Urinary mutagenicity as a biomarker in workers exposed to benzidine: correlation with urinary metabolites and urothelial DNA adducts

Urinary mutagenicity has been used in occupational and epidemiological studies for over two decades as a cost-effective, general biomarker of exposure to genotoxic agents. However, few studies have compared urinary mutagenicity to additional biomarkers determined among low- and high-exposed groups. To address this issue, we evaluated the relationship between urinary mutagenicity and other types of biomarkers in a cross-sectional study involving 15 workers exposed to the urinary bladder carcinogen benzidine (BZ, high exposure), 15 workers exposed to BZ-dyes (low exposure), and 13 unexposed controls in Ahmedabad, India. Urinary organics were extracted by C18/methanol and evaluated for mutagenicity in the presence of S9 in the Salmonella strain YG1024, which is a frameshift strain that overproduces acetyltransferase. The results were compared to biomarker data reported recently from the same urine samples (Rothman et al., Proc. Natl Acad. Sci. USA, 93, 5084- 5089, 1996) that included a metabolite biomarker (the sum of the urinary levels of BZ + N-acetylbenzidine + N,N'-diacetylbenzidine) and a DNA adduct biomarker [a presumptive N-(3'-phosphodeoxyguanosin-8-yl)- N'-acetylbenzidine (C8dG-ABZ) DNA adduct in exfoliated urothelial cells]. The mean +/- SE urinary mutagenicity (revertants/micromol of creatinine) of the low-exposure (BZ-dye) workers was 8.2 +/- 2.4, which was significantly different from the mean of the controls (2.8 +/- 0.7, P = 0.04) as was that of the mean of the high-exposure (BZ) workers (123.2 +/- 26.1, P < 0.0001). Urinary mutagenicity showed strong, positive correlations with urinary metabolites (r = 0.88, P < 0.0001) and the level of the presumptive C8dG-ABZ urothelial DNA adduct (r = 0.59, P = 0.0006). A strong association was found between tobacco use (bidi smoking) and urinary mutagenicity among the controls (r = 0.68, P = 0.01) but not among the exposed workers (r = 0.18, P = 0.11). This study confirms the ability of a biomarker such as urinary mutagenicity to detect low-dose exposures, identify additional genotoxic exposures among the controls, and correlate strongly with urinary metabolites and DNA adducts in the target tissue (urinary bladder epithelia) in humans.      

Comprehensive Australasian multicentre dosimetric intercomparison: Issues,logistics and recommendations

The present paper describes the logistics of the 2004–2008 Australasian Level III Dosimetry Intercomparison. Dosimetric intercomparisons (or ‘audits’) can be used in radiotherapy to evaluate the accuracy and quality of radiation delivery. An intercomparison was undertaken in New Zealand and Australia to evaluate the feasibility and logistics of ongoing dosimetric intercomparisons that evaluate all steps in the radiotherapy treatment process, known as a ‘Level III’ intercomparison. The study commenced in 2002 with the establishment of a study team, definition of the study protocol, acquisition of appropriate equipment and recruitment of participating radiotherapy centres. Measurements were undertaken between October 2004 and March 2008, and included collation of data on time, costs and logistics of the study. Forty independent Australian and New Zealand radiotherapy centres agreed to participate. Measurement visits were made to 37 of these centres. Data is presented on the costs of the study and the level of support required. The study involved the participation of 16 staff at the study centre who invested over 4000 hours in the study, and of over 200 professionals at participating centres. Recommendations are provided for future phantom‐based intercomparisons. It is hoped that the present paper will be of benefit to any centres or groups contemplating similar activities by identifying the processes involved in establishing the study, the potential hazards and pitfalls, and expected resource requirements.     

Measurement of Lung Tissue Mass in Interstitial Lung Disease

A gamma camera and 99m Technetium were used to obtain transmissionand emission scans of the thorax in order to estimate transthoracictissue thickness, and volumes of blood and interstitial tissuein each pixel of the gamma camera image. This technique hasbeen applied to six patients with stage 2/3 pulmonary sarcoidosisand eight with cryptogenic fibrosing alveolitis and age andsex-matcehed control groups without lung disease. In both conditionstransthoracic tissue thickness was significantly increased:mean values (SD) were 14.6 (1.8) cm in cryptogenic fibrosingalveolitis and 12.3 (2.2) cm in stage 2/3 sarcoidosis. Thiswas partially accounted for by an increase in the interstitialfluid compartment. Blood volume was unaffected. Measurementof transthoracic tissue thickness involves minimal radiationexposure and may be of value in monitoring these diseases; measurementof interstitial fluid volume may give information on diseaseactivity.     

