Adequacy of phosphodiesterase inhibitor in prevention and treatment of LPS induced organ failure in BALB/c mice

Background: Even though with immense improvement and extensive understanding of pathophysiology of sepsis induced organ failure and affected population, it continues to put hundreds of people worldwide to eternal sleep due to lack of targeted therapy. Newer treatment modalities is the dire need of time. The present study was aimed to ascertain the adequacy of phosphodiesterases inhibitor - pentoxifylline (75mg/kg i.p) in endotoxin/LPS induced hepatotoxicity in BALB/c mice.Methods: The number of animals in each group was six. Endotoxin/lipopolysaccharides induced hepatotoxicity was reproduced in mice by giving lipopolysaccharide of serotype E. coli intraperitoneally. To ascertain the Preventive role, pentoxifylline was administered forehand LPS injection whereas therapeutic potential adjuged via post LPS delivering. The extent of liver damage was evaluated through serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with histopathological examination of liver tissue.Results: Results set forth that serum ALT, AST levels and histological alteration abated considerably (p ?0.05) both in animals subjected to pentoxifylline pre and post-treatment.Conclusions: Pentoxifylline set up promising results in endotoxin induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis induced liver failure.

Risk factors for acquiring Strongyloides stercoralis infection among patients attending a tertiary hospital in south India.

Purpose: Strongyloides stercoralis causes persistent and fatal disseminated infections in immunocompromised hosts. In this study, we aimed to determine the risk factors for acquiring strongyloidiasis and the associated morbidity in south India. Materials and Methods: The study was carried out in two parts. This included a 6-month chart review of cases with strongyloidiasis and randomly selected controls conducted to determine the association with immunocompromised states. Secondly, a cross-sectional study was conducted to investigate hyperinfection in human immunodeficiency virus (HIV)-infected adults where the stool and sputum samples were examined by microscopy for Strongyloides larvae. Results: In the chart review, 118 cases were compared with 240 controls. A higher proportion of patients on corticosteroids [8 (53.3%)] and with HIV infection [3 (60%)] had the risk of acquiring strongyloidiasis than not, although the difference was not statistically significant in this population. In the cross-sectional study, 14/239 HIV-positive individuals had Strongyloides larvae in the stool samples but none had Strongyloides detectable in their sputum samples. The CD4 cell counts were significantly lower in cases with Strongyloides compared with HIV-infected individuals with no parasites in their stool samples (P < 0.001). Conclusions: In this setting, strongyloidiasis was seen more often in patients on corticosteroid therapy and with HIV infection. In HIV, an association with lower CD4 counts indicates the need for inclusion of Strongyloides as an opportunistic parasite. Gram negative sepsis was an important complication of strongyloidiasis hyperinfection in both HIV and steroid therapy. Further prospective studies on the risk of developing complicated Strongyloides infection are required.

Restriction of Cephalosporins and Control of Extended Spectrum β-Lactamase Producing Gram Negative Bacteria in a Neonatal Intensive Care Unit.

This interventional study with historical controls was conducted to study the effect of cephalosporin restriction on the incidence of extended spectrum betalactamase (ESBL) gram negative infections in neonates admitted to intensive care unit. All gram negative isolates from the blood were evaluated for beta lactamase production. The incidence of ESBL production was compared before (year 2007) and after cephalosporin restriction (year 2008). Thirty two neonates (3% of NICU admissions) in the year 2007 and fifty six (5.2%) in the year 2008, had gram negative septicemia. The incidence of ESBL gram negatives decreased by 22% (47% to 25%, P=0.03). Restriction of all class of cephalosporins significantly decreased the incidence of ESBL gram negative infections.

BRIEF HYPOXIA PRECEDING E. COLI BACTEREMIA DOWNREGULATES HEPATIC TNF-α PRODUCTION / 药物分析学报

Hepatic TNF-α production following gram-negative bacteremia or hypovolemic shock predisposes to acute lung injury. However, TNF-α expression may be modified by the manner in which the hepatic O2 supply is reduced and equally important, its timing relative to bacteremia. Brief secondary hypoxic stress of buffer-perfused rat livers downregulates E. Coli (EC)-induced TNF-α expression whereas low-flow ischemia preceding EC increases subsequent TNF-α production owing to reactive O2 species (ROS). Here we determined whether 30 min of constant-flow hypoxia preceding 109 intraportal EC likewise increases antigenic and bioactive TNF-α protein concentrations during reoxygenation via production of ROS. Multiple groups (n＝38) were studied over 180 minutes, circulation antigenic TNF-α decreased in H/R+EC vs. EC controls (1 939±640 vs. 12 407±2 476 μg/L at t＝180 min; P＜0.01, along with TNF-α bioactivity). TNF-α protein were not restored to control levels in ALLO+H/R+EC. Thus, EC-induced hepatic TNF-α production and export is strongly O2-dependent in intact liver regardless of the generation of ROS or the sequence of bacteremia and modest hypoxic stress.