组织多普勒Tei指数与冠状动脉病变程度的关系

目的评价组织多普勒Tei指数(DTI-Tei指数)与冠状动脉病变严重程度的关系。方法将126例行冠状动脉造影或介入治疗的非心肌梗死患者分为冠心病组与非冠心病组,根据Gensini评分分为无病变组、轻度病变组、严重病变组,应用组织多普勒(DTI)测定所有患者的Tei指数,观察DTI-Tei指数与冠状动脉病变Gensini评分的相关性及对严重冠状动脉病变的预测价值。结果冠心病组与非冠心病组相比较DTI-Tei指数差异具有统计学意义(分别是0.41±0.06和0.46±0.09,P<0.01),比较无病变组、轻度病变组、严重病变组的SBP[(135±18)mmHg、(148±19)mmHg和(156±20)mmHg、PP[(58±12)mmHg、(68±13)mmHg和(75±17)mmHg]、HDL-C[(1.29±0.21)mmol/L、(1.25±0.31)mmol/L和(1.11±0.32)mmol/L]、DTI-Tei值(0.41±0.06、0.43±0.07和0.51±0.07)差异有统计学意义(P<0.05),观察SBP、PP值,严重病变组及轻度病变组高于无病变组(P<0.05),严重病变组与轻度病变...     

Human papillomavirus genotype and oropharynx cancer survival in the United States of America

BackgroundThe presence of human papillomavirus (HPV) DNA in oropharyngeal squamous cell cancer (OPSCC) tissue appears to be a strong predictor of improved prognosis, but this observation has not been explored in a population-based sample with generalisable findings.MethodsFollow-up data from a large sample of OPSCC patients identified through six population-based cancer registries in the United States of America (USA) were used to characterise the association of tumour HPV status with survival.ResultsHPV DNA was detected in tumour tissue from 71% (378 in 529) of the OPSCC patients. A total of 65% of patients with HPV16-associated tumours survived 5 years compared to 46% of patients with other HPV types and 28% of patients with HPV-negative tumours (p log-rank test <0.0001). The OPSCC patients with detectable HPV16 DNA had a 62% reduced hazard of death at 5 years, and patients with other HPV types had a 42% reduced hazard of death at 5 years compared to HPV-negative patients. Compared to non-Hispanic Whites, Blacks with OPSCC had a 2.6-fold greater risk of death at 5 years after adjustment for HPV status and other prognostic variables. Both surgery and radiation therapy were associated with a reduced 5-year risk of death, but no evidence was found for an interaction between HPV status and radiotherapy or surgery on survival time.ConclusionsData from this US study suggest that HPV16-positive OPSCC patients survive longer than HPV-negative patients regardless of treatment, highlighting the prognostic importance of HPV status for this malignancy. Optimal treatment regimens for OPSCC could be tailored to each patient’s HPV status and prognostic profile.     

Oritavancin for acute bacterial skin and skin structure infections

Introduction: Inpatient treatment of acute bacterial skin and skin structure infections (ABSSSIs) exerts a significant economic burden on the healthcare system. Oritavancin is a concentration-dependent, rapid bactericidal agent approved for the treatment of ABSSSIs. Its prolonged half-life with one-time intravenous (i.v.) dosing offers a potential solution to this burden. In addition, oritavancin represents an alternative therapy for Streptococci and multidrug-resistant Gram-positive bacteria including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Animal models have also shown promising results with oritavancin for other disease states including those that require long courses of i.v. therapy.

Areas covered: This review covers oritavancin’s basic chemistry, spectrum of activity, pharmacodynamics/pharmacokinetics and efficacy in clinical trials, and provides expert opinion on future directions. To compose this review, a search of PubMed was performed, and articles written in the English language were selected based on full text availability.

Expert opinion: If oritavancin is proven to be a cost-effective strategy for outpatient treatment and prevents complications of prolonged i.v. therapy, it will be sought as an alternative antibiotic therapy for ABSSSIs. In addition, further clinical data demonstrating efficacy in Gram-positive infections requiring prolonged therapy such as endocarditis and osteomyelitis could support oritavancin’s success in the current market.     

