Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seventy-four patients with beta-thalassemia major were studied to test the hypothesis that a deficiency of protein C (PC) and antithrombin III (AT III), both antithrombotic proteins, could contribute to the pathogenesis of CNS thromboembolic lesions. In 70 patients, PC levels were found to be significantly lower than normal, whereas AT III activity was found to be lower only in 41 patients. The lowest values of PC and AT III were found in older splenectomized patients, a low PC value only was found in chronic hepatitis patients. Prothrombin time and fibrinogen were found to be particularly abnormal in patients with chronic hepatitis and without spleen. A relatively poor correlation was observed between PC and AT III (p less than 0.02). PC correlated with age (p less than 0.001), transfusional iron (p less than 0.001) and ferritin (p less than 0.001). It also correlated with serum albumin (p less than 0.001), prothrombin time (p less than 0.001) and fibrinogen (p less than 0.02) and with serum transaminases (GPT) (p less than 0.001). The same indexes correlated less significantly with AT III activity. Nevertheless, only 2 of our patients had CNS thromboembolic complications. It is probable that low clotting factors, hyperfibrinolysis and thrombocytopenia (which are common in chronic liver disease) could have the opposite effect on hemostasis from that of low levels of anticoagulant proteins such as PC and AT III.
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PMID:Protein C and antithrombin III in polytransfused thalassemic patients. 310 18

Thromboembolism is a serious complication after Fontan operation, which may be caused by alterations of the coagulation system. We therefore investigated pro- and anticoagulant factors in 20 patients aged 4 to 21 years, 4 to 63 months following total cavopulmonary connection. Furthermore we compared markers of thrombin activation and fibrinolysis and in vitro clotting and clot-lysis to age-matched healthy subjects. Compared to results of age-matched controls, the Fontan operated individuals had significant decreases in levels of protein C (0.88 U/ml in controls, 0.67 U/ml in patients; p <0.001) and protein S (1.05 in controls, 0.93 U/ml in patients; p <0.05). Moreover, half of the patients had high values of FVIII (>1.5 IU/ml), which are associated with an increased thrombotic risk. These changes may result in enhanced generation of thrombin and plasmin, indicated by our finding of increased thrombin-antithrombin III (TAT) and plasmin-antiplasmin (PAP) levels and a similar trend in prothrombin fragments F1+2. Clot lysis tests, global coagulation tests, red blood cell count, liver enzymes AST, ALT, but not GGT, were generally within the normal ranges.
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PMID:Hemostatic changes following the modified Fontan operation (total cavopulmonary connection). 1181 32

We analyzed retrospectively the relationship between coagulation profile, and either hepatic function or hemodynamics, in patients who had undergone a Fontan-type procedure, comparing them, first, with a control group of 12 patients without significant hemodynamic abnormality, and, second, with a group of 14 patients who had not undergone a Fontan procedure, but whose mean right atrial pressure exceeded 8 mmHg. Follow-up catheterization had been performed in all 30 patients submitted to the Fontan-type operation. Prothrombin time, and factor XIII, were significantly lower in those who had undergone the Fontan procedure than in the other groups. Those submitted to the Fontan operation also had lower levels of protein C than controls, and their levels of plasminogen were lower than the patients with high right atrial pressure. Both aspartate aminotransferase and alanine aminotransferase were higher in those undergoing the Fontan procedure than in the other groups, while gamma-glutamyltranspeptidase in these patients was higher than in the control group. Mean right atrial pressure was highest in those undergoing the Fontan procedure, while cardiac index was lowest. Prothrombin time was correlated to some extent with aspartate aminotransferase, mean right atrial pressure, and cardiac index. Protein C correlated with both aspartate aminotransferase and mean right atrial pressure, while factor XIII correlated with alanine aminotransferase, mean right atrial pressure, and cardiac index. Aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltranspeptidase, parameters of hepatic function, correlated significantly with mean right atrial pressure. In those who had undergone the Fontan procedure, decreased synthesis of pro-and anti-coagulant factors is a risk factor for both thrombosis and bleeding. Abnormal hemodynamics, in the absence of a right sided pumping chamber, may predispose to subclinical hepatic dysfunction, leading to selective disturbances of protein synthesis.
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PMID:Coagulation profile, hepatic function, and hemodynamics following Fontan-type operations. 1123 99

