Exposure to varenicline protects against locomotor alteration in a MPTP mouse model of Parkinson's disease.

The beneficial effects of drugs that act via nicotinic acetylcholine receptors (nAChRs) on Parkinson's disease (PD) symptomatology may explain the negative correlation between cigarette smoking and risk of this neurological condition. Varenicline, an α4ß2 nAChR partial agonist approved for smoking cessation treatments, could be valuable for PD treatment. Here, we investigated varenicline effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) PD mouse model. From postnatal day (PN) 90 to PN119, male C57BL/6 mice were exposed daily to varenicline (2 mg/kg) by gavage. After that, MPTP was injected (30 mg/kg, ip) once a day for five days. At PN125, locomotor and anxiety-like effects were assessed with the open field test. At PN126, immobile behavior was assessed with the forced swimming test. At PN127, the frontal cerebral cortex was collected to evaluate dopamine and DOPAC levels. To verify whether varenicline was protective during the MPTP insult, a separate group of MPTP animals received varenicline from PN90 to PN124. MPTP reduced cortical dopamine content and increased dopamine turnover. Those effects were not reversed by varenicline treatment. Interestingly, varenicline reversed the MPTP-induced hyperactivity in the open field. Both maintenance of varenicline treatment during MPTP exposure or its interruption before MPTP exposure elicited similar results. No alterations were observed in anxiety-like behavior or in immobility time. Altogether, these findings suggested that varenicline treatment reduced the MPTP-induced hyperactivity, but did not protect against dopaminergic damage. Based on this partial protective effect, varenicline could exert neuroprotective effects on circuits that control motor activity in PD.

Exposure to varenicline protects against locomotor alteration in a MPTP mouse model of Parkinson's disease

The beneficial effects of drugs that act via nicotinic acetylcholine receptors (nAChRs) on Parkinson's disease (PD) symptomatology may explain the negative correlation between cigarette smoking and risk of this neurological condition. Varenicline, an α4β2 nAChR partial agonist approved for smoking cessation treatments, could be valuable for PD treatment. Here, we investigated varenicline effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) PD mouse model. From postnatal day (PN) 90 to PN119, male C57BL/6 mice were exposed daily to varenicline (2 mg/kg) by gavage. After that, MPTP was injected (30 mg/kg, ip) once a day for five days. At PN125, locomotor and anxiety-like effects were assessed with the open field test. At PN126, immobile behavior was assessed with the forced swimming test. At PN127, the frontal cerebral cortex was collected to evaluate dopamine and DOPAC levels. To verify whether varenicline was protective during the MPTP insult, a separate group of MPTP animals received varenicline from PN90 to PN124. MPTP reduced cortical dopamine content and increased dopamine turnover. Those effects were not reversed by varenicline treatment. Interestingly, varenicline reversed the MPTP-induced hyperactivity in the open field. Both maintenance of varenicline treatment during MPTP exposure or its interruption before MPTP exposure elicited similar results. No alterations were observed in anxiety-like behavior or in immobility time. Altogether, these findings suggested that varenicline treatment reduced the MPTP-induced hyperactivity, but did not protect against dopaminergic damage. Based on this partial protective effect, varenicline could exert neuroprotective effects on circuits that control motor activity in PD.

[Terminolateral esophagojejunostomy after gastrectomy with the biofragmentable anastomosis ring in the dog model]. / End-zu-Seit Osophagojejunostomie mit dem biofragmentierbaren Anastomosenring nach Gastrektomie am Hundemodell.

