肾毒性物质致急性肾衰治疗体会

近三年,在我院收治的急性肾衰(ARF)病例有36例,均为使用肾毒性物质引起,现把治疗体会总结如下: 1临床资料1.1一般资料36例病人均在使用肾毒性物质之后起病,并能除外其他疾病所致。其中男性28例,女性8例,年龄21-67岁(平均43.4岁)。所使用肾毒物及途径见附表。

氯化汞中毒对大鼠肾小管上皮细胞碳酸酐酶活性的影响

目的 研究氯化汞对肾小管上皮细胞碳酸酐酶活性的影响 ,探讨组织细胞化学方法在研究汞中毒的价值。方法 用改良的 Hansson法通过电镜观察碳酸酐酶反应颗粒的改变。结果 汞中毒引起肾小管上皮细胞超微结构变化及定位于近曲小管刷状缘质膜、内吞泡膜、线粒体被膜和远曲小管上皮细胞线粒体被膜上碳酸酐酶活性下降。结论 汞中毒明显抑制肾小管上皮细胞碳酸酐酶活性 。

Development of a New Azithromycin Glutamate for Parenteral Preparation, the Toxicity in Sprague-Dawley Rats and Pharmacokinetics in Human Healthy Volunteers

Aim In order to improve the solubility of azithromycin, the objectives of the present study were to screen an appropriate salt for azithromycin by comparing acute hepatic and renal toxicities in animals, and study the pharmacokinetics of final chosen azithromycin salt. Methods Various salts of azithromycin, such as glutamate, citrate, hydrochloride, sulphate, dihydrogen phosphate, lactobionate, tartrate, and aspartate were given intravenously to Sprague Dawley rats at a dose of 10 mg once daily for 14 consecutive days via tail vein. The acute hepatic and renal indicators were measured before and after administration. A pharmacokinetic study was performed on 12 healthy human volunteers. The subjects were equally divided into two groups by a randomized crossover design. Azithromycin glutamate injection was administered by intravenous infusion or intramuscular injection at a single dose of 500 mg, respectively. Azithromycin concentrations in plasma were determined by microbial inhibition zone assay, and the pharmacokinetic parameters were calculated using a practical pharmacokinetic software 3P87 program. Results Azithromycin glutamate was least toxic to the liver and kidney of the rats, thus being selected as a final salt for parenteral preparation of azithromycin. Pharmacokinetic results showed that the area under the plasma concentration-time curves （AUC0-120h） were 21.47 ± 1.57 h·μg·mL^-1 for intravenous infusion, and 19.36 ± 2.44 h·μg·mL^-1 for intramuscular injection. The absolute bioavailability of intramuscular injection was 92.59%. Conclusion Azithromycin glutamate is suitable for the future clinical application, and its pharmacokinetics is characterized in human volunteers in the present study.

A prospective cohort study on the relationship between vancomycin steady-state trough concentration and efficacy and safety in Chinese adults

Clinical guidelines recommend a steady-state vancomycin(VCM)trough concentration(SVTC)of 10–15 mg/L for regular infections and 15–20 mg/L for severe infections.However,clinical trials have shown that increasing SVTC is not beneficial for efficacy,and instead it leads to nephrotoxicity.To verify whether increasing the SVTC results in improved clinical outcomes with sustainable adverse effects,we prospectively determined its correlation with clinical efficacy and safety.The participants included patients hospitalized with Gram-positive bacterial infections from March 2017 through October 2018.The patients were classified into group I(SVTC<10 mg/L),II(10≤SVTC≤20 mg/L),or III(SVTC>20 mg/L).Clinical,microbiological,and laboratory data were collected.Clinical outcomes between group I and II were matched after propensity score matching(PSM).A total of 331 patients were included in this study.Clinical failure occurred in 59(29%)of 204 patients on day 14,with no significant difference between groups I and II(P=0.535).Infection recurred at 28 d in 62(30%)of 204 patients,and no significant difference in infection recurrence was observed between both the groups(log-rank,P=0.674).Except for a significant increase in the incidence of acute kidney injury in group II,no significant difference was observed between two groups for any clinical results.The incidence of adverse events in groups I and II was significantly lower than that in group III(P<0.001).SVTC had an applicable cut-off point at 14.55 mg/L.SVTC was not correlated with VCM clinical efficacy,while it was a good indicator of nephrotoxicity.

Effect of Helichrysum plicatum DC. subsp. plicatum ethanol extract on gentamicin-induced nephrotoxicity in rats

The aim of this study was to evaluate the possible therapeutic or protective effects of Helichrysum plicatum DC.subsp.plicatum ethanol extract（HPE）against gentamicin-induced nephrotoxicity.Thirty-six Sprague Dawley male rats weighing between 200 and 250 g were used as live material.They were formed into six groups containing 6rats each and were allowed to adapt to laboratory conditions for 7 d.Group Ⅰ：control,5%DMSO intraperitoneal（i.p.）;Group Ⅱ：HPE 100 mg/（kg·d）i.p.;Group Ⅲ：HPE 200 mg/（kg·d）i.p.;Group Ⅳ：gentamicin as 80 mg/（kg·d）i.p.;Group Ⅴ：gentamicin as 80 mg/（kg·d）i.p.＋HPE 100 mg/（kg·d）i.p.;and Group Ⅵ：gentamicin as 80 mg/（kg·d）i.p.＋HPE 200 mg/（kg·d）i.p.for 8 d.Following treatment,serum,liver,and kidney tissues were used to assess blood urea nitrogen（BUN）,creatinine,enzymatic and non-enzymatic antioxidants,and lipid peroxidation.Gentamicin significantly increased serum BUN,creatinin,and liver and kidney levels of malondialdehyde（MDA）.It also decreased the activity of catalase（CAT）,glutathione peroxidase（GPx）,and superoxide dismutase（SOD）.Treatment with the HPE 100 mg/kg reversed gentamicin-induced alterations as evidenced by decreased serum BUN and creatinin,liver and kidney oxidant marker,and tubular necrosis as well as by an increase in antioxidant enzymes.It was found that HPE 200 mg/kg significantly increased liver and kidney tissue MDA levels in nephrotoxicity in rats.As a result,these findings support the proposition that HPE in 100 mg/kg dose demonstrates in the kidney and liver as free radicals and scavenger to prevent the toxic effects of gentamicin in both the biochemical and histopathology parameters.