686 results about "Reperfusion injury" patented technology

Methods are provided herein for affecting a region of a subject's body, comprising exposing the region to a cooling element under conditions effective to cool subcutaneous adipose tissue in said region; and increasing the blood flow rate to the cooled tissue by exposing the tissue to an energy source. Methods are also provided for treating subcutaneous adipose tissue in a region of a subject's body, comprising exposing said region to a cooling element under conditions effective to cool said tissue; and exposing the tissue to an energy source to increase the blood flow rate to the cooled tissue, thereby stimulating reperfusion in, and / or causing an ischemia-reperfusion injury to, the cooled tissue.

Methods are provided herein for affecting a region of a subject's body, comprising exposing the region to a cooling element under conditions effective to cool subcutaneous adipose tissue in said region; and increasing the blood flow rate to the cooled tissue by exposing the tissue to an energy source. Methods are also provided for treating subcutaneous adipose tissue in a region of a subject's body, comprising exposing said region to a cooling element under conditions effective to cool said tissue; and exposing the tissue to an energy source to increase the blood flow rate to the cooled tissue, thereby stimulating reperfusion in, and / or causing an ischemia-reperfusion injury to, the cooled tissue.

It has been surprisingly discovered that administration of nitrite to subjects causes a reduction in blood pressure and an increase in blood flow to tissues. The effect is particularly beneficial, for example, to tissues in regions of low oxygen tension. This discovery provides useful treatments to regulate a subject's blood pressure and blood flow, for example, by the administration of nitrite salts. Provided herein are methods of administering a pharmaceutically-acceptable nitrite salt to a subject, for treating, preventing or ameliorating a condition selected from: (a) ischemia-reperfusion injury (e.g., hepatic or cardiac or brain ischemia-reperfusion injury); (b) pulmonary hypertension (e.g., neonatal pulmonary hypertension); or (c) cerebral artery vasospasm.

The invention generally relates to methods for preserving tissue, preventing reperfusion injury to implanted tissue, preventing transplant rejection or preserving a cell to be transplanted, comprising contacting tissue or a cell with an effective amount of a JNK Inhibitor. The invention further relates to compositions useful for the preservation of tissue, the compositions comprising an effective amount of a JNK Inhibitor.

The present invention relates to compounds of formula I:and pharmaceutically acceptable salts, stereoisomers or tautomers thereof which are inhibitors of poly (ADP-ribose) polymerase (PARP) and thus useful for the treatment of cancer, inflammatory diseases, reperfusion injuries, ischemic conditions, stroke, renal failure, cardiovascular diseases, vascular diseases other than cardiovascular diseases, diabetes, neurodegenerative diseases, retroviral infection, retinal damage or skin senescence and UV-induced skin damage, and as chemo- and / or radiosensitizers for cancer treatment.

Disclosed are novel inhibitors of the alternative complement pathway and particularly, novel anti-factor B antibodies. Also disclosed is the use of such inhibitors to reduce or prevent airway hyperresponsiveness and / or airway inflammation by selectively inhibiting the alternative complement pathway, thereby treating diseases in which such conditions play a role. Also disclosed is the use of such inhibitors to reduce or prevent other diseases and conditions, including ischemia-reperfusion injury, by inhibition of the alternative complement pathway.

New devices, systems, and methods are disclosed for preventing, treating, and / or at least minimizing ischemia and / or reperfusion injury by restoring and / or modulating blood flow, particularly in the cerebral vasculature where blood vessels are narrow and tortuous. These devices, systems, and methods make it possible for a clinician to adequately and systematically restore blood flow to ischemic tissue while simultaneously modulating the blood flow to minimize reperfusion injury. New thrombectomy devices and systems, which, for example, expand with greater radial force, further enable improved binding with clots and restoration of blood flow.

Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise, for example, high affinity antibodies that specifically bind HMG1 and antigenic fragments thereof. The high affinity antibodies of the present invention and pharmaceutical compositions comprising the same are useful for many purposes, for example, as therapeutics against a wide range of inflammatory diseases and disorders such as sepsis, rheumatoid arthritis, peritonitis, Crohn's disease, reperfusion injury, septicemia, endotoxic shock, cystic fibrosis, endocarditis, psoriasis, psoriatic arthritis, arthritis, anaphylactic shock, organ ischemia, reperfusion injury, and allograft rejection. In addition, the high affinity antibodies of the present inventions are useful as diagnostic antibodies.

