Mutagenicity of bisphenol A (4,4'-isopropylidenediphenol) in vitro: effects of nitrosylation

Bisphenol A (4,4'-isopropylidenediphenol) is a common component of polycarbonate plastics and epoxy resins. Since bisphenol A-containing plastics and resins have found uses in food-contact items, its potential migration into foodstuffs and possible health consequences have been the focus of many recent studies. However, the potential mutagenic activation of bisphenol A by nitrosylation has received little attention. Incubation of bisphenol A with sodium nitrite under acidic conditions produced a yellow-brown product. When nitrosylated bisphenol A was tested in the Ames Salmonella/microsome assay at 100 ng to 1 mg/plate, dose-dependent increases in mutagenicity were found in both TA98 and TA100 Salmonella strains. These results indicated the presence of a direct-acting mutagenic activity causing both frameshift and base pair mutations, respectively. When compared to colony formation in untreated controls, the addition of rat liver S9 for metabolic activation had little influence on revertant colony formation. Unreacted bisphenol A dissolved in DMSO, acidic buffer, or inactivated nitrosylation solution showed negligible mutagenicity. When the nature of the mutagenic changes was examined using the Ames II trade mark Assay, a variety of base pair changes was found including T:A to A:T - S9, G:C to A:T +/- S9,C:G to A:T +/- S9 and C:G to G:C +/- S9. Bisphenol A also induced frameshift mutations at G:C sites. In addition, the presence of electrophiles was shown by the production of an intensely coloured orange-red product upon incubation of nitrosylated bisphenol A with the nucleophile 4-(4'-nitrobenzyl)pyridine. These findings suggest that migration of bisphenol A into nitrite containing foodstuffs, or its ingestion in the presence of nitrite, could lead to the formation of mutagenic compounds.     

Factors associated with career satisfaction among general practitioners in Canada.

INTRODUCTION: There are important differences in rural, regional and urban general practice environments. The purpose of this study was to articulate models that explain career satisfaction among general practitioners (GPs) in these practice environments. METHODS: Of 4958 eligible physicians across Canada, 2810 (56.7%) completed a 12- page survey between January and March 2004, from whom a total of 256 GPs in rural, regional and urban communities were selected. Response bias was checked and found to be negligible. We used hierarchical regression analysis to record cumulative R2, standardized beta and significance levels as each predictor was entered. We applied weighting factors to reflect the actual physician population in Canada. RESULTS: The models explained 88.5% of the variance in career satisfaction for GPs in small towns, 88.9% for GPs in regional communities and 86.3% for GPs in urban cities. The explanatory variables consisted of distress and coping, role in community activities, the quality of health care services and access to them, intrinsic and extrinsic rewards, workload and organizational structure. CONCLUSION: Career satisfaction for small-town doctors is associated with being able to cope with stress in handling a wide variety of clinical conditions, largely on their own, but with effective collaboration from physicians in larger centres. Rural GPs also enjoy academic responsibilities. Satisfaction for GPs in regional communities also depends on coping with stress and the ability to maintain an efficiently operating set of secondary- level health services in their community. Satisfaction for urban GPs is associated with collegiality, which dampens stress, and access to a full range of health services, including community, hospital, mental health and rehabilitation services. Career satisfaction for all GPs is associated with equity, manageable workloads and effective practice management; however, all of these professional issues contribute, in small increments, to satisfaction.     

Environmental conditions and variation in levels of sun exposure among children in child care

Sun exposure in childhood is 1 of the risk factors for developing skin cancer, yet little is known about levels of exposure at this age. This is particularly important in countries with high levels of ultraviolet radiation (UVR) such as Australia. Among 49 children 3 to 5 years of age attending child care centers, UVR exposure was studied under 4 conditions in a repeated measures design; sunny days, cloudy days, teacher’s instruction to stay in the shade, and a health professionals instruction to apply sunscreen. Three different data collection methods were employed: (a) completion of questionnaire or diary by parents and researcher, (b) polysulphone dosimeter readings, and (c) observational audits (video recording). Results of this study indicated that more than half the children had been sunburnt (pink or red) and more than a third had experienced painful sunburn (sore or tender) in the last summer. Most wore short sleeve shirts, short skirts or shorts and cap, that do not provide optimal levels of skin protection. However, sunscreen was applied to all exposed parts before the children went out to the playground. Over the period of 1 hr (9–10 a.m.) the average amount of time children spent in full sun was 22 min. On sunny days there was more variation across children in the amount of sun exposure received. While the potential amount of UVR exposure for young children during the hour they were outside on a sunny day was 1.45 MED (Minimum Erythemal Dose), they received on average 0.35 MED, which is an insufficient amount to result in an erythemal response on fair skin even without the use of sunscreen.     

