Sulfotransferase 1A1 genotype as a potential modifier of breast cancer risk among premenopausal women

SULT1A1 is involved in biotransformation of many endogenous and exogenous substrates, such as drugs, hormones and tobacco smoke carcinogens. A polymorphism in the sulfotransferase 1A1 gene (SULT1A1) results in an amino acid change from Arg to His at codon 213. The His allele (SULT1A1*2) has been shown to encode a protein with much lower catalytic activity than the protein encoded by the Arg allele (SULT1A1*1). We examined whether this polymorphism modified breast cancer risk in a Finnish-Caucasian study population consisting of 483 breast cancer patients and 482 healthy population controls. No significant genotype effects were seen in the overall breast cancer risk. However, a decreased risk of breast cancer was found among premenopausal women with at least three pregnancies and at least one SULT1A1*2 allele (odds ratio = 0.23, 95% confidence interval = 0.09-0.63) compared to women with two SULT1A1*1 alleles. Our results suggest that the SULT1A1 genotype is not an important risk factor for breast cancer in general, but may modify the risk among premenopausaul women with high parity.     

Vitamin D receptor gene polymorphism as an important modifier of positive family history related breast cancer risk

The association between vitamin D receptor (VDR) gene polymorphisms and diseases such as breast cancer, prostate cancer and osteoporosis has been extensively investigated during recent years. To date, several polymorphisms have been found in the VDR gene. In this Finnish case-control study, comprising 483 breast cancer patients and 482 healthy population controls, we investigated the association between altered breast cancer risk and two polymorphisms in the 3' end of the gene detectable with ApaI and TaqI restriction enzymes. A statistically significant difference was observed in the ApaI genotype distribution between cases and controls. Women with the VDR variant a allele containing genotypes showed a decreased risk for breast cancer [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.54-0.98] compared to women with the AA genotype. This association was especially strong among women with a positive family history of breast cancer (OR 0.14, 95% CI 0.03-0.76). Moreover, there was a trend (P for trend = 0.0007) for decreased risk with increasing number of variant alleles. The lowest risk of breast cancer was seen for the women with the aa genotype (OR 0.03, 95% CI 0.003-0.31) compared to women with the AA genotype. A tendency of decreased risk of breast cancer was also observed for the TaqI T allele containing genotypes (Tt and TT) (OR 0.68, 95% CI 0.41-1.12), but because the distribution of Taql alleles in the controls missed the Hardy-Weinberg equilibrium (P = 0.01), we were unable to properly assess the potential impact of the TaqI polymorphism in breast cancer susceptibility. In conclusion, our results suggest that the VDR ApaI genotype may be an important modifier of individual breast cancer risk among Finnish women, especially if they have a positive family history of breast cancer.     

Regional effects of donepezil and rivastigmine on cortical acetylcholinesterase activity in Alzheimer's disease

Donepezil and rivastigmine are acetylcholinesterase (AChE) inhibitors used to improve cholinergic neurotransmission and cognitive function in Alzheimer's disease (AD). This study examined direct effects of these drugs on AChE activity in the frontal, temporal, and parietal cortices in AD. Six AD patients were scanned with positron emission tomography before and after 3 months of treatment with donepezil (10 mg/day), and five AD patients were scanned before and after 3 to 5 months of treatment with rivastigmine (9 mg/day). Healthy unmedicated controls were imaged twice to evaluate the reproducibility of the method. A specific AChE tracer, [methyl-11C]N-methyl-piperidyl-4-acetate, and a 3D positron emission tomography system with MRI coregistration were used for imaging. Treatment with donepezil reduced the AChE activity (k3 values) in the AD brain by 39% in the frontal (p < 0.001, Bonferroni corrected), 29% in the temporal (p = 0.02, corrected) and 28% in the parietal cortex (p = 0.05, corrected). The corresponding levels of inhibition for rivastigmine were 37% (p = 0.003, corrected), 28% (p = 0.03, uncorrected) and 28% (p = 0.05, corrected). When the treatment groups were combined, the level of AChE inhibition was significantly greater in the frontal cortex compared to the temporal cortex (p = 0.03, corrected). The test-retest analysis with healthy subjects indicated good reproducibility for the method, with a nonsignificant 0% to 7% intrasubject variability between scans. The present study provides first evidence for the effect of rivastigmine on cortical AChE activity. Our results indicate that the pooled effects of donepezil and rivastigmine on brain AChE are greater in the frontal cortex compared to the temporal cortex in AD. This regional difference is probably related to the prominent temporoparietal reduction of AChE in AD. We hypothesize that the clinical improvement in behavioral and attentional symptoms of AD due to AChE inhibitors is associated with the frontal AChE inhibition.     

