Urinary disposition of ethylbenzene and m-xylene in man following separate and combined exposure

Summary Four volunteer subjects were exposed to 150ppm (655 mg/m³) of ethylbenzene and 150ppm (655mg/m³) of m-xylene both separately and in combination. The biotransformation of the solvents was studied on the basis of the metabolites found in the urine. The metabolic conversion of both m-xylene and ethylbenzene proceeded mainly through oxidation of side chains. Ring oxidation seemed to be of minor importance; in the case of ethylbenzene it accounted for 4.0% (combined share of 4-ethylphenol, p- and m-hydroxyacetophenones) and in case of m-xylene for 2.5% (2,4 dimethylphenol), respectively. Mandelic and phenylglyoxylic acids amounted to 90% of the ethylbenzene metabolites, whereas m-xylene were excreted to 97% in the form of m-methylhippuric acid. Almost equimolar amounts in the form of metabolites of both solvents were found in the urine during 24h from the onset of exposure. Most of the ethylbenzene metabolites were excreted at substantially slower rates than those of m-xylene. The combined exposure resulted in a mutual inhibition of the metabolism of ethylbenzene and m-xylene, which was demonstrated by delayed excretion and decreased amounts of metabolites excreted. No sign of alteration in the urinary metabolite patterns of either ethylbenzene or m-xylene could be detected.     

Efficacy of a combination of praziquantel and artesunate in the treatment of urinary schistosomiasis in Nigeria

The combined effects of praziquantel and artesunate in the treatment of urinary schistosomiasis were assessed among 312 randomly selected schoolchildren aged 4-20 years in Adim community, Nigeria. In the preliminary screening, infection was confirmed in 327 (38.5%) of the 850 subjects screened. Infected subjects who reported for treatment were then divided into six treatment groups of 52 subjects each; 44 subjects in each group completed their treatment regimens and submitted their urine for post-treatment assessment. Praziquantel and artesunate were administered orally at 40 mg/kg and 4 mg/kg body weight, respectively. Adverse effects due to drug reactions were assessed 72 h after medication and all perceived episodes of illness were treated. Morbidity indicators were assessed 56 days after the final dose of the drug regimens. All treatment regimens were well tolerated. The cure rates were 72.7% in the praziquantel plus placebo-treated group and 70.5% in the artesunate plus placebo group, while the artesunate plus praziquantel group had the highest cure rate (88.6%). Haematuria and proteinuria were extensively reduced after treatment with the three drug regimens. This study confirmed that the treatment of urinary schistosomiasis with the combination of praziquantel and artesunate is safe and more effective than treatment with either drug alone.     

Exposure assessment of phthalate esters in Japanese pregnant women by using urinary metabolite analysis

Objectives  Our objectives were (1) to evaluate whether single spot urine is suitable media for longer-term phthalate esters exposure assessment, and (2) to estimate intake level of phthalate esters of Japanese pregnant women using urinary metabolites as an indicator of prenatal exposure level in their offspring. Methods  We analyzed nine metabolites (MMP, MEP, MnBP, MBzP, MEHP, MEOHP, MEHHP, MINP, MnOP) of seven phthalate esters in spot urine samples from 50 pregnant women by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Using four urine samples collected from each of 12 subjects from 50 pregnant women within 5–12 weeks, we compared intra- and interindividual variation in urinary metabolites by calculation of intraclass correlation coefficient (ICC). We estimated daily intakes of 50 pregnant women from their urinary metabolite concentrations. Results  ICCs for seven phthalate metabolite concentrations in single spot urine samples were: MMP (0.57), MEP (0.47), MnBP (0.69), MBzP (0.28), MEHP (0.51), MEHHP (0.43), and MEOHP (0.41) in 12 pregnant women. Phthalate ester metabolites had high detection rates in 50 subjects. The mean daily intake ranged from 0.01 to 2 μg/kg per day. The daily intake levels in all subjects were lower than corresponding tolerable daily intake (TDI) set by the European Food Safety Authority (EFSA), though maximum value for DnBP of 6.91 μg/kg per day accounted for 70% of TDI value. Conclusions  Higher ICCs indicated that phthalate metabolite levels in single spot urine could reflect longer-term exposure to the corresponding diesters of subjects. Although the current exposure level was less than TDIs, further studies and exposure monitoring are needed to reveal the toxicity of phthalate esters to sensitive subpopulation.     

