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:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synthetic cyclic growth-hormone release-inhibiting hormone (G.H.-R.I.H.) impaired platelet aggregation in each of four healthy men given 6-hour infusions. The effects lasted over 24 hours in three of them. There was no consistent change in platelet-counts during the infusions, but 18 hours after the end of the infusions there was a slight but significant increase in platelet-count. There was no change in prothrombin-time, partial thromboplastin-time, fibrinogen titres, and fibrinogen-degradation products. Incubation of G.H.-R.I.H. with blood in vitro did not affect platelet aggregation. Similar impairment of platelet function has been reported by others in baboons given linear G.H.-R.I.H. Infusions in the four healthy men studied also produced abdominal pain, dizziness, and diarrhoea in three, as have been reported in patients similarly infused. Although other side-effects or impairment of platelet-counts or bleeding-tendencies have not been reported in patients infused for up to 72 hours, caution should be exercised when using G.H.-R.I.H. over extended periods until further data on its toxicity are available.
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PMID:Impairment of platelet function by growth-hormone release-inhibiting hormone. 4 78

A 52-week oral repeated dose toxicity study of suplatast tosilate (IPD-1151T), a newly developed anti-allergic agent, was carried out in beagles by oral administration of 30, 90, 270 and 810 mg/kg/day for 52 weeks. The recovery study was carried out by the withdrawal for 5 weeks using control and the 810 mg/kg groups. The results are as follows: 1. Observation of general conditions revealed soft feces, mucous feces, and diarrhea in both sexes of the 270 and 810 mg/kg groups during the administration period, and these findings disappeared during the withdrawal period. One female of the 810 mg/kg group exhibited tremors in the legs and neck, staggering, a decrease of spontaneous motor activity, and clonic convulsions in Week 17 of administration and died on Day 118. One male of the same group exhibited whole body tremors and staggering from Week 32 to Week 52. 2. Body weight gain tended to be inhibited in males of the 810 mg/kg group during the administration period. The body weight of the female that died decreased rapidly after the appearance of neurological symptoms. The body weight of the male that exhibited neurological symptoms decreased after their appearance but later increased. 3. There were no abnormal changes in food consumption in all of the sacrificed dogs. The female that died did not eat at all after the appearance of neurological symptoms. The male that exhibited neurological symptoms did not eat at all for 1 week after their appearance, but the food consumption returned to normal thereafter. 4. Prothrombin times were prolonged in males of the 270 and 810 mg/kg groups at Week 26, and activated partial thromboplastin times were prolonged in males of the 810 mg/kg group at Week 52. 5. Plasma levels of alkaline phosphatase, GPT and LDH were elevated in some males and females of the 810 mg/kg groups. 6. No abnormalities due to IPD-1151T administration were found in urinalysis, opthalmological examination, electrocardiography, and fecal occult blood examination, or organ weights. 7. Autopsies including histopathological and electron microscopic examinations on the sacrificed dogs revealed no abnormalities. Subserosal hemorrhage in the base of the heart, congestion in the lungs, congestion and vacuolation in the liver and slight cell infiltration around vessels of the brain were found in the female that died.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[A fifty two-week oral repeated dose toxicity study of suplatast tosilate (IPD-1151T) in dogs]. 132 Dec 56

A cas is reported of a 23-year-old man who voluntarily took a massive dose of arsenic (at least 8 g). In spite of the ingested amount and the acute nature of the poisoning, the patient survived 8 days. Gastrointestinal, neurologic and cardiac features were predominant including nausea, vomiting, choleroid diarrhoea, encephalopathy, peripheral neuropathy, and finally a fatal toxic cardiomyopathy. Metabolic acidosis, moderate cytolysis and an anticoagulant effect were also observed. This unique characteristic was partly due to a circulating anticoagulant with prothrombinase activity, as well as direct antivitamin K activity. Postmortem examination revealed: a congestive oesophagitis; a necrosing gastritis involving all the stomach wall; diffuse hepatic steatosis; skin lesions with vascular congestion and dermoepidermal detachment; discrete subepicardial congestive lesions. Arsenic was found in all tissues.
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PMID:[Subacute arsenic poisoning]. 185 59