Triclosan exhibits a tendency to accumulate in the epididymis and shows sperm toxicity in male sprague‐dawley rats

Triclosan (TCS) is considered a potent endocrine disruptor that causes reproductive toxicity in non‐mammals, but it is still unclear exactly whether TCS has adverse effects on the sperm or reproductive organs in mammals. In this study, we aimed to evaluate the distribution status of TCS in male reproductive organs of rats, and seek the correlation with the TCS‐induced sperm toxicity or reproductive organ damage. Male rats were intragastrically administered with TCS at a dose of 50 mg/kg, the kinetics of TCS in the plasma and reproductive organs were investigated. TCS in testes and prostates both showed a lower‐level distritbution compared to that in the plasma, which indicates it has no tendency to accumulate in those organs. However, TCS in the epididymides showed a longer elimination half‐life (t_1/2z), a longer the mean retention time (MRT), and a lower clearance (CL_Z/F) compared with those in the plasma. Besides, the ratios of mean area under the concentration‐time curve (AUC)_{0–96h(epididymides/plasma)} and AUC_{0–∞(epididymides/plasma)} were 1.13 and 1.51, respectively. These kinetic parameters suggest TCS has an accumulation tendency in the epididymides. Based on this, we investigated the TCS‐induced sperm toxicity and histopathological changes of reproductive organs in rats. TCS was given intragastrically at doses of 10, 50, and 200 mg/kg for 8 weeks. Rats treated with the high dose (200 mg/kg) of TCS showed a significant decrease in daily sperm production (DSP), changes in sperm morphology and epididymal histopathology. Considering the histopathological change in the epididymides, TCS may induce the epididymal damage due to the epididymal accumulation of that. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 83–91, 2015.     

Shaving effects on percutaneous penetration: clinical implications

Context: Human/animal shaving biology.

Objective: To assess the effect of shaving on percutaneous penetration and skin function.

Methods: We screened 500+publications in Pub Med, Scopus, Cochrane Library and pertinent journals out of which only 17 were deemed relevant. Terms for searches included shaving and skin, percutaneous penetration and shaving, skin absorption and shaving, absorption of dyes and shaving, skin penetration, effects of shaving and absorption, shave and dyes, axillary shaving and stratum corneum, shaving and breast cancer, shaving and infections, etc.

Result: Shaving appears to have an exaggerated effect on percutaneous absorption; however, some studies do not support this evidence.

Conclusion: Shaving enhances percutaneous penetration of some chemicals; however this effect is species and chemical specific. Further investigations of chemicals of varying physio-chemical properties are mandated before a generalized theory can be promulgated.     

Hexyl cinnamal: consideration of skin-sensitizing properties and suitability as a positive control

Background: Hexyl cinnamal (HCA) is a widely used fragrance chemical, the low skin-sensitizing potency of which has made it a common choice for the use as a positive control for predictive toxicology assays. However, HCA is commonly negative in current candidate in vitro alternatives test methods.

Objective: To review the evidence that HCA is a classifiable skin sensitizer against the standards set by the Globally Harmonized Scheme (GHS), and determine whether it represents an appropriate choice for a positive control substance for predictive testing.

Methods: Using the GHS criteria, mechanistic data, and in vitro, in vivo and human evidence relating to HCA and skin sensitization have been reviewed.

Results: The chemistry of HCA is consistent with potential for skin sensitization and predictive in vivo test data support this conclusion. However, the human data are relatively sparse, consistent with HCA possessing a low capacity to induce skin sensitization under conditions of consumer exposures.

Conclusions: Using GHS criteria (and applying a precautionary approach) HCA would classify as a weaker skin sensitizer than predicted by the local lymph node assay (LLNA). However, given the human experience, it is necessary to consider whether HCA is the most appropriate choice for use as a positive regulatory control.     

尼索地平对单硝酸异山梨酯在小鼠体内组织分布的影响

目的考察尼索地平对单硝酸异山梨酯在小鼠体内组织分布的影响。方法 30只健康昆明种小鼠,♂,随机分成2组,分别为单独给药组和联合给药组,HPLC测定组织中单硝酸异山梨酯的浓度。结果小鼠组织中单硝酸异山梨酯浓度在给药后0.083 h为小肠>胃>心>肝>肾,给药后0.5 h为胃>小肠>肾>心>肝。胃中最大浓度出现时间因给药方案不同而异:单独给药组在给药后0.5 h单硝酸异山梨酯浓度最大,联合给药组在给药后0.083 h浓度最大。胃中单硝酸异山梨酯最大浓度,2组具有显著性差异(P<0.05)。结论尼索地平对单硝酸异山梨酯在小鼠组织中的分布具有一定影响。     

延胡索醋制前后小鼠眼组织中Cu、Zn、Mn含量比较研究

摘 要 目的： 研究延胡索醋制前后对眼组织中微量元素含量的影响,探讨醋制能使延胡索归肝经的真实性。方法: 将小鼠分为延胡索生品组、醋品组和阴性组分别给药,测定并比较其眼底血和眼球玻璃体中的锌、锰、铜含量。结果:延胡索能显著增加小鼠眼底血中Cu、Zn及眼球玻璃体中Zn、Mn含量,醋制延胡索效果更为明显。结论: 醋制延胡索能提高微量元素在眼组织的分布,因肝开窍于目,为延胡索醋制后归肝经提供依据。