Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0341503 (bacterial peritonitis)
 1,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erythrocytes (RBC) in the peritoneal cavity significantly increase the lethality of bacterial peritonitis. The lethality is known to be associated with, and perhaps due to, increased bacterial counts in the peritoneal cavity. The mechanism is unknown. In this study, we investigated the hypothesis that RBC scavenge reactive oxygen intermediates (ROI) and nitric oxide (NO), so that the counterprotective effect is due to a loss of the microbiostatic activity of both ROI and NO. To study this effect, rats were subjected to a peritoneal inoculation of live Escherichia coli without RBC (nonlethal dose) or with RBC (lethal dose). The adjuvant effect of RBC was not modified by NG-monomethyl-L-arginine (NMA, an NO synthase inhibitor), superoxide dismutase, catalase, mannitol, or a combination of these agents. Furthermore, the increased number of bacteria in the peritoneal cavity in the presence of RBC was unaffected by these treatments. The administration of NMA with bacteria alone (no RBC) converted a nonlethal model into a lethal one associated with higher intraperitoneal bacterial counts. A similar effect was seen with superoxide dismutase and catalase but not with mannitol. During bacterial peritonitis in the absence of RBC, superoxide and NO formation (determined by the total nitrite plus nitrate formed) was detected in the ascites and inducible NO synthase mRNA expression was present in the peritoneal cells. In the absence of RBC, superoxide was detected and oxidation of dihydrorhodamine to rhodamine was observed, indicating that peroxynitrite was produced. Both were blocked by the inclusion of RBC. Preinjection with a low inoculum of killed bacteria protected the rats from a subsequent lethal peritoneal bacterial challenge; this effect was reversed by scavenging ROI and NO. The protective effect of killed bacterial pretreatment was lost when RBC were placed in the peritoneal cavity. In vitro bactericidal activity of NO- and ROI-generating macrophages was also inhibited by RBC or by inhibiting ROI and NO formation. Taken together, these data are consistent with the hypothesis that RBC can impair bacterial clearance by removing both NO and ROI, suggesting that NO in combination with superoxide may be important to the antimicrobial defenses of the peritoneal cavity.
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PMID:Counterprotective effect of erythrocytes in experimental bacterial peritonitis is due to scavenging of nitric oxide and reactive oxygen intermediates. 875 36

The present study assessed whether peritoneal macrophages isolated from cirrhotic patients produce nitric oxide (NO) and express NO synthase type II (NOS II) mRNA and protein. Patients with cirrhosis and ascites without peritonitis or with unresolved or resolved spontaneous bacterial peritonitis (SBP) were studied. Following paracentesis, ascites NO(2)(-) + NO(3)(-) content (NOx) was measured. Peritoneal macrophages from ascites were seeded on well plates, and NO(2)(-) in the medium was determined. NOx was higher in patients with unresolved or resolved SBP than in cirrhotic patients without peritonitis. Macrophages of patients with SBP or resolved SBP produced NO(2)(-) after 30 hours in culture, but those obtained from patients without peritonitis did not. Reverse-transcription polymerase chain reaction (RT-PCR) and immunocytochemical analysis revealed the presence of a clear signal for NOS II mRNA and protein in macrophages of SBP patients, regardless of whether or not the infection subsided. Therefore, peritoneal macrophages isolated from cirrhotic patients with unresolved or resolved SBP produce NO and express the NOS II mRNA and protein, suggesting that NOS II may contribute to the control of SBP, or to its associated pathology, in human cirrhosis.
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PMID:Nitric oxide production and inducible nitric oxide synthase expression in peritoneal macrophages of cirrhotic patients. 1046 73

