Abstract: The invention provides methods, compositions, and medical kits comprising a nitrite-reductase promoter, such as an allosteric modulator of hemoglobin, for use in treating medical disorders and preservation of blood products. In one aspect, the invention provides methods, compositions, and medical kits comprising an inorganic nitrite salt and a nitrite-reductase promoter, such as an allosteric modulator of hemoglobin, for use in treating medical disorders, such as cancer, cardiovascular disorders, ischemic conditions, hemolytic conditions, and bacterial infections. Exemplary inorganic nitrite salts include sodium nitrite and arginine nitrite. Exemplary allosteric modulators of hemoglobin described herein include alkyl-substituted and acyl-substituted di-nitroheterocycles.

Abstract: The invention provides methods, compositions, and medical kits comprising a nitrite-reductase promoter, such as an allosteric modulator of hemoglobin, for use in treating medical disorders and preservation of blood products. In one aspect, the invention provides methods, compositions, and medical kits comprising an inorganic nitrite salt and a nitrite-reductase promoter, such as an allosteric modulator of hemoglobin, for use in treating medical disorders, such as cancer, cardiovascular disorders, ischemic conditions, hemolytic conditions, and bacterial infections. Exemplary inorganic nitrite salts include sodium nitrite and arginine nitrite. Exemplary allosteric modulators of hemoglobin described herein include alkyl-substituted and acyl-substituted di-nitroheterocycles.

Abstract: The present invention relates to methods for treating systemic inflammation. In certain embodiments, the method comprises administering a therapeutically effective amount of curcumin-selenium loaded nanoparticles. The curcumin-selenium loaded nanoparticles can comprise a matrix of chitosan, polyethylene glycol and tetramethoxysilane encapsulating curcumin and selenium. In certain embodiments, the method comprises administering a therapeutically effective amount of nitric oxide-releasing nanoparticles. The nitric oxide-releasing nanoparticles can comprise a matrix of chitosan encapsulating nitric oxide. In certain embodiments, the systemic inflammation can be caused by endotoxemia. In certain embodiments, the systemic inflammation can be caused by a Filovirus, including an Ebola virus or a Marburg virus. In certain embodiments, the methods for treating systemic inflammation in a subject result in the reduction of proinflammatory cytokines in a subject.

Abstract: Described herein is a method of inducing vascular inflammation using modified paramagnetic nanoparticles with improved therapeutic loading efficiency and enhanced circulation properties. The method comprises loading lipophilic agent into the fatty acid coatings of a paramagnetic nanoparticle (PMNP). In certain embodiment, the lipophilic agent is lipopolysaccharides (LPS). Described herein is a method of inducing vascular leakiness. In certain embodiment, the method induces a significant enhancement of vascular leakiness in a human body. In certain embodiments, the vascular leakiness allows for enhanced local delivery of nanoparticle and non-nanoparticle based therapeutics, imaging agents and theranostics. Also described herein is a method of using the PMNP for the treatment of diseases. In certain embodiments, the method of treatment is a combination therapy. Described herein are imaging of therapeutic delivery of PMNP and diagnostic methods using the PMNP.

Abstract: The invention contemplates compositions for the treatment of malaria comprising an anti-malaria drug and an adjuvant which promotes vasodilation and methods of using same.

Abstract: Described herein are hydrogel-based nanoparticles which release nitric oxide (NO) or other bioactive forms of NO including nitrosothiols, nitrofatty acids and dinitrogen trioxide into stored red blood cells (RBCs). Also provided herein is a method for using hydrogel-based nanoparticles to supplement stored RBCs with NO to enhance red blood cell (RBC) storage time, improve survivability in circulation, minimize toxicity associated with transfusion, and improve transfusion safety by eliminating infective organisms in stored blood.

Abstract: Nanoparticles are provided that comprise S-nitrosothiol (SNO) groups covalently bonded to the nanoparticles and/or S-nitrosothiol containing molecules encapsulated within the nanoparticles, as well as methods of making and using the nanoparticles. The invention also provides methods of preparing nanoparticles comprising Snitrosothiol (SNO) groups covalently bonded to the nanoparticles, where the methods comprise a) providing a buffer solution comprising chitosan, polyethylene glycol, nitrite, glucose, and hydrolyzed 3-mercaptopropyltrimethoxysilane (MPTS); b) adding hydrolyzed tetramethoxysilane (TMOS) to the buffer solution to produce a sol-gel; and c) lyophilizing and ball milling the sol-gel to produce nanoparticles of a desired size.

Abstract: Techniques are disclosed that interfere with breakdown of the mucosal barrier in the stomach and the intestine under conditions of hypoxia by administrating a therapeutic dose of an oxygen rich solution. Such solution may include one or more of perflurocarbon, ATP solution or buffer solution.

Abstract: The invention provides methods, compositions, and medical kits comprising a nitrite-reductase promoter, such as an allosteric modulator of hemoglobin, for use in treating medical disorders and preservation of blood products. In one aspect, the invention provides methods, compositions, and medical kits comprising an inorganic nitrite salt and a nitrite-reductase promoter, such as an allosteric modulator of hemoglobin, for use in treating medical disorders, such as cancer, cardiovascular disorders, ischemic conditions, hemolytic conditions, and bacterial infections. Exemplary inorganic nitrite salts include sodium nitrite and arginine nitrite. Exemplary allosteric modulators of hemoglobin described herein include alkyl-substituted and acyl-substituted di-nitroheterocycles.

Abstract: The inventors have unexpectedly discovered that shock and/or potential multi-organ failure due to shock can be effectively treated by administration of liquid high-dose protease inhibitor formulations to a location upstream of where pancreatic proteases are introduced into the gastrointestinal tract. Most preferably, administration is directly to the stomach, for example, via nasogastric tube under a protocol effective to treat shock by such administration without the need of providing significant quantities of the protease inhibitor to the jejunum and/or ileum.

Abstract: Described herein is a composition and process for synthesizing a human serum albumin (HSA) based plasma replacement composition that includes a polymerized HSA (PolyHSA) that is chemically stabilized by the reduction of Schiff bases. The PolyHSA may have a molecular weight of at least about 100 kDa and may optionally have a cross-linker to HSA molar ratio of at least about 10:1. The PolyHSA composition is useful for restoring a subject's circulatory volume.

Abstract: The present invention is directed to uses of PEGylated albumins which include methods of treating reduced functional capillary density, reduced blood volume, septic shock and cardiac arrhythmia in a subject, which comprise administering to the subject a therapeutically effective amount of a PEGylated albumin.

Abstract: The invention provides methods for delivering a NO molecule or precursor thereof to a vascular compartment of a subject comprising: administering to the subject, a NO particle formulation, via an intravascular, intraperitoneal, or intramuscular administration, in an amount sufficient to induce vascular smooth muscle relaxation thereby delivering the NO molecule or precursor thereof to the vascular compartment of the subject, wherein the NO particle formulation comprises NO attached to a nanoparticle or microparticle.

Abstract: The invention contemplates compositions for the treatment of malaria comprising an anti-malaria drug and an adjuvant which promotes vasodilation and methods of using same.

Abstract: The present invention is directed to uses of PEGylated albumins which include methods of treating reduced functional capillary density, reduced blood volume, septic shock and cardiac arrhythmia in a subject, which comprise administering to the subject a therapeutically effective amount of a PEGylated albumin.