Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gabexate mesilate (FOY), a synthetic serine proteinase inhibitor, has an anticoagulant activity in the absence of antithrombin-III. We investigated FOY therapy for the treatment of disseminated intravascular coagulation (DIC) associated with sepsis in 15 patients (group F), and compared it with heparin therapy in 8 patients (group H). Successful treatment was observed in 13 patients in group F and in 4 patients in group H. The efficacy of the therapy in both groups was not significantly different. However, in patients whose antithrombin-III values were less than 20 mg/dl at the initiation of the therapy, FOY therapy was successful in 6 of 7 patients, whereas heparin therapy was not at all successful in 4 patients (rho less than 0.05). We conclude that FOY can be used as effectively as heparin for the treatment of DIC, and that FOY therapy is superior to heparin therapy in DIC associated with decreased antithrombin-III.
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PMID:Gabexate mesilate (FOY) therapy of disseminated intravascular coagulation due to sepsis. 641 32

Gabexate mesilate (FOY), a synthetic serine proteinase inhibitor, prevented and controlled bleeding during hemodialysis of 3 patients with active bleeding sites and/or hemorrhagic tendencies. The effectiveness of regional anticoagulation was evaluated by activated coagulation time (ACT). The ACTs of blood sampled from the outlet of dialyzer were significantly prolonged; however, systemic ACTs were almost normal. ACTs immediately after dialysis were not prolonged compared with those before dialysis. In 1 patients, renal function was improved after dialysis. No harmful side effects of FOY were observed. We consider FOY to be superior to other drugs for hemodialysis in that: (1) it can provide sufficient regional anticoagulation; (2) it has a very short half-life and need not be antagonized after dialysis; and (3) it can be used in patients with sepsis and/or disseminated intravascular coagulation (DIC) because it inhibits proteinase and also prevents platelet aggregation.
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PMID:New approach to regional anticoagulation in hemodialysis using gabexate mesilate (FOY). 681 24

Gabexate mesilate (FOY) was used to treat 215 patients with disseminated intravascular coagulation (DIC) and 146 patients with a predisposition to DIC (pre-DIC). Sixty percent of DIC patients and 48% of pre-DIC patients exhibited pretreatment organ failure, which resolved after FOY treatment in 16% of DIC patients and 17% of pre-DIC patients. Seventy percent of DIC patients and 49% of pre-DIC patients had a pretreatment bleeding tendency that was ameliorated by FOY treatment in 32% of DIC patients and 30% of pre-DIC patients. Comparison of pretreatment and posttreatment hemostatic studies of the DIC patients revealed that platelet count and levels of fibrinogen degradation products (FDP), thrombin-antithrombin-III complex, and FDP-D-dimer decreased significantly; fibrinogen level increased markedly; and prothrombin time was prolonged. DIC scores were significantly lowered in both leukemic and nonleukemic patients from the third day of treatment with FOY. Among leukemic DIC patients, 59% showed complete remission (CR), 21% partial remission (PR), and 7% exacerbation of their condition; 46% of the nonleukemic DIC patients demonstrated CR, 17% PR, and 17% exacerbation. Of the leukemic pre-DIC patients, 59% showed improvement and 7% exacerbation, whereas 55% of the nonleukemic pre-DIC patients showed improvement and 27% exacerbation.
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PMID:Treatment of disseminated intravascular coagulation with gabexate mesilate. 811 5

We report a 53-year-old woman who developed a cerebral infarction in the left middle cerebral artery area. Although she did not have a hemorrhagic tendency, the results of her examination showed a chronic disseminated intravascular coagulation (DIC) and a left ovarian carcinoma. Gabexate mesilate (FOY) and nafamostat mesilate (FUT) were not effective for her DIC. One month after admission, she had another cerebral infarction in the right posterior cerebral artery area. She was treated by heparin sodium and her chronic DIC improved. Then, she was operated on for ovarian carcinoma; the histologic finding was clear cell adenocarcinoma. No recurrence of DIC nor cerebral infarction was observed postoperatively. Patients with cerebral infarctions caused by chronic DIC due to ovarian carcinoma have been reported in the literature, but few patients had a favorable prognosis such as the present case. Heparin therapy appears to be the treatment of choice for chronic DIC rather than FOY or FUT, if there is no hemorrhagic tendency. When a patient with DIC develops cerebral infarction, one should always investigate for possible malignant tumors.
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PMID:[Favorable prognosis in a case of recurrent cerebral infarctions caused by chronic disseminated intravascular coagulation due to ovarian carcinoma]. 870 62

Gabexate mesylate (GM; commercialized under the brand name FOY) is a nonantigenic synthetic inhibitor of plasmatic and pancreatic serine proteinases that is used therapeutically in the treatment of pancreatitis and disseminated intravascular coagulation and as a regional anticoagulant for hemodialysis. The inhibitory effect of GM on nitric oxide synthase as well as serine proteinases and swine kidney copper amine oxidase, all acting on cationic substrates, has been investigated. On the basis of the available X-ray crystal structures of the enzymes considered, the possible binding mode(s) of GM has(have) been analyzed. The enzyme cross-inhibition by GM suggests that the use of this drug should be under careful control. With the aim to improve the scarce plasma stability of GM, the positively charged drug has been complexed to the surface of preformed anionic liposomes. The liposome-complexed GM half-life increases about five-fold, indicating the protective effect of liposomes on GM degradation. Moreover, the GM complexation with liposomes does not alter its inhibitory activity on NOS-I and porcine pancreatic trypsin.
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PMID:Cross-enzyme inhibition by gabexate mesylate: formulation and reactivity study. 981 86

