Avaliação do potencial cancerígeno do Diuron [3-(3,4-Diclorofenil)-1,1-Dimetiluréia] no modelo de iniciação-promoção cutânea em camundongos swiss

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação da susceptibilidade de camundongos BALB/c e Swiss, hamster e Proechimys roberti à infecção por Leishmania (Viannia) Naiffi e Leishmania (Viannia) Lindenbergi

Leishmania (Viannia) naiffi e Leishmania (Viannia) lindenbergi são espécies causadoras da leishmaniose cutânea na Amazônia e apresentam grande similaridade no seu perfil isoenzimático, anticorpos monoclonais e produção de infecção inaparente em hamsters. O fato de não se ter um modelo experimental altamente suscetível à infecção por L. (V.) naiffi e L. (V.) lindenbergi, o objetivo deste estudo foi avaliar a susceptibilidade de camundongos BALB/c e Swiss, hamster e Proechimys roberti à infecção por essas duas espécies. Foram preparados inóculos com glândulas salivares e sem glândulas, associados às formas promastigotas das duas espécies de Leishmania. Doze animais de cada espécie foram divididos em quatro grupos (machos e fêmeas inoculados com glândulas salivares e machos e fêmeas sem glândulas salivares). Todos foram inoculados intradermicamente na face dorsal das duas patas traseiras e foram observados durante 90 dias. No período de 30, 60 e 90 dias pós-inoculação, os animais foram sacrificados e diferentes fragmentos de pele do local de inoculação foram divididos e utilizados na cultura in vitro, exame microscópico direto e reação em cadeia da polimerase (PCR). Não foi possível observar lesões nos animais inoculados com L. (V.) naiffi e L. (V.) lindenbergi tanto na presença ou ausência de glândulas salivares. Assim como, formas amastigotas durante 30, 60 e 90 dias após a inoculação. Na cultura, todos os animais inoculados com L. (V.) lindenbergi não desenvolveram formas promastigotas. Por outro lado, todos os grupos de camundongos BALB/c inoculados com L. (V.) naiffi apresentaram positividade quando sacrificados com 30 dias após inoculação e até 90 dias nos machos inoculados com glândulas salivares e fêmeas inoculadas sem glândulas salivares. A PCR apresentou baixa sensibilidade comparada à cultura. Desse modo, concluímos que L. (V.) naiffi e L.(V.) lindenbergi são espécies que apresentam baixa infectividade e nenhum dos animais utilizados no estudo podem ser considerados modelo experimental altamente susceptíveis à infecção por essas duas espécies.

The antioxidant response of the liver of male Swiss mice raised on a AIN 93 or commercial diet

Background: Reactive oxygen species (ROS) are formed under natural physiological conditions and are thought to play an important role in many human diseases. A wide range of antioxidants are involved in cellular defense mechanisms against ROS, which can be generated in excess during stressful conditions, these include enzymes and non-enzymatic antioxidants. The aim of this study was to evaluate the antioxidant responses of mice to two diets control, commercial and the purified AIN 93 diet, commonly used in experiments with rodents. Results: Malondialdehyde (MDA) and hydrogen peroxide (H2O2) concentrations and superoxide dismutase (SOD) and glutathione reductase (GR) activities determined in the liver were lower in the group of mice fed with the AIN 93 diet, while catalase (CAT) activity was higher in the same group, when compared to the group fed on the commercial diet. Liver glutathione peroxidase (GSH-Px) activity was similar in the groups fed on either AIN 93 or the commercial diets. Two SOD isoforms, Mn-SODII and a Cu/Zn-SODV, were specifically reduced in the liver of the AIN 93 diet fed animals. Conclusions: The clear differences in antioxidant responses observed in the livers of mice fed on the two diets suggest that the macro- and micro-nutrient components with antioxidant properties, including vitamin E, can promote changes in the activity of enzymes involved in the removal of the ROS generated by cell metabolism.

