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)

In a prospective, randomized, double-blind, placebo-controlled trial, rhSOD was given to cadaveric renal allograft recipients intravenously in a dose of 200 mg during surgery, and its effect on both acute and chronic rejection was investigated. The results showed that rhSOD exerts a beneficial effect on acute rejection episodes as indicated by a statistically significant reduction of first acute rejection episodes to 18.5% compared with 33.3% in controls, and a reduction in early irreversible acute rejection to 3.7% compared with 12.5% in controls. With regard to longterm results, there was a statistically significant improvement in the actual 5-year graft survival rate for rhSOD-treated patients to 68% (with a corresponding 13-year half-life) compared with 50% in controls (with a corresponding 6-year half-life). The incidence of acute rejection episodes did not prove to be a risk factor for long-term graft outcome. Rather only the combination of acute rejection episodes and the presence of uninfluenced reperfusion injury appeared to have a detrimental effect on long-term prognosis. The beneficial effect of rhSOD observed in this trial is not well understood, although one can assume that the effect is brought about by interference of rhSOD with ischemia or reperfusion injury to the allograft by oxygen-free radicals. In this sense, rhSOD may mitigate increased MHC expression and presentation, cytokine-adhesion molecule expression, and APC activation induced by reperfusion injury. In addition, in accordance with the "response-to-injury" hypothesis to explain the pathogenesis of arteriosclerosis, rhSOD may mitigate acceleration of chronic obliterative rejection or arterio-/arteriolosclerosis induced by reperfusion injury. In this sense, rhSOD may act indirectly by reducing acute rejection-mediated endothelial injury, or directly, by ablation of reperfusion-mediated acute endothelial injury.
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PMID:The impact of free radical-mediated reperfusion injury on acute and chronic rejection events following cadaveric renal transplantation. 791 55

Superior mesenteric venous (SMV) thrombosis is an uncommon cause of mesenteric ischemia, frequently presenting with nonspecific and subacute symptoms. We report a case of a 28-yr-old man presenting with symptoms and radiographic changes suggestive of Crohn's disease who, upon further evaluation, was found to have SMV thrombosis. A search for a precipitating condition revealed a strong family history of thromboembolic disease and deficiency of protein C. The patient responded to supportive therapy and anticoagulation.
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PMID:Superior mesenteric venous thrombosis masquerading as Crohn's disease. 801 90

Eight tests of hemostasis were measured in 233 horses with colic. Blood samples were obtained at admission and for 4 consecutive days of hospitalization. Data were analyzed retrospectively by outcome, by broad-category diagnosis group, by small intestinal disorder, and by smaller categories for comparing specific diseases. Nonsurviving horses and horses with the most severe forms of intestinal ischemia had changes interpreted as hypercoagulative, the intensity of which was increased on the first and second mornings (sample times 2 and 3) after admission, when most significant differences for results of specific tests were detected. Nonsurvivors had decreased antithrombin III activity and prolonged prothrombin and activated partial thromboplastin times; those with strangulating obstructions also had decreased protein C and plasminogen activities. During hospitalization and with survival, these changes tended to reverse. In most horses, regardless of diagnosis or outcome, concentration of fibrin degradation products and fibrinogen, and alpha 2-antiplasmin activity increased over time. Whether these changes reflected specific effects of colic or of the acute-phase response was not determined. In comparisons of small intestinal disorders (proximal enteritis, strangulations, and impactions), diagnostically distinguishing features were not found. Likewise, in comparisons of specific diseases (small vs large intestinal impaction, proximal enteritis vs colitis, small vs large intestinal obstruction), diagnostically distinguishing features were not found.
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PMID:Analysis of hemostasis in horses with colic. 840 38

Calciphylaxis is a rare and life-threatening complication that is estimated to occur in 1% of patients with ESRD each year. Typically, extensive microvascular calcification and occlusion/thrombosis leads to violaceous skin lesions, which progress to nonhealing ulcers and sepsis. Secondary infection of skin lesions is common, often leading to sepsis and death. The lower extremities are predominantly involved (roughly 90% of patients). Patients with skin involvement over the trunk or proximal extremities have a poorer prognosis. Although most calciphylaxis patients have abnormalities of the calcium:phosphate axis or elevated levels of parathyroid hormone, these abnormalities do not appear to be fundamental to the pathophysiology of the disorder, and the etiology of calciphylaxis remains unclear. Recently, functional protein C deficiency has been hypothesized to cause a hypercoagulable state that could induce thrombosis in small vessels, with resulting skin ischemia, necrosis, and gangrene. The lack of understanding of the pathophysiology of the disease results in treatments that are equally unsatisfactory. Patients who undergo parathyroidectomy have a tendency to improve, but the prognosis for the disease is poor and mortality remains high.
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PMID:Calciphylaxis in chronic renal failure. 882 11