A 32-year-old woman was admitted with a diagnosis of impending premature delivery. In the 37th week of pregnancy, vaginal examination was performed. After ten minutes, vomiting, whole body flushing, and cold sweat appeared suddenly. Because fetal heart rate became 60-70 beats.min-1, emergency caesarean section was scheduled. When she arrived at the operating room, blood pressure was 75/45 and heart rate was 122 beats.min-1. Five minutes later, anesthesia was induced with thiopental and vecuronium, and operation was instituted concomitantly. After the delivery, pentazocine and midazolam were administered. During the operation, premature separation of normally implanted placenta or pressed cord was not observed. Hydrocortisone was administered for circulatory collapse. Gabexate mesilate was administered for the prevention of DIC. The scratch test, performed ten days later, revealed that latex was positive but lidocaine was negative. Therefore, it was concluded that anaphylaxis induced by latex gloves caused shock after internal examination.
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PMID:[A case of emergency caesarean section as a result of anaphylaxis to latex]. 1003 99

Gabexate mesylate is a non-antigenic synthetic inhibitor of trypsin-like serine proteinases that is therapeutically used in the treatment of pancreatitis and disseminated intravascular coagulation and as a regional anticoagulant for hemodialysis. Considering the structural similarity between gabexate mesylate and arginine-based inhibitors of trypsin-like serine proteinases, the effect of gabexate mesylate on human and bovine mast cell tryptase action was investigated. Values of the inhibition constant (K(i)) for gabexate mesylate binding to human and bovine tryptase were 3.4 x 10(-9) M and 1.8 x 10(-7) M (at pH 7.4 and 37.0 degrees ), respectively. Furthermore, gabexate mesylate inhibited the fibrinogenolytic activity of human tryptase. On the basis of the available x-ray crystal structure of human tryptase, the possible binding mode of gabexate mesylate to human and bovine tryptase was analyzed. Human tryptase inhibition by gabexate mesylate may account for the reported prevention of inflammation, erosion, and ulceration of skin and mucosae.
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PMID:Selective inhibition of human mast cell tryptase by gabexate mesylate, an antiproteinase drug. 1117 30

The management of disseminated intravascular coagulation (DIC) in a 22-year-old female patient with antiphospholipid syndrome is reported. Gabexate mesilate was given by continuous drip infusion at 1.5 g/day. No effect was seen, therefore Dalteparin sodium (DS) was administered by continuous drip infusion at 70 U/kg/day. The DIC score improved gradually during the first 4 days to normalization by 10 days. However, convulsive seizure was developed. Computed tomographic scan of brain demonstrated brain abscess at lt-basal ganglia. Continuous drainage was performed while administered continuous drip infusion of DS. Follow-up CT after operation showed reduction of low density area which means brain abscess. Finding in this case suggest that DS may play a role in the management of DIC accompanying intracranial infection.
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PMID:[Successful treatment for disseminated intra-vascular coagulation due to sepsis and brain abscess with low molecular weight heparin in a patient with antiphospholipid syndrome]. 1118 90

Gabexate mesylate, a non-antigenic synthetic inhibitor of trypsin-like serine proteinases, is a drug used efficiently in the treatment of pancreatitis and disseminated intravascular coagulation and as a regional anticoagulant for haemodialysis. Considering the structural similarity between L-arginine and gabexate mesylate, the effect of this drug on L-arginine transport, nitric oxide (NO) formation and constitutive NO synthase activity in human platelets was investigated. Data have shown that gabexate mesylate inhibited competitively L-arginine uptake by increasing the K(m) value from 22+/-2 to 86+/-6 microM. The K(i) value was 158 microM at pH 7.4 and 37 degrees. Furthermore, gabexate mesylate decreased dose and time-dependent nitrite and nitrate formation (NO(x) release) and cGMP accumulation in whole cells. In addition, gabexate mesylate inhibited constitutive nitric oxide synthase in a cell-free extract. We concluded that gabexate mesylate could be considered an effective modulator of cellular NO synthesis.
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PMID:Modulation of L-arginine transport and nitric oxide production by gabexate mesylate. 1212 48

Gabexate mesilate, a synthetic protease inhibitor, was shown to be effective in treating patients with sepsis-associated disseminated intravascular coagulation in which tumor necrosis factor-alpha (TNF-alpha) plays a critical role. We demonstrated that gabexate mesilate reduced lipopolysaccharide (LPS)-induced tissue injury by inhibiting TNF-alpha production in rats. In the present study, we analyzed the mechanism(s) by which gabexate mesilate inhibits LPS-induced TNF-alpha production in human monocytes in vitro. Gabexate mesilate inhibited the production of TNF-alpha in monocytes stimulated with LPS. Gabexate mesilate inhibited both the binding of nuclear factor-kappaB (NF-kappaB) to target sites and the degradation of inhibitory kappaBalpha. Gabexate mesilate also inhibited both the binding of activator protein-1 (AP-1) to target sites and the activation of mitogen-activated protein kinase pathways. These observations strongly suggest that gabexate mesilate inhibited LPS-induced TNF-alpha production in human monocytes by inhibiting activation of both NF-kappaB and AP-1. Inhibition of TNF-alpha production by gabexate mesilate might explain at least partly its therapeutic effects in animals given LPS and those in patients with sepsis.
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PMID:Gabexate mesilate, a synthetic protease inhibitor, inhibits lipopolysaccharide-induced tumor necrosis factor-alpha production by inhibiting activation of both nuclear factor-kappaB and activator protein-1 in human monocytes. 1264 82


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