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)

We analyzed historical control data of clinical pathology testings provided by sixty-seven member companies of the Japan Pharmaceutical Manufacturers Association covering study populations of approximately 7,000 rats/sex, 5,000 dogs/sex, and 700 monkeys/sex. This paper assesses the relationship between conditions of sample collection, methods of measurement, etc. and potential factors contributing to variations in reference data, based on weighted means and standard deviations thereof derived from data for rats, dogs and monkeys for those parameters measured using methods most common to the participating facilities. Parameters included erythrocyte count (RBC), hematocrit (Ht), hemoglobin concentration(Hb), reticulocyte count (Rt), platelet count, total leukocyte count (WBC), differential leukocyte count (%WBC), coagulation time (activated partial thromboplastin time: APTT, prothrombin time: PT), and serum/plasma levels of GOT, GPT, ALP, LDH, glucose, cholesterol, triglycerides (TG), total protein, albumin, urea nitrogen (UN), creatinine, sodium (Na), potassium (K), calcium (Ca), chloride (Cl), inorganic phosphorus (Ip), and CPK. Analyses of the data revealed species differences in RBC, Ht, Rt, platelet count, WBC, %WBC, ALP, LDH, glucose, cholesterol, TG, total protein, UN, creatinine, Ca, Ip, and CPK. There were strain differences in rats in platelet count, WBC, GOT, ALP, UN, creatinine, and CPK. Sex differences were noted for Hb, Ht, WBC, ALP, glucose, cholesterol, TG, total protein, A/G ratio, UN, and Ip. Age differences were observed with RBC, Hb, Ht, Rt, %WBC, GOT, GPT, ALP, LDH, cholesterol, TG total protein, Ip, and CPK. APTT, PT, ALP, glucose, TG and UN were found to be subject to the influence of fasting/feeding. In rats, Ht, WBC, CPK and K showed differences by the site of bleeding. Observed values for LDH and CPK varied with specimen type, plasma or serum; serum assay values showed greater variation than plasma values.
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PMID:Clinical pathology reference ranges of laboratory animals. Working Group II, Nonclinical Safety Evaluation Subcommittee of the Japan Pharmaceutical Manufacturers Association. 835 5

A direct survey was taken of 1,238 members of the Society of Cardiovascular and Interventional Radiology (SCVIR) concerning the routine use of 14 tests (most frequently, prothrombin and partial thromboplastin times, complete blood cell counts, and blood urea nitrogen and serum creatinine levels) performed before 10 invasive percutaneous procedures (peripheral angiography, neuroangiography, transluminal angioplasty, thrombolysis, percutaneous needle biopsy, abscess drainage, percutaneous nephrostomy, biliary drainage, myelography, and venography). The survey was undertaken to determine the current practices and appropriateness of current routine use of preprocedural tests. The response rate was 34%, representing a cumulative annual volume of 322,208 cases. The practice of performing routine preprocedural tests is common among interventional radiologists. Data provided by this survey suggest that use of these tests is excessive. Adherence to suggested proposals derived from previously reported experience would result in an annual estimated savings of $20.0-$34.9 million (extrapolated for all procedures performed by SCVIR members in 1989).
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PMID:Use of preprocedural tests by interventional radiologists. 841 67

We investigated the effect of activated protein C (APC) on lipopolysaccharide (LPS)-induced pulmonary vascular injury in rats to investigate the possible usefulness of APC as a treatment for adult respiratory distress syndrome. Intravenously administered LPS (5 mg/kg) significantly increased pulmonary vascular permeability. APC prevented the LPS-induced increase in pulmonary vascular permeability observed at 6 hours. Heparin plus antithrombin III (ATIII) and active site-blocked factor Xa (DEGR-Xa), a selective inhibitor of thrombin generation, inhibited LPS-induced coagulopathy but did not prevent LPS-induced pulmonary vascular injury. LPS-induced pulmonary vascular injury was significantly attenuated in rats with nitrogen mustard-induced leukocytopenia and in rats treated with ONO-5046, a potent granulocyte elastase inhibitor. Administration of LPS also increased pulmonary accumulation of leukocytes, as evaluated by measurement of myeloperoxidase activity in the lungs. APC significantly reduced LPS-induced increases in pulmonary accumulation of leukocytes at 1 hour. Neither ATIII plus heparin nor DEGR-Xa inhibited leukocyte accumulation. Active site-blocked APC (DIP-APC) prevented neither the LPS-induced pulmonary accumulation of leukocytes nor the LPS-induced increase in pulmonary vascular permeability. These results suggest that the mechanism of APC inhibition of LPS-induced pulmonary vascular injury was independent of its anticoagulant activity and was related to its ability to inhibit accumulation of leukocytes. In addition, these findings suggest that the serine protease activity of APC may be essential to its inhibitory effect on LPS-induced pulmonary accumulation of leukocytes and subsequent pulmonary vascular injury.
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PMID:Activated protein C attenuates endotoxin-induced pulmonary vascular injury by inhibiting activated leukocytes in rats. 855 86