Functional and morphological effects of styrene on the auditory system of the rat

The effect of inhaled styrene on the structure and function of the auditory organ of the male Wistar rat was studied. The animals were exposed either to 600, 300 or 100 ppm styrene (12 h/day, 5 days/week, for 4 weeks). Auditory sensitivity was tested prior to and after the exposure by auditory brain stem audiometry (ABR) at frequencies of 1.0, 2.0, 4.0 and 8.0 kHz. Inner ear morphological changes were studied by light- and electron-microscopy. Exposure to 600 ppm styrene caused a 3 dB hearing loss only at the highest test frequency (8 kHz). Quantitative morphological analysis of cochlear hair cells (cytocochleograms) showed that 600 ppm styrene caused a severe outer hair cell (OHC) loss particularly in the third OHC row of the upper basal and lower middle coil. The inner hair cells were usually intact. Exposure to lower styrene concentrations (100 and 300 ppm) caused no unequivocal functional deficit or hair cell damage. We conclude that there appears to be a concentration threshold for styrene ototoxicity in rats (between 300 and 600 ppm).     

Insulin- and exercise-stimulated skeletal muscle blood flow and glucose uptake in obese men

OBJECTIVE: Insulin resistance in obese subjects results in the impaired use of glucose by insulin-sensitive tissues, e.g., skeletal muscle. In the present study, we determined whether insulin resistance in obesity is associated with an impaired ability of exercise to stimulate muscle blood flow, oxygen delivery, or glucose uptake. RESEARCH METHODS AND PROCEDURES: Nine obese (body mass index = 36 +/- 2 kg/m(2)) and 11 age-matched nonobese men (body mass index = 22 +/- 1 kg/m(2)) performed one-legged isometric exercise during hyperinsulinemia. Rates of femoral muscle blood flow, oxygen consumption, and glucose uptake were measured simultaneously in both legs using [(15)O]H(2)O, [(15)O]O(2), [(18)F]fluoro-deoxy-glucose, and positron emission tomography. RESULTS: The obese subjects exhibited resistance to insulin stimulation of glucose uptake in resting muscle, regardless of whether glucose uptake was expressed per kilogram of femoral muscle mass (p = 0.001) or per the total mass of quadriceps femoris muscle. At similar workloads, oxygen consumption, blood flow, and glucose uptake were lower in the obese than the nonobese subjects when expressed per kilogram of muscle, but similar when expressed per quadriceps femoris muscle mass. DISCUSSION: We conclude that obesity is characterized by insulin resistance of glucose uptake in resting skeletal muscle regardless of how glucose uptake is expressed. When compared with nonobese individuals at similar absolute workloads and under identical hyperinsulinemic conditions, the ability of exercise to increase muscle oxygen uptake, blood flow, and glucose uptake per muscle mass is blunted in obese insulin-resistant subjects. However, these defects are compensated for by an increase in muscle mass.     

