Abstract: Nitric oxide (NO) interacts with hemoglobin (Hb) at its metal centers, whereas S-nitrosothiols (RSNOs) can donate the NO group to ?93 cysteine residues, thereby shielding the NO functionality from heme inactivation. S-nitrosylation of Hb is under the allosteric control of oxygen and the oxidation state of heme. NO group release from S-nitrosohemoglobin (SNO-Hb) is further facilitated by intracellular low molecular weight thiols, forming RSNOs which can be exported from the erythrocyte to regulate blood pressure. Hence, a dynamic cycle is established in which S-nitrosylation of Hb is initiated in the lung following oxygenation of red blood cells and is completed by SNO-Hb metabolism during arterial-venous transit. SNO-Hb can be formed by reaction of Hb with S-nitrosothiol. This procedure avoids oxidation of the heme.

Abstract: The occurrence of hypercapneic acidosis in a fetus during a laparoscopic procedure carried out on a pregnant female, is prevented or ameliorated by inclusion in or addition to the carbon dioxide insufflation gas, of a nitric oxide donor, e.g., ethyl nitrite. Administration of nitric oxide donor in insufflation gas causes increase in fetal cerebral oxygenation.

Abstract: Disclosed are novel polymers derivatized with at least one —NOx group per 1200 atomic mass unit of the polymer. X is one or two. In one embodiment, the polymer is an S-nitrosylated polymer and is prepared by reacting a polythiolated polymer with a nitrosylating agent under conditions suitable for nitrosylating free thiol groups. The polymers of the present invention can be used to coat medical devices to deliver nitric oxide in vivo to treatment sites.

Abstract: Nitrosylhemoglobin can be produced by introducing gaseous NO into an aqueous solution of hemoglobin. It has been demonstrated that nitrosylhemoglobin in aqueous solution can be converted to SNO-hemoglobin upon introduction of oxygen to the solution, as is postulated to occur in the lungs. Nitrosylhemoglobin can be used in methods to produce the physiological effects of NO, for example, to reduce vasoconstriction and to inhibit platelet aggregation.

Abstract: A patient with a disease associated with a receptor having a cysteine residue is treated with a thiol reactive agent. The diseases include neurodegenerative diseases. Diseases characterized by skeletal muscle atrophy are also treated.

Abstract: A blood-flow decrease preventing agent is used to negate or reduce the decreased oxygen delivery in abdominal organs caused by insufflating gas. Preferably a gas is delivered into the abdominal cavity consisting essentially of the insufflating gas and the blood-flow decrease preventing agent. Very preferably, a gas is used consisting essentially of carbon dioxide as the insulating gas and ethyl nitrite as the blood-flow to abdominal organ decrease preventing agent.

Abstract: The present invention is directed to the treatment of cystic fibrosis that involves the administration of a nitrosylating agent, such as S-nitrosoglutathione or ethyl nitrite.

Abstract: This invention provides a modified yeast two-hybrid system in order to identify NO-dependent protein-protein interactions. Bait proteins implicated in apoptotic signaling pathways were used to identify NO-dependent interactions. The physiological relevance of these interactions is demonstrated by their occurrence and dependence on endogenous NO in mammalian cells, and by the functional interrelatedness of bait and prey.

Abstract: Desensitization of receptors that control disease is prevented by inhibiting G-protein receptor kinases. This has applicability, e.g., for patients with heart failure or on a left ventricular heart device or a heart pump after surgery or about to undergo surgery and at high risk for a cardiac event or on an opiate or addicted to opiate or with cystic fibrosis or rheumatoid arthritis.

Abstract: The present invention provides novel aminoadamantane derivatives, methods of making the derivatives, compositions including the novel aminoadamantane derivatives, and methods for the treatment and prevention of neurological diseases using the derivatives and compositions.

Abstract: Disclosed are novel NO-releasing compounds which comprise a stabilized S-nitrosyl group and a free alcohol or a free thiol group. Also disclosed is a method of preparing the NO-releasing compounds. The method comprises reacting a polythiol or a thioalcohol with a nitrosylating agent. Also disclosed are medical devices coated with the disclosed compounds, methods of delivering NO to treatments sites in a subject by utilizing the medical devices and methods of sterilizing surfaces.

Abstract: A therapeutic or prophylactic treatment method of myocardial ischemia, such as due to myocardial infarction, by administering erythropoietin, alone or in combination with other drugs, to a patient suffering from or at risk of cardiac injury, such as myocardial ischemia. The erythropoietin is administered in a concentration such that the subject's hematocrit level or production of red blood cells is not significantly affected.