Overtraining is associated with DNA damage in blood and skeletal muscle cells of Swiss mice

Abstract: Background: The alkaline version of the single-cell gel (comet) assay is a useful method for quantifying DNA damage. Although some studies on chronic and acute effects of exercise on DNA damage measured by the comet assay have been performed, it is unknown if an aerobic training protocol with intensity, volume, and load clearly defined will improve performance without leading to peripheral blood cell DNA damage. In addition, the effects of overtraining on DNA damage are unknown. Therefore, this study aimed to examine the effects of aerobic training and overtraining on DNA damage in peripheral blood and skeletal muscle cells in Swiss mice. To examine possible changes in these parameters with oxidative stress, we measured reduced glutathione (GSH) levels in total blood, and GSH levels and lipid peroxidation in muscle samples. Results: Performance evaluations (i.e., incremental load and exhaustive tests) showed significant intra and inter-group differences. The overtrained (OTR) group showed a significant increase in the percentage of DNA in the tail compared with the control (C) and trained (TR) groups. GSH levels were significantly lower in the OTR group than in the C and TR groups. The OTR group had significantly higher lipid peroxidation levels compared with the C and TR groups. Conclusions Aerobic and anaerobic performance parameters can be improved in training at maximal lactate steady state during 8 weeks without leading to DNA damage in peripheral blood and skeletal muscle cells or to oxidative stress in skeletal muscle cells. However, overtraining induced by downhill running training sessions is associated with DNA damage in peripheral blood and skeletal muscle cells, and with oxidative stress in skeletal muscle cells and total blood.

Fine particulate matter measurements in Swiss restaurants, cafés and bars: what is the effect of spatial separation between smoking and non-smoking areas?

We performed 124 measurements of particulate matter (PM(2.5)) in 95 hospitality venues such as restaurants, bars, cafés, and a disco, which had differing smoking regulations. We evaluated the impact of spatial separation between smoking and non-smoking areas on mean PM(2.5) concentration, taking relevant characteristics of the venue, such as the type of ventilation or the presence of additional PM(2.5) sources, into account. We differentiated five smoking environments: (i) completely smoke-free location, (ii) non-smoking room spatially separated from a smoking room, (iii) non-smoking area with a smoking area located in the same room, (iv) smoking area with a non-smoking area located in the same room, and (v) smoking location which could be either a room where smoking was allowed that was spatially separated from non-smoking room or a hospitality venue without smoking restriction. In these five groups, the geometric mean PM(2.5) levels were (i) 20.4, (ii) 43.9, (iii) 71.9, (iv) 110.4, and (v) 110.3 microg/m(3), respectively. This study showed that even if non-smoking and smoking areas were spatially separated into two rooms, geometric mean PM(2.5) levels in non-smoking rooms were considerably higher than in completely smoke-free hospitality venues. PRACTICAL IMPLICATIONS: PM(2.5) levels are considerably increased in the non-smoking area if smoking is allowed anywhere in the same location. Even locating the smoking area in another room resulted in a more than doubling of the PM(2.5) levels in the non-smoking room compared with venues where smoking was not allowed at all. In practice, spatial separation of rooms where smoking is allowed does not prevent exposure to environmental tobacco smoke in nearby non-smoking areas.

Molecular epidemiology of the nasal colonization by methicillin-susceptible Staphylococcus aureus in Swiss children

Nasal carriage of Staphylococcus aureus contributes to an increased risk of developing an infection with the same bacterial strain. Genetic regulatory elements and toxin-expressing genes are virulence factors associated with the pathogenic potential of S. aureus. We undertook an extensive molecular characterization of methicillin-susceptible S. aureus (MSSA) carried by children. MSSA were recovered from the nostrils of children. The presence of Panton-Valentine leukocidin (PVL), exfoliatins A and B (exfoA and exfoB), and the toxic-shock staphylococcal toxin (TSST-1) and agr group typing were determined by quantitative PCR. A multiple-locus variable-number of tandem repeat analysis (MLVA) assay was also performed for genotyping. Five hundred and seventy-two strains of MSSA were analysed. Overall, 30% were positive for toxin-expressing genes: 29% contained one toxin and 1.6% two toxins. The most commonly detected toxin gene was tst, which was present in 145 (25%) strains. The TSST-1 gene was significantly associated with the agr group 3 (OR 56.8, 95% CI 32.0-100.8). MLVA analysis revealed a large diversity of genetic content and no clonal relationship was demonstrated among the analysed MSSA strains. Multilocus sequence typing confirmed this observation of diversity and identified ST45 as a frequent colonizer. This broad diversity in MSSA carriage strains suggests a limited selection pressure in our geographical area.

