Permeant lipophilicity and vehicle composition influence accumulation of dyes in hair follicles of human skin

In skin and hair research drug targeting to the hair follicle is of great interest. Therefore the influence of permeant lipophilicity and vehicle composition on local accumulation has been examined using confocal laser scanning microscopy (CLSM). Formulations saturated with either Oregon Green^® 488, Bodipy^® FL C₅ or Bodipy^® 564/570 C₅ were prepared. The dyes were applied in citric acid buffer, 8% (w/v) surfactants in citric acid buffer or 8% (w/v) surfactants/20% (w/v) propylene glycol in citric acid buffer. Flow-through diffusion experiments were performed with fresh human scalp skin, after which the skin was imaged using CLSM. Diffusion studies showed for Oregon Green^® 488 (low lipophilicity) a higher flux when applied in citric acid buffer compared to surfactants. In contrast the fluxes of the more lipophilic dyes (Bodipy^® FL C₅ and Bodipy^® 564/570 C₅) are highest when applied in surfactants/propylene glycol. CLSM studies revealed that follicular accumulation increased with (i) a lipophilic dye and (ii) application of lipophilic dyes in surfactants–propylene glycol. Therefore we conclude that targeting to the hair follicle can be increased by the use of lipophilic drugs in combination with surfactant solutions and propylene glycol.     

Coagulation markers in healthy human subjects exposed to diesel exhaust

BACKGROUND: Ambient particulate matter (PM) is associated with cardiovascular morbidity and mortality. It has been proposed that PM induces a pro-thrombotic process, increasing the risk of cardiovascular events, with some support from epidemiological and laboratory-based models. Diesel exhaust is a major contributor to urban PM, and we conducted a controlled human exposure of diesel exhaust in healthy subjects. OBJECTIVE: To evaluate diesel exhaust exposure effects on fibrinolytic burden (D-dimer), platelet number, and endothelial injury (von Willebrand's factor, VWF), inhibition of the fibrinolytic pathway (plasminogen activator inhibitor-1 [PAI-1]), and inflammation (C-reactive protein, CRP). MATERIALS AND METHODS: Randomized, crossover, double-blinded design, with 13 healthy participants exposed on three different days (>or=2 weeks washout) to diesel exhaust at 0 (filtered air), 100 microg PM(2.5)/m(3) and 200 microg PM(2.5)/m(3). We assessed diesel exhaust-associated changes in D-dimer, VWF, PAI-1 and platelets at 3, 6 and 22 h, and CRP at 22 h, after exposure initiation. RESULT: Significant changes did not occur in any primary endpoints. Among secondary endpoints, diesel exhaust (200 microg PM(2.5)/m(3)) effect on PAI-1 levels at 22 h was of borderline significance, with a 1.32-fold decrease after exposure to diesel exhaust (200 microg PM(2.5)/m(3)), relative to filtered air (CI 1.00 to 1.54). Diurnal patterns in D-dimer and PAI-1 were observed. CONCLUSIONS: In healthy individuals, exposure to 200 microg PM(2.5)/m(3) diesel exhaust did not affect primary pro-thrombotic endpoints. Thus, these data do not support a diesel exhaust-induced pro-thrombotic phenomenon. Replication of these studies should be carried out to ascertain whether or not they inform our mechanistic understanding of air pollution's cardiovascular effects.     

Convulsant effect of diphenyl diselenide in rats and mice and its relationship to plasma levels

Diphenyl diselenide [(PhSe)₂], an organoselenium compound, presents pharmacological and toxicological properties in rodents. The aim of this study was to carry out the determination and quantification of (PhSe)₂ in plasma after oral administration (p.o.) of this compound (500 mg/kg), dissolved in canola oil, in rats and mice. The second objective was to verify the involvement of different routes of administration ((p.o.), intraperitoneal (i.p.) and subcutaneous (s.c.)) and vehicle solutions (canola oil and dimethyl sulfoxide (DMSO)) in the appearance of seizure episodes and in the plasmatic levels of (PhSe)₂ in rats and mice. Analysis of (PhSe)₂ in blood samples was performed by gas chromatography/flame ionized detector system (GC/FID). Rat and mouse peak plasma (PhSe)₂ levels were 13.13 and 10.11 μg/ml (C_max), respectively, and occurred at 0.5 h (T_max) post-dosing. The use of different administration routes (p.o., i.p. and s.c.) and vehicle solutions (canola oil or DMSO) in rats and mice indicated that the appearance of seizures and (PhSe)₂ plasmatic levels are dependent of administration routes (i.p. > p.o. > s.c.), vehicle solutions (DMSO > canola oil) and animal species (mice > rat).     

Occupational stress factors and alcohol-related behavior in urban transit operators

BACKGROUND: If alcohol consumption mitigates psychological and physiological aspects of the response to stressors, then alcohol consumption might be elevated for individuals exposed to high occupational stressors. Frequency of work stressors and reaction to those stressors were studied in relation to several alcohol-related outcomes. METHODS: During the period 1993-1995, 1979 transit operators underwent medical examinations for commercial driver's license renewal. Questionnaire and interview data concerning occupational stress factors and alcohol-related outcomes were available for 1386 (70.2%) of the operators. RESULTS: A positive association was found between the two job stressor-related measures and each of six alcohol-related outcomes. Of these 12 associations, ten were statistically significant. Individuals experiencing high self-reported frequency of job stressors and a higher perceived severity of those job stressors were more likely to drink and more likely to be heavy drinkers. They reported more consequences of alcohol consumption, reported increased consumption since beginning work as transit drivers, and were more likely to report drinking to deal with work stress. They also drank more, but this effect was not significant for either job stress measure. There was virtually no association between either stressor-related measure and alcohol dependency (CAGE). CONCLUSIONS: Together with other published findings, these results suggest increased alcohol-related outcomes in the presence of work stressors. This conclusion has potential implications for worksite health promotion and job design. Because our findings are cross-sectional, further research is needed to clarify the causal nature of the work stressor-alcohol association. Further research also is needed to clarify the role of individual differences and context.     

