Repeat oral dose toxicity studies of melamine in rats and monkeys

Melamine is an important and widely used organic industrial chemical. Recently, clinical findings of renal failure and kidney stones in infants have been associated with ingestion of melamine-contaminated infant formula. To understand the toxicity and clinical outcome of melamine exposure, repeated oral dose studies in rats and monkeys were performed to characterize the subchronic toxicity of melamine. Assessment of toxicity was based on mortality, clinical signs, body weights, ophthalmic findings, clinical pathology, gross pathology, organ weights, and microscopic observations. The first rat study was intended to be a 14-day oral study followed by an 8-day recovery period. The dose levels were 140, 700, and 1,400 mg/kg/day (lowered to 1,000 mg/kg/day subsequently due to mortality). Oral administration of melamine at 700 mg/kg/day for 14 consecutive days in rats produced compound-related clinical signs (red urine), decreased body weights, and changes in clinical pathology (increased serum urea nitrogen and creatinine) and anatomical pathology (renal tubular cell debris, crystal deposition, and hyperactive regeneration of renal tubular epithelium). The kidney was identified as the target organ. Oral administration at 1,400 mg/kg/day (subsequently lowered to 1,000 mg/kg/day) resulted in animal death and moribundity. There were no treatment-related findings in the 140 mg/kg/day group. There were no compound-related findings in the high-dose recovery animals. The second rat study was a 5-day oral toxicity study with genomic biomarkers assayed in the kidney tissues. At the top dose of 1,050 mg/kg/day, similar clinical and anatomical pathology findings as described above were observed. The genes measured, Kim-1, Clu, Spp1, A2m, Lcn2, Tcfrsf12a, Gpnmb, and CD44, were significantly up-regulated (fivefold to 550-fold), while Tff3 was significantly down-regulated (fivefold). These results indicated that genomic markers could sensitively diagnose melamine-induced kidney injury. A 3-month oral study with 4-week recovery in monkeys was also conducted. In this monkey study, the animals were treated with melamine at doses of 60, 200, or 700 mg/kg/day. The administration of 700 mg/kg/day melamine by nasal-gastric gavage to monkeys resulted in test article-related clinical signs including turbid and whitish urine, urine crystals, red blood cell changes, increased serum alanine aminotransferase and kidney and/or liver weights, and microscopic findings including nephrotoxicity, pericarditis, and increased hematopoiesis. Nephrotoxicity was also noted at 200 mg/kg/day. It was concluded that the kidney is the primary target organ and the NOAEL was estimated to be 140 mg/kg/day in rats following a 14-day oral administration and 60 mg/kg/day in the monkey study.     

充分利用全自动片剂摆药机,提升药学服务水平

目的 实现住院药房中心摆药的自动化.方法 介绍我院全自动片剂摆药机的主要构造、运行环境、工作原理、调剂流程及流程改善环节,并与传统手工摆药模式相比较.结果 全自动片剂摆药机的应用可提高药师摆药、发药的速度和准确性,改善卫生状况,避免病人二次感染,缩短护士的取药时间,提高病人的用药依从性.结论 全自动片剂摆药机适合住院药房使用,可提升药房的药学服务水平.     

Metallothionein as a compensatory component prevents intermittent hypoxia-induced cardiomyopathy in mice

Obstructive sleep apnea (OSA) causes chronic intermittent hypoxia (IH) to induce cardiovascular disease, which may be related to oxidative damage. Metallothionein (MT) has been extensively proved to be an endogenous and highly inducible antioxidant protein expressed in the heart. Therefore, we tested the hypotheses that oxidative stress plays a critical role in OSA induced cardiac damage and MT protects the heart from OSA-induced cardiomyopathy. To mimic hypoxia/reoxygenation events that occur in adult OSA patients, mice were exposed to IH for 3 days to 8 weeks. The IH paradigm consisted of alternating cycles of 20.9% O₂/8% O₂ F_IO₂ (30 episodes per hour) with 20 s at the nadir F_IO₂ for 12 h a day during daylight. IH significantly increased the ratio of heart weight to tibia length at 4 weeks with a decrease in cardiac function from 4 to 8 weeks. Cardiac oxidative damage and fibrosis were observed after 4 and 8 weeks of IH exposures. Endogenous MT expression was up-regulated in response to 3-day IH, but significantly decreased at 4 and 8 weeks of IH. In support of MT as a major compensatory component, mice with cardiac overexpression of MT gene and mice with global MT gene deletion were completely resistant, and highly sensitive, respectively, to chronic IH induced cardiac effects. These findings suggest that chronic IH induces cardiomyopathy characterized by oxidative stress-mediated cardiac damage and the antioxidant MT protects the heart from such pathological and functional changes.     

某三甲医院医患双方分级诊疗认知度分析

目的 了解医患双方对分级诊疗的认知情况,探讨影响患者就医意愿及医患双方对分级诊疗认知度的因素.方法 采用偶遇法进行方便抽样,对滨州市某三甲医院的183名患者和92名医务人员,分别采用问卷和无结构式访谈的形式展开调查,根据logistic回归,分析影响医患双方对分级诊疗认知的因素.结果 被调查对象中,38.2％的患者表示...     

