Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten yearling white-tailed deer (Odocoileus virginianus) were inoculated with bluetongue virus serotype 17. Two yearling white-tailed deer were inoculated with sonicated heparinized noninfected blood and served as controls. Clinical signs of bluetongue virus infection included increased rectal temperature, erythema, facial edema, coronitis, and stomatitis. By postinoculation day (PID) 8, excessive bleeding and hematoma formation at venipuncture sites, dehydration, and diarrhea developed. At necropsy, the most consistent findings were oral lesions and widespread hemorrhage, which ranged from petechia to massive hematoma formation. Bluetongue virus caused progressive prolongation of activated partial thromboplastin time and prothrombin time, and progressive reduction of Factors VIII and XII plasma activities beginning on PID 6. A progressive decrease in platelet numbers also developed on PID 6. Changes in platelet size were not detected. Mean thrombin time was shortened, but prolongation developed in 1 deer. Mean fibrinogen concentration and Factor V plasma activity initially increased and then decreased, but remained above preinoculation values. Factor V activity was low in a few deer. Results of screening tests for inhibitors of the intrinsic coagulation system were positive in 2 deer. High concentrations of fibrin(ogen) degradation products were first detected between PID 3 and 6. Hematologic changes included leukopenia, lymphopenia, neutrophilia, and low total plasma protein concentration. Differences in PCV, hemoglobin concentration, or RBC counts were not detected between infected and control deer. Serum total bilirubin concentration increased by PID 6, primarily because of increased unconjugated bilirubin concentration. Mild to severe increases in serum aspartate transaminase activity were accompanied by more marked increases in creatine kinase activity. Indirect Coombs test results were negative in all deer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Experimentally induced bluetongue virus infection in white-tailed deer: coagulation, clinical pathologic, and gross pathologic changes. 285 9

Misoprostol has been evaluated in healthy subjects for both antisecretory and pharmacological activity. Doses used were determined initially from acute and chronic tolerance testing in healthy subjects. In the single dosage range of 50-200 micrograms, misoprostol inhibits gastric acid secretion in a dose-related manner both in the basal state and after stimuli such as histamine and standard test meals. The 200 micrograms dose differs significantly from placebo as an antisecretory agent. A preliminary study in six subjects suggested that the 400 micrograms dose does not produce a substantial increase in activity over the 200 micrograms dose. Furthermore, side-effects such as diarrhea and abdominal cramps appear to be dose related. The antisecretory action of misoprostol is maximal one hour after drug administration and is negligible after 4-5 hours. These factors have until now dictated a 50-200 micrograms q.i.d. dosing regimen for misoprostol in clinical trials against peptic ulcer. Misoprostol does not significantly affect platelet function in terms of ADP-, collagen- and thrombin-induced platelet aggregation. Measurements of FEV1, vital capacity, and peak expiratory flow rate have revealed that misoprostol has no significant bronchodilating or bronchoconstricting effect. Studies of endocrine function revealed only a slight rise within the normal range in serum cortisol in women.
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PMID:Misoprostol clinical pharmacology. Establishment of activity in man. 393 46

Hemostatic profiles were determined in 30 horses with clinical colic. Blood samples were obtained at the time of the animal's admission, and the following hemostatic tests were done: blood platelet count, plasma fibrinogen, plasma antithrombin, prothrombin time, partial thromboplastin time, thrombin time, protamine sulfate test for soluble fibrin monomer, and fibrin-fibrinogen degradation products. The patients were categorized in retrospect, according to the cause of the colic: group 1--colic associated with colitis and/or severe diarrhea, group 2--colic associated with torsion or obstruction of the intestine, and group 3--colic associated with impaction of the intestine or the presence of enteroliths. Of the 30 horses with colic, 28 had at least 1 abnormality in their coagulogram--the most frequent abnormalities being high plasma fibrinogen concentration, high circulating soluble fibrin monomer, or a long partial thromboplastin time or thrombin time. The horses in group 1 seemed to have the most severe coagulopathies, as indicated by the average number of demonstrable abnormalities. The horses in group 3 showed the fewest abnormalities--usually a high plasma concentrations of fibrinogen and/or soluble fibrin monomer. The results indicated that hemostatic abnormalities are not uncommon in horses with gastrointestinal disease and colic--the degree of severity depending to some extent on the cause of the colic.
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PMID:Hemostatic abnormalities in equine colic. 395 19