Postexercise rehydration in man: The effects of osmolality and carbohydrate content of ingested drinks

ObjectiveThis study investigated the effect of the osmolality and carbohydrate content of drinks on their rehydration effectiveness after exercise-induced dehydration.MethodsSix healthy male volunteers were dehydrated by 1.9 ± 0.1% of body mass by intermittent cycle ergometer exercise in the heat before ingesting one of three solutions with different carbohydrate contents and osmolalities over a period of 1 h. Thirty minutes after the cessation of exercise, subjects drank a volume that amounted to 150% (130–150, median [range]) of their body mass loss. Drinks contained 25 mmol/L Na⁺ and 0%, 2%, or 10% glucose with osmolalities of (mean ± SD) 79 ± 4, 193 ± 5, and 667 ± 12 mosm/kg, respectively. Blood and urine samples were collected before exercise, after exercise, and 0, 1, 2, 3, 4, and 6 h after the end of the rehydration period.ResultsSignificantly more of the ingested fluid was retained in the 10% trial (46 ± 9%) than in the 0% trial (27 ± 13%), with 40 ± 14% retained in the 2% trial. Subjects remained euhydrated for 1 h longer in the 10% glucose trial than in the 2% glucose trial. In the 2% glucose trial, plasma volume was elevated immediately after and 1 h after rehydration.ConclusionThis study suggests that, following the rehydration protocol used, hypertonic glucose-sodium drinks may be more effective at restoring and maintaining hydration status after sweat loss than more dilute solutions when the sodium concentration is comparable.     

Longitudinal Effects of LAAM and Methadone Maintenance on Heroin Addict Behavior

Levo-alpha-acetylmethadol maintenance (LAAM) was compared to methadone maintenance (MM) on the behavioral performance of 315 heroin addicts before, during, and after 12 months of fully subsidized treatment. Assessments of drug use, criminal behavior, HIV risk behaviors, and employment and residential status were obtained at treatment intake and at 6, 12, and 18 months after admission. Treatment retention and in-treatment suppression of heroin use were significantly better for the LAAM group than for the MM group. Improvements were also noted during treatment in criminal behavior, criminal justice involvement, and employment status, and there were reductions in injection HIV risk and number of sexual partners. Most significant effects were primarily related to active participation in maintenance treatment. Under subsidized treatment, retention rates were two to four times that of similar clients in local community programs during the same period. LAAM was a useful and a potentially important addition to treatment options for opiate addiction, conferring greater retention and opiate suppression benefits. Its removal from application provides a historical lesson concerning the introduction of new medications into addiction health services. Douglas Longshore died December 2005.     

基于“血不利则为水”理论探讨乳腺癌术后上肢淋巴水肿辨治

“血不利则为水”乃《金匮要略》提出的著名论断,由此形成的“血水同治法”极大丰富了水肿病治疗。本文结合乳腺癌术后上肢淋巴水肿的临床特点,通过探讨“血不利则为水”的内涵及其病变过程中因“血不利”而致上肢肿胀的机理,认为活血利水法是防治乳腺癌术后上肢淋巴水肿的关键大法,具体应用中当结合益气行气、滋阴清热、疏肝健脾、化痰通络等法。     

An expanded role for dietitians in maximising retention in nutrition and lifestyle intervention trials: implications for clinical practice

The demand for clinical trials targeting lifestyle intervention has increased as a result of the escalation in obesity, diabetes mellitus and cardiovascular disease. Little is published about the strategies that dietitians have used to successfully screen potential study volunteers, implement interventions and maximise adherence and retention in large multicentre National Institutes of Health funded nutrition and lifestyle intervention clinical trials. This paper discusses an expanded role for the contributions of dietitians as members of an interdisciplinary team based on research experiences in the Diabetes Control and Complications Trial, Diabetes Prevention Program and Look AHEAD (Action for Health in Diabetes). Many of the strategies and insights discussed are also relevant to effective clinical practice. Dietitians need to broaden their scope of practice so that they are integrated proactively into the screening and intervention phases of large clinical trials to maximise retention and adherence to assigned nutrition, lifestyle and behavioural interventions. The skills of dietitians are a unique fit for this work and it is important that investigators and project managers consider including them in both the screening and intervention phases of such clinical trials to maximise retention results.     

