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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This is an overview of cytokine-induced cholestasis, justified by the insufficient knowledge of this frequent type of cholestasis. In the presence of an infectious agent a systemic and intrahepatic production of proinflammatory cytokines results (TNF-alpha, IL-1beta, IL-6 etc.), stimulated by microbial lipopolysaccharides. In patients having systemic infections, the liver has several major functions: source of the inflammatory cytokines produced as a response to infection and a target of these inflammation mediators. The inflammatory cytokines interfere with the activity of both the sinusoidal and canalicular transporting systems. One of the potential consequences of this process is the appearance of cholestasis. An infection can lead to cholestasis despite the absence of direct invasion of the liver by the infectious agent. Particularly the cholestasis produced when the infection generating agent is not located in the liver (sepsis or extrahepatic infections) has been emphasized. The clinical aspect of the diseases associated with this type of cholestasis and the effects of anti-infectious therapy on cholestasis are presented. Cytokine-induced cholestasis represents a common pathogenic path for several diseases: hepatitides that present with an intrahepatic cholestatic pattern (viral, ethanol-induced, NSAID-induced), but also many other infections, which are sometimes overlooked because of the lack of clinical signs. When a preexistent liver disease is present, the cholestasis incidence is higher. In this latter condition, ignorance of this possible mechanism of cholestasis will lead to misdiagnosis and unnecessary tests, sometimes expensive and useless.
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PMID:Correlation between cholestasis and infection. 1505 22

Alcohol abuse increases the incidence of acute respiratory distress syndrome more than threefold in patients with septic shock. We have shown that chronic ethanol ingestion in a rat model impairs alveolar epithelial barrier function and enhances lung injury during sepsis. We speculated that transforming growth factor beta(1) (TGFbeta(1)), a pluripotent cytokine implicated in models of epithelial barrier disruption and lung injury, could mediate alveolar epithelial injury in the alcoholic lung. We report that chronic ethanol ingestion (6 weeks) in rats increased both TGFbeta(1) mRNA and protein tissue expression (p < 0.05), but alone did not induce the release of TGFbeta(1) into the alveolar space. However, during endotoxemia, ethanol-fed rats released fivefold more TGFbeta(1) protein (by ELISA, p < 0.05) into the alveolar space than control-fed rats. Furthermore, lung lavage fluid from endotoxemic, ethanol-fed rats had more biologically active TGFbeta(1) protein than control-fed rats (p < 0.05), as reflected by anti-TGFbeta(1) antibody-inhibitable induction of permeability in rat alveolar epithelial monolayers in vitro. We conclude that chronic ethanol ingestion increases lung expression of TGFbeta(1,) which, during endotoxemia, is released and activated in the alveolar space in which it can disrupt the normally tight epithelial barrier. We speculate that this mechanism could contribute to the increased risk of acute respiratory distress syndrome in alcoholic patients.
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PMID:Transforming growth factor beta1 expression and activation is increased in the alcoholic rat lung. 1510 63

Catheter-related sepsis (CRS) is a common complication of long-term parenteral nutrition. Conventional antibiotic therapy is often effective in the short-term but, because of poor activity against intraluminal microbial biofilms, may not prevent relapse. Ethanol is an effective antiseptic. We describe a case of a patient with recurrent CRS successfully treated with 70% ethanol locks.
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PMID:Use of ethanol locks to prevent recurrent central line sepsis. 1629 Dec 89

Because chronic alcohol abuse alters immune defenses and increases infection in adults, we tested the hypothesis that maternal alcohol use during pregnancy would increase the risk of sepsis in very low birth weight (VLBW) premature newborns. We performed a case-controlled analysis of VLBW newborns born at Grady Memorial Hospital (Atlanta, GA). Alcohol exposure, as the predictive variable, was assessed by maternal self-report. The outcome variables were early-onset and multiple late-onset sepsis. Univariate analysis with Fisher exact test and multivariate analysis with the use of binary logistic regression were performed. Early-onset sepsis was 15-fold higher in the alcohol-exposed group (n=20) compared with findings for the matched control group (n=168) [alcohol-exposed group, 10%, vs. control group, 0.6%: odds ratio (OR) 6.8 (95% confidence interval [CI], 2.7-17.1), P < or = .05]. Early-onset sepsis in the alcohol+cocaine-exposed group (n=64) did not differ from findings for the control group. The prevalence of multiple late-onset sepsis did not differ among the exposure groups. Logistic regression analysis, controlling for chorioamnionitis and premature prolonged rupture of membranes, demonstrated an independent, increased risk of early-onset sepsis with alcohol exposure [OR 16 (95% CI, 1.2-210), P < or = .05]. We conclude that alcohol exposure significantly increased the risk of early-onset sepsis in this group of VLBW newborns. The effects of maternal alcohol abuse during pregnancy on the risk of infection in the VLBW newborn require further analysis.
Alcohol 2004 Jun
PMID:Is maternal alcohol use a risk factor for early-onset sepsis in premature newborns? 1552 11