A polyethylene glycol conjugate of L-asparaginase (PEGLA) was administered to 21 patients with refractory non-Hodgkin's lymphoma. The dose given was 2,000 mu/m2 intramuscularly every 2 weeks. Eligibility required at least one prior trial of chemotherapy and ambulatory performance status. At entry, all patients had measurable lesions and documented disease progression. The median age of the patients was 61 years; 18 (86%) were ambulatory with minimal symptoms, 12 patients (57%) had 3 or more prior regimens, and 13 (62%) had stage IV disease. Histologic subtype was low grade in 11 patients (52%), intermediate in 7 (33%), high grade in 2 (10%) and unclassifiable in one (5%). There were two partial responses (11%) noted (95% confidence interval of response of 1-30%). Eleven patients (52%) were removed from study due to disease progression. Nine patients (43%), required removal for toxicity (7 for protracted nausea and vomiting and 2 for confusion). One patient died of sepsis while on study but this was not considered drug related. Almost one third of patients complained of fatigue or loss of appetite. Nausea and vomiting occurred in approximately half the patients and was moderate to severe in 9. Diarrhea and abdominal pain were also noted in one-third of those treated. Changes in the partial thromboplastin time and fibrinogen were noted in most patients but resulted in no bleeding complications. In this trial, PEGLA displayed modest activity in a heterogenous group of patients with progressive non-Hodgkin's lymphoma.
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PMID:A phase II trial of PEG-L-asparaginase in the treatment of non-Hodgkins lymphoma. 234 67

Primary nonfunction following orthotopic liver transplantation is characterized by rapidly rising serum transaminases, minimal bile production, and severe coagulopathy, which can progress to hypoglycemia, hepatic encephalopathy, and acute renal failure. Untreated it has a mortality of over 80% and to date the only treatment has been retransplantation. As a result of the beneficial effect of Prostaglandin E1 infusion in patients with fulminant hepatic failure, this trial was conducted to determine whether PGE1 would be of value in primary nonfunction. We have encountered 16 cases of primary nonfunction in 94 liver transplants, an incidence of 17%. Initially in the program, there were 6 occurrences of nonfunction that did not receive PGE1; 3 underwent retransplantation (2 survivors), 2 died awaiting another liver, and in one recovery of hepatocellular function occurred with supportive care but the patient died of cytomegalovirus infection. Ten patients received PGE1 within 4-34 hr of transplantation. Within 12 hr of treatment, 8 patients responded with a significant fall in the AST (129 U/hr) whereas, in the untreated group, the AST continued to rise (267 +/- 102 U/hr) at the same rate as prediagnosis (337 +/- 95 U/hr). At the conclusion of the infusion (4-7 days) in the 8 responders, there were significant decreases in AST (4386 +/- 546 U/L to 102 +/- 21 U/L), prothrombin time (22 +/- 2 to 12 +/- .4 sec) and partial thromboplastin time (45 +/- 3-29 +/- 4 sec), and significant increases in coagulation factor V (26 +/- 8 to 95 +/- 12%) and factor VII (10 +/- 5 to 61 +/- 4%). No serious side effects occurred, although 2 patients developed diarrhea, and abdominal cramps. Two patients treated with PGE1 were retransplanted at 10-36 hr and were considered nonresponders. Graft survival was 80% in the PGE1-treated group and 17% in the untreated group (P less than 0.05) and patient survival was 90% and 33%, respectively. This study suggests a potential benefit of PGE1 in the treatment of primary nonfunction.
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PMID:Treatment of primary liver graft nonfunction with prostaglandin E1. 267 5