Volatile oil composition and antiproliferative activity of Laurus nobilis, Origanum syriacum, Origanum vulgare, and Salvia triloba against human breast adenocarcinoma cells

Medicinal plants and culinary herbs have gained importance in the last decade as cytotoxic and antitumor agents. We hypothesized that some of the commonly used spices with reported antimicrobial activity might have antiproliferative activity. In the present study, selected spices used in Jordan were chemically analyzed and investigated for their antiproliferative activity to the adenocarcinoma of breast cell line (MCF7). The composition of the essential oils of Laurus nobilis L, Origanum syriacum L, Origanum vulgare L, and Salvia triloba L was analyzed by gas chromatography-mass spectrometry. The antiproliferative activities of the hydrodistilled volatile oils and the crude ethanol and water extracts were evaluated using the sulphorhodamine B assay. 1,8-Cineol was the major constituent in the hydrodistilled oils of both plants, L nobilis and S triloba, with concentrations of 40.91% and 45.16%, respectively. The major constituent of O syriacum was the carvacrol (47.10%), whereas that of O vulgare was trans-sabinene hydrate (27.19%). The ethanol crude extracts of O syriacum, L nobilis, and S triloba showed antiproliferative activity to MCF7 with IC₅₀ values 6.40, 24.49, and 25.25 μg/mL, respectively. However, none of the hydrodistilled essential oils of the tested plant species or their aqueous extracts demonstrated cytotoxic activity.     

2型糖尿病患者动态动脉硬化指数与尿白蛋白/肌酐比值的关系

目的探讨2型糖尿病患者动态动脉硬化指数(ambulatory arterial stiffness index,AASI)与尿白蛋白/肌酐比值的关系。方法纳入152例糖尿病患者,其中合并高血压者82例,11例无糖尿病、高血压者为正常对照,进行24 h动态血压监测,计算AASI,并检测尿白蛋白、肌酐,计算尿白蛋白/肌酐比值(ACR)。检测血脂,血肌酐等指标,计算肾小球滤过率(GFR)。结果糖尿病合并高血压患者的AASI、ACR高于非合并高血压者(P0.05)。正常对照组、正常白蛋白尿组、微量白蛋白尿组和大量白蛋白尿组糖尿病患者的AASI分别为(0.33±0.07),(0.46±0.12),(0.57±0.10),(0.74±0.08),两两相比均有差异(P0.05)。AASI≥0.55组与AASI0.55组的糖尿病患者的ACR相比增高(P0.05)。(2)单因素分析显示AASI与ACR呈正相关(r=0.692,P=0.000),与GFR负相关(r=-0.16,P=0.042);多元回归分析发现AASI仅与ACR正相关。结论 2型糖尿病患者合并高血压患者的AASI高于非合并高血压患者,AASI与ACR有关。     

多因素干预降低2型糖尿病患者尿白蛋白与肌酐比率

目的观察为期两年的多因素强化干预治疗对2型糖尿病(T2DM)患者尿白蛋白/肌酐比率(UACR)的影响。方法对102例T2DM患者强化控制血糖、血压和血脂,随访2年,追踪观察强化控制前后的85例患者血糖、血压、血脂、BMI和UACR的变化,并进行相关及回归分析。结果T2DM患者血糖、血压和血脂强化治疗后,UACR降低[(31±26)mg/gvs(44±46)mg/g,P0.05];相关及回归分析显示糖化血红蛋白和收缩压的变化值与UACR变化值呈显著正相关(r值分别为0.507和0.358,P0.05),糖化血红蛋白和收缩压的变化值是影响UACR变化的主要因素。结论血糖、血压及血脂的强化控制,尤其是严格控制糖化血红蛋白及收缩压,能降低T2DM患者的UACR,减低糖尿病并发症发生的风险。