Abstract: A blood-flow decrease preventing agent is used to negate or reduce the decreased oxygen delivery in abdominal organs caused by insufflating gas. Preferably a gas is delivered into the abdominal cavity consisting essentially of the insufflating gas and the blood-flow decrease preventing agent. Very preferably, a gas is used consisting essentially of carbon dioxide as the insufflating gas and ethyl nitrite as the blood-flow to abdominal organ decrease preventing agent.

Abstract: A C-nitroso compound having a molecular weight ranging from 225 to 1,000 (from 225 to 600 for oral administration) on a monomeric basis wherein a nitroso group is attached to a tertiary carbon, which is obtained by nitrosylation of a carbon acid having a pKa less than about 25, is useful as an NO donor. When the compound is obtained from a carbon acid with a pKa less than about 10, it provides vascular relaxing effect when used at micromolar concentrations and this activity is potentiated by glutathione to be obtained at nanomolar concentrations. When the compound is obtained from a carbon acid with a pKa ranging from about 15 to 20, vascular relaxing effect is obtained at nanomolar concentrations without glutathione. In another embodiment, a biocompatible polymer incorporates a C-nitroso moiety.

Abstract: Disclosed are novel polymers derivatized with at least one —SNO group per 1200 atomic mass unit of the polymer. In one embodiment, the S-nitrosylated polymer has stabilized —S-nitrosyl groups. In another embodiment the S-nitrosylated polymer prepared by polymerizing a compound represented by the following structural formula: R is an organic radical. Each X′ is an independently chosen aliphatic group or substituted aliphatic group. Preferably, each X′ is the same and is a C2-C6 alkylene group, more preferably —CH2—, —CH2CH2—, —CH2CH2CH2— or —CH2CH2CH2CH2—. p and m are independently a positive integer such that p+m is greater than two. The polymers of the present invention can be used to coat medical devices to deliver nitric oxide in vivo to treatment sites.

Abstract: Composition comprising nitrosylating agent is administered to a patient having cystic fibrosis.

Abstract: Mammals are treated for infections or for conditions associated with pathologically proliferating mammalian cell growth (for example certain cancers, restenosis, benign prostatic hypertrophy) by administration of a manipulator of nitrosative stress to selectively kill or reduce the growth of the microbes or helminths causing the infection or of host cells infected with the microbes or of the pathologically proliferating mammalian cells. Novel agents include &agr;-alkyl-S-alkyl-homocysteine sulfoximines wherein the &agr;-alkyl contains 2 to 8 carbon atoms, and the S-alkyl-contains 1 to 10 carbon atoms. In another invention herein, mammals in need of increased nitrosative stress defenses are treated, e.g., humans at risk for a stroke because of having had a transient ischemic attack, are treated.

Abstract: Nitrosylhemoglobin can be produced by introducing gaseous NO into an aqueous solution of hemoglobin. It has been demonstrated that nitrosylhemoglobin in aqueous solution can be converted to SNO-hemoglobin upon introduction of oxygen to the solution, as is postulated to occur in the lungs. Nitrosylhemoglobin can be used in methods to produce the physiological effects of NO, for example, to reduce vasoconstriction and to inhibit platelet aggregation.

Abstract: Desensitization of receptors that control disease is prevented by inhibiting G-protein receptor kinases. This has applicability, e.g., for patients with heart failure or on a left ventricular heart device or a heart pump after surgery or about to undergo surgery and at high risk for a cardiac event or on an opiate or addicted to opiate or with cystic fibrosis or rheumatoid arthritis.

Abstract: A C-nitroso compound having a molecular weight ranging from about 225 to about 1,000 (from about 225 to about 600 for oral administration) on a monomeric basis wherein a nitroso group is attached to a tertiary carbon, which is obtained by nitrosylation of a carbon acid having a pKa less than about 25, is useful as an NO donor. When the compound is obtained from a carbon acid with a pKa less than about 10, it provides vascular relaxing effect when used at micromolar concentrations and this activity is potentiated by glutathione to be obtained at nanomolar concentrations. When the compound is obtained from a carbon acid with a pKa ranging from about 15 to about 20, vascular relaxing effect is obtained at nanomolar concentrations without glutathione. The compound is preferably water-soluble and preferably contains a carbon alpha to the nitrosylated carbon which is part of a ketone group.