A case of acute intestinal vascular necrosis in a 19-year-old user of oral contraceptives (OCs) is described, and hypotheses explaining the digestive complications of synthetic estrogens are reviewed. The patient had originally presented with a violent gastric pain that subsequently spread to the entire abdomen. An abrupt worsening of her condition involved cardiovascular collapse associated with a peritoneal syndrome, vomiting and dehydration, and hyperleukocytosis. Emergency opening of the peritoneum was followed by evacuation of a large quantity of fetid gas and alimentary debris, and observation of a completely necrosed stomach. A careful lavage of the entire intestinal cavity led to temporary improvement, but it became clear during an attempt at gastrectomy that further treatment would be unavailing and the patient died shortly thereafter. Estrogens were believed to be responsible for the digestive necrosis because it occurred in a young woman who had used an estrogen-rich OC for 3 years and who smoked; a hapatic biopsy confirmed the diagnosis. No traces of other risk factors such as hypertension, hyperlipidemia, diabetes, neoplasia, or obesity were observed. Recent publications indicate that OCs are responsible for a certain number of digestive problems, which may include acceleration of intestinal transit, severe diarrhea, rectorrhagia, ischemic or ulcerative colitis, intestinal infarct which is usually localized, and hepatocellular problems ranging from moderate hepatic insufficiency to malignant tumor and Budd-Chiari syndrome. OCs do not modify hemodynamic regimes, but they may cause elevation of fibrinogen and thrombin, diminution of antithrombin III acitivty, increased platelet adhesivity, and decreased fibrinolysis leading to hypercoagulability. These modifications in hemostasis occur in all OC users and are not statistically correlated with occurence of thrombotic accidents. OCs are probably responsible for parietal vascular lesions; experimental injection of synthetic estrogens is associated with both arterial and venous lesions. The most characteristic anomaly is at the level of the intima, with proliferation of smooth muscle cells and increased conjunctive tissue fibers associated with proliferation of the media or the endothelium. The absence of lipid deposits, the simultaneous appearance of arterial and venous lesions, and other evidence argues against and atheromatous origin of parietal lesions. A significant correlation has been found between high levels of anti-synthetic ethinyl estradiol antibodies and the presence of vascular lesions. It is hypothesized that these circulating immune complexes penetrate the vascular walls of OC users and produce lesions, which may depend on factors such as smoking.
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PMID:[Digestive complications of oral contraceptives: a case of extensive digestive necrosis in a young woman]. 647 54

Magnesium (Mg) deficiency occurs frequently in chronic alcoholism and may contribute to the increased incidence of osteoporosis and cardiovascular disease seen in this population. Mg deficiency is primarily due to renal Mg-wasting and is exacerbated by dietary Mg deprivation, gastrointestinal losses with diarrhea or vomiting, as well as concomitant use of drugs such as diuretics and aminoglycosides. Osteoporosis is prevalent in the alcoholic population. Mg deficiency may contribute to increased bone loss by its effects on mineral homeostasis. In Mg depletion, there is often hypocalcemia due to impaired parathyroid hormone (PTH) secretion, as well as renal and skeletal resistance to PTH action. Serum concentrations of 1,25-vitamin D are also low. These changes are seen with even mild degrees of Mg deficiency and may contribute to the metabolic bone disease seen in chronic alcoholics. Hypomagnesemia in alcoholics may also contribute to increased cardiovascular disease by altering platelet function. Mg deficiency has been demonstrated to enhance platelet reactivity. In these studies, Mg was shown to inhibit platelet aggregation against various aggregation agents. Patients with Mg deficiency were shown to have increased platelet aggregation that was normalized with Mg therapy. The antiplatelet effect of Mg may be related to the finding that Mg inhibits the synthesis of thromboxane A2 and 12-hydroxyeicosatetraenoic acid, eicosanoids thought to be involved in platelet aggregation. Mg also inhibits the thrombin-induced Ca2+ influx in platelets, as well as stimulates synthesis of prostaglandin I2, the potent antiaggregatory eicosanoid. Therefore, Mg deficiency may increase platelet aggregation and cause increased hypertension and atherosclerotic cardiovascular disease in alcoholics.
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PMID:Magnesium deficiency in alcoholism: possible contribution to osteoporosis and cardiovascular disease in alcoholics. 784 87