INTRODUCTION: Esophagojejunostomy after total gastrectomy still remains a high risk anastomosis with a considerable morbidity and mortality. The majority of these anastomoses are performed by the intraluminal stapler technique, yet stenoses are a known late complication even after an uneventful postoperative course. In the present study, the osophagojejunostomy with the biofragmentable anastomosis ring (BAR) was examined in dogs. METHODS: 28 dogs were randomized into a group of manual suture (n = 14) and a BAR-group (n = 14). After gastrectomy, the esophagojejunostomy was performed by hand-suture with polypropylene 4-0 in the manual suture group, and with the 25/1.5 mm BAR in the BAR-group. In both groups the Roux-en-Y jejunojejunostomy was performed by hand-suture. The dogs were evaluated on postoperative days 4, 7 and 14 with regard to macroscopy, bursting strength, tissue hydroxyproline and histology. RESULTS: There was one leakage without clinical effect in the hand-sewn group on postoperative day 4; there was no leak in the BAR-group. In observing fibre-free enteral feeding, neither functional disorders nor obstruction of the BAR were observed. The general anastomosis parameters were matchable between the groups. CONCLUSION: The infracarinal BAR-esophagojejunostomy is comparable to the hand-sewn anastomosis in the dog-model.

[Use of dust and air as indicators of environmental pollution in areas adjacent to a source of stationary lead emission]. / Uso da poeira e do ar como indicadores de contaminação ambiental em áreas circunvizinhas a uma fonte de emissão estacionária de chumbo.

This study measured lead concentrations in both the outdoor air and household dust from houses located around a lead-acid battery repair shop. Such installations are one of the largest sources of lead exposure, since outdated technology is still used, coupled with the lack of strict air-quality control programs. Measurements of the air lead concentration around the repair shop were carried out at 6 points, approximately 25 and 500 m from the shop. Over 50% of the air samples exceeded the limit of 1.5 microg Pb.m-3 (range 0.03 - 183.3 microg Pb.m-3). House dust samples were collected from 6 places in houses located at approximately 25, 50, and 500 m from the repair shop, and the concentration of 1,500 microg Pb.m-2 for lead in house dust was exceeded in 44% of the samples, with results varying from 2.2 to 54,338.9 microg Pb.m-2.

[Biological monitoring: concepts and applications in public health]. / Monitoramento biológico: conceitos e aplicações em saúde pública.

This study provides an overview of the theoretical discussion on potential uses for biological monitoring of exposure to chemical substances as related to human health, considering different concepts: definitions, uses, and limitations of internal dose and biological effect indicators and their availability for the substances to be quantified; knowledge of reference values, action levels, and limits based on health and negotiated patterns in biological monitoring interpretation and perspectives; and ethical and social problems in practice and within different preventive practices and their use in public health. Biological monitoring is the result of an exposure situation with conclusions based on scientific and consensus values, rules, and legislation. Biological monitoring as a continuous process and related to actually observed cases has helped establish technological exposure reference values and consensus levels as indicators for improving the environment and the workplace. As a step in the decision-making process in risk analysis, biological monitoring needs to be critically assessed as to its ethical aspects in light of the end use of results and values, which are references for application of this methodology.

[Occupational lead exposure assessment: a proposal for a strategy to monitor prevention of clinical and subclinical effects]. / Avaliação da exposição ocupacional ao chumbo: proposta de um estratégia de monitoramento para prevenção dos efeitos clínicos e subclínicos.

In developing countries, lead-acid battery factories are one of the heaviest consumers of lead. Due to lead's toxicological properties and prevalent working conditions in such factories, workers are subject to high exposure and health risk. This study discusses results obtained by lead exposure assessment of workers from a Rio de Janeiro battery factory, in light of Brazilian legislation and recent scientific data. Evaluation methods used were environmental (personal air sampling) and biological (determination of lead in blood, Pb-B) monitoring, showing a high personal exposure both in air (>0.1 mg/m3) and blood (55% of Pb-B >25 microg/dl). These results confirmed the inefficiency of current control measures, with a possible 46% of workers presenting a Pb-B range of 25-60 microg/dl in risk areas. Recent data suggest that Pb-B levels above 25 microg/dl are related to subclinical alterations in human body that should be investigated during clinical examination. Finally, we propose a strategy based on environmental and biological monitoring to prevent both clinical and subclinical effects.