Adult respiratory distress syndrome (ARDS) is a serious complication of disseminated intravascular coagulation (DIC) or multiple organ failure. To determine whether recombinant soluble human thrombomodulin (rsTM) may be useful in treating ARDS due to sepsis, we investigated the effect of rsTM on lipopolysaccharide (LPS)-induced pulmonary vascular injury in rats. The intravenous administration of rsTM prevented the increase in pulmonary vascular permeability induced by LPS. Neither heparin plus antithrombin III (AT III) nor dansyl Glu Gly Arg chloromethyl ketone-treated factor Xa (DEGR-Xa), a selective inhibitor of thrombin generation, prevented LPS-induced vascular injury. The agents rsTM, heparin plus AT III, and DEGR-Xa all significantly inhibited the LPS-induced intravascular coagulation. Recombinant soluble TM pretreated with a monoclonal antibody (moAb) that inhibits protein C activation by rsTM did not prevent the LPS-induced vascular injury; in contrast, rsTM pretreated with a moAb that does not affect thrombin binding or protein C activation by rsTM prevented vascular injury. Administration of activated protein C (APC) also prevented vascular injury. LPS-induced pulmonary vascular injury was significantly reduced in rats with leukopenia induced by nitrogen mustard and by ONO-5046, a potent inhibitor of granulocyte elastase. Results suggest that rsTM prevents LPS-induced pulmonary vascular injury via protein C activation and that the APC-induced prevention of vascular injury is independent of its anticoagulant activity, but dependent on its ability to inhibit leukocyte activation.
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PMID:Recombinant human soluble thrombomodulin reduces endotoxin-induced pulmonary vascular injury via protein C activation in rats. 860 7

To determine whether abnormal results of admission serum chemistry profiles (P7: sodium (Na), potassium (K), chloride (Cl), carbon dioxide content (CO2), blood urea nitrogen (BUN), creatinine (Cr), and glucose (GLU), amylase (AMY), and coagulation profiles (CP: prothrombin time (PT) and partial thromboplastin time (PTT) in trauma patients lead to clinical interventions, and to characterize frequency of abnormal results, we prospectively gathered laboratory data on 500 consecutive patients seen in our Level 1 trauma center. Clinicians were blinded to the study. Abnormal results were found in 93% of P7s, 7% of AMYs, and 59% of CPs. Interventions were made for < 1% of abnormal P7s, 0% of abnormal amylase, and 5% of patients with abnormal CP. We conclude that information provided by routine admission chemistry and coagulation profiles in trauma patients seldom lead to clinical interventions. These tests should not be ordered routinely on admission in trauma patients.
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PMID:Utility of admission chemistry and coagulation profiles in trauma patients: a reappraisal of traditional practice. 867 19