Alcohol, Central Nervous System Injury, and Time to Fatal Motor Vehicle Crashes

Objectives: Motor vehicle crash (MVC) studies have found that alcohol (ALC) is associated with increased mortality and decreased time to death (TTD). Clinical and experimental data suggest that ALC potentiates central nervous system injury (CNSI). We hypothesize that ALC-intoxicated, MVC fatalities with CNSI are more likely to die in the immediate postinjury period than are sober victims with CNSI. Methods: Design—A retrospective cohort of 401 MVC fatalities from four Michigan counties for the time period 1985 to 1991 was studied. Measurements—Medical examiner records were reviewed to determine age, blood alcohol concentration (BAC), and TTD. Injury severity was calculated with the Abbreviated Injury Scale (1985 version). Anatomical profile scores and G scores were also calculated and used to identify CNSI subjects. Analysis—χ² and Student's t test were used, and odds ratios with 0.95 confidence intervals (CIs) were calculated. Results: ALC(+) cases (BAC ≥ 100 mg/dl) (n= 99) were significantly younger and more frequently had TTD < 1 hr than ALC(-) cases (n= 233): odds ratio 1.62 [0.95 CI (1.02 to 2.50)]. Overall, CNSI cases (n= 297) were significantly younger and had fewer thoracic injuries, but did not have significantly shorter TTD, compared with non-CNSI cases. However, ALC(+) CNSI cases (n= 77) were over twice as likely to have TTD < 1 hr (odds ratio 2.04 [0.95 CI (1.13 to 3.70)]}. For ALC(+) isolated CNSI cases, the odds ratio for TTD < 1 hr, compared with nonisolated CNSI cases was 8.25 (0.95; CI 0.66 to 102.5). Injury Severity Score, anatomical profile, and G scores were not Significantly different for ALC(+) CNSI cases, compared with ALC(-) CNSI cases, whether isolated or nonisolated. Conclusions: These data suggest that alcohol intoxication is associated with increased frequency of early death in MVC victims with CNSI, despite there being no detectable difference in anatomical injury scoring.     

Considerations in Seating and Positioning Severely Disabled Drivers

Seating and positioning methods and products have taken a lead in clinical intervention with the disabled client. The seating clinician has emerged as an important member of the rehabilitation team working toward maximizing independence and function of the clients they serve. Seating and positioning interventions have proven to be very effective in stabilizing the client's trunk and torso, making it possible to achieve the once impossible task of driving a motor vehicle. The areas of acceleration deterioration, improved head height, and design of a secure wheelchair base are all concerns for the rehabilitation team working on driving. Addressing these issues early in the driver rehabilitation program can maximize successful outcomes and create a safer driving environment.     

Influence of membrane-solvent-solute interactions on solute permeation in skin

The relative importance of solubility parameters and other solvent properties on membrane diffusion processes has not been fully elucidated in the literature. Previously, we have studied the effect of different vehicles on the permeation of caffeine, benzoic acid (BA) and salicylic acid (SA) through silicone membranes. The present paper investigates diffusion of the selected permeants from different saturated solutions through human epidermis.

The permeation of caffeine was strongly affected by the vehicle chosen and the maximum enhancement observed for the permeation of caffeine was 288-fold. A maximum of 12-fold enhancement in the flux was observed for the permeation of SA and a maximum of 10-fold enhancement was observed for the permeation of BA. The diffusion profiles obtained for SA in the different solvents were very similar when compared with those obtained for BA but the permeation rates were higher for BA than for SA. This similarity results from the similar chemical structure and lipophilicity.     

重庆市主要交通干道机动车尾气污染状况

目的：探讨重庆市机动车尾气污染状况,为研究其对人群健康的影响提供依据.方法：测定重庆市主要交通干道空气中铅含量、苯并（a）芘[B（a）P]浓度、总悬浮颗粒、PM10、PM2.5和PM1浓度并进行相关分析.结果：重庆市各主要交通干道尾气污染物浓度均超过国家环境卫生标准.结论：该市应采取措施控制机动车尾气污染环境.     

骨髓间充质干细胞在胶质瘤研究中的应用

骨髓间充质干细胞(MSC)在体内具有向肿瘤部位定向迁移能力,是比较理想的基因治疗"细胞载体".通过转染或转导的方法,在体外使MSC携带目的 基因,并获得稳定表达,然后将它们移植到宿主体内,发挥治疗作用.这种先体外后体内的过程在胶质瘤等多个系统肿瘤中进行了研究,获得阳性结果.MSC移植的安全性值得关注,其中与宿主肿瘤细胞...     

全面质量管理在流动采血车的应用

流动采血车是无偿献血的重要场所。从人员、设备、物料、方法、环境及车辆安全与卫生等6方面,对流动采血车进行全方位的日常监管,为献血者提供了安全、优质服务,为临床提供了安全、有效血液,保障了血液安全。