Plasma antithrombin-III (AT-III), protein S, and protein C were measured during myocardial stunning (MS) and acute myocardial infarction (AMI). The effects of magnesium (Mg), diltiazem, and a Mac-1 inhibitor on their plasma levels were elucidated. Forty-nine open-chest swine underwent brief (8 min) or prolonged (50 min) coronary artery occlusion followed by reperfusion. During MS an increase in the plasma AT-III (from 98.5 +/- 3.38% to 138.1 +/- 3.6%) during the early occlusion phase, without any further changes was observed. The profile of total protein S was not changed during MS. Protein C increased at the end of occlusion (from 45.3 +/- 1.8% to 55.7 +/- 1.4%) reaching a peak (64.5 +/- 1.4%) at the beginning of reperfusion. When compared with controls, no significant differences were found in the antithrombotics profile during MS after pretreatment with Mac-1 inhibitor. For the AMI, the AT-III decreased during occlusion (from 98.5 +/- 3.4% to 61.0 +/- 3.6%). The protein S decreased during occlusion with the lowest level at 1 h of reperfusion (from 71.8 +/- 2.2% to 46.7 +/- 1.0%), followed by an increase during late reperfusion (59.2 +/- 1.5%). Contrarily, protein C increased during occlusion and early reperfusion (from 44.7 +/- 2.6% to 79.4 +/- 2.4%), but declined to 49.6 +/- 2.5% thereafter. In both Mg and diltiazem-treated swine, protein C was higher at the end of occlusion and during the entire reperfusion period compared with controls. Mg and diltiazem therapy was associated with the slight elevation of plasma AT-III. The patterns for protein S level during ischemia-reperfusion were similar with the controls. Protein S was higher at the end of occlusion and through the entire reperfusion in the NPC 15669-treated animals when compared with the controls. Mac-1 inhibition was associated with the elevated protein C during late reperfusion. Ability of Mg, diltiazem, and Mac-1 inhibitor to favorably modulate the plasma level of antithrombotics have direct clinical implications for the use of these agents in patients with acute coronary artery syndromes.
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PMID:Serial changes of natural antithrombotics during myocardial ischemia-reperfusion in swine. Effects of magnesium, diltiazem, and a novel Mac-1 inhibitor. 889 53

Myocardial stunning (MS) is a transient contractile dysfunction occurring subsequent to an episode of ischemia followed by reperfusion. NPC 15669 is a leumedin, which inhibits leukocyte adhesion to the endothelium by blocking Mac-1 upregulation. The effect of NPC 15669 supplementation on the hemostasis during MS is unknown. We linked the potential changes in the hemostasis with NPC 15669 therapy during mild MS. Twelve Yorkshire swine underwent coronary artery occlusion for 8 min followed by 90 min of reperfusion. NP 15669 (10 mg/kg loading dose followed by constant infusion a 6 mg kg-1 h-1) was administered to 6 of the animals; another swine received saline and served as the controls. Concentrations of antithrombin III (AT-III), protein C, total protein S, fibronectin, endothelin 1 (ET-1) and the stable metabolites of thromboxane (TxB2) and prostacyclin (6-keto-PGF1 alpha) were measured in the systemic circulation. NPC 15669 therapy was associated with diminished ET-1 (37.4%) and 6-keto-PGF1 alpha (47.1%) levels and increased fibronectin (77.6%) concentrations during MS. There were no changes in the plasma concentrations of TxB2, total protein S, protein C and AT-III in the NPC 15669 group when compared with controls. Mild MS in associated with substantial changes in the hemostatic profile. NPC 15669 administration in a swine model of MS affects certain hemostatic parameters. These data provide support for the involvement of cellular mechanisms in the pathogenesis of MS. The ability of leumedins to modulate hemostasis may have implications for their use in cardiovascular disease.
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PMID:Mac-1 inhibitor affects certain hemostatic parameters during myocardial stunning in swine. 890 73

