Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calciphylaxis is a rare condition of induced systemic hypersensitivity in which tissues respond to appropriate challenging agents with a sudden local calcification. It is characterized by acute calcium deposition in the medial layer of small and intermediate dermal vasculature that can lead to epidermal ischemia, ulceration, and necrosis. Calciphylaxis typically occurs in patients with end-stage renal disease who are undergoing dialysis and who have secondary hyperparathyroidism. Even in this population the incidence is less than 1%. The cause of calciphylaxis is unknown. However, it has been suggested that deficiencies of protein C and protein S may play a role in the pathophysiology of this disorder. Our patient is the fourth with cirrhosis to be reported to have developed calciphylaxis and adds further evidence that low levels of these anticoagulant factors may be an important etiologic factor for development of calciphylaxis. This report should alert the clinician that calciphylaxis occurs in patients with cirrhosis and should stimulate further research concerning the possible role of protein C and protein S deficiency in calciphylaxis.
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PMID:Calciphylaxis: a rare association with alcoholic cirrhosis. Are deficiencies in protein C and S the cause? 1610 46

The aim of this study was to investigate the therapeutic effect of platonin, a cyanine photosensitizing dye as well as an inhibitor of proinflammatory cytokines, in an animal model of heat stroke. Anesthetized rats, immediately after the onset of heat stroke, were divided into two major groups and given the following: normal saline (1 mL per kg body weight) intravenously, or platonin (12.5-50 microg/mL per kg body weight) intravenously. They were exposed to ambient temperature of 43 degrees C to induce heat stroke. Another group of rats was exposed to room temperature (26 degrees C) and used as normothermic controls. Their physiologic and biochemical parameters were continuously monitored. When the vehicle-treated rats underwent heat exposure, their survival time values were found to be 18 to 22 min. Resuscitation with intravenous doses of platonin, but not normal saline, immediately at the onset of heat stroke, significantly improved survival during heat stroke (41-147 min). All heat-stressed animals displayed systemic inflammation and activated coagulation, evidenced by increased tumor necrosis factor-alpha, prothrombin time, activated partial thromboplastin time, fibrinogen degradation products, and D-dimer, and decreased platelet count and protein C. Biochemical markers evidenced cellular ischemia and injury/dysfunction: plasma levels of blood urea nitrogen, creatinine, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and alkaline phosphatase, and striatal levels of partial pressure of oxygen, local cerebral blood flow, glycerol, glutamate, and lactate/pyruvate were all elevated during heat stroke. The systemic inflammation, hypercoagulable state, and cerebral ischemia and injury during heat stroke were all significantly suppressed by platonin. The data demonstrate that platonin therapy may resuscitate heat stroke victims by reducing circulatory shock, systemic inflammation, hypercoagulable state, and tissue ischemia and injury.
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PMID:Platonin, a cyanine photosensitizing dye, causes attenuation of circulatory shock, hypercoagulable state, and tissue ischemia during heat stroke. 1631 90

The purpose of the present study was to assess the therapeutic effect of hypothermic retrograde jugular vein flush (HRJVF) on heatstroke. HRJVF was accomplished by infusion of 4 degrees C isotonic sodium chloride solution via the external jugular vein (1.7 mL/100 g of body weight over 5 min). Immediately after the onset of heatstroke, anesthetized rats were divided into 2 major groups and given the following: 36 degrees C or 4 degrees C isotonic sodium chloride solution, i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. When the 36 degrees C saline-treated rats underwent heat exposure, their survival time values were found to be 23 to 28 min. Immediately after the onset of heatstroke, resuscitation with an i.v. dose of 4 degrees C saline significantly improved survival during heatstroke (208-252 min). All heat-stressed animals displayed systemic inflammation and activated coagulation, evidenced by increased tumor necrosis factor alpha, prothrombin time, activated partial thromboplastin time, and d-dimer, and decreased platelet count and protein C. Biochemical markers evidenced cellular ischemia and injury/dysfunction: plasma levels of blood urea nitrogen, creatinine, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and alkaline phosphatase; and striatal levels of glycerol, glutamate, and lactate/pyruvate; dihydroxy benzoic acid, lipid peroxidation, oxidized-form glutathione reduced-form glutathione, dopamine, and serotonin were all elevated during heatstroke. Core and brain temperatures and intracranial pressure were also increased during heatstroke. In contrast, the values of mean arterial pressure, cerebral perfusion pressure, and striatal levels of local blood flow, partial pressure of oxygen, superoxide dismutase, catalase, glutathione peroxidase, and glutathions reductase activities were all significantly lower during heatstroke. The circulatory dysfunction, systemic inflammation, hypercoagulable state, and cerebral oxidative stress, ischemia, and damage during heatstroke were all significantly suppressed by HRJVF. These findings demonstrate that brain cooling caused by HRJVF therapy may resuscitate persons who had a stroke by attenuating cerebral oxidative stress, systemic inflammation, activated coagulation, and tissue ischemia/injury during heatstroke.
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PMID:Brain cooling causes attenuation of cerebral oxidative stress, systemic inflammation, activated coagulation, and tissue ischemia/injury during heatstroke. 1687 31