Diarrhoea-associated haemolytic uraemic syndrome (D+ HUS) is usually caused by verotoxin producing Eschericia coli. We hypothesized that verotoxin binding to glomerular endothelial cells causes localised endothelial cell activation and thus activation of coagulation and reduction of fibrinolytic potential. We also proposed that treatment with fresh frozen plasma or dialysis would not affect these changes. Markers of activation of coagulation and fibrinolysis were measured in 30 children with acute D+ HUS serially, in healthy children and in children on dialysis. In acute D+ HUS, levels of thrombin-antithrombin III complex and prothrombin fragment 1+2 were significantly increased (p <0.001). The source of thrombin generation was unclear. Factor XIIa levels were increased in patients and controls with renal failure. Factor VIIa levels were not significantly raised in children with acute D+ HUS. D-dimers were increased, but fibrinolytic potential as measured by fibrin plate was reduced. Levels of plasminogen activator inhibitor antigen and activity and tissue plasminogen activator antigen were increased. Neither peritoneal dialysis nor administration of blood products, the most common treatments, altered parameters of coagulation or fibrinolysis.
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PMID:Activation of coagulation and fibrinolysis in childhood diarrhoea-associated haemolytic uraemic syndrome. 942 93

Endoleaks remain a significant challenge after endovascular abdominal aortic aneurysm repair (EVAR). Translumbar thrombin injection of the aneurysm sac has been used to treat endoleaks, with low reported morbidity. We present an unusual case of ischemic colitis following translumbar thrombin injection of an endoleak. A 67-year-old male with a 5.8-cm abdominal aortic aneurysm (AAA) was evaluated for endograft repair. The patient underwent preoperative embolization of the right hypogastric artery. The AAA was repaired using a unibody bifurcated graft (Ancure). Completion aortogram revealed no endoleak and a widely patent left hypogastric artery. Computed tomography (CT) at 2 months showed an endoleak appearing to originate from a lumbar artery near the proximal attachment site with outflow via the inferior mesenteric artery (IMA). The endoleak was successfully treated with CT-guided translumbar injection of 8000 units of thrombin into the aneurysm sac. The patient subsequently developed chronic abdominal pain, diarrhea, and a weight loss of 20 lbs. Colonoscopy revealed ischemic colitis of the rectosigmoid colon. Duplex evaluation indicated a patent superior mesenteric artery and IMA distal to its origin. Medical treatment failed and the patient underwent a low anterior resection 2 months later (4 months post-EVAR). Subsequently, the aneurysm has decreased to 5.4 cm, with no evidence of endoleak at 1 year. We conclude that ischemic colitis may occur following translumbar thrombin injection. Thrombin embolization into the rectosigmoid arcade via the IMA was most likely the cause in this case. This problem can potentially be avoided by treating the IMA endoleak outflow prior to translumbar thrombin injection of the aneurysm sac. Thorough arteriographic evaluation of endoleaks should be performed prior to any interventions.
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PMID:Ischemic colitis following translumbar thrombin injection for treatment of endoleak. 1471 80