Ten scientific organizations formed a joint international committee to provide expert recommendations for clinical pathology testing of laboratory animal species used in regulated toxicity and safety studies. For repeated-dose studies in rodent species, clinical pathology testing is necessary at study termination. Interim study testing may not be necessary in long-duration studies provided that it has been done in short-duration studies using dose levels not substantially lower than those used in the long-duration studies. For repeated-dose studies in nonrodent species, clinical pathology testing is recommended at study termination and at least once at an earlier interval. For studies of 2 to 6 weeks in duration in nonrodent species, testing is also recommended within 7 days of initiation of dosing, unless it compromises the health of the animals. If a study contains recovery groups, clinical pathology testing at study termination is recommended. The core hematology tests recommended are total leukocyte (white blood cell) count, absolute differential leukocyte count, erythrocyte (red blood cell) count, evaluation of red blood cell morphology, platelet (thrombocyte) count, hemoglobin concentration, hematocrit (or packed cell volume), mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. In the absence of automated reticulocyte counting capabilities, blood smears from each animal should be prepared for reticulocyte counts. Bone marrow cytology slides should be prepared from each animal at termination. Prothrombin time and activated partial thromboplastin time (or appropriate alternatives) and platelet count are the minimum recommended laboratory tests of hemostasis. The core clinical chemistry tests recommended are glucose, urea nitrogen, creatinine, total protein, albumin, calculated globulin, calcium, sodium, potassium, total cholesterol, and appropriate hepatocellular and hepatobiliary tests. For hepatocellular evaluation, measurement of a minimum of two scientifically appropriate blood tests is recommended, e.g., alanine aminotransferase, aspartate aminotransferase, sorbitol dehydrogenase, glutamate dehydrogenase, or total bile acids. For hepatobiliary evaluation, measurement of a minimum of two scientifically appropriate blood tests is recommended, e.g., alkaline phosphatase, gamma glutamyltransferase, 5' -nucleotidase, total bilirubin, or total bile acids. Urinalysis should be conducted at least once during a study. For routine urinalysis, an overnight collection (approximately 16 hr) is recommended. It is recommended that the core tests should include an assessment of urine appearance (color and turbidity), volume, specific gravity or osmolality, pH, and either the quantitative or semiquantitative determination of total protein and glucose. For carcinogenicity studies, only blood smears should be made from unscheduled sacrifices (decedents) and at study termination to aid in the identification and differentiation of hematopoietic neoplasia.
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PMID:Harmonization of animal clinical pathology testing in toxicity and safety studies. The Joint Scientific Committee for International Harmonization of Clinical Pathology Testing. 874 16

We found a new, highly selective plasma kallikrein inhibitor, trans-4-aminomethyl-cyclohexanecarbonylphenylalanine 4-carboxymethylanilide hydrochloride, called PKSI-527 in our laboratories. This study was conducted to evaluate PKSI-527, on thromboplastin (TP)- and endotoxin (LPS)-induced disseminated intravascular coagulation (DIC) in rats. PKSI-527 was infused intravenously at 0.1 mg/kg/min for 250 min. Three of the parameters of the coagulation and fibrinolysis system, fibrinogen level, platelet counts and fibrin(ogen) degradation products (FDP) level were assayed. PKSI-527 prevented the change in the coagulation and fibrinolysis system in LPS-induced DIC, however it was not clearly effective in TP-induced DIC. The parameters of organ failure, such as serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), creatine phosphokinase (CPK), lactate, blood urea nitrogen and beta-glucuronidase, were assayed. Although the changes in the fibrinogen level, platelet counts and FDP level were almost the same in both models, the parameters of organ failure apparently increased in LPS-induced DIC more so than in TP-induced DIC. PKSI-527 significantly suppressed the increases in GOT and GPT in LPS-induced DIC. These results indicate that plasma kallikrein may play a significant role in LPS-induced DIC. Therefore, PKSI-527, as a synthetic plasma kallikrein inhibitor may be a valuable tool to explore the mechanism of DIC and the accompanying organ failure.
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PMID:Effects of a highly selective synthetic inhibitor of plasma kallikrein on disseminated intravascular coagulation in rats. 874 31

