Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In our intensive care unit we were able to prevent almost all bleedings from stress ulcerations in patients with insufficiency of various organs (1,6%) by administering the H2-receptor blocker cimetidine in doses of 8 X 200 mg per day. However, stress ulcer bleedings occurred in 14% of those patients also suffering from a sepsis. At lower doses of cimetidine, the rate of bleeding was comparable to that encountered in patients treated with antacids, i.e. 12,5% patients with multiple organ insufficiency and 42,7% with sepsis. Cimetidine was able to stop less extensive bleedings, but did not show any therapeutic effect in case of bleeding which led to a significant fall in hemoglobin concentration.
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PMID:[Prevention and therapy of gastroduodenal stress bleeding with cimetidine]. 741 53

The cytoprotective and acid-inhibitory effects of cimetidine and 16,16-dimethyl PGE2 were evaluated in a septic canine erosive gastritis model. In 21 dogs, total gastric fistulas were created, and after a 3-wk recovery period, basal, food-, and pentagastrin-stimulated acid output were measured. Then bacterial peritonitis was created by the intraperitoneal instillation of Pseudomonas, Bacteroides, Streptococcus Fecalis, Klebsiella and canine gallbladder bile. In 5 dogs no drug were given throughout the septic period while in 16 dogs either cimetidine, 6 or 12 mg/kg i.m. every 6 h, or 16,16-dimethyl PGE2, 0.2 or 0.4 microgram/kg i.m. every 6 h, was given 24 h before the induction of peritonitis and continued for 3 days. All 21 dogs had positive blood cultures on the 1st septic day. In the control animals, basal, food-, and pentagastrin-stimulated acid output significantly increased during the first 2 septic days, and gastroscopy demonstrated bleeding acute fundic erosions. Cimetidine decreased basal, food-, and pentagastrin-stimulated acid output in a dose-related manner, and only with the higher dose did it prevent gastric mucosal damage. 16,16-Dimethyl PGE2, 0.4 microgram/kg, significantly decreased acid output and prevented gastric mucosal damage. 16,16-Dimethyl PGE2 0.2 microgram/kg, although having no apparent effect on basal, food-, and pentagastrin-stimulated acid output, prevented the development of acute gastric erosions. Thus, in the canine septic model, acid output significantly increases during sepsis. Cimetidine prevents the development of sepsis-induced gastric erosions by inhibition of acid secretion and 16,16-dimethyl PGE2 by cytoprotection.
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PMID:Prevention of sepsis-induced gastric lesions in dogs by cimetidine via inhibition of gastric secretion and by prostaglandin via cytoprotection. 745 Apr 26

Tumor necrosis factor-alpha (TNF), an inflammatory cytokine released by macrophages, may be a mediator of lung injury during septicemia. We previously reported that the cyclooxygenase inhibitor ibuprofen and histamine receptor antagonists cimetidine (H2 antagonist) and diphenhydramine (H1 antagonist) attenuate lung injury and reduce circulating TNF surges during porcine sepsis. Since pulmonary alveolar macrophages (PAM) may participate in early sepsis by producing TNF, we hypothesized that the TNF activity of PAM is reduced by ibuprofen, cimetidine, and diphenhydramine. To test this, we examined changes in PAM-derived TNF bioactivity and cell viability of freshly isolated porcine PAM during exposure to bacterial endotoxin (LPS), ibuprofen, cimetidine, and diphenhydramine. The TNF activity (% L929 cytotoxicity of PAM conditioned medium) was elevated in LPS-stimulated PAM cultures (15 to 25% increase at 1 to 6 h and 40 to 43% increase at 6 to 48 h, compared with non-LPS-stimulated cultures), and ibuprofen (150 micrograms/ml) added with LPS decreased the TNF activity for 24 h (20 to 28% reduction at 1 to 24 h). Ibuprofen added 1 h after LPS was less effective in reducing the PAM-derived TNF activity (20 to 22% reduction at 2 to 6 h). Cimetidine (112 micrograms/ml) reduced the TNF activity of LPS-stimulated PAM cultures during the first 4 h of LPS exposure (15 to 24% decrease at 1 to 4 h). Diphenhydramine (150 micrograms/ml) attenuated the PAM-derived TNF activity but also decreased viability of PAM, indicating a toxic effect of this agent on PAM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacologic reduction in tumor necrosis factor activity of pulmonary alveolar macrophages. 809 99

Despite extensive world-wide research no effective therapy has been devised for the treatment and cure of patients exposed to sulfur mustard (S-M). A severe suppression of the immune system still remains the major cause of opportunist infections, septicemia and death in patients injured by S-M. In this report we present a model of S-M contamination in mice which is suitable for immunomodulation studies. Results show that differing doses of S-M caused an overall suppression of the immune response to SRBC as indicated by agglutination titers, (DTH) tests, spleen histology and spleen weight indices. In the second stage two immunomodulating agents; pyrimethamine and cimetidine were employed and their effectiveness in augmenting immune responses after S-M induced immunosuppression was evaluated. Pyrimethamine, at all doses employed, enhanced antibody titers to SRBC, augmented DTH responses, and restored splenic follicles as compared with controls only exposed to S-M. Cimetidine augmented antibody titers and enhanced DTH responses at doses of 10 and 15 mg/kg as compared with controls. At a dose of 5 mg/kg cimetidine did not exhibit any effect on titers or DTH responses. Histological studies revealed that cimetidine restored splenic follicles and increased macrophage numbers and phagocytic activity at all three doses. Spleen weight indices were not augmented by either drug. These data provide evidence that immunomodulating drugs may prove effective in countering the immunosuppressive effects of S-M.
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PMID:Effect of immunomodulators pyrimethamine and cimetidine on immunosuppression induced by sulfur mustard in mice. 836 27

Despite recent advances in burn wound management, sepsis remains the main cause of death in patients resuscitated after major thermal injury. Increased susceptibility to infections has been related to severe suppression of the immune system.The aim of this study was to induce immune suppression with blister fluid injection, and to modulate immune response by use of cimetidine and pyrimethamine in animal model.Male Balb/c mice were injected with blister fluid intrapritoneally (ip). Fluids were collected from parital-thickness burn blisters and then the delayed type hypersensitivity (DTH) to sheep red blood cell (SRBC) and the effects of different doses of immunomodulators (Cimetidine and Pyrimethamine) on this response were quantitated.A marked suppression of DTH was observed in mice injected with blister fluid. Pyrimethamine and Cimetidine at all three doses caused a significant enhancement of DTH response to SRBC compared with blister fluid injected in control group.This finding represents evidence of a host defense defect within the burn wound and also indicates the blister fluid exhibit immunosuppressor factor that can modulate with immunomadulatory drugs like cimetidine and pyrimethamine.
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PMID:Effect of immunomodulator pyrimethamine and cimetidine on immunosuppression induced by burn blister fluid. 1730 5


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