BMI in the Trois‐Rivières study: Child–adult and child–parent relationships

This study evaluated intraindividual child–adult and interindividual child–parent relationships of body mass index (BMI) using data from the Trois‐Rivières semilongitudinal study of growth and development. Intraindividual correlations between age 12 and 35 years were substantial (r² = 36% of variance in women, 30% of variance in men). Interindividual child–parent correlations for mothers and fathers age 36.6 ± 0.4 and 39.5 ± 0.4 years, respectively, were very low to low for daughters age 12 years (r = 0.09, NS and 0.34, P < 0.001 vs. father and mother, respectively) but all very low for sons age 12 years (r = 0.07, NS and 0.16, NS vs. father and mother, respectively). A multiple regression analysis predicted adult BMI from the individual's BMI at 10, 11, 12 years plus the maternal and paternal BMIs as calculated from self‐reported heights and weights. The BMI at age 12 years was a better predictor of adult BMI than the parental BMI in both men and women (P < 0.001) and multivariate analysis revealed that this index at age 12 years was the sole significant predictor of adult BMI for both men and women. The results from our study do not support the hypothesis that parental BMI is a stronger predictor of adult BMI than childhood BMI. However, useful information for the prediction and prevention of adult overweight can be obtained from the BMI at age 12 years. Our results suggest that environmental influences may be the major factor in the present obesity epidemic. Am. J. Hum. Biol. 15:187–191, 2003. © 2003 Wiley‐Liss, Inc.     

Indomethacin-mediated improvement following middle cerebral artery occlusion in cats. Effects of anesthesia

Focal cerebral ischemia initiates multiple detrimental effects in the brain. Chief among these are the regional development of ischemic edema, decreased local perfusion, altered neuronal function, and eventual infarction. To determine if pretreatment with the cyclo-oxygenase inhibitor, indomethacin, would result in improvement in these parameters, adult cats were given indomethacin or control solvent (4 mg/kg intraperitoneally twice daily) and were studied for periods up to 24 hours after right middle cerebral artery occlusion. The interaction of anesthetic agents with indomethacin was also examined in separate groups of experimental animals using pentobarbital and ketamine. In cats allowed to recover from pentobarbital anesthesia, indomethacin reduced gray and white matter edema at 6 and 24 hours after occlusion (p less than 0.05). This was noted in densely areas (indomethacin = 84.3%, control = 87.5%), "penumbra" regions (indomethacin = 82.5%, control = 85.3%), and in nonischemic zones (indomethacin = 81.5%, control = 82.3%) at 24 hours. Somatosensory evoked potential amplitude and central latency were also improved in the indomethacin group (p less than 0.05), as was cerebral perfusion (p less than 0.05). In animals anesthetized with continuous ketamine administration, cerebral edema and perfusion as well as evoked potentials were not significantly improved in any region by indomethacin. Regional cerebral blood flow in the group was increased by indomethacin in the nonischemic opposite hemisphere (indomethacin = 64.7 cc/100 gm/min, control = 48.5 cc/100 gm/min, p less than 0.05), but not in the penumbra region of the ischemic hemisphere (indomethacin = 15.0 cc/100 gm/min, control = 18.6 cc/100 gm/min, p less than 0.05), when measured 4 hours after occlusion. This suggested a steal phenomenon. Beneficial effects of indomethacin were evident in the presence of pentobarbital, but not after ketamine anesthesia. This suggests a synergism dependent on decreased arachidonic acid production from pentobarbital-stabilized membranes coupled with diminished production of cyclic endoperoxides from available arachidonate due to inhibition of cyclo-oxygenase with indomethacin.     

Anastomotic false aneurysms with aortic Dacron graft after twenty-five years

One of the early diamond crimped knitted polyester (Dacron) grafts was surgically excised after implantation for 25 years in the aorto-billiac position because of false aneurysm formation at the three anastomotic sites. The sutures were no longer visible. While the areas around the false aneurysm were poorly incorporated, the graft limbs were well encapsulated with some endothelial-like cells on the luminal surface. The integrity of the graft was well preserved despite mild fraying and the disruption of one stitch.