Recent in vitro and ex vivo studies disclosed an enhancement of the activity of antimicrobials on multidrug-resistant Pseudomonas aeruginosa by n-6 polyunsaturated fatty acids (PUFAS); therefore their effect was evaluated in experimental sepsis in 60 rabbits. Solutions of gamma-linolenic acid (GLA) and arachidonic acid (AA) were administered intravenously with ceftazidime and amikacin in rabbits with sepsis caused by one multidrug-resistant isolate. Therapy was started after bacterial challenge in five groups comprising 12 animals in each group: A, normal saline; B, antimicrobials; C, 99% ethanol and antimicrobials; D, GLA and antimicrobials; and E, AA and antimicrobials. Blood was sampled for the estimation of levels of endotoxins in serum (lipopolysaccharide), leukocytes, tumor necrosis factor alpha (TNF-alpha) and antimicrobials. Animals were sacrificed 210 min after bacterial challenge for tissue cultures. All animals had considerable endotoxemia and evolved leukopenia. The number of viable cells in blood, lung, and mesenteric lymph nodes was significantly reduced in groups D and E compared to that in other groups. Levels of antimicrobials in serum were inadequate to achieve bacterial killing due to the level of resistance. n-6 PUFAs did not influence TNF-alpha. It is concluded that intravenous coadministration of n-6 PUFAs and antimicrobials enhanced antimicrobial bacterial killing in experimental sepsis caused by multidrug-resistant P. aeruginosa.
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PMID:n-6 polyunsaturated fatty acids enhance the activities of ceftazidime and amikacin in experimental sepsis caused by multidrug-resistant Pseudomonas aeruginosa. 1556 48

Although pulmonary function is not altered, a history of alcohol abuse is an independent outcome variable in the development of acute respiratory distress syndrome. In the absence of cirrhosis, alcohol abuse decreased glutathione, the key antioxidant lining the alveolar space, by 80% and is associated with alveolar barrier leak. Neither the glutathione pool nor barrier leak was corrected by abstinence for 1 week. This aberrant glutathione homeostasis may contribute to enhanced alveolar permeability, thereby increasing susceptibility to the development of acute respiratory distress syndrome. In a rat model, chronic ingestion of ethanol decreased pulmonary glutathione concentration, increased alveolar barrier permeability, and increased the risk of acute lung injury. In alveolar type II cells, chronic ingestion of ethanol altered cellular functions such as decreased surfactant processing, decreased barrier integrity, and increased sensitivity to cytotoxin-induced apoptosis in vitro and in vivo. In alveolar macrophages, chronic ingestion of ethanol decreased phagocytosis of microorganisms and decreased cell viability, events that would increase the risk of pneumonia. A central role for glutathione availability was demonstrated by the normalization of cellular function and viability of type II cells and macrophages as well as decreased sensitivity to endotoxemia-induced acute lung injury when glutathione precursors were added to the ethanol diet. These results support the suggestion that chronic ingestion of ethanol increased the risk of acute lung injury not through ethanol per se but through the chronic oxidative stress that resulted from ethanol-induced glutathione depletion. Because chronic oxidative stress alters cellular functions and viability, the lung becomes more susceptible when a second hit such as sepsis occurs.
Alcohol 2004 Jul
PMID:Chronic ethanol ingestion and the risk of acute lung injury: a role for glutathione availability? 1559 87

Ethanol renders the lung susceptible to acute lung injury in the setting of insults such as sepsis. The mechanisms mediating this effect are unknown, but activation of tissue remodeling is considered key to this process. We found that chronic ethanol ingestion in rats increased the expression of fibronectin, a matrix glycoprotein implicated in acute lung injury. In cultured NIH/3T3 cells and in primary rat and mouse lung fibroblasts, ethanol induced fibronectin mRNA and protein expression in a dose- and time-dependent fashion. The effect of ethanol was prevented by inhibitors of protein kinase C and mitogen-activated protein kinases and was associated with the phosphorylation and increased DNA binding of the transcription factor cAMP response element binding protein, followed by increased transcription of the fibronectin gene. Fibroblasts were found to express alpha(7) nicotinic acetylcholine receptor (nAChR), and ethanol induction of fibronectin was abolished by alpha-bungarotoxin and methyllcaconitine, inhibitors of alpha(7) nAChRs. However, ethanol was able to induce fibronectin mRNA and protein in primary lung fibroblasts isolated from alpha(7) nAChR knockout mice. The ethanol-induced fibronectin response was dependent on ethanol metabolism since 4-methylpyrazole, an inhibitor of alcohol dehydrogenase, abolished the effect and acetaldehyde induced it. These observations suggest that ethanol or ethanol metabolites stimulate lung fibroblasts to produce fibronectin by inducing specific signals transmitted via nAChRs independent of the alpha(7-)subunit, and this might represent a mechanism by which ethanol renders the lung susceptible to acute lung injury.
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PMID:Ethanol stimulates the expression of fibronectin in lung fibroblasts via kinase-dependent signals that activate CREB. 1565 13