We investigated the role of anticoagulant in the ischemia/reperfusion injury of the liver, using activated protein C (APC), active human urinary thrombomodulin (UTM), and factor Xa blocked at the active site (DEGR-Xa). Liver ischemia was induced in male Wistar rats by occlusion of the portal vein with a microvascular clip for 30 minutes. Each anticoagulant was injected intravenously 10 minutes before clamping the portal vein. Serum concentrations of cytokine-induced neutrophil chemoattractant (CINC) were determined by enzyme-linked immunosorbent assay. The serum levels of CINC increased significantly following reperfusion, reaching a peak in 6 hours, and then decreasing gradually to control levels by 24 hours. CINC levels in rats pretreated with APC (500 U/kg), UTM (3,000 TMU/kg), or DEGR-Xa (10 mg/kg) peaked 3 hours following reperfusion and decreased rapidly to baseline level within 6 and 12 hours, respectively. These peak values were significantly lower than those observed in untreated rats (P < .01). Expression of CINC transcripts in liver tissue of untreated rats was evaluated by Northern blot analysis and peaked 3 hours following reperfusion. Pretreatment with these anticoagulants significantly decreased the expression of CINC messenger RNA transcripts as compared with untreated animals. Myeloperoxidase activity and the number of neutrophils accumulated into the liver 24 hours following ischemia/reperfusion were also significantly decreased in animals pretreated with these anticoagulants. In addition, correlations between the peak values of liver enzymes and serum CINC levels were found to be significant (P < .001). The inactive derivative of factor Xa, a selective inhibitor of thrombin generation, inhibited ischemia/reperfusion-induced increases in the serum concentration and messenger RNA transcript quantities of CINC. The inactive factor Xa also reduced hepatic accumulation of neutrophils after ischemia/reperfusion. These results indicate that the release of CINC is likely related to the hepatic microcirculation disturbance induced by microthrombotic occlusion following ischemia/reperfusion.
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PMID:Pretreatment with activated protein C or active human urinary thrombomodulin attenuates the production of cytokine-induced neutrophil chemoattractant following ischemia/reperfusion in rat liver. 914 30

Mesenteric ischemic process can lead to bowel infarction or indolent low-grade ischemia. Inherited thrombophilia represents about 30 to 40% of mesenteric vein thrombosis. Analysis of thromboembolism sites occurring during genetic defect of coagulant factors showed that mesenteric thrombosis is the third localization after lung and legs, in equal incidence with cerebral thrombosis. The genetic defects known to be associated with thrombophilia, as deficiencies of protein C, protein S, antithrombin III, and dysfibrinogenemia, are discussed. A special interest is devoted to resistance to activated protein C. Acquired diseases, as myeloproliferative disease or paroxysmal nocturnal hemoglobinemia, inducing thrombosis are also discussed. Recent advances in both basic and clinical research have provided new insights that may be integrated into diagnostic and therapeutic practices.
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PMID:[Role of coagulation disorders in mesenteric ischemia]. 929 19

A case of diffuse pulmonary ossification in association with congenital protein C deficiency is presented. We propose that multiple pulmonary thrombi secondary to a long-term hypercoagulable state produced pulmonary ischemia that predisposed to intralveolar ossification.
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PMID:Pulmonary ossification in association with congenital protein C deficiency. 960 26

NPC 15669, a member of the leumedins family, inhibits leukocyte adhesion to the endothelium by blockage of upregulation of a member of beta2 integrin family Mac-1 (CD11b/CD18). Inhibition of neutrophil-endothelial interactions may alter the course of myocardial reperfusion injury. However, the effects of NPC 15669 supplementation on the hemostatic profile during ischemia-reperfusion are unknown. The aim of the present study was to define changes in the certain hemostatic factors in the natural course of preconditioned myocardial infarction. Twelve consecutive Yorkshire swine underwent myocardial stunning (8 min. left anterior descending artery occlusion followed by 90 min. of reperfusion) and then preconditioned myocardial infarction (50 min. occlusion followed by 3 hours of reperfusion) experiments. NPC 15669 (10 mg/kg loading dose followed by constant infusion at 6 mg x kg(-1) x h(-1)) was administered in 6 animals; another 6 swine received saline and served as controls. Blood samples were obtained at baseline, twice during occlusion; and three times during reperfusion. The levels of antithrombin-III, Protein C, total Protein S, fibronectin, endothelin-1, as well as the stable metabolites of thromboxane (TxB2) and prostacyclin (6-keto-PGF1a), were determined. NPC 15669 treatment was associated with diminished endothelin-1, TxB2 levels and increased fibronectin, 6-keto-PGF1a, Protein C and total Protein S concentrations in the setting of preconditioned myocardial infarction. There were no changes in the plasma concentrations of antithrombin-III in NPC 15669 group when compared with controls. The increase in Protein C, total Protein S, and 6-keto-PGF1a (favoring antithrombosis), and decrease in endothelin-1 and TxB2 levels (favoring vasodilatation), following NPC 15669 may explain the reduction in infarct size previously reported with this agent.
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PMID:Effects of a novel Mac-1 inhibitor, NPC 15669, on hemostatic parameters during preconditioned myocardial infarction. 1053 Aug 2


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