Compositions and methods and are provided for treating disorders associated with compromised vasculostasis. Invention methods and compositions are useful for treating a variety of disorders including for example, stroke, myocardial infarction, cancer, ischemia / reperfusion injury, autoimmune diseases such as rheumatoid arthritis, eye diseases such as retinopathies or macular degeneration or other vitreoretinal diseases, inflammatory diseases, vascular leakage syndrome, edema, transplant rejection, adult / acute respiratory distress syndrome (ARDS), and the like.

Compositions and methods and are provided for treating disorders associated with compromised vasculostasis. Invention methods and compositions are useful for treating a variety of disorders including for example, stroke, myocardial infarction, cancer, ischemia / reperfusion injury, autoimmune diseases such as rheumatoid arthritis, eye diseases such as retinopathies or macular degeneration or other vitreoretinal diseases , inflammatory diseases, vascular leakage syndrome, edema, transplant rejection, adult / acute respiratory distress syndrome (ARDS), and the like.

Disclosed are novel inhibitors of the alternative complement pathway and particularly, novel anti-factor B antibodies. Also disclosed is the use of such inhibitors to reduce or prevent airway hyperresponsiveness and / or airway inflammation by selectively inhibiting the alternative complement pathway, thereby treating diseases in which such conditions play a role. Also disclosed is the use of such inhibitors to reduce or prevent other diseases and conditions, including ischemia-reperfusion injury, by inhibition of the alternative complement pathway.

The invention relates to N-hydroxylsulfonamide derivatives that donate nitroxyl (HNO) under physiological conditions and are useful in treating and / or preventing the onset and / or development of diseases or conditions that are responsive to nitroxyl therapy, including heart failure and ischemia / reperfusion injury. Novel N-hydroxylsulfonamide derivatives release NHO at a controlled rate under physiological conditions, and the rate of HNO release is modulated by varying the nature and location of functional groups on the N-hydroxylsulfonamide derivatives.

A method is provided for resuscitating a patient from cardiac arrest. This may be done by (a) performing chest compressions for a first period of time at a depth of between about 1.5 to about 3 inches, and (b) ceasing chest compressions for a second period of time. Steps (a) and (b) may be repeated at least two times in order to prevent reperfusion injury after cardiac arrest.

The present invention provides solid forms of Compound (I), pharmaceutical compositions thereof, and methods for the treatment or prevention of diseases including, but not limited to a liver disease, cancer, a cardiovascular disease, a metabolic disease, a renal disease, an autoimmune condition, an inflammatory condition, macular degeneration, pain and related syndromes, disease-related wasting, an asbestos-related condition, pulmonary hypertension, ischemia / reperfusion injury, central nervous system (CNS) injury / damage or a disease treatable or preventable by the inhibition of JNK. In particular, the invention relates to certain novel crystal forms of the compound 1-(5-(1H-1,2,4-triazol-5-yl)(1H-indazol-3-yl))-3-(2-piperidylethoxy)benzene.

A compound and method for using the compound to reduce injury associated with ischemia and reperfusion of mammalian organs such as the heart. The compound, either Deltorphin A and / or Dermorphin H, may be administered as part of a preconditioning strategy which reduces the extent of injury and improves organ function following cessation and restoration of blood flow. The compound may be used in preparation for planned ischemia or in a prophylactic manner in anticipation of further ischemic events.

Ischemia-reperfusion injury commonly results from any surgical procedure requiring stopping of blood supply to an organ followed by reperfusion such as in heart bypass, angioplasty or organ transplant. The invention discloses a method to harness the innate power of repetitive transient ischemia in protecting organs against imminent ischemia-reperfusion, or any patho-physiological insults. This method of optimal remote ischemic preconditioning (ORIP) comprises of utilizing a pair of programmable pneumatic cuffs that inflate / deflate alternately occluding blood circulation to each of the limbs for pre-defined time intervals. The apparatus delivers maximal ORIP dose in shortest possible time either as an EMS procedure during patient transportation to hospital, as elective pre-surgery treatment, or in critical care for preventing multiple-organ-dysfunction-syndrome. ORIP can be self-administered and remotely monitored by clinician especially in chronic patients for homeostasis of malfunctioning target organs. ORIP may also be deployed as adjunct in angioplasty, gene / stem cell heart repair therapies.