Patients receiving maintenance hemodialysis (HD) present with hemostatic abnormalities, which may be aggravated by comorbid conditions, especially liver disease. The factors that influence plasma levels of thrombomodulin (TM), an initiator of the anticoagulant protein C pathway, and those of tissue factor (TF), which triggers the extrinsic coagulation pathway, were assessed. In 63 HD patients, TM and TF levels were higher than those in healthy controls. In bivariate analysis, TF positively correlated with TM, and both were directly associated with the presence of viral hepatitis B or C marker, serum liver enzymes, use of erythropoietin therapy, hemoglobin levels, and duration of HD therapy, and inversely correlated with body mass index. TF was also positively associated with plasma von Willebrand factor (vWF) antigen, and inversely associated with activated partial thromboplastin time. In multivariate analysis, increased vWF, alanine aminotransferase, and use of erythropoietin independently predicted both TF and TM levels. HD patients with vWF and ALT levels lower than middle, and not treated with erythropoietin had normal TF but increased TM concentrations compared with levels in healthy controls. Increased plasma levels of TM and TF in patients on maintenance HD are surrogates of vascular endothelial injury. Liver disease and use of erythropoietin treatment are also important determinants of these markers, and should be considered in further studies.
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PMID:Tissue factor and thrombomodulin in hemodialysis patients: associations with endothelial injury, liver disease, and erythropoietin therapy. 1465 47

Portal vein thrombosis (PVT) has rarely been documented in patients after splenectomy for gastric malignancy. We report a case of PVT that occurred after splenectomy as part of an en-bloc node dissection performed to treat gastric malignant lymphoma. A 38-year-old man underwent total gastrectomy and splenectomy with en-bloc D2 lymph node dissection. The spleen weighed 480 g. On postoperative day (POD) 31, the patient complained of abdominal pain in the right upper quadrant accompanied by fever. Moderate elevations of C-reactive protein (CRP), aspartate transaminase (AST), and alanine transaminase (ALT) were noted. Contrast-enhanced computed tomography (CT) and ultrasonography disclosed thrombus in the portal vein and the splenic vein. There were no abnormalities in the levels of lupus anticoagulant, protein C antigen, protein S antigen, or antithrombin III (AT III). A diagnosis of PVT was made, and prompt treatment, including intravenous heparin combined with tissue plasminogen activator (tPA) was initiated, followed by longterm warfarin. This treatment resulted in clinical improvement, but failed to achieve thrombolysis in the portal vein. At follow-up after 6 months, the patient complained of postprandial abdominal pain with persistent peripheral edema and ascites. This case indicates that splenectomy for en-bloc node dissection in gastric malignancy is a possible cause of PVT. Because both the symptoms and the laboratory data in PVT are nonspecific, a high level of clinical suspicion and a low threshold for obtaining imaging examinations are important in the early diagnosis of PVT. Surgeons should remember PVT among several other complications whenever patients treated with radical gastrectomies are symptomatic and imaging studies are considered necessary.
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PMID:Portal vein thrombosis after splenectomy for gastric malignant lymphoma. 1471 20

In vivo protective effects of s-allyl cysteine (SAC) and s-propyl cysteine (SPC) against acetaminophen-induced hepatotoxicity in Balb/cA mice were studied. SAC and SPC at 1g/L were added into drinking water for four weeks and followed by acetaminophen treatment. Acetaminophen treatment significantly depleted glutathione content, increased oxidation stress and elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities (P < 0.05); however, the intake of SAC or SPC significantly alleviated glutathione depletion and the elevation of ALT and AST, enhanced glutathione peroxidase activity, and lowered malondialdehyde formation (P < 0.05). Plasma levels of C-reactive protein (CRP), von Willebrand factor (vWF), IL-6, IL-10 and TNF-alpha were significantly increased by acetaminophen treatment (P < 0.05); and SAC or SPC intake significantly suppressed acetaminophen-induced elevation of CRP, vWF and the three cytokines (P < 0.05). Acetaminophen treatment also significantly increased plasminogen activator inhibitor-1 (PAI-1) activity and plasma fibrinogen level, and decreased antithrombin III (AT-III) and protein C activities (P < 0.05). SAC or SPC intake alleviated AT-III and protein C reduction (P < 0.05); but did not affect PAI-1 activity and plasma fibrinogen level (P > 0.05). These data suggest that SAC and SPC are potential multiple-protective agents against acetaminophen-induced hepatotoxicity.
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PMID:Protective effect of s-allyl cysteine and s-propyl cysteine on acetaminophen-induced hepatotoxicity in mice. 1618 16

