Metabotropic glutamate type 5 receptor binding availability during dextroamphetamine sensitization in mice and humans.

Background: Glutamate transmission is implicated in drug-induced behavioural sensitization and the associated long-lasting increases in mesolimbic output. Metabotropic glutamate type 5 (mGlu5) receptors might be particularly important, but most details are poorly understood. Methods: We first assessed in mice (n = 51, all male) the effects of repeated dextroamphetamine administration (2.0 mg/kg, i.p.) on locomotor activity and binding of the mGlu5 ligand [3H]ABP688. In a parallel study, in 19 stimulant-drug-naïve healthy human volunteers (14 female) we administered 3 doses of dextroamphetamine (0.3 mg/kg, p.o.) or placebo, followed by a fourth dose 2 weeks later. We measured [11C]ABP688 binding using positron emission tomography before and after the induction phase. We assessed psychomotