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Endotoxic Shock (endotoxic + shock)
Selected AbstractsEffect of Hemodiafiltration on Pulmonary Hemodynamics in Endotoxic ShockARTIFICIAL ORGANS, Issue 12 2003B. Lambermont Abstract:, Hemofiltration can improve pulmonary hemodynamics during septic shock. The main objective of the study was to determine whether hemodiafiltration (HDF) would also have beneficial effects on pulmonary hemodynamics during septic shock. In the Endo group, six anesthetized pigs received a 0.5 mg/kg endotoxin infusion over 30 min. In the HDF group (n = 6), HDF was started 30 min after the end of the endotoxin infusion, while in the Control group (n = 4) they received HDF but no endotoxin infusion. Pulmonary hemodynamics were analyzed in detail with a four-element windkessel model. Although in the Control group, HDF did not alter pulmonary hemodynamic parameters, in the HDF group, it was responsible for an amplification of the deleterious pulmonary vascular response to endotoxin insult. Our results show that HDF must be used cautiously in septic shock since it can precipitate right heart failure by increasing pulmonary vascular resistance. [source] Dexamethasone inhibits lipopolysaccharide-induced hydrogen sulphide biosynthesis in intact cells and in an animal model of endotoxic shockJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Ling Li Abstract Dexamethasone (1 mg/kg, i.p.) administered either 1 hr before or 1 hr after E. coli lipopolysaccharide (LPS, 4 mg/kg, i.p.) in conscious rats inhibited the subsequent (4 hrs) rise in plasma cytokine (interleukin [IL]-1,, tumour necrosis factor [TNF]-,), nitrate/nitrite (NO×), soluble intercellular adhesion molecule-1 (sICAM-1) concentration and lung/liver myeloperoxidase activity indicative of an anti-inflammatory effect. Dexamethasone also reduced the LPS-evoked rise in plasma hydrogen sulphide (H2S) concentration, liver H2S synthesizing activity and expression of cystathionine , lyase (CSE) and inducible nitric oxide synthase (iNOS). Mifepristone (RU-486) inhibited these effects. Dexamethasone (1,10 ,M) reduced the LPS-evoked release of IL-1,, TNF-, and L-selectin, decreased expression of CSE and iNOS and diminished nuclear factor ,B (NF-,B)-DNA binding in isolated rat neutrophils. In contrast, NaHS (100 ,M) increased L-selectin release from rat neutrophils. Dexamethasone also reduced LPS-induced up-regulation of CSE in foetal liver cells. 6-amino-4-(4-phenoxyphenylethylamino) quinazoline (QNZ, 10 nM), a selective inhibitor of transcription via the NF-,B pathway, abolished LPS-induced up-regulation of CSE expression. We propose that inhibition of CSE expression and reduction in formation of the pro-inflammatory component of H2S activity contributes to the anti-inflammatory effect of dexamethasone in endotoxic shock. Whether H2S plays a part in the anti-inflammatory effect of this steroid in other forms of inflammation such as arthritis or asthma warrants further study. [source] Regulation of lipopolysaccharide-induced inflammatory response and endotoxemia by ,-arrestins,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2010Katie J. Porter ,-Arrestins are scaffolding proteins implicated as negative regulators of TLR4 signaling in macrophages and fibroblasts. Unexpectedly, we found that ,-arrestin-1 (,-arr-1) and -2 knockout (KO) mice are protected from TLR4-mediated endotoxic shock and lethality. To identify the potential mechanisms involved, we examined the plasma levels of inflammatory cytokines/chemokines in the wild-type (WT) and ,-arr-1 and -2 KO mice after lipopolysaccharide (LPS, a TLR4 ligand) injection. Consistent with lethality, LPS-induced inflammatory cytokine levels in the plasma were markedly decreased in both ,-arr-1 and -2 KO, compared to WT mice. To further explore the cellular mechanisms, we obtained splenocytes (separated into CD11b+ and CD11b, populations) from WT, ,-arr-1, and -2 KO mice and examined the effect of LPS on cytokine production. Similar to the in vivo observations, LPS-induced inflammatory cytokines were significantly blocked in both splenocyte populations from the ,-arr-2 KO compared to the WT mice. This effect in the ,-arr-1 KO mice, however, was restricted to the CD11b, splenocytes. Our studies further indicate that regulation of cytokine production by ,-arrestins is likely independent of MAPK and I,B,-NF,B pathways. Our results, however, suggest that LPS-induced chromatin modification is dependent on ,-arrestin levels and may be the underlying mechanistic basis for regulation of cytokine levels by ,-arrestins in vivo. Taken together, these results indicate that ,-arr-1 and -2 mediate LPS-induced cytokine secretion in a cell-type specific manner and that both ,-arrestins have overlapping but non-redundant roles in regulating inflammatory cytokine production and endotoxic shock in mice. J. Cell. Physiol. 225: 406,416, 2010. © 2010 Wiley-Liss, Inc. [source] Melatonin prevents endotoxin-induced circulatory failure in ratsJOURNAL OF PINEAL RESEARCH, Issue 3 2001Chin-Chen Wu The pineal secretory product melatonin was found to exert protective effects in septic shock. In a host infected by bacterial lipopolysaccharide (LPS), the expression and release of proinflammatory tumor necrosis factor-, (TNF-,) is rapidly increased, suggesting that TNF-, is associated with the etiology of endotoxic shock. Recent reports show that the expression of NO synthase (NOS) II and the production of superoxide anion ( in aortae. In addition, the infiltration of polymorphonuclear neutrophils into the liver from the surviving LPS mice treated with melatonin was reduced. Thus, our results support the clinical use of melatonin in endotoxemia. [source] Mechanisms involved in the early increase of serotonin contraction evoked by endotoxin in rat middle cerebral arteriesBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2003Raquel Hernanz The present study investigated the mechanisms involved in the increased 5-hydroxytryptamine (5-HT) vasoconstriction observed in rat middle cerebral arteries exposed in vitro to lipopolysaccharide (LPS, 10 ,g ml,1) for 1,5 h. Functional, immunohistochemical and Western blot analysis and superoxide anion measurements by ethidium fluorescence were performed. LPS exposure increased 5-HT (10 ,M) vasoconstriction only during the first 4 h. In contrast to control tissue, indomethacin (10 ,M), the COX-2 inhibitor NS 398 (10 ,M), the TXA2/PGH2 receptor antagonist SQ 29,548 (1 ,M) and the TXA2 synthase inhibitor furegrelate (1 ,M) reduced 5-HT contraction of LPS-treated arteries from hour one. The iNOS inhibitor aminoguanidine (0.1 mM) increased 5-HT contraction from hour three of LPS incubation. The superoxide anion scavenger superoxide dismutase (SOD, 100 U ml,1) and the H2O2 scavenger catalase (1000 U ml,1), as well as the respective inhibitors of NAD(P)H oxidase and xanthine oxidase, apocynin (0.3 mM) and allopurinol (0.3 mM), reduced 5-HT contraction after LPS incubation. LPS induced an increase in superoxide anion levels that was abolished by PEG-SOD. Subthreshold concentrations of the TXA2 analogue U 46619, xanthine/xanthine oxidase and H2O2 potentiated, whereas those of sodium nitroprusside inhibited, the 5-HT contraction. COX-2 expression was increased at 1 and 5 h of LPS incubation, while that of iNOS, Cu/Zn-SOD and Mn-SOD was only increased after 5 h. All the three vascular layers expressed COX-2 and Cu/Zn-SOD. iNOS expression was detected in the endothelium and adventitia after LPS. In conclusion, increased production of TXA2 from COX-2, superoxide anion and H2O2 enhanced vasoconstriction to 5-HT during the first few hours of LPS exposure; iNOS and SOD expression counteracted that increase at 5 h. These changes can contribute to the disturbance of cerebral blood flow in endotoxic shock. British Journal of Pharmacology (2003) 140, 671,680. doi:10.1038/sj.bjp.0705501 [source] New approach in flow-cytometric determination of endotoxin during endotoxic shockBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2000K.