[Swiss registry for TNF-alpha blockers in children and adolescents with rheumatological diseases]

We created a registry to evaluate long term outcome, efficacy and adverse events for children treated wit TNF-alpha inhibitors in Switzerland. 106 patients (68 female/38 male) were included. 61 patients were treated with Etanercept (Enbrel) and 45 with Infliximab (Remicade). Concomitant treatment at baseline included corticosteroids in 26% and Methotrexate in 75% of the patients. Subjective disease activity three months after initiation of TNF-alpha was better in 81%, worse in 4% and stable in 15% of the patients. In total 24 adverse events in 21 patients were reported. Treatment with TNF-alpha inhibitors seems to be safe and effective for children and adolescents with rheumatologic diseases.

Lack of prophylaxis before the onset of acute venous thromboembolism among hospitalized cancer patients: the SWIss Venous ThromboEmbolism Registry (SWIVTER)

Venous thromboembolism (VTE) prophylaxis remains underutilized, particularly in cancer patients. We explored clinical predictors of prophylaxis in hospitalized cancer patients before the onset of acute VTE.

Progression of coronary artery disease during long-term follow-up of the Swiss Interventional Study on Silent Ischemia Type II (SWISSI II)

Background: This study evaluates cardiovascular risk factors associated with progression of coronary artery disease (CAD) in patientswith silent ischemia followingmyocardial infarction. Hypothesis: Coronary artery disease only progresses slowly with comprehensive risk factor intervention. Methods: A total of 104 of 201 patients (51.7%) of the Swiss Interventional Study on Silent Ischemia Type II (SWISSI II) with baseline and follow-up coronary angiography were included. All patients received comprehensive cardiovascular risk factor intervention according to study protocol. Logistic regression was used to evaluate associationsbetween baseline cardiovascular risk factors and CAD progression. Results: The mean duration of follow-upwas 10.3 ± 2.4 years. At baseline, 77.9% of patients were smokers, 45.2% had hypertension, 73.1% had dyslipidemia, 7.7% had diabetes, and 48.1% had a family history of CAD. At last follow-up, only 27 patients of the initial 81 smokers still smoked, only 2.1% of the patients had uncontrolled hypertension, 10.6%of the patientshad uncontrolled dyslipidemia, and 2.1%of the patientshad uncontrolled diabetes. Coronary artery disease progression was found in up to 81 (77.9%) patients. Baseline diabetes and younger age were associatedwith increased odds of CAD progression.The time intervalbetween baseline and follow-up angiography was also associatedwith CAD progression. Conclusion: Coronary artery disease progressionwas highly prevalent in these patients despite comprehensive risk factor intervention. Further research is needed to optimize treatment of known risk factors and to identify other unknown and potentiallymodifiable risk factors.

Inherited cavernous malformations of the central nervous system: clinical and genetic features in 19 Swiss families

Cavernous malformations (CCMs) are benign, well-circumscribed, and mulberry-like vascular malformations that may be found in the central nervous system in up to 0.5% of the population. Cavernous malformations can be sporadic or inherited. The common symptoms are epilepsy, hemorrhages, focal neurological deficits, and headaches. However, CCMs are often asymptomatic. The familiar form is associated with three gene loci, namely 7q21-q22 (CCM1), 7p13-p15 (CCM2), and 3q25.2-q27 (CCM3) and is inherited as an autosomal dominant trait with incomplete penetrance. The CCM genes are identified as Krit 1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3). Here, we present the clinical and genetic features of CCMs in 19 Swiss families. Furthermore, surgical aspects in such families are also discussed.

