Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ticlopidine, when orally administered to rats, resulted in activation of basal and prostaglandin E1 (PGE1)-stimulated adenylate cylase activity through increase in affinity of the cyclase in platelet membrane to PGE1, although it failed to affect adenosine- or sodium fluoride-stimulated activity of the enzyme. In washed platelets, Ticlopidine also activated basal and PGE1-stimulated activity of the cyclase and prevented reduction in the cyclase activity caused by low concentrations of PGE2. Furthermore, Ticlopidine inhibited malondialdehyde formation in platelets induced by thrombin but failed to inhibit that caused by exogenous arachidonic acid. Adenosine 3',5'-cyclic monophosphate (c-AMP): phosphodiesterase activity of platelet lysate was not significantly affected by Ticlopidine treatment. These findings indicate that Ticlopidine inhibits platelet aggregation and prostaglandin synthesis from endogenous substrate through activating basal and PGE1-stimulated activity of the cyclase, preventing PGE2-induced depression of the cyclase activity and thus increasing platelet c-AMP level.
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PMID:Mode of action of ticlopidine in inhibition of platelet aggregation in the rat. 22 22

Numerous studies have demonstrated that reticuloendothelial system (RES) depression induced by colloid blockade increases susceptibility to circulatory shock following trauma and sepsis. Recent data have suggested that this may relate to the failure of the RES to clear potentially embolic material derived from activation of the hemostatic system. The present study thus compared the hypotensive response precipitated by trauma or sepsis with that resulting from induction of intravascular coagulation. Mean arterial blood pressure (MABP) was monitored for 120 minutes after sublethal NCD trauma and after intra-aortic injection of live E coli (approximately 10(10) organisms per rat), E coli endotoxin (0.1 mg/100 gm), or bovine thrombin (10 units/100 gm) in 400-500 gm rats 30 minutes after RE blockade (50 mg/100 gm gelatinized lipid colloid) or saline injection. All rats were anesthetized with sodium pentobarbital. No hypotension was observed in blockaded control rats. After trauma, MABP decreased by 20 minutes after injury and recovered to normal levels by 1 hour post-trauma. MABP decreased in blockaded rats after trauma and remained diminished through 2 hours. After live E coli endotoxin or thrombin, both the normal and the blockaded groups underwent an initial hypotension of similar magnitude. A second period of hypotension was much more pronounced in the RE-blockaded animals. Reduced MABP persisted in these animals through 2 hours. These data indicate that RE blockade enhances the hypotensive response to intravascular coagulation and that resulting from trauma or sepsis. This effect was especially apparent during the second phase of hypotension during sepsis and intravascular coagulation. It was suggested that the RES manifests some protective effect against the agents inducing this secondary hypotensive response.
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PMID:Effect of reticuloendothelial blockade on the development of hypotension after trauma, sepsis, and intravascular coagulation. 26 5

We have devised an improved high pressure liquid chromatographic technique whereby serotonin, nucleosides, cyclic nucleotides, namely cAMP and cGMP, and 5'mono-, 5'di-, and 5'tri-nucleotides can be analyzed. The cyclic nucleotides have been measured in picomolar quantities. All nucleotides can be quantitated in a single step separation in 75 min using a 0.0015 M phosphoric acids vs. 1M pH 4.8 ammonium phosphate gradient. 5/10 ml of platelet-rich plasma furnishes an adequate sample for complete analysis. Nucleotide levels in platelets from 16 normal donors expressed in 10(11) platelets are as follows: cAMP, 6.32 (4.15) nanomoles and AMP, 0.32 (0.14); ADP, 2.48 (0.67); ATP 3.78 (0.68); GDP 0.38 (0.07) and GTP, 0.45 (0.07) micromoles. ADP and ATP values are lower than those previously published. However, the total nucleotide level approaches published values. Upon aggregation with thrombin, approximately 50% of ADP and 40% ATP is releaseed. Release is complete by 2 min. Thrombin is the most potent releasing agent with collagen and ADP occupying an intermediate role and epinephrine being the least effective. Upon aggregation cyclic AMP levels diminish along the other nucleotides. Patients with asthma showed depression of ADP, ATP, GDP and GTP levels.
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PMID:Measurement of nucleotide pools in platelets using high pressure liquid chromatography. 57