-H. Staubach Background Serum endotoxin was formerly measured with the non-specific Limulus lysate assay. The present approach was to quantitate the amount of endotoxin bound by peripheral mononuclear cells in order to develop a method for the diagnosis of early septic shock. Methods Using a murine monoclonal antibody (WN1-222/5), which binds highly specifically to lipopolysaccharide (LPS), a new method for measuring the amount of LPS bound to peripheral mononuclear cells was developed. Ten pigs were studied under sedation and peripheral mononuclear cells were taken every 4 h to determine the concentration of endotoxin by flow cytometry. The results are shown in the Table. Results Time after LPS infusion (h) 0 1 4 6 8 Marked cells (%) 32 61 75 72 85 The percentage of marked mononuclear cells increased during shock. Only in the last hours before death did the rate of increase decline. Conclusion Preliminary data on marked mononuclear cells showed that the amount of natural incorporated endotoxin, i.e. the quantity of bound endotoxin before infusion, was 32 per cent. © 2000 British Journal of Surgery Society Ltd [source] Pharmacological Profile and Therapeutic Potential of BM-573, a Combined Thromboxane Receptor Antagonist and Synthase InhibitorCARDIOVASCULAR THERAPEUTICS, Issue 1 2005Alexandre Ghuysen ABSTRACT BM-573 (N-terbutyl-N,-[2-(4,-methylphenylamino)-5-nitro-benzenesulfonyl]urea), a torsemide derivative, is a novel non-carboxylic dual TXA2 synthase inhibitor and receptor antagonist. The pharmacological profile of the drug is characterized by a higher affinity for the thromboxane receptor than that of SQ-29548, one of the most powerful antagonists described to date, by a complete prevention of human platelet aggregation induced by arachidonic acid at a lower dose than either torsemide or sulotroban, and by a significantly prolonged closure time measured by the platelet function analyser (PFA-100®). Moreover, at the concentrations of 1 and 10 ,M, BM-573 completely prevented production of TXB2 by human platelets activated by 0.6 mM of arachidonic acid. BM-573 prevents rat fundus contraction induced by U-46619 but not by prostacyclin or other prostaglandins. Despite possessing a chemical structure very similar to that of a diuretic torsemide, BM-573 has no diuretic activity. BM-573 does not prolong bleeding time and, unlike some of the other sulfonylureas, has no effect on blood glucose levels. In vivo, BM-573 appears to have antiplatelet and antithrombotic activities since it reduced thrombus weight and prolonged the time to abdominal aorta occlusion induced by ferric chloride. BM-573 also relaxed rat aorta and guinea pig trachea precontracted with U-46619. In pigs, BM-573 completely antagonized pulmonary hypertensive effects of U-46619 and reduced the early phase of pulmonary hypertension in models of endotoxic shock and pulmonary embolism. Finally, BM-573 protected pigs from myocardial infarction induced by coronary thrombosis. These results suggest that BM-573 should be viewed as a promising therapeutic agent in the treatment of pulmonary hypertension and syndromes associated with platelet activation. [source] Cardiovascular Properties of Yangambin, a Lignan Isolated from Brazilian PlantsCARDIOVASCULAR THERAPEUTICS, Issue 4 2001Eduardo Tibiriçá ABSTRACT Yangambin was initially selected from a number of lignans isolated from Brazilian plants for its ability to antagonize Platelet-Activating Factor (PAF, 1- O -hexadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine)-induced biological effects. Subsequently it was shown that, besides its antagonistic properties at PAF receptors, yangambin also prevents the cardiovascular collapse observed during anaphylactic and endotoxic/septic shocks, as well as the vascular and cardiac hyporesponsiveness to catecholamines in endotoxic shock. It is suggested that this naturally occurring compound could be of potential interest in the adjunctive management of the above mentioned pathologies. In the present article, we review the main studies investigating the pharmacological properties of yangambin related to the cardiovascular function. 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