The present study was performed to assess the prophylactic effect of platonin, a cyanine photosensitizing dye and an inhibitor of proinflammatory cytokines, in an animal model of heatstroke. Anesthetized rats were immediately divided into 2 major groups after the start of heat stress and administered either isotonic sodium chloride solution (dose, 1 mL/kg of body weight i.v.) or platonin (dose, 12.5-50 microg/mL per kilogram of body weight i.v.). They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Their physiological and biochemical parameters were continuously monitored. When the isotonic sodium chloride solution-pretreated rats underwent heat stress, their survival time values were found to be from 20 to 24 min. Pretreatment with intravenous doses of platonin (12.5-50 microg/mL per kilogram of body weight) immediately after the start of heat exposure significantly improved survival time during heatstroke (duration, 63-185 min). As compared with normothermic controls, all vehicle-pretreated heatstroke animals displayed higher levels of creatinine, serum urea nitrogen, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor alpha, prothrombin time, activated partial thromboplastin time and D-dimer in the plasma, cellular ischemia and injury markers in striatum, and intracranial pressure. In contrast, all vehicle-pretreated heatstroke animals had lower levels of mean arterial pressure, cerebral perfusion pressure, cerebral blood flow, brain Po2, and platelet count and protein C in the plasma. Immediately after the start of heat exposure, the previous administration of platonin significantly improved survival time by reducing the systemic inflammation, hypercoagulable state, and tissue ischemia and damage during heatstroke. The results demonstrate that platonin is effective for attenuation of heatstroke reactions.
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PMID:Platonin, a cyanine photosensitizing dye, is effective for attenuation of heatstroke in rats. 1711 36

Heparin-induced thrombocytopenia, or HIT, can present in many ways, ranging from common-isolated thrombocytopenia, venous thromboembolism, acute limb ischemia-to less common but specific presentations-necrotizing skin lesions at heparin injection sites, post-bolus acute systemic reactions, and adrenal hemorrhagic necrosis (secondary to adrenal vein thrombosis). Many patients with HIT have mild or moderate thrombocytopenia: the median platelet count nadir is 60 x 10(9)/L, and ranges from 15 to 150 x 10(9)/L in 90% of patients, most of whom evince a 50% or greater fall in the platelet count. HIT that begins after stopping heparin ("delayed-onset HIT") is increasingly recognized. Factors influencing risk of HIT include type of heparin (unfractionated heparin > low-molecular-weight heparin), type of patient (surgical > medical), and gender (female > male). Since timely diagnosis and treatment of HIT may reduce the risk of adverse outcomes, this review focuses on those clinical circumstances that should prompt the clinician to "think of HIT." Coumarin anticoagulants such as warfarin are ineffective in acute HIT and can even be deleterious by predisposing to micro-thrombosis via protein C depletion (venous limb gangrene and skin necrosis syndromes). Thus, it is important to avoid or postpone coumarin while managing HIT hypercoagulability, focusing on agents that inhibit thrombin directly (lepirudin, argatroban) or that inhibit its generation (danaparoid, fondaparinux). Post-marketing experience suggests that standard dosing of lepirudin is too high; current recommendations are to avoid the initial lepirudin bolus and to begin with lower infusion rates, even in patients without overt renal dysfunction.
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PMID:Think of HIT. 1712 91

Activated protein C (APC), a plasma serine protease, is best known for its ability to inhibit blood clot formation. APC acts as an anticoagulant by degrading coagulation cofactors Va and VIIIa, thereby attenuating the coagulation cascade. Over the past 15 years, impressive research advances have provided novel insights into the diverse biological activities of this molecule. APC is now viewed not only as an anticoagulant but also as a signaling molecule that provides a pivotal link between the pathways of coagulation, inflammation, apoptosis, and vascular permeability. The protective effect of APC supplementation in patients with severe sepsis likely reflects the ability of APC to modulate multiple pathways implicated in sepsis pathophysiology. This review attempts to summarize key studies that support the therapeutic potential of APC in conditions beyond sepsis such as stroke, ischemia-reperfusion injury, lung injury, asthma, pancreatitis, wound healing, and angiogenesis. A comprehensive PUBMED literature review up to May 2006 was conducted.
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PMID:Activated protein C in sepsis and beyond: update 2006. 1712 35

Sepsis-induced purpura fulminans is a rare but life-threatening disorder, characterized by hemorrhagic infarction of the skin caused by disseminated intravascular coagulation and dermal vascular thrombosis. The pathogenesis is linked to enhanced expression of the natural procoagulants and depletion of the natural anticoagulant proteins particularly protein C. Meningococcal sepsis is the most common cause, followed by pneumococcal sepsis in adults. The syndrome is associated with more than 50% mortality secondary to multiple organ dysfunction syndrome and is accompanied by long-term morbidity. Necrotic lesions usually progress to distal ischemia, and skin grafting and extremities or limb amputation are often required. Early antibiotic administration and intensive care management according to the recommendations of severe sepsis and shock is crucial for patients' survival. Adjuvant therapies against inflammatory and coagulation cascades and augmenting fibrinolysis are still controversial and need further assessment. Among them activated protein C and supplementation therapy have given promising results.
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PMID:Purpura fulminans in sepsis. 1717 Jun 24

