Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with cirrhosis present an increased susceptibility to bacterial infections, which are the cause of hospital admission in about 10% of patients and are present in about 40% of those admitted for ongoing complications. Lastly, about a third of patients develop nosocomial infections. Spontaneous bacterial peritonitis (SBP) is the most frequent infection in advanced cirrhosis; it is mostly caused by Gram-negative bacteria of intestinal origin, but Gram-positive cocci can be involved in nosocomial-acquired SBP. Its occurrence is associated with complications, such as renal and circulatory failure, cardiac dysfunction, coagulopathy, encephalopathy, and relative adrenal insufficiency, ultimately leading to multi-organ failure and death within a few days or weeks in about 30% of cases. The main mechanism underlying the development of SBP, as well as other bacterial infections in cirrhosis, is represented by bacterial translocation from the intestinal lumen to mesenteric lymph nodes or other extraintestinal organs and sites. This process is facilitated by several factors, including changes in intestinal flora, portal hypertension, and, mainly, impairment in local/systemic immune defense mechanisms. Bacterial infections in advanced cirrhosis evoke an enhanced systemic inflammatory response, which explains the ominous fate of PBS. Indeed, an exaggerated production of cytokines ensues, which ultimately activates vasodilating systems and generates reactive oxygen species. Primary antibiotic prophylaxis of PBS is warranted in those conditions implying an increased incidence of bacterial infections, such as gastro-intestinal bleeding and low protein content in ascites associated with severe liver and/or renal dysfunction. Fluoroquinolones are commonly employed, but the frequent occurrence of resistant bacterial strains make third generation cephalosporins preferable in specific settings. The high PBS recurrence indicates secondary antibiotic prophylaxis.
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PMID:Spontaneous bacterial peritonitis: from pathophysiology to prevention. 2086 73

Advanced chronic liver disease (aCLD) represents a major public health concern. aCLD is more prevalent and severe in the elderly, carrying a higher risk of decompensation. We aimed at understanding how aging may impact on the pathophysiology of aCLD in aged rats and humans and secondly, at evaluating simvastatin as a therapeutic option in aged animals. aCLD was induced in young (1 month) and old (16 months) rats. A subgroup of aCLD-old animals received simvastatin (5 mg/kg) or vehicle (PBS) for 15 days. Hepatic and systemic hemodynamic, liver cells phenotype and hepatic fibrosis were evaluated. Additionally, the gene expression signature of cirrhosis was evaluated in a cohort of young and aged cirrhotic patients. Aged animals developed a more severe form of aCLD. Portal hypertension and liver fibrosis were exacerbated as a consequence of profound deregulations in the phenotype of the main hepatic cells: hepatocytes presented more extensive cell-death and poorer function, LSEC were further capillarized, HSC over-activated and macrophage infiltration was significantly increased. The gene expression signature of cirrhosis significantly differed comparing young and aged patients, indicating alterations in sinusoidal-protective pathways and confirming the pre-clinical observations. Simvastatin administration for 15-day to aged cirrhotic rats improved the hepatic sinusoidal milieu, leading to significant amelioration in portal hypertension. This study provides evidence that aCLD pathobiology is different in aged individuals. As the median age of patients with aCLD is increasing, we propose a real-life pre-clinical model to develop more reliable therapeutic strategies. Simvastatin effects in this model further demonstrate its translational potential.
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PMID:Aging Influences Hepatic Microvascular Biology and Liver Fibrosis in Advanced Chronic Liver Disease. 3144 Mar 76