[Effect of augmented renal clearance on plasma concentration of vancomycin and treatment outcome in children with methicillin-resistant Staphylococcus aureus infection].

OBJECTIVE: To investigate the effect of augmented renal clearance (ARC) on plasma concentration of vancomycin, bacteriological outcome, and clinical outcome in children with methicillin-resistant Staphylococcus aureus (MRSA) infection treated by vancomycin. METHODS: A retrospective analysis was performed for the clinical data of 60 critically ill children who were treated with vancomycin due to MRSA infection from January 2013 to July 2017 and underwent plasma concentration monitoring. According to estimated glomerular filtration rate, these children were divided into an ARC group with 19 children and a normal renal function group with 41 children. The two groups were compared in terms of the use of vancomycin, plasma concentration of vancomycin, and treatment outcome. RESULTS: The children in the ARC group had an age of 1-12 years, and the ARC group had significantly higher body weight and body surface area than the normal renal function group (P<0.05). Compared with the normal renal function group, the ARC group had a significantly lower initial trough concentration of vancomycin and a significantly lower proportion of children who achieved the effective trough concentration of vancomycin (10-20 mg/L) (P<0.05). There were no significant differences in bacteriological outcome and clinical outcome between the two groups (P>0.05), but the ARC group had significantly longer length of stay in the pediatric intensive care unit (PICU) and length of hospital stay than the normal renal function group (P<0.05). CONCLUSIONS: ARC can significantly reduce the trough concentration of vancomycin and prolong the length of PICU stay and the length of hospital stay in children with MRSA infection. Idividualized medication should be administered to children with ARC.

Panax notoginseng saponins attenuate atherosclerosis in rats by regulating the blood lipid profile and an anti-inflammatory action.

Previous studies have reported on the anti-atherosclerotic effects of Panax notoginseng saponins (PNS). The aim of the present study was to explore the molecular mechanisms responsible for the anti-atherosclerotic effects of PNS and the inflammatory response. Thirty rats were randomly divided into three groups, namely a control group, a group, in which zymosan A was used to induce inflammation (Zym group) and a PNS-treated group. Rats in the three groups were administered liquid paraffin (i.p.), zymosan A (20 mg/kg, i.p., once every 3 days) or zymosan A and PNS (100 mg/kg, i.p., once daily), respectively. All animals were fed a high-fat diet for 9 weeks. At scheduled times, rats were killed, blood was collected and the aorta was removed. Pathological changes in aortas were observed using Sudan IV staining and transmission electron microscopy. Serum lipids were measured enzymatically. Whole-blood viscosity was observed at different shear rates. The expression of cardiovascular disease-specific genes was determined using GEArray (SuperArray, Frederick, MA, USA). Western blotting was used to evaluate the expression levels of nuclear factor (NF)-kappaB/p65 and its inhibitor IkappaBalpha in the aortic wall. In the present study, typical pathological changes associated with atherosclerosis in rats following induction by zymosan A were alleviated by PNS treatment. In the PNS-treated group, there was a marked reduction in total serum cholesterol, triglycerides and blood viscosity. In addition, PNS treatment significantly decreased the gene expression of some inflammatory factors, such as integrins, interleukin (IL)-18, IL-1beta and matrix metalloproteinases 2 and 9. The expression of NF-kappaB/p65 was attenuated, whereas the expression of IkappaBalpha was significantly increased, after treatment with PNS. In conclusion, it appears that PNS exerts its therapeutic effects on atherosclerosis through an anti-inflammatory action and regulation of the blood lipid profile and that an NF-kappaB signalling pathway is involved.

Panax notoginseng saponins attenuate atherosclerosis via reciprocal regulation of lipid metabolism and inflammation by inducing liver X receptor alpha expression.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax notoginseng (Burk.) F.H. Chen has been used as a health product and natural remedy in traditional medicine for cardiovascular diseases for more than 1000 years in Asia, including China, Japan, and Korea. Panax notoginseng saponins (PNS) are the major effective ingredients extracted from Panax notoginseng. AIM OF THE STUDY: The purpose of this study was to investigate whether Panax notoginseng saponins (PNS) attenuated atherosclerosis by inducing liver X receptor alpha (LXRα) expression and to elucidate the mechanisms responsible for the effects. MATERIALS AND METHODS: The AS rats were treated once daily with PNS (100 mg/kg, i.p.), and pathological changes in the aorta were observed using Sudan IV staining. The expression of LXRα in the aortic wall was measured by Western blot analysis. THP-1 macrophages were cultured with PNS in the presence or absence of geranylgeranyl pyrophosphate ammonium salt (GGPP), an LXRα antagonist. The expression of LXRα and its target genes ATP-binding cassette A1 and G1 (ABCA1, ABCG1) were determined by qRT-PCR. The transcriptional activation of the LXRα gene promoter was analyzed by a reporter assay. The NF-κB DNA binding activity and the expression of interleukin (IL)-6, monocyte chemotactic protein-1 (MCP-1) was evaluated respectively by Trans-AM NF-κB ELISA and ELISA in THP-1 macrophages that were stimulated with LPS after treatment with PNS and GGPP. RESULTS: PNS treatment alleviated the typical pathological changes associated with atherosclerosis in rats. The expression of LXRα was increased in rat aortas after treatment with PNS. In vitro, PNS increased LXRα mRNA levels in THP-1 macrophages. The reporter assays showed that PNS enhanced transcriptional activation of the LXRα gene promoter and led to the upregulation of ABCA1 and ABCG1 expression. This upregulation could be reversed by treatment with GGPP. Additionally, PNS inhibited NF-κB DNA binding activity and reduced secretion of IL-6 and MCP-1 in LPS-stimulated THP-1 macrophages. These effects could be reversed by GGPP. CONCLUSIONS: The results indicated that the PNS-mediated attenuation of AS may, at least partly, due to LXRα uprergulation. The mechanisms of action included enhancement transcriptional activation of the LXRα gene promoter by PNS and subsequent upregulation of ABCA1 and ABCG1 and inhibition of NF-κB DNA binding activity.