This study was conducted to evaluate some anticoagulants' (protein C, protein S and antithrombin) activities among epileptic children treated with VPA and to learn if thromboembolic events occur among these children or their parents. Twenty-five boys and 15 girls using VPA for at least 3 months were included in the VPA group. The control group consisted of 28 boys and 12 girls who had no infection and did not use any medication that could alter protein C activity. Complete blood counts, ALT, AST, PT, aPTT, fibrinogen, protein C, protein S and AT tests were studied in both groups. Serum VPA levels were determined in the VPA group. Protein C and protein S activities of the children in the VPA group were significantly lower than those in the control group (89.5+/-19.3% vs 104.9+/-21.7% and 44.6+/-16.3% vs 59.4+/-28.4%, respectively). Neither children using VPA, nor their parents had any thromboembolic events in medical history. Platelet counts, ALT and fibrinogen levels in the VPA group were significantly lower than those in the controls. A negative correlation was found between serum VPA level and platelet counts. There were also negative correlations between fibrinogen and serum VPA levels, and between fibrinogen level and protein S activity. The children in the VPA group had lower PT and higher aPTT levels than the children in the control group. Since other factors known to alter the anticoagulant activities and liver functions were eliminated initially, the decreases of protein C and protein S activities, thrombocyte counts, ALT, PT and fibrinogen levels and increase in aPTT level may be attributed to VPA. VPA hepatotoxicity can be the cause of decreased pro- and anticoagulant activities.
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PMID:Protein C, protein S and other pro- and anticoagulant activities among epileptic children using sodium valproate. 1684 52

There are many complex pathophysiologic changes of the coagulation system in sepsis. The fibrinolytic system was evaluated in septic children using the global fibrinolytic capacity (GFC), a new technique reflecting the overall fibrinolytic activity. The study consisted of 24 children with sepsis, 36 children with sepsis plus disseminated intravascular coagulation (DIC), and 20 healthy age-matched control individuals. Compared with controls, 86% of sepsis patients and 87% of sepsis plus DIC patients had decreased GFC levels. Between the sepsis plus DIC and sepsis groups there was no significant difference in terms of GFC levels. While 19 patients (52.7%) died in the sepsis plus DIC group, only three patients (12.5%) died in the sepsis group. When survivors and nonsurvivors were compared in terms of coagulation tests, there were significant differences for protein C, antithrombin, platelet, fibrinogen, aspartate aminotransferase, alanine aminotransferase, prothrombin time, and white blood cell values. In conclusion, the level of GFC reduced in most of the pediatric sepsis patients but no difference was observed between patients with sepsis and patients with sepsis plus DIC. While inhibition of fibrinolysis is an important finding in sepsis, the mortality is mainly associated with the presence of end-organ damage and the status of coagulation parameters.
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PMID:Global fibrinolytic capacity in pediatric patients with sepsis and disseminated intravascular coagulation. 1698 53

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

Beta-thalassemia/hemoglobin (Hb) E is a hereditary hemolytic anemia with varying degrees of severity. Severely affected patients are treated with blood transfusion and/or splenectomy in order to maintain an optimum level of hemoglobin for normal growth and physical activities. As thrombosis has been observed among splenectomized patients, we have investigated alterations in coagulation and fibrinolysis in beta-thalassemia/Hb E patients. Plasma levels of prothrombin, fibrinogen, factors V, VII, VIII, IX and XI, protein C, protein S, thrombin activatable fibrinolysis inhibitor (TAFI) and prothrombin fragment 1+2 were determined in 61 patients (21 non-severe non-splenectomized, 18 severe non-splenectomized, 22 severe splenectomized) and 28 healthy individuals. Serum levels of D-dimer, ferritin, aspartate transaminase and alanine transaminase were also measured. All severe patients received regular blood transfusion. Prothrombin fragment 1+2 and D-dimer were significantly elevated in splenectomized patients compared to the healthy control subjects, whereas levels of proteins C, protein S, TAFI, fibrinogen, and factors V and VIII in the splenectomized groups were statistically lower than those in control group. There are no statistical differences for the other parameters measured between patients and controls. Coagulation tests showed only significantly reduction in TAFI and factor V and VIII levels in severe splenectomized group in comparison with severe non-splenectomized patients. These results demonstrate the existence of a low grade consumptive coagulopathy among blood-transfused splenectomized patients with severe clinical manifestations, indicating that these patients may have a higher risk for thrombosis than comparable patients with intact spleen.
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PMID:Hemostatic alterations in splenectomized and non-splenectomized patients with beta-thalassemia/hemoglobin E disease. 1738 94


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