We previously described a long-lasting overproduction of nitric oxide (NO) in cirrhotic patients with spontaneous bacterial peritonitis. The aim of the present study was to investigate the presence of the inducible NO pathway in peritoneal macrophages. Ascitic fluids were collected from 29 patients with cirrhosis, aged between 35 and 82 years. Peritoneal macrophages were isolated and cultured in the presence or absence of 1 microg/ml lipopolysaccharide and/or 500 units/ml interferon-gamma (IFN-gamma) for 6 days. NO production was measured as nitrate+nitrite (NO(x)), inducible NO synthase (iNOS) protein expression was analysed by immunocytochemistry and Western blot analysis using a specific anti-(human iNOS) antibody, and the catalytic activity of NOS was revealed by cytochemical staining for NADPH-dependent diaphorase. Cultured macrophages spontaneously released small amounts of NO(x) [median (10-90th percentile) of 18 separate experiments: 3.3 (0-8) micromol/l]. Addition of lipopolysaccharide alone or in combination with IFN-gamma to the culture medium did not change the levels of NO(x), while IFN-gamma alone dramatically increased NO production [13.4 (3.5-28.3) micromol/l; P<0.001]. Macrophages were stimulated by IFN-gamma to a greater extent in patients with recent spontaneous bacterial peritonitis (n=13) than in those in a stable clinical condition (n=18) [19.8 (10.5-30.1) and 10.0 (3.2-14.5) micromol/l respectively; P<0.001]. Macrophages freshly isolated or stimulated with IFN-gamma expressed iNOS protein, as shown by Western blot and immunocytochemical analysis, and stained for NADPH diaphorase. Our findings demonstrate the presence of iNOS protein in peritoneal macrophages from cirrhotic patients. The role of IFN-gamma appears to be a determinant for the up-regulation of NO production, particularly under conditions of infection. Therefore peritoneal macrophages producing large amounts of NO at the site of infection may contribute to maintaining splanchnic vasodilation in these patients.
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PMID:Up-regulation of nitric oxide production by interferon-gamma in cultured peritoneal macrophages from patients with cirrhosis. 1049 39

Pharmacologic studies suggest that the release of nitric oxide (NO) by endothelial NO synthase (eNOS) contributes to functional alterations of the peritoneal membrane (PM) induced by acute peritonitis. In this study, peritoneal permeability parameters in a mouse model of peritoneal dialysis were characterized, and the effects of eNOS deletion on the PM structure and permeability at baseline and after catheter-induced bacterial peritonitis were examined. Exposure of C57BL/6 mice to standard dialysate yielded a transport of urea and glucose, a sodium sieving, and a net ultrafiltration that were remarkably similar to the values obtained in rats. In comparison with controls, mice with catheter-induced peritonitis were characterized by structural changes in the PM (mononuclear cells infiltrate, vascular proliferation), upregulation of endothelial and inducible NOS, increased permeability for urea and glucose, decreased ultrafiltration, and increased protein loss in the dialysate. Comparison of eNOS wild-type and knockout mice revealed that the permeability modifications and structural changes induced by acute peritonitis were significantly reversed in eNOS knockout mice, resulting in a net increase in ultrafiltration. In contrast, the deletion of eNOS in mouse peritoneum was not reflected by permeability modifications or structural changes at baseline. These results are the first to take advantage of a knockout mouse model to demonstrate directly the crucial importance of eNOS in the permeability and structural modifications caused by acute peritonitis. The characterization of this mouse model suggests that genetically modified mice represent useful tools to investigate the molecular bases of the peritoneal changes during peritoneal dialysis.
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PMID:Mice that lack endothelial nitric oxide synthase are protected against functional and structural modifications induced by acute peritonitis. 1463 19

Sepsis is a systemic inflammatory response to the presence of infection, mediated via the production of many cytokines, including tumour necrosis factor (TNF-), interleukin (IL)-6, and IL-1, which cause changes in the circulation and in the coagulation cascade. There is stagnation of blood flow and poor oxygenation, subclinical coagulopathy with elevated D-dimers, and increased production of superoxide from nitric oxide synthase. All of these changes favour endothelial apoptosis and necrosis as well as increased oxidant stress. Reduced levels of activated protein C, which is normally anti-inflammatory and antiapoptotic, can lead to further tissue injury. Cirrhotic patients are particularly susceptible to bacterial infections because of increased bacterial translocation, possibly related to liver dysfunction and reduced reticuloendothelial function. Sepsis ensues when there is overactivation of pathways involved in the development of the sepsis syndrome, associated with complications such as renal failure, encephalopathy, gastrointestinal bleed, and shock with decreased survival. Thus the treating physician needs to be vigilant in diagnosing and treating bacterial infections in cirrhosis early, in order to prevent the development and downward spiral of the sepsis syndrome. Recent advances in management strategies of infections in cirrhosis have helped to improve the prognosis of these patients. These include the use of prophylactic antibiotics in patients with gastrointestinal bleed to prevent infection and the use of albumin in patients with spontaneous bacterial peritonitis to reduce the incidence of renal impairment. The use of antibiotics has to be judicious, as their indiscriminate use can lead to antibiotic resistance with potentially disastrous consequences.
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PMID:Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club. 1583 23

