Biliary tract external drainage improves inflammatory mediators and pathomorphology of the intestine, liver, and lung in septic rats.

BACKGROUND: To investigate the effect of biliary tract external drainage (BTED) on inflammatory mediators and pathomorphism of intestine, liver, and lung in septic rats. METHOD: 48 SD rats (n = 8 per group) were randomized into six groups: control, sepsis, sepsis plus BTED, normal bile (obtained from eight healthy rats), and septic bile infusion for 6 hours respectively to test the effects of BTED bile infusion on cytokines' expression and tissue injury in the intestine, liver, and lung of septic/normal rats. Co-cultivation of intestinal epithelial cells (IEC-6) with bile for 12 hours was performed to evaluate the potential cytotoxicity of septic bile. Survival rate for sepsis plus BTED rats was detected compared with sepsis without BTED group (n = 20 per group) at 24, 48, and 72 hours, respectively. RESULTS: BTED for 6 hours significantly reduced the mRNA expression levels of tumor necrosis factor alpha (TNF-α) and IL-1ß (all p < 0.05 vs. sepsis group), whereas mRNA expression of TNF-α and IL-1ß in the intestine was increased after 6 hours' septic bile infusion compared with normal bile infusion group (all p < 0.05). TNF-α concentration in septic bile was significantly higher than that in the control group (p < 0.001). Tissue injury was significantly attenuated after 6 hours' BTED. CONCLUSIONS: BTED can significantly restrain the mRNA expression of TNF-α and IL-1ß in the intestine, liver, and lung and attenuate histological damage in septic rats.

The pivotal role of HIF-1α in lung inflammatory injury induced by septic mesenteric lymph.

Hypoxia inducible factor-1α (HIF-1α) plays an essential role in hypoxia and inflammatory response. Oxygen metabolic dysfunction and cascade amplification of inflammatory response are prominent pathophysiological characteristics in sepsis induced acute lung injury (ALI). In this study, we started with septic mesenteric lymph injection model to investigate whether HIF-1α played a role in the pathogenesis of ALI induced by septic lymph. The data demonstrated that rats injected with septic lymph showed a significant higher Lung Injury Scale and MPO(myeloperoxidase) levels than that of rats injected with normal saline/lymph. ALI was associated with a higher degree of HIF-1α expression in the lungs infused by septic lymph. Intratracheal delivery of YC-1(3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole) significantly attenuated lung inflammatory damages. Furthermore, in vitro studies, human alveolar type II epithelial cell (A549)/human pulmonary microvascular endothelial cell (HPMEC) incubated by septic lymph showed dramatically decreased cell viability, higher levels of inflammatory cytokines (TNF-α, IL-6 and IL-1ß) and excitation of HIF-1α expression (Immunofluorescence localization/RT-PCR test) simultaneously. Nevertheless, compared with the non-silencing cell lines, A549/HPMEC with HIF-1α gene silencing manifested increased viability and restrained cytokines' expression after incubation with septic lymph. These results indicate that HIF-1α expression can be induced and activated in rats during the acute lung inflammatory damages triggered by septic lymph injection and that lung inflammatory injuries occur via a HIF-1α-dependent pathway.

Klotho: a novel and early biomarker of acute kidney injury after cardiac valve replacement surgery in adults.

Klotho is a potential biomarker and therapeutic target in a model of acute kidney injury (AKI) induced in rats by ischemia-reperfusion injury. However, the sensitivity and specificity of serum Klotho for early detecting clinical AKI are unknown. This prospective study evaluated the significance of serum Klotho for early detection of postoperative AKI among adult patients undergoing cardiac valve replacement surgery. Moreover, we also compared the utilities of serum Klotho, serum creatinine and cystatin C in early detection of AKI. There was no marked difference between AKI and non-AKI groups in preoperative serum Klotho levels. Immediately after the operation, serum Klotho decreased significantly in patients with AKl. In spite of the poor specificity, its diagnostic sensitivity was excellent. On postoperative 1 d, with the rapid recovery toward the preoperative level, the ability of serum Klotho for early detecting AKI declined. Changes in serum Klotho levels at every time point among patients without AKI did not reveal any statistical significance. We showed that AKI is a state of transient Klotho deficiency in patients undergoing cardiac valve replacement surgery. Serum Klotho levels were drastically decreased beginning at 0h with ideal ROC-AUC, sensitivity but poor specificity, which didn't exceed 4 h after operation, suggesting that serum Klotho could serve as a potential biomarker for CSA-AKI, especially during the short period after cardiac surgery. A larger multicentre cohort study of population in different ages undergoing on-pump cardiac surgery is required to identify the optimal timing of serum Klotho measurement and the optimal cut-off points for clinical use to further refine the optimal timing for early detection of AKI.

Total coenzyme Q10 concentrations in Asian men following multiple oral 50-mg doses administered as coenzyme Q10 sustained release tablets or regular tablets.

Coenzyme Q(10) (CoQ(10)), a highly lipophilic compound present in the inner mitochondrial membrane, is essential for production of cellular energy in the form of ATP. CoQ(10) is used as a dietary supplement and for treatment of various cardiovascular disorders. Our goal was to compare the CoQ(10) levels in Asians following multiple oral doses administered as sustained release or regular tablets. Twenty healthy male volunteers (19-23 years old) were divided into two equal groups. Each subject in Group I received 50 mg oral doses of coenzyme Q(10) as sustained release tablets once a day for fifteen days, while subject in Group II received 50 mg doses of coenzyme Q(10) regular tablets. The CoQ(10) levels were measured by HPLC-UV (reverse phase ODS column, 10 microm, 250 x 4.6 mm; oven temperature 30 degrees C). Mobile phase was constituted by methanol-ethanol 9 : 1 v/v. Flow rate was 1.5 ml/min and UV detection was carried out at 275 nm. Coenzyme Q(9) was used as an internal standard. CoQ(10) baseline in the morning was 0.88+/-0.48 mg/l. Following 1 week 50 mg/d dosing of CoQ(10), plasma CoQ(10) concentrations increased to 1.85+/-1.03 mg/l for sustained release tablets and up to 1.37+/-0.74mg/l for regular tablets. The net increment proportion in AUC for sustained release and regular tablets were 148.26+/-176.56%, 102.57+/-130.00%, respectively. Both preparations significantly increased the systemic exposure when compared to endogenous baseline.