A method for preventing or treating tissue damage associated with ischemia-reperfusion injury and thoraco-abdominal aortic aneurysm (TAAA) repair by administering a tissue damage preventing or treating amount of a complement inhibitor to a patient likely to suffer from or suffering from tissue damage associated with ischemia-reperfusion injury or TAAA repair. The complement inhibitors are preferably antibodies that bind to and inhibit complement proteins involved in the formation of the membrane attach complex, preferably antibodies that inhibit MBL, MASP1, MASP2, and MASP3 in the lectin pathway. The complement inhibitors can be used alone or in combination to decrease the morbidity and mortality caused by tissue damage associated with ischemia-reperfusion injury or TAAA repair.

An apparatus to minimize and / or eliminate the effects associated with reperfusion injury consisting of an external pump, heat exchanger and control unit creating a flow loop whereby blood is moved from the body via a pump, cooled by an external heat exchanger and reintroduced into a specific location, thereby locally cooling the surrounding tissue and inducing localized hypothermia to minimize tissue injury resulting from ischemia and the effects associated with reperfusion injury as an obstruction is removed and normal blood flow is restored and including the ability to locally measure pressure and temperature in the body.

The present invention relates to compounds for treatment that protects the endothelium, prevents pathologic thrombus formation in the microcirculation and preserves platelet number and function and thus may be related to treatment or prevention of ischemic events in patients with cardiovascular disease. The present invention is particularly useful for patients having or being at increased risk of development of an ischemic event such as an acute myocardial infarction and / or no-reflow phenomena and / or ischemia-reperfusion injury by administration of agent(s) modulating and / or preserving endothelial integrity. The compounds may be administered in combination with standard treatment of acute cardiovascular ischemic events such as Platelet inhibitors such as aspirin (ASA), Thienopyridins, GPIIb / IIIa inhibitors), Parenteral anticoagulants such as unfractioned heparin (UFH), bivalirudin, enoxaparin, and fondaparinux, Verapamil, Adenosine, Sodium nitroprusside, Nitroglycerin, Epinephrine, Beta-blockers and surgical methods such as percutaneous coronary intervention (PCI), PCI with thrombus aspiration, PCI with stents.

A compound of formula 1awhich is useful for treating reperfusion injury, and salts, prodrugs, and related compounds.

The present invention relates to pyridines, pyrimidines and derivatives thereof, and pharmaceutically acceptable salts thereof. Also included is a method of treatment of inflammation, rheumatoid arthritis, Pagets disease, osteoporosis, multiple myeloma, uveititis, acute or chronic myelogenous leukemia, pancreatic β cell destruction, osteoarthritis, rheumatoid spondylitis, gouty arthritis, inflammatory bowel disease, adult respiratory distress syndrome (ARDS), psoriasis, Crohn's disease, allergic rhinitis, ulcerative colitis, anaphylaxis, contact dermatitis, asthma, muscle degeneration, cachexia, Reiter's syndrome, type I diabetes, type II diabetes, bone resorption diseases, graft vs. host reaction, Alzheimer's disease, stroke, myocardial infarction, ischemia reperfusion injury, atherosclerosis, brain trauma, multiple sclerosis, cerebral malaria, sepsis, septic shock, toxic shock syndrome, fever, myalgias due to HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses or herpes zoster infection in a mammal comprising administering an effective amount a compound as described above.

The invention relates to N-hydroxysulfonamide derivatives that donate nitroxyl (HNO) under physiological conditions and are useful in treating and / or preventing the onset and / or development of diseases or conditions that are responsive to nitroxyl therapy, including heart failure and ischemia / reperfusion injury. Novel N-hydroxysulfonamide derivatives release NHO at a controlled rate under physiological conditions, and the rate of HNO release is modulated by varying the nature and location of functional groups on the N-hydroxysulfonamide derivatives.

