substituted with one to three double or triple bonds, --SR'", --OR'", --NHR'", --CH.sub.3, or COOR.sub.1, and wherein R.sub.1 represents hydrogen or lower alkyl;wherein R'" represents alkyl, alkylthioalkyl, alkoxyalkyl, substituted aminoalkyl, optionally substituted with a phenyl, benzoyl or heterocyclic group;wherein R' represents hydrogen, alkyl, alkoxy, acyloxy, alkylthio, hydroxy, --(CH2).sub.

Abstract: A hair revitalizing tonic composition comprising (i) an amine oxide and (ii) a compound having a calmodulin inhibitory activity and/or a compound having an activity as a calcium antagonist.

Abstract: This invention relates to a method for administering systemically active agents including therapeutic agents through the skin or mucosal membranes of humans and animals in a transdermal device or formulation comprising topically administering with said systemic agent an effective amount of a membrane penetration enhancer having the structural formula ##STR1## wherein X is selected from the group consisting of oxygen and sulfur; R' is H or a lower alkyl group having 1-4 carbon atoms; m is 2-6; n is 0-17 and R is --CH.sub.3 ; wherein R is H or a lower alkyl group, m is 5-7 and n is 0-17.