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

10-Ethyl-10-deazaaminopterin (10-EDAM) is an analogue of methotrexate with improved preclinical anticancer activity, more selective entry, and greater conversion to polyglutamate forms in neoplastic cells. In this Phase I trial, we have treated 62 adults with advanced solid tumors, giving 10-EDAM i.v. on either a weekly x 3 schedule (35 patients) or a weekly schedule (27 patients). The dosage levels ranged from 5 to 120 mg/m2. The toxicity observed with 10-EDAM was qualitatively similar to that of methotrexate. Oral mucositis was the dose-limiting toxicity; diarrhea, skin rash, leukopenia, thrombocytopenia, and mild elevations of serum glutamic-oxaloacetic transaminase, prothrombin, and partial thromboplastin times were also observed, but were not dose limiting. A weekly dosage of 80 mg/m2 with escalation or attenuation in accordance with patient tolerance, or 100 mg/m2 weekly for 3 weeks, followed by a 2-week "rest period" are recommended for Phase II assessment. 10-EDAM produced partial remissions in three patients with non-small cell lung cancer and one patient with breast cancer lasting 6, 40+, 26+, and 15 months, respectively. Pharmacokinetic studies carried out at the 5, 30, and 100 mg/m2 dosage levels demonstrated the drug to have a triphasic disappearance from plasma. Elimination was independent of dose over the range tested, with mean plasma half-lives of: alpha = 12.9 min, beta = 1.5 h, and gamma = 11.9 h. Cumulative urinary excretion of the drug ranged from 13 to 55% of the administered dose (mean = 33%); 88% of the urinary drug appeared within the first 4 h following drug administration. The pharmacokinetic behavior of the first and second weekly dosages were consistent within a given patient. The metabolites 7-hydroxy-10-EDAM, and 10-ethyl-10-deaza-2,4-diamino-pteroic acid were demonstrated in the plasma and urine of treated patients. In studies of tissue homogenates from two patients with skin metastases, more extensive retention of the drug and of its polyglutamates was observed in the breast cancer metastases than in the metastases from a kidney cancer or in normal skin.
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PMID:Phase I trial and clinical pharmacological evaluation of 10-ethyl-10-deazaaminopterin in adult patients with advanced cancer. 341 10

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

Intravenous injection of crude marijuana extract led to development of an acute illness with multisystem involvement. Gastrointestinal manifestations consisted of severe vomiting, diarrhea, and crampy abdominal pain. Hypotension, tachycardia, and peripheral vasodilation constituted the main cardiovascular manifestations of the disease. Moderate azotemia and oliguria, presumed to be of prerenal origin, were present and rapidly resolved with administration of intravenous fluids. Hematologic manifestations consisted of leukocytosis with a left shift, thrombocytopenia, prolonged partial thromboplastin time, increased fibrin degradation products, and positive protamine sulfate test. The observed coagulation abnormalities may suggest intravascular coagulation. C3, C4, and total hemolytic complement were reduced, suggesting possible activation of the complement system. Hyperventilation, hypoxemia, pulmonary edema, obstructive, and restrictive pulmonary function abnormalities and bilateral pleural effusions highlighted the pulmonary manifestations of the disease. Rhadbomyolysis and mild hepatic function abnormalities were also present. All observed abnormalities reversed in a few days with no significant sequelae.
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PMID:Toxicity with intravenous injection of crude marijuana extract. 723 64

The single intravenous administration of purified T-2 toxin to rabbits to 0.5 mg per kg body weight produced a decrease in hematocrit, while blood cell count, and serum alkaline phosphatase activity. The plasma clotting time, as measured by the activated partial thromboplastin time assay, was prolonged after intravenous T-2 toxin administration. In contrast, the administration of T-2 toxin to rabbits at 2.0 mg per kg body weight by gastric intubation produced oral lesions, diarrhea and anorexia in the animals but did not cause significant alteration in hematological and biochemical parameters. The results suggest that the rabbit may be a suitable model for further examination of the biochemical mechanisms involved in the cytotoxic action of T-2 toxin.
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PMID:Effect of fusarium T-2 toxin on hematological and biochemical parameters in the rabbit. 733 72


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