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The spontaneously hypertensive rat (SHR) has an increased tubuloglomerular feedback (TGF) and a reduced buffering by juxtaglomerular apparatus (JGA)-derived NO. The hypothesis that these effects are caused by reductions in nitric oxide synthase (NOS) expression or limited availability of L-arginine or tetrahydrobiopterin (BH4). Findings showed that there is a decreased role for NO from neuronal NOS in blunting TGF in SHR which cannot be caused by limited NOS expression or availability of substrate or BH4.

Abstract: AHNAK is a giant protein of approximately 700kDa identified in human neuroblastomas and skin epithelial cells. Recently, we found that AHNAK knock-out (AHNAK−/−) mice have a strong resistance to high-fat diet-induced obesity. In this study, we applied 1H NMR-based metabolomics with multivariate statistical analysis to compare the altered metabolic patterns detected in urine from high-fat diet (HFD) fed wild-type and AHNAK−/− mice and investigate the mechanisms underlying the resistance to high-fat diet-induced obesity in AHNAK−/− mice. In global profiling, principal components analysis showed a clear separation between the chow diet and HFD groups; wild-type and AHNAK−/− mice were more distinctly separated in the HFD group compared to the chow diet group. Based on target profiling, the urinary metabolites of HFD-fed AHNAK−/− mice gave higher levels of methionine, putrescine, tartrate, urocanate, sucrose, glucose, threonine, and 3-hydroxyisovalerate. Furthermore, two-way ANOVAs indicated that diet type, genetic type, and their interaction (gene×diet) affect the metabolite changes differently. Most metabolites were affected by diet type, and putrescine, threonine, urocanate, and tartrate were also affected by genetic type. In addition, cis-aconitate, succinate, glycine, histidine, methylamine (MA), phenylacetylglycine (PAG), methionine, putrescine, uroconate, and tartrate showed interaction effects. Through the pattern changes in urinary metabolites of HFD-fed AHNAK−/− mice, our data suggest that the strong resistance to HFD-induced obesity in AHNAK−/− mice comes from perturbations of amino acids, such as methionine, putrescine, threonine, and histidine, which are related to fat metabolism. The changes in metabolites affected by microflora such as PAG and MA were also observed. In addition, resistance to obesity in HFD-fed AHNAK−/− mice was not related to an activated tricarboxylic acid cycle. These findings demonstrate that 1H NMR-based metabolic profiling of urine is suitable for elucidating possible biological pathways perturbed by functional loss of AHNAK on HFD feeding and could elucidate the mechanism underlying the resistance to high-fat diet-induced obesity in AHNAK−/− mice. [Copyright &y& Elsevier]

Selective intestinal decontamination (SID) with norfloxacin has been widely used for the prophylaxis of spontaneous bacterial peritonitis (SBP) because of a high recurrence rate and preventive effect of SID for SBP. However, it does select resistant gut flora and may lead to SBP caused by unusual pathogens such as quinolone-resistant gram-negative bacilli or gram-positive cocci. Enterococcus hirae is known to cause infections mainly in animals, but is rarely encountered in humans. We report the first case of SBP by E. hirae in a cirrhotic patient who have previously received an oral administration of norfloxacin against SBP caused by Klebsiella pneumoniae and presented in septic shock.

A study was designed to elucidate the mechanism of anti-hypertensive effects of danshen in the two-kidney, one clip (2K1C) Goldblatt renovascular hypertensive model, which is the renin-angiotensin system (RAS)-dependent hypertensive model. We investigated the effects of water extracts of danshen on the angiotensin converting enzyme (ACE) activities, systolic blood pressure (SBP), and hormone levels in the plasma of 2K1C rats. ACE activity was inhibited by the addition of danshen extract in a dose-dependent manner. SBP was decreased significantly after administration of danshen extract in 2K1C, whereas plasma renin activity (PRA) was not changed. The plasma concentration of aldosterone (PAC) was decreased significantly in 2K1C group administered with Danshen extract, whereas the plasma concentration of ANP was increased by administration of danshen extract for three weeks. These results suggest that danshen has an anti-hypertensive effect through the inhibition of ACE, an essential regulatory enzyme of RAS.