Hepatorenal syndrome (HRS) is a type of renal failure that occurs in patients with advanced cirrhosis. It is a result of splanchnic arterial vasodilation, renal vasoconstriction, reduced effective arterial volume, and potentially reduced cardiac output. Often, HRS is a fatal complication, and the only definitive treatment currently available is liver or liver-kidney transplantation. A number of other treatment modalities have been tested for the management of HRS, but most evidence is derived from small noncontrolled studies. The primary role of these treatment options is to provide a bridge to liver transplantation. Treatment may also provide acute reversal of renal failure and some symptomatic relief, but relapse is a common occurrence. The best therapeutic options appear to be those that reverse portal hypertension, splanchnic vasodilation, and/or renal vasoconstriction. Vasopressin analogs, particularly terlipressin, have emerged as the preferred pharmacologic therapies for management of HRS. Albumin is an appropriate adjunctive therapy to terlipressin and can be used to prevent HRS in patients with spontaneous bacterial peritonitis. Transjugular intrahepatic portosystemic shunt may provide a surgical option for qualified patients with HRS. Octreotide is ineffective as monotherapy but may be used as adjunctive therapy to other vasoactive agents. Dopamine agonists, endothelin antagonists, natriuretic peptides, and nitric oxide synthase inhibitors have not been effective for reversing HRS. Artificial hepatic support therapies have demonstrated the ability to improve laboratory abnormalities in patients with HRS, but their effect on clinical outcomes has not been determined. The role of renal replacement therapies or the newer artificial hepatic support therapies need further evaluation before they can be routinely recommended.
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PMID:Treatment of hepatorenal syndrome. 1979 93

Livercirrhosis can be complicated by a hyperdynamic circulatory syndrome. This is due to translocation of bacteria and bacterial product (bacterial DNA and endotoxins), which stimulate the splanchnic nitric oxide synthase and leads to splanchnic vasodilatation and haemodynamic derangement. This review focuses on how broad spectrum antibiotics can ameliorate the haemodynamic consequences of bacterial translocation. It is possible that the use of broad spectrum antibiotics in the future may be used to prevent other complications of liver cirrhosis than spontaneous bacterial peritonitis and infections after gastrointestinal bleeding.
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PMID:[Antibiotics can ameliorate circulatory complications of liver cirrhosis]. 2188 64

Connexin 43 (Cx43) deficiency was found to increase mortality in a mouse model of bacterial peritonitis, and Cx43 is upregulated in macrophages by LPS treatment. In this study, we characterized a novel signaling pathway for LPS-induced Cx43 expression in RAW264.7 cells and thioglycolate-elicited peritoneal macrophages (TGEMs). LPS alone or LPS-containing conditioned medium (CM) upregulated Cx43. Overexpression or silencing of Cx43 led to the enhancement or inhibition, respectively, of CM-induced TGEM migration. This response involved the inducible NO synthase (iNOS)/focal adhesion kinase (FAK)/Src pathways. Moreover, CM-induced migration was compromised in TGEMs from Cx43+/- mice compared with TGEMs from Cx43+/+ littermates. Cx43 was upregulated by a serum/glucocorticoid-regulated kinase 1 (SGK) activator and downregulated, along with inhibition of CM-induced TGEM migration, by knockdown of the SGK gene or blockade of the SGK pathway. LPS-induced SGK activation was abrogated by Torin2, whereas LPS-induced Cx43 was downregulated by both Torin2 and rapamycin. Analysis of the effects of FK506 and methylprednisolone, common immunosuppressive agents following organ transplantation, suggested a link between these immunosuppressive drugs and impaired macrophage migration via the Cx43/iNOS/Src/FAK pathway. In a model of Escherichia coli infectious peritonitis, GSK650349-, an SGK inhibitor, or Torin2-treated mice showed less accumulation of F4/80+CD11b+ macrophages in the peritoneal cavity, with a delay in the elimination of bacteria. Furthermore, following pretreatment with Gap19, a selective Cx43 hemichannel blocker, the survival of model mice was significantly reduced. Taken together, our study suggested that Cx43 in macrophages was associated with macrophage migration, an important immune process in host defense to infection.
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PMID:mTOR- and SGK-Mediated Connexin 43 Expression Participates in Lipopolysaccharide-Stimulated Macrophage Migration through the iNOS/Src/FAK Axis. 3034 Nov 86