The present study evaluated the influence of experimentally produced intravascular coagulation on reticuloendothelial (RE) stability. Intravascular coagulation was initiated by the intraperitoneal injection of bovine thrombin (500 U/100 g body wt) into male rats. RE function was evaluated by the vascular clearance of an 131I-labeled RE test colloid. Thrombin injection resulted in a transient (0.5-2 h) (P less than .05) depression of the phagocytic index (K) with maximal depression at 1 h postthrombin challenge. The phagocytic index was unaltered after injection of saline or heat-inactivated thrombin. Vascular clearance depression was primarily due to a 37% decrease (P less than .001) in hepatic Kupffer cell colloid clearance and was associated with increments in lung (82%) and marrow (100%) colloid localization with no splenic alterations. While intravascular coagulation was associated with decreased hepatic blood flow at 30 min and 120 min, sinusoidal flow was normal during maximum RE impairment at 60 min. The in vivo clearance depression was not reflected as an intrinsic Kupffer cellular deficit when evaluated in an in vitro system. The results indicate a transient RE dysfunction during intravascular coagulation, the mechanism of which remains to be elucidated.
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PMID:Low-grade intravascular coagulation and reticuloendothelial function. 64 71

During pentobarbital (25 mg/kg i.v. in 2 min), pentothal (15 mg/kg i.v. in 2 min) and ketamine (10 mg/kg i.v. in 2 min) narcosis, rabbits showed reduced platelet reactivity ot the direct aggregating effect of ADP (2 X 10(-5) M) and the indirect effect of thrombin (0.1 U/ml). Certain arousal drugs, specifically those of metabolic type such as SAMe (20 mg/kg i.v. in 2 min) and Thiola (166 mg/kg i.v. in 2 min) and of haemodynamic type such as nicergoline (6.66 mg/kg i.v. in 2 min) and hexobendine (5 mg/kg i.v. in 2 min) administered 31 min after narcosis induction, impede the depression brought on by narcosis on on platelet reactivity.
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PMID:[Narcosis, platelet aggregation and arousing drugs]. 68 73

Decrease in 131I-thrombin clearance and decrease in absorption of complexes of thrombin with other substances in liver tissue were observed under conditions of depression of anticoagulation system found in animals maintained on altherogenic diet. Prolonged administration of an antisclerotic drug "Linetol" and of vitamin A into these animals promoted restoration of anticoagulation system. The restoration was tested by intensification of 131I-thrombin clearance and by accumulation of 131I-thrombin-heparin complex in liver tissue. Decrease in thrombin clearance, in combination with other tests, could be used for diagnosis of prethrombosis under conditions of experimental depression of anti-coagulation system.
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PMID:[Delay in thrombin clearance as a diagnostic test of prethrombosis in depression of the anticoagulation system caused by atherogenic diet]. 102 48

Rabbits treated for 4 days with cortisone to prepare for the generalized Shwartzman reaction (GSR) were infused with thrombin or endotoxin. Whereas endotoxin induced the GSR, infusion of from 120--400 U/kg of thrombin over 1 to 2 1/2 hr failed to induce the GSR. Mean values for fibrinogen consumption after thrombin or endotoxin, calculated from changes in plasma fibrinogen concentration and plasma 125I-fibrinogen radioactivity, were as follows: for rabbits infused with thrombin, from 43 to 61 mg/kg over a 3 hr period; for rabbits infused with endotoxin, 58.5 mg/kg over a 6 hr period. A small peak of non-clottable protein radioactivity, indicative of secondary fibrinolysis, was found in animals infused with thrombin but not in animals infused with endotoxin. A striking late rise in plasma fibrinogen levels was noted in animals infused with endotoxin. It was not noted in animals infused with thrombin. This observation provides further evidence that endotoxin stimulates fibrinogen synthesis by mechanisms independent of intravascular clotting or fibrinolysis. The failure to produce the GSR with thrombin in cortisone-treated rabbits leads us to conclude that depression of reticuloendothelial cell clearance of fibrin can not account for the preparatory effect of cortisone for the GSR after endotoxin.
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PMID:The effects of infusion of thrombin or endotoxin in rabbits treated with cortisone. 118 9