Microvascular thrombosis is a major cause of organ damage in Shiga toxin-mediated hemolytic uremic syndrome (Stx-HUS). In vitro and clinical studies implicate thrombin-mediated mechanisms in the pathogenesis of Stx microvascular thrombosis. In a greyhound model, administration of 0.03 microg/kg to 0.05 microg/kg Stx1 or Stx2 causes severe bloody diarrhea and HUS with microvascular thrombosis requiring humane euthanasia within 65 hours. Using a greyhound model of Stx-HUS we analyzed early hemostatic changes, and tested the hypothesis that thrombin blockade with lepirudin would prevent lethal Stx effects. Two Stx1-exposed greyhounds were analyzed for hemostatic changes prior to onset of clinical manifestations. Serial hemostasis studies after Stx1 challenge revealed trends of increased aPTT, fibrinogen levels, and prothrombin fragment 1+2, and appearance of abnormally large von Willebrand factor multimers. Three greyhounds were anticoagulated with lepirudin to maintain activated partial thromboplastin times (aPTT) >2.5-fold normal, followed by administration of Stx2 and observation of clinical responses. Among the 3 lepirudin-treated, Stx2-challenged greyhounds, one developed severe illness requiring euthanasia. Remarkably, 2 of the 3 greyhounds developed only hypersalivation and restlessness that resolved (P <.03 compared to 14 historical controls). These two greyhounds were clinically, hematologically and biochemically normal 74 hours after Stx administration, well beyond the time of euthanasia of any previous greyhound. This study suggests that greyhounds exposed to Stx develop procoagulant changes similar to humans, and that thrombin may be a critical factor in the pathogenesis and treatment of Stx-HUS.
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PMID:Lepirudin prevents lethal effects of Shiga toxin in a canine model. 1526 15

Campylobacter jejuni is a major food-borne pathogen and a leading cause of diarrhoea. A cytotoxin is most likely involved in the pathogenesis of inflammatory diarrhoea due to C. jejuni. A 45-kDa outer membrane protein encoded by the porA gene was reported to exhibit cytotoxic activity for cultured mammalian cells in vitro. We cloned and expressed the porA gene in Escherichia coli BL21 codon plus RIL strain using the fusion vector pGEX-4T-1. The fusion protein solubilised in urea in denatured form or solubilised in Empigen BB in native form or their thrombin-cleaved products did not exhibit cytotoxic activity for Chinese hamster ovary (CHO) cells. The urea-solubilised fusion protein did not induce fluid accumulation in the rabbit ileal loop assay. All 76 clinical isolates of Campylobacter spp. tested were positive for porA by PCR, but only 13 isolates were positive for cytotoxin on CHO cells. Both cytotoxin-positive as well as cytotoxin-negative strains expressed PorA as determined by immunoblot analysis. These findings show that the porA gene product of C. jejuni is not a cytotoxin mediating inflammatory diarrhoea.
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PMID:PorA protein of Campylobacter jejuni is not a cytotoxin mediating inflammatory diarrhoea. 1587 82

Changes in blood coagulation parameters were followed in four red deer (Cervus elaphus) experimentally infected with malignant catarrhal fever (MCF) of deer. Blood platelet counts, activated partial thromboplastin time (APTT), one-stage prothrombin time (OSPT), activated clotting time (ACT), plasma anti-thrombin III (ATIII) activity, fibrinogen degradation production (FDP) and fibrinogen levels were measured. Inoculated deer became pyrexic after 17 or 19 days. Thereafter they developed watery diarrhoea which rapidly became haemorrhagic. The course of the clinical disease ranged from four to six days before the animals were killed or died. All inoculated deer developed abnormalities in laboratory parameters of blood coagulation. These varied within and between animals, but the coagulation profiles of all four animals remained abnormal until death. Post-mortem findings included extensive systemic petechiation, severe haemorrhage in the alimentary canal and vasculitis with disseminated thrombosis. Abnormal coagulation parameters included extension of APTT and OSPT, increased FDP, decreased ATIII and platelet counts and increased fibrinogen levels. The increases in fibrinogen were compatible with the acute phase response. The other coagulation abnormalities and haemorrhage and thrombosis were indicative of disseminated intravascular coagulation (DIC) with consumption coagulopathy, ACT remained normal in all deer although final clot quality was considered poor.
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PMID:Changes in blood coagulation parameters of red deer (Cervus elaphus) experimentally infected with malignant catarrhal fever. 1603 12


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