Hyperbaric oxygen has been found to be beneficial in treating heatstroke animals. We attempted to further assess the possible mechanism of therapeutic protection offered by hyperbaric oxygen in experimental heatstroke. Anesthetized rats, immediately after the onset of heatstroke, were randomized into the following groups and given: a) hyperbaric oxygen (100% O(2) at 253 kPa for 1 h); or b) normal air. They were exposed to 43 degrees C temperature to induce heatstroke. When the untreated rats underwent heat stress, their survival time values were found to be 20-24 min. Resuscitation with hyperbaric oxygen increased the survival time to new values of 152-176 min. All untreated heatstroke rats displayed cerebrovascular dysfunction (evidenced by hypotension, intracranial hypertension, and cerebral hypoperfusion, hypoxia, and ischemia), hypercoagulable state (evidenced by increased levels of activated partial thromboplastin time, prothrombin time, and D-dimer, but decreased values of platelet count and protein C in plasma), and tissue ischemia/injury (evidenced by increased levels of creatinine, serum urea nitrogen, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase in plasma, and dihydrobenzoic acid, lipid peroxidation, and oxidized-form glutathione/reduced-form of glutathione ratio in hypothalamus). The cerebrovascular dysfunctions, hypercoagulable state, tissue ischemia/injury, and brain oxidative stress that occurred during heatstroke were all suppressed by hyperbaric oxygen therapy. The current results indicate that hyperbaric oxygen therapy may resuscitate rats that had a heatstroke by decreasing multiple organ dysfunction and brain oxidative stress.
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PMID:Hyperbaric oxygen improves survival in heatstroke rats by reducing multiorgan dysfunction and brain oxidative stress. 1750 57

Portal vein thrombosis secondary to protein C deficiency is a rare finding. Diagnosing a portal vein thrombosis itself is difficult due to nonspecific symptoms such as nausea, vomiting, anorexia, and weight loss. Proving that a protein C deficiency is the cause of a portal vein thrombosis is even more difficult as an extensive and thorough workup is required to rule out malignancies, myeloproliferative disorders, and hypercoaguable states which can all lead to thromboses. Patients require anticoagulation to prevent two dangerous complications of portal vein thrombosis; portal hypertension leading to esophageal varices with massive hemetemesis and extension of thrombus from the portal vein into the mesenteric veins leading to intestinal ischemia and death. In this case report, we present a patient with the complaint of painless jaundice who was found to have an incidental finding of portal vein thrombosis secondary to protein C deficiency. The different etiologies of portal vein thrombosis, along with diagnosis and treatment options will be discussed and highlighted.
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PMID:A rare incidental finding in a case of painless jaundice. 3071 33

Perinatal hypoxia-ischemia remains the single most important cause of brain injury in the newborn, leading to death or lifelong sequelae. White matter injuries in newborn infants have long-term effects on physical, visual, motor, sensory, cognitive and social development in human infants. There is no known cure for neonatal hypoxic ischemic encephalopathy (NHIE). Activated protein C has potent anticoagulant activity due to its ability to inactivate factor Va and VIIIa. APC is the first effective biological therapy approved for the treatment of severe sepsis. Although APC is well defined as a physiological anticoagulant, emerging data suggest that it also has cytoprotective, anti-inflammatory and antiapoptotic properties. APC has been shown to provide neuroprotection in ischemic brain and spinal cord injury. Here, we propose that APC, which modulates many of these processes, may represent a promising therapeutic agent for NHIE. Seven days old Wistar Albino rat pups have been used in the study (n=42). Experimental groups in the study were: sham-operated group, APC treated group, and vehicle treated group. In hypoxia-ischemia groups, the left common carotid artery was ligated permanently on the seventh postnatal day. Two hours after the procedure, hypoxia (92% nitrogen and 8% oxygen) was applied for 2.5 h. APC were injected (intraperitoneally; i.p.) as a single dose immediately after the hypoxia period. Brain nitrite levels, neuronal cell death, and apoptosis were evaluated in both hemispheres 72 h after the hypoxic-ischemic insult. Histopathological evaluation demonstrated that APC significantly diminished the number of "apoptotic cells" in the hippocampal CA1, CA2, CA3 and gyrus dentatus regions in both hemispheres. APC treatment significantly reduced "apoptotic cell death" in both hemispheres, when compared with vehicle treated group. APC significantly preserved the number of neurons CA1, CA3 regions of the hippocampus, when compared with vehicle treated group. Our results showed that hypoxic-ischemic injury caused a significant increase in NO production. The APC-treated animals were reduced brain nitrite levels in carotid ligated hemispheres. To our knowledge, this is the first study that demonstrates a protective effect of the APC against hypoxia-ischemia in the developing brain.
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PMID:Effects of activated protein C on neonatal hypoxic ischemic brain injury. 1842 Jan 81


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