We examined the frequency, reasons and outcome after conversion from Tacrolimus to Cyclosporine A. From August 1989 to December 1992, 1000 consecutive liver transplantation patients were studied, which included 834 adults (age>18 yr.) and 166 children with mean follow-up of 77 months (range 56 to 96). A prospectively populated electronic database was queried to identify patients that underwent conversion, the clinical indication and outcomes. Thirty-seven out of 834 adult recipients (4.43%), mean age of 48.4+/-12.9 years, 19 male (51.35%) and 18 females (48.64%) required conversion from Tacrolimus to Cyclosporine A baseline immunosuppressive therapy. No pediatric patient required conversion. The mean time interval from liver transplantation to Cyclosporine A conversion was 443.45+/-441.44 days (range 22 to 1641). The clinical indications for conversion included: 20 neurological (54%), 6 gastrointestinal (16%), 5 hematological (14%), and 6 other (16%) scenarios. Seven of the 37 patients (18.9%) died. The causes of death were multi-organ failure (2), sepsis (2), pancreatitis (1), hepatic failure due to relapse of ethanol abuse (1), and unknown cause (1). Nine out of 37 patients (24.32%) had to be reconverted to Tacrolimus (mean 282.22+/-499.79 days; range 15 to 1583 day with a median of 135) after institution of Cyclosporine A; none showed recurrence of the original symptoms. The reasons for these re-conversions were acute cellular rejection (44%, n=4), chronic rejection (11%, n=1), increased hepatic enzymes (33%, n=3) and progressively worsening neurological symptoms (11%, n=1). The frequency of conversion from Tacrolimus to Cyclosporine A was 4.43%. Conversion is safe and efficacious if done in a controlled setting. Additionally, re-conversion to Tacrolimus for lack of efficacy of Cyclosporine A did not appear to be associated with a recurrence of the condition that caused the initial switch.
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PMID:Conversion from tacrolimus to cyclosporine--a based immunosuppression following liver transplantation. 1585 7

Alcohol abuse markedly increases the risk of sepsis-mediated acute lung injury. In a rat model, ethanol ingestion alone (in the absence of any other stress) causes pulmonary glutathione depletion, increased expression of transforming growth factor-beta1 (TGF-beta1), and alveolar epithelial barrier dysfunction, even though the lung appears grossly normal. However, during endotoxemia, ethanol-fed rats release more activated TGF-beta1 into the alveolar space where it can exacerbate epithelial barrier dysfunction and lung edema. Ethanol ingestion activates the renin-angiotensin system, and angiotensin II is capable of inducing oxidative stress and TGF-beta1 expression. We determined that lisinopril, an angiotensin-converting enzyme inhibitor that decreases angiotensin II formation, limited lung glutathione depletion, and treatment with either lisinopril or losartan, a selective angiotensin II type 1 receptor blocker, normalized TGF-beta1 expression. The glutathione precursor procysteine also prevented TGF-beta1 expression, suggesting that TGF-beta1 may be induced indirectly by angiotensin II-mediated oxidative stress and glutathione depletion. Importantly, lisinopril treatment normalized barrier function in alveolar epithelial cell monolayers from ethanol-fed rats, and treatment with either lisinopril or losartan normalized alveolar epithelial barrier function in ethanol-fed rats in vivo, as reflected by lung liquid clearance of an intratracheal saline challenge, even during endotoxemia. In parallel, lisinopril treatment limited TGF-beta1 protein release into the alveolar space during endotoxemia. Together, these results suggest that angiotensin II mediates oxidative stress and the consequent TGF-beta1 expression and alveolar epithelial barrier dysfunction that characterize the alcoholic lung.
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PMID:Angiotensin II mediates glutathione depletion, transforming growth factor-beta1 expression, and epithelial barrier dysfunction in the alcoholic rat lung. 1590 76

Alcohol is the most commonly used and abused drug in the United States. The deleterious health effects of alcohol can be attributed both to its acute intoxicating effects, which result in temporary impairment of judgment and motor skills, and to its more chronic and toxic effects on the liver, pancreas, heart, and brain, all of which may result in irreversible organ damage. Although recognized for more than a century as a major risk factor for pneumonia, alcohol abuse was until recently perceived to have no significant effects on lung structure and/or function. However, within the past decade, epidemiologic studies have revealed that alcohol abuse independently increases the risk of acute respiratory distress syndrome (ARDS) two- to fourfold in patients with sepsis or trauma and may play a role in ARDS pathogenesis in as many as half of all patients with the syndrome. Although alcohol abuse alone does not cause acute lung injury, it renders the lung susceptible to dysfunction in response to the inflammatory stresses of sepsis, trauma, and other clinical conditions recognized to cause ARDS. Recent investigations in both animal models of chronic ethanol ingestion and in human subjects with a history of alcohol abuse have explored this previously unrecognized connection between alcohol and acute lung injury and have uncovered multiple derangements, which we now characterize as the "alcoholic lung." This review summarizes the epidemiologic association between alcohol abuse and acute lung injury and the recent experimental findings that are unraveling the underlying pathophysiology.
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PMID:Alcohol abuse and acute lung injury: epidemiology and pathophysiology of a recently recognized association. 1604 57


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