The objective of this study was to extend our understanding of the stability of heparin. Sodium heparin, derived from porcine intestinal mucosa, was first incubated in 0.1 N hydrochloric acid and 0.1 N sodium hydroxide at 30 and 60 degrees C and sampled at times ranging from 0 to 1000 h. The absorbance spectra of the products formed under basic conditions showed an ultraviolet maxima at 232 nm associated with chemically catalyzed beta-elimination at the uronic acid residues. The products formed under acidic conditions showed a decreased staining intensity consistent with desulfation and a decrease in molecular weight corresponding to hydrolysis of glycosidic linkages when analyzed by gradient polyacrylamide gel electrophoresis. Heparin samples were next prepared in 10 mM sodium phosphate buffer at pH 7.0 in sealed ampules that had been flushed with nitrogen and incubated at 100 degrees C. Samples taken at times ranging from 0 to 4000 h were then analyzed. Heparin was relatively stable over the first 500 h, after which it rapidly degraded. Heparin, assayed using both anti-factor Xa and anti-factor IIa amidolytic methods retained 80-90% of its activity over the first 500 h, but these activities dropped precipitously, to approximately 6% and approximately 0.5% of the initial activity at 1000 h and 2000 h, respectively. This rapid decomposition began only after the buffering capacity of the solution was overwhelmed by acidic degradants, which caused the pH to decrease. Decomposition processes observed under these conditions included the endolytic hydrolysis of glycosidic linkages and loss of sulfation, particularly N-sulfate groups, and were similar to the degradation processes observed in 0.1 N hydrochloric acid. This study provides initial observations on heparin degradation pathways. More complete, quantitative studies and studies leading to the isolation and characterization of specific degradants are still required.
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PMID:Accelerated stability studies of heparin. 892 82

The effect of oxidized starch (OS) which contained 15% of COOH groups and its nitroether (NOS) with 4% of nitrogen on coagulation properties of rat blood was studied in vitro and in vivo. The results of the study in vitro showed that OS did not affect the function of the coagulation system. In contrast to OS, a dose-dependent increase in prothrombin-, thrombin time, and activated partial thromboplastin time was observed for NOS. The activity of the components of the internal coagulation pathway changed when the NOS concentration reached 0.1 mg/ml. At a concentration of 0.6 mg/ml and higher this compound affect the external pathway and final stage of coagulation. According to the efficiency (in vitro) of the influence on the thrombine time I mg/ml NOS corresponded to 0.2 U/ml of heparine. The anticoagulant effect of NOS was also observed in vivo along with reliable changes in thromboplastin and thrombin time. Antithrombin activity of plasma remained the same. Standard test was negative and indicated to the absence of fibrin monomers. The pronounced anticoagulant effect of NOS in the experiments in vitro and quick response in the experiments in vivo make it possible to consider this compound as anticoagulant of direct action.
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PMID:[The anticoagulant action of the nitric acid ester of oxidized starch]. 897 59

Menorrhagia--technically defined as menses lasting longer than 7 days or a blood loss volume in excess of 60 to 80 mL--is one of the most common gynecologic complaints. It has been reported that 15% to 20% of otherwise healthy women experience debilitating menorrhagia. In the past, definitive treatment for abnormal uterine bleeding has been either abdominal or vaginal hysterectomy. Alternatives to hysterectomy are now stressed in light of the fact that nearly 50% of uterine specimens obtained during hysterectomies for menorrhagia are disease-free on pathologic examination. Etiologies are generally either endocrinologic or organic. Among the organic causes are coagulation disorders; organ dysfunction, such as liver or renal disease; endometrial hyperplasia; infection; iatrogenic causes, such as chemotherapy, anticoagulants, steroid therapy, and use of IUD; and anatomic causes, which include uterine leiomyoma, endometrial polyps, and pregnancy. Besides the history and physical exam, useful lab tests include CBC, serum pregnancy test, cervical specimens for gonorrhea and chlamydia, Pap smear, thyroid function tests, serum transaminases, luteinizing hormone, follicle-stimulating hormone, estradiol, prothrombin time, activated partial thromboplastin time, bleeding time, serum prolactin, quantitative beta human chorionic gonadotropin, blood urea nitrogen, serum creatinine, and adrenal function tests. Since many lesions are missed in office sampling or dilation and curettage, imaging studies, including ultrasound and hysteroscopy, can be useful in diagnosing the cause of menorrhagia. Medical treatments include drugs such as NSAIDS, progestins, oral contraceptives, and gonadotropin-releasing hormone agonists. Surgical modalities range from the relatively simple, such as D & C, to major surgical procedures such as hysterectomy. Laser ablation and thermal balloon ablation are promising new procedures.
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PMID:Contemporary Concepts in Managing Menorrhagia. 974 66


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