Oral mucosal findings related to tobacco use and alcohol consumption: a study on Swiss army recruits involving self-reported and clinical data

PURPOSE: The aim of the present study was to assess the oral mucosal health status of young male adults (aged 18 to 24 years) in Switzerland and to correlate their clinical findings with self-reported risk factors such as tobacco use and alcohol consumption. MATERIALS AND METHODS: Data on the oral health status of 615 Swiss Army recruits were collected using a standardised self-reported questionnaire, followed by an intraoral examination. Positive clinical findings were classified as (1) common conditions and anatomical variants, (2) reactive lesions, (3) benign tumour lesions and (4) premalignant lesions. The main locations of the oral mucosal findings were recorded on a topographical classification chart. Using correlational statistics, the findings were further associated with the known risk factors such as tobacco use and alcohol consumption. RESULTS: A total of 468 findings were diagnosed in 327 (53.17%) of the 615 subjects. In total, 445 findings (95.09%) were classified as common conditions, anatomical variants and reactive soft-tissue lesions. In the group of reactive soft-tissue lesions, there was a significantly higher percentage of smokers (P < 0.001) and subjects with a combination of smoking and alcohol consumption (P < 0.001). Eight lesions were clinically diagnosed as oral leukoplakias associated with smokeless tobacco. The prevalence of precursor lesions in the population examined was over 1%. CONCLUSIONS: Among young male adults in Switzerland, a significant number of oral mucosal lesions can be identified, which strongly correlate with tobacco use. To improve primary and secondary prevention, young adults should therefore be informed more extensively about the negative effects of tobacco use on oral health.

Referral practice among Swiss and non-Swiss walk-in patients in an urban surgical emergency department

To assess the relationship between nationality, gender and age and use of health services among patients visiting an urban university hospital emergency department (ED).

Supply sensitive services in Swiss ambulatory care: an analysis of basic health insurance records for 2003-2007

Swiss ambulatory care is characterized by independent, and primarily practice-based, physicians, receiving fee for service reimbursement. This study analyses supply sensitive services using ambulatory care claims data from mandatory health insurance. A first research question was aimed at the hypothesis that physicians with large patient lists decrease their intensity of services and bill less per patient to health insurance, and vice versa: physicians with smaller patient lists compensate for the lack of patients with additional visits and services. A second research question relates to the fact that several cantons are allowing physicians to directly dispense drugs to patients ('self-dispensation') whereas other cantons restrict such direct sales to emergencies only. This second question was based on the assumption that patterns of rescheduling patients for consultations may differ across channels of dispensing prescription drugs and therefore the hypothesis of different consultation costs in this context was investigated.

Antiretroviral therapy during pregnancy and premature birth: analysis of Swiss data

Background There is an ongoing debate as to whether combined antiretroviral treatment (cART) during pregnancy is an independent risk factor for prematurity in HIV-1-infected women. Objective The aim of the study was to examine (1) crude effects of different ART regimens on prematurity, (2) the association between duration of cART and duration of pregnancy, and (3) the role of possibly confounding risk factors for prematurity. Method We analysed data from 1180 pregnancies prospectively collected by the Swiss Mother and Child HIV Cohort Study (MoCHiV) and the Swiss HIV Cohort Study (SHCS). Results Odds ratios for prematurity in women receiving mono/dual therapy and cART were 1.8 [95% confidence interval (CI) 0.85–3.6] and 2.5 (95% CI 1.4–4.3) compared with women not receiving ART during pregnancy (P=0.004). In a subgroup of 365 pregnancies with comprehensive information on maternal clinical, demographic and lifestyle characteristics, there was no indication that maternal viral load, age, ethnicity or history of injecting drug use affected prematurity rates associated with the use of cART. Duration of cART before delivery was also not associated with duration of pregnancy. Conclusion Our study indicates that confounding by maternal risk factors or duration of cART exposure is not a likely explanation for the effects of ART on prematurity in HIV-1-infected women.

The Swiss IMRT dosimetry intercomparison using a thorax phantom

In 2008, a national intensity modulated radiation therapy (IMRT) dosimetry intercomparison was carried out for all 23 radiation oncology institutions in Switzerland. It was the aim to check the treatment chain focused on the planning, dose calculation, and irradiation process.