ResultsNo rats died because of technical errors or during the experimental time period, Ivacaftor cystic fibrosis therefore all animals were included in the analysis.Rats subjected to CLP exhibited classic signs of sepsis, including piloerection, tachypnea, diarrhea, periorbital exudates and lethargy from the first hours after CLP. Baseline TNF-�� levels were similar in sham-operated and CLP-treated rats. TNF-�� plasma levels were significantly increased at 3 hours after CLP compared to sham-operated animals (17.5 �� 6.2 ng/mL versus 9 �� 2.5; P <0.05 CLP versus sham-operated, at least n = 5 rats each group) and remained significantly higher at 7 hours after CLP (20.7 �� 5.6 versus 8.7 �� 2.1; P <0.05 versus sham-operated, at least n = 5 rats each group).

Peritoneal inflammation and purulent ascites were observed when the abdomen was reopened for kidney specimen collection at 3 and 7 hours after CLP. Cultured peritoneal fluid revealed polymicrobial flora (>104 Colony Forming Units/mL). The most frequently isolated microorganisms were Escherichia coli (72%), Enterococcus faecalis (43%), Streptococcus viridans (15%), and coagulase-negative staphylococci (72%).Functional damageCreatinine serum levels were not different in septic animals at 3 and 7 hours after surgery as compared to sham-operated ones (0.22 �� 0.01 mg/dL in sham-operated animal versus 0.22 �� 0.03 mg/dL at 3 hours and 0.26 �� 0.04 mg/dL at 7 hours in septic rats). Similarly, creatinine clearance remained stable at 3 and 7 hours after CLP (sham-operated 0.89 �� 0.03 mL/min/100 g; CLP 0.81 �� 0.42 and 0.82 �� 0.

08 mL/min/100 g at 3 and 7 hours, respectively; ns versus sham-operated). On the contrary, whereas albumin/urinary creatinine ratio remained unchanged during the study period in sham-operated animals, it increased in CLP animals by 152% and 288% at 3 h and 7 hours, respectively (for details see Figure Figure1).1). Data obtained by SDS electrophoresis clearly indicated that proteins present in the urine were limited to albumin (derived from alteration in GFB permeability) and proteins of lower molecular weight (likely ‘tubular proteins’, which are normally filtered by the GFB but usually reabsorbed by tubular cells).Figure 1GFB permeability to albumin was increased after sepsis. Sepsis induced a dramatic increase in the amount of albumin measured in urine when compared to sham-injury (* P <0.

05 CLP versus sham-operated at 3 and 7 hours, n = at least 5 rats each group). …Morphological assessment of damageMicroscopy and confocal analysisWe next assessed whether albuminuria observed in the septic rats was associated with structural and ultrastructural alterations of renal corpuscles Carfilzomib and of the GFB.Major changes were encountered only in a few renal corpuscles (approximately 6% to 12% of the total at 3 and 7 hours of sepsis, respectively, P <0.05 CLP versus sham-operated).