雷公藤红素抑制抗体形成及抗炎作用

雷公藤红素是雷公藤主妻活性成分之一,本支报道它在试管内及整体均明显抑制小鼠脾细胞溶血空斑细胞的形成,此作用与浓度呈依赖关系。对手大鼠实验性棉球肉芽肿的形成,小鼠二硝基氧苯。(DNCB)所致迟发型超敏反应均有明显抑制作用,回时还观察到它能延长戊巴比妥钠致小鼠睡眠时间。     

Performance and thermoregulatory effects of chronic bupropion administration in the heat

The combination of acute dopamine/noradrenaline reuptake inhibition (bupropion; BUP) and heat stress (30°C) significantly improves performance (9%). Furthermore the maintenance of a higher power output resulted in the attainment of significantly higher heart rates and rectal temperatures—above 40°C—in the BUP trial compared to the placebo trial. Since BUP is an aid to cease smoking that is taken for longer periods, question remains if similar performance and thermoregulatory effects are found following administration of BUP over several days (10 days). The purpose of the present study was to examine the effects of chronic BUP on exercise performance, thermoregulation and hormonal variables in the heat. Eight trained male cyclists participated in the study. Subjects completed two trials consisting of 60 min fixed intensity exercise (55% W _max) followed by a time trial (TT) in a double-blind randomized crossover design. Exercise was performed in 30°C. Subjects took either placebo (PLAC) or BUP (Zyban™) for 3 days (150 mg), followed by 300 mg for 7 days. Chronic BUP did not influence TT performance (BUP 40′42″ ± 4′18″; PLAC 41′36″ ± 5′12″), but significantly increased core temperature (P = 0.030). BUP significantly increased circulating growth hormone levels (PLAC: 9.8 ± 5.8 ng L⁻¹; BUP: 13 ± 6.8 ng L⁻¹; P < 0.008). Discussion/conclusion: Chronic BUP did not influence TT performance in 30°C and subjects did not reach core temperature values as high as observed during the acute BUP study. It seems that chronic administration results in an adaptation of central neurotransmitter homeostasis, resulting in a different response to the drug.     

Effect of Ca(OH)2 Addition on the Engineering Properties of Sodium Sulfate Activated Slag

Alkali-activated slag is considered as a sustainable construction material due to its environmentally friendly nature. To further promote the sustainable nature of alkali-activated slag, a sodium sulfate activator is suggested to be used since it can be obtained naturally and generates lower greenhouse gas emissions. However, the mixtures activated by sodium sulfate exhibit low early strength and very long setting times. This study investigates the effects of calcium hydroxide (Ca(OH)₂) addition on some engineering properties such as rheology, setting time, mechanical properties, porosity, and microstructure of sodium sulfate activated ground granulated blast furnace slag (GGBFS). Furthermore, the changes of chemical groups in reaction products and phase identification have been evaluated by Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction. Test results showed that Ca(OH)₂ addition can substantially increase the reaction rate and the compressive strength at early ages. In addition, the very long setting times of the sodium sulfate-activated mixtures were shortened by the addition of Ca(OH)₂. SEM analysis confirmed that the incorporation of excessive amounts of Ca(OH)₂ could lead to a less well-packed microstructure although the reaction degree of GGBFS remained the same at later ages as compared to the sodium sulfate mixture. It was also revealed that in case of the Ca(OH)₂ addition into sodium sulfate activator, the main reaction products are chain-structured C-A-S-H gels and ettringite.     

Corticospinal state variability and hemispheric asymmetries in motivational tendencies

This transcranial magnetic stimulation (TMS) study examined interrelations between asymmetrical hemispheric differences in the degree of variability of corticospinal excitability levels and motivational tendencies. The relative standard deviation in motor evoked potentials (MEP) to single pulse TMS over the left and right primary motor cortex, and approach- and avoidance-related motivational tendencies were investigated in sixty right-handed healthy volunteers. Results showed that subjects exhibited significantly higher state variability in the left as compared to the right frontal cortex and subjects displayed a dominant pattern of approach versus avoidance related motivational tendencies. Differences in left-right corticospinal state variability and approach-avoidance related motivation were significantly correlated and are consistent with the frontal lateralization model of motivational direction. This study demonstrates that MEP variability may provide an additional means for studying non-stationary properties of corticospinal excitability in relation to hemispheric asymmetries and motivational tendencies.