Comparison of knowledge, attitudes and behaviour regarding smoking among Estonian and Finnish physicians

Summary. Objectives: To compare smoking behaviour, attitudes and opinions towards smoking and smoking cessation among Estonian and Finnish physicians. Methods: A cross-sectional postal survey using a self-administered questionnaire was carried out among 2 480 Estonian and 2 075 Finnish physicians. Results: Daily smoking prevalence was higher among Estonian physicians than among their Finnish counterparts in both male (18.6% and 6.7%) and female (6.6% and 3.6%). Compared to Estonia, physicians in Finland more often agreed that smoking is very harmful to their health, that trying to convince people to stop smoking is their responsibility and that smoking prevention should be part of the normal and special training of health professionals. In both countries, non-smoking physicians held more unfavourable attitudes towards smoking than those who were smoking. Conclusions: Physicians’ own smoking patterns and quitting behaviour are important because physicians serve as models for their patients and play a key role in the reinforcement of smoke-free health facilities. These results remain a challenge to medical educators, especially in Estonia. Estonia needs to improve medical education in terms of motivating physicians to ask about the smoking patterns of their patients and of training medical students and resident physicians to counsel their patients to stop smoking.

---

Zusammenfassung. Vergleich der Kenntnisse, Einstellungen und des eigenen Verhaltens bezüglich des Rauchens zwischen der estnischen und der finnischen ?rzteschaft Fragestellung: Es werden die Unterschiede in den Rauchgewohnheiten, in der Einstellung und den Ansichten über das Rauchen und die Raucherentw?hnung zwischen estnischen und finnischen ?rzten untersucht. Methoden: Eine Querschnittsstudie mit selbstauszufüllendem Fragebogen wurde bei 2 480 estnischen und 2 075 finnischen ?rzten durchgeführt. Resultate: Die t?gliche Rauchpr?valenz war sowohl bei den ?rzten (18,6%) als auch bei den ?rztinnen (6,6%) in Estland h?her als bei ihren finnischen Kollegen (6,7%) und Kolleginnen (3,6%). Verglichen mit Estland, waren ?rzte in Finnland ?fters der Meinung, dass Rauchen sehr sch?dlich für ihre Gesundheit ist, dass sie dafür verantwortlich sind, ihre Patienten davon zu überzeugen, dass es wichtig ist, aufzuh?ren zu rauchen, und dass Tabakpr?vention ein Teil der normalen und speziellen Ausbildung von Gesundheitsfachleuten sein sollte. In beiden L?ndern hatten nichtrauchende ?rzte gegenüber dem Rauchen eine st?rker ausgepr?gte negative Haltung als die rauchenden. Schlussfolgerung: Dem Rauchverhalten der ?rzteschaft selbst kommt wegen deren Vorbildfunktion gegenüber den Patienten eine Schlüsselrolle bei der Erreichung von rauchfreien Gesundheitseinrichtungen zu. Diese Resultate zeigen, dass die medizinische Ausbildung vor allem in Estland betreffend Rauchen noch ein Verbesserungspotential hat. Estland muss die medizinische Ausbildung so verbessern, dass ?rzte mehr motiviert sind, mit ihren Patienten über das Rauchen zu sprechen. Zudem sollten Studierende der medizinischen F?cher aber auch bereits praktizierende ?rzte dahingehend geschult werden, dass sie ihre Patienten st?rker zur Raucherentw?hnung motivieren k?nnen.

---

Résumé. Connaissances, attitudes et comportements des médecins estoniens et finlandais envers le tabagisme Objectifs: Comparer les habitudes de consommation de tabac, les attitudes et les opinions concernant le tabagisme et la cessation tabagique parmi les médecins estoniens et finlandais. Méthodes: Enquête par questionnaire auto administré, auprès de 2 480 médecins estoniens et de 2 075 médecins finlandais. Résultats: La prévalence du tabagisme était plus élevée parmi les médecins estoniens que parmi leurs collègues finlandais, tant pour les hommes (18,6% et 6,7%) que pour les femmes (6,6% et 3,6%). Les médecins en Finlande ont accepté plus souvent qu’en Estonie l’idée que le tabagisme est très nuisible pour leur santé, qu’il est de leur responsabilité de convaincre les gens de cesser de fumer et que la prévention du tabagisme devrait être un sujet normalement abordé dans la formation des professionnels de la santé. Dans les deux pays, les médecins non-fumeurs avaient une attitude plus défavorable envers le tabagisme que les médecins fumeurs. Conclusion: L’attitude des médecins concernant le tabagisme et la cessation tabagique est importante car ils servent de modèles pour leurs patients et ils jouent un r?le-clé pour assurer que le système de santé offre un environnement sans tabac. L’Estonie surtout a besoin d’améliorer la formation des médecins pour inciter ces derniers à interroger leurs patients sur leurs habitudes tabagiques et pour enseigner aux étudiants et aux internes comment informer leurs patients sur les programmes de cessation tabagique.