This invention discloses isolated short peptides comprising the amino acid sequence Cys-Glu-Phe-His (CEFH) and analogs thereof as well as compositions comprising CEFH peptides and analogs thereof. The CEFH peptides disclosed herein are effective in mediating the denitration of 3-nitrotyrosines (3-NT) in cellular proteins thereby preventing tissue damage associated with excess nitric oxide (NO) and its reactive species. The CEFH peptides disclosed herein are useful in the treatment of ischemia / reperfusion (I / R) injury of various tissues (e.g., I / R injury of heart muscle associated with heart attack or cardiac surgery, I / R injury of brain tissue associated with stroke, I / R injury of liver tissue, skeletal muscles, etc.), septic shock, anaphylactic shock, neurodegenerative diseases (e.g., Alzheimer's and Parkinson's diseases), neuronal injury, atherosclerosis, diabetes, multiple sclerosis, autoimmune uveitis, pulmonary fibrosis, oobliterative bronchiolitis, bronchopulmonary dysplasia (BPD), amyotrophic lateral sclerosis (ALS), sepsis, inflammatory bowel disease, arthritis, allograft rejection, autoimmune myocarditis, myocardial inflammation, pulmonary granulomatous inflammation, influenza- or HSV-induced pneumonia, chronic cerebral vasospasm, allergic encephalomyelitis, central nervous system (CNS) inflammation, Heliobacterium pylori gastritis, necrotizing entrerocolitis, celliac disease, peritonitis, early prosthesis failure, inclusion body myositis, preeclamptic pregnancies, skin lesions with anaphylactoid purpura, nephrosclerosis, ileitis, leishmaniasis, cancer, and related disorders.

The current invention provides a new organ preservation solution, suitable for machine perfusion, for maintaining viability of organs, parts of organs and tissues. This solution has been designed to overcome a number of problems associated with hypothermic machine perfusion of donor organs, in particular organs obtained from non-heart-beating donors. The solution prevents or minimizes the adverse affects caused by ischemia, hypoxia, energy and nutrient depletion, acidification, hypothermia and reperfusion injury. The preservation solutions according to the current invention are superior to current state of the art preservation solutions, in particular for preservation and perfusion of organs obtained from non-heart-bearing donors, by supplying increased concentrations and an optimized balance of amino acids, vitamins, anti-oxidants, high molecular weight additives and enhanced buffering capacity. In addition, the preservation solution according to the invention combines optimal physical and chemical properties with the use of readily available, inexpensive and pharmaceutically tested and acceptable compounds, reducing the cost of manufacturing and facilitating medical certification of solutions according to the current invention.

According to one embodiment, a device for delivering an anesthetic to an individual to reduce reperfusion injury during the performance of cardiopulmonary resuscitation (CPR) is provided. The device includes a patient connection mechanism for coupling with an airway of the individual and an anesthetic delivery mechanism for receiving the anesthetic and for delivering the anesthetic to the individual via the patient connection mechanism. In some embodiments, the anesthetic is delivered with the assistance of an intrathoracic pressure regulation (IPR) mechanism or an impedance threshold device (ITD) coupled with the patient connection mechanism. The IPR mechanism may be configured to change a pressure in the airway and a thorax of the individual via application of a vacuum source. The ITD device may be configured to prevent respiratory gases from entering the lungs for at least some time during a decompression or relaxation phase of CPR.

Methods and devices are provided for the local delivery of anti-ischemic agents which reduce myocardial tissue damage due to ischemia or reperfusion, in combination with compounds that sensitize the response of the tissue to the anti-ischemic agent. The therapeutic agents are delivered to the myocardial tissue over an administration period sufficient to achieve reduction in ischemic or reperfusion injury of the tissue.

The invention relates to N-hydroxylsulfonamide derivatives that donate nitroxyl (HNO) under physiological conditions and are useful in treating and / or preventing the onset and / or development of diseases or conditions that are responsive to nitroxyl therapy, including heart failure and ischemia / reperfusion injury. Novel N-hydroxylsulfonamide derivatives release NHO at a controlled rate under physiological conditions, and the rate of HNO release is modulated by varying the nature and location of functional groups on the N-hydroxylsulfonamide derivatives.

It has been surprisingly discovered that administration of nitrite to subjects causes a reduction in blood pressure and an increase in blood flow to tissues. The effect is particularly beneficial, for example, to tissues in regions of low oxygen tension. This discovery provides useful treatments to regulate a subject's blood pressure and blood flow, for example, by the administration of nitrite salts. Provided herein are methods of administering a pharmaceutically-acceptable nitrite salt to a subject, for treating, preventing or ameliorating a condition selected from: (a) ischemia-reperfusion injury (e.g., hepatic or cardiac or brain ischemia-reperfusion injury); (b) pulmonary hypertension (e.g., neonatal pulmonary hypertension); or (c) cerebral artery vasospasm.