Disease-directed design of biodegradable polymers: Reactive oxygen species and pH-responsive micellar nanoparticles for anticancer drug delivery

Herein, we report reactive oxygen species (ROS)- and pH-responsive biodegradable polyethylene glycol (PEG)-block-polycarbonate by installing thioether groups onto the polycarbonate and its self-assembled core/shell structured micelles for anticancer drug delivery. Oxidation of thioethers to sulfoxide and subsequently sulfone induces an increase in hydrophilicity, resulting in more hydrophilic micellar core. This phase-change caused the micelles to swell and enhance cargo release. Carboxylic acid groups have also been installed onto thioether-containing polycarbonate to promote loading of amine-containing anticancer doxorubicin through electrostatic interaction. Urea-functionalized thioether-containing PEG-block-polycarbonates were synthesized to mix with the acid-functionalized PEG-block-polycarbonate for stabilizing micelle structure through hydrogen-bonding interaction. The mixed micelles were 50?nm in diameter and had a 25?wt% loading capacity for doxorubicin. Enhanced drug release from the micelles was triggered by low pH and high content of ROS. Drug-encapsulated micelles accumulated in tumors through leaky tumor vasculature in PC-3 human prostate cancer xenograft mouse model.     

Bioactivity-guided isolation and structural characterization of the antifungal compound,plumbagin, from Nepenthes gracilis

Context: Despite several phytochemical studies of Nepenthes gracilis Korth (Nepenthaceae), the biological activities of this pitcher plant remain to be explored.

Objective: This study evaluates the antifungal activity of N. gracilis extracts, isolates, and characterizes its bioactive compound and evaluates the cytotoxicity of the isolated compound.

Materials and methods: Fresh leaves of N. gracilis were sequentially extracted. The fungistatic and fungicidal activities of the extracts were evaluated against six species of fungi of medical importance using a colorimetric broth microdilution method. The most active extract was fractionated by liquid–liquid partitioning and further purified by a preparative thin layer chromatography. Structural elucidation was carried out using FT-IR, GC-MS, and NMR. Cytotoxicity testing against rhesus monkey kidney epithelial cells (LLC-MK2) was assessed by a neutral red uptake (NRU) assay.

Results: The hexane extract, which showed the lowest minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC), both at 20?μg/mL against Candida albicans, Issatchenkia orientalis, and Trichophyton mentagrophytes, was subjected to bioactivity-guided fractionation. The isolated compound exhibited potent activity with the MIC values ranging from 2 to 31?μg/mL against all the fungi. The active compound was identified as plumbagin (5-hydroxy-2-methyl-naphthalene-1,4-dione). The 50% cytotoxicity concentration (CC₅₀) of plumbagin was 0.60?μg/mL.

Discussion and conclusion: The selectivity indices of plumbagin against all the fungi were less than 1.0, indicating that plumbagin is more toxic to mammalian than fungal cells. This study provides information on the antifungal properties of N. gracilis leaf extracts, as well as the antifungal and cytotoxicity properties of plumbagin.     

Marijuana and Alcohol Use and Attempted Smoking Cessation in Adolescent Boys and Girls

ABSTRACT. Background: This study sought to determine the relationship between the frequency of current marijuana and alcohol use and cigarette quit attempts in male and female adolescent smokers. Methods: Data from a cross-sectional survey of health behaviors in high-school-aged adolescents were analyzed. Current cigarette smokers (n = 804) who reported use of at least 1 cigarette in the past month were divided into those with and without a history of at least 1 quit attempt (a self-reported episode of trying to “stop smoking”). Logistic regression models were fit to describe the association between the frequency of marijuana/alcohol use and a history of cigarette quit attempts. Results: Among the total sample, higher-frequency marijuana use (more than 6 times in the past 30 days) and frequent binge drinking (more than 5 days of binge drinking in the past 30 days) decreased the odds of having a past cigarette quit attempt (higher-frequency marijuana: adjusted odds ratio [AOR] = 0.56, 95% confidence interval [CI] = 0.36–0.86; frequent binge drinking: AOR = 0.49, 95% CI = 0.29–0.83). A significant gender interaction was observed for the relationship between higher-frequency marijuana use and a history of cigarette quit attempts (P = .03), with decreased odds in boys (AOR = 0.41, 95% CI = 0.22–0.77) but not in girls (AOR = 0.71, 95% CI = 0.37–1.33). Conclusions: Adolescent smokers who report higher-frequency marijuana use or frequent binge drinking have a decreased likelihood of a history of a cigarette quit attempt. The gender-related association between higher-frequency marijuana use and a history of quit attempts suggests that boys with greater substance use may need particularly intensive support to initiate quit attempts.     

血府逐瘀汤对术后早期炎性肠梗阻的治疗意义

目的探讨血府逐瘀汤对术后早期炎性肠梗阻的治疗效果。方法对2012年3月~2014年10月收治的61例术后早期炎性肠梗阻患者进行随机分组,其中31例使用血府逐瘀汤保留灌肠进行治疗(观察组),其他30例患者作对照(对照组)。观察组除使用血府逐瘀汤保留灌肠外,其他治疗与对照组相同。观察治疗后两组临床情况。结果观察组在肠鸣音恢复时间、排气恢复时间、排便恢复时间、症状完全消失时间以及痊愈出院时间方面比对照组恢复速度明显,差异有显著性(P<0.05)。结论血府逐瘀汤治疗术后早期炎性肠梗阻有明显效果,值得临床推广。     

七味红花殊胜丸质量标准研究

目的：建立七味红花殊胜丸质量标准。方法：采用薄层色谱法（TLC）对处方中红花进行定性鉴别;用高效液相色谱法（HPLC）测定羟基红花黄色素A含量。结果：TLC定性鉴别分离效果好,斑点显色清晰。羟基红花黄色素A的进样浓度在13.18~79.10μg·ml-1范围内与峰面积积分值呈良好线性关系（r=0.9998）;平均回收率为98.2%,RSD=1.27%（n=6）;每丸含红花以羟基红花黄色素A计应不少于1.0mg。结论：标准可用于该制剂的质量控制。