     

Infection with Possible Novel Parapoxvirus in Horse,Finland, 2013

A horse in Finland exhibited generalized granulomatous inflammation and severe proliferative dermatitis. After euthanization, we detected poxvirus DNA from a skin lesion sample. The virus sequence grouped with parapoxviruses, closely resembling a novel poxvirus detected in humans in the United States after horse contact. Our findings indicate horses may be a reservoir for zoonotic parapoxvirus.     

Toxicokinetics of methyl tert-butyl ether (MTBE) and tert-amyl methyl ether (TAME) in humans, and implications to their biological monitoring

Healthy male volunteers were exposed via inhalation to gasoline oxygenates methyl tert-butyl ether (MTBE) or tert-amyl methyl ether (TAME). The 4-hr exposures were carried out in a dynamic chamber at 25 and 75 ppm for MTBE and at 15 and 50 ppm for TAME. The overall mean pulmonary retention of MTBE was 43 +/- 2.6%; the corresponding mean for TAME was 51 +/- 3.9%. Approximately 52% of the absorbed dose of MTBE was exhaled within 44 hr following the exposure; for TAME, the corresponding figure was 30%. MTBE and TAME in blood and exhaled air reached their highest concentrations at the end of exposure, whereas the concentrations of the metabolites tert-butanol (TBA) and tert-amyl alcohol (TAA) concentrations were highest 0.5-1 hr after the exposure and then declined slowly. Two consecutive half-times were observed for the disappearance of MTBE and TAME from blood and exhaled air. The half-times for MTBE in blood were about 1.7 and 3.8 hr and those for TAME 1.2 and 4.9 hr. For TAA, a single half-time of about 6 hr best described the disappearance from blood and exhaled air; for TBA, the disappearance was slow and seemed to follow zero-order kinetics for 24 hr. In urine, maximal concentrations of MTBE and TAME were observed toward the end of exposure or slightly (< or = 1 hr) after the exposure and showed half-times of about 4 hr and 8 hr, respectively. Urinary concentrations of TAA followed first-order kinetics with a half-time of about 8 hr, whereas the disappearance of TBA was slower and showed zero-order kinetics at concentrations above approx. 10 micro mol/L. Approximately 0.2% of the inhaled dose of MTBE and 0.1% of the dose of TAME was excreted unchanged in urine, whereas the urinary excretion of free TBA and TAA was 1.2% and 0.3% within 48 hr. The blood/air and oil/blood partition coefficients, determined in vitro, were 20 and 14 for MTBE and 20 and 37 for TAME. By intrapolation from the two experimental exposure concentrations, biomonitoring action limits corresponding to an 8-hr time-weighted average (TWA) exposure of 50 ppm was estimated to be 20 micro mol/L for post-shift urinary MTBE, 1 mu mol/L for exhaled air MTBE in a post-shift sample, and 30 micro mol/L for urinary TBA in a next-morning specimen. For TAME and TAA, concentrations corresponding to an 8-hr TWA exposure at 20 ppm were estimated to be 6 micro mol/L (TAME in post-shift urine), 0.2 micro mol/L (TAME in post-shift exhaled air), and 3 micro mol/L (TAA in next morning urine).