On depression of the anticoagulating system's function due to a prolonged keeping of animals on aterogenic diet, a decrease in the speed of clearance of thrombin-J131 was observed in the blood flow, the absorption of non-fermentative dissolvents of unstabilized fibrin (the heparin complex compounds) is sharply reduced in the liver and lungs tissues, and the fatty dystrophy of the liver cells followed by appearance of vacuoles in cytoplasm and decrease of the RNA and total protein contents in the cells, was observed.
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PMID:[An analysis of the mechanisms of depression of the blood's anticoagulating system]. 121 4

The objective of this study was to characterize the hemostatic defect in dogs with infectious canine hepatitis (ICH), a naturally occurring viral disease of dogs. Five littermate dogs were inoculated with 10(3) TCID50 of ICH virus intravenously. Two littermates were controls. The clinicopathologic manifestations of ICH were fever, depression, anorexia, hematemesis, melena, widespread mucocutaneous petechiae, prolonged bleeding from venipunctures, faceial edema, leukopenia, and proteinuria. The hemostatic defect of ICH was characterized by thrombocytopenia, abnormal platelet function, prolonged one-stage prothrombin time and activated partial thromboplastin time, normal thrombin times, depressed factor VIII activity, and increased fibrin-fibrinogen degradation products. These findings suggested that the central pathologic mechanism of the abnormal hemostasis in ICH was disseminated intravascular coagulation (DIC). ICH is an example of DIC induced by viral infection. This disease is a suitable model for investigation of the detection, pathogenesis, and therapy of DIC.
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PMID:Infectious canine hepatitis: animal model for viral-induced disseminated intravascular coagulation. 124 23

Monitoring of anticoagulant treatment is not yet satisfactory. Otherwise optimal treatment control in special situations as low dose heparin prophylaxis in hip surgery or high dose anticoagulant treatment in patients after coronary stent implantation may be desirable. Recently available thrombin markers were analyzed in 51 patients under low dose (group 1) and 30 patients under high dose therapy with unfractionated heparin (group 2a and b) as well as in controls (n = 26). Before therapy these parameters were significantly elevated in both patient groups. Elevated thrombin-antithrombin III-complexes (TAT) despite adequate prolongation of aPTT under high dose heparin in 38.2% of patients indicate that therapeutic concentrations of heparin in these cases are insufficient for depressing this parameter completely. During low dose therapy only prothrombin fragment (F1 + 2) significantly decreased. This may be explained by catalytic induction of TAT-complex formation by heparin. Decrease of D-Dimer under heparin therapy in both groups does not parallel with TAT and F1 + 2 but was more prolonged. This can be explained by dependence of the D-Dimer level on spontaneous fibrinolytic activity and by a longer plasma half-life as well as a chronic and continuous fibrinolytic process in an older thrombus. In conclusion, thrombin markers seem to be helpful in estimating anticoagulant treatment efficacy. As a consequence, anticoagulant treatment has to be intensified in high-risk patients for complete depression of these markers. Whether the benefit of higher heparin doses is worth the risk of drug-induced hemorrhage, however, remains to be clarified in clinical studies.
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PMID:Influence of heparin treatment on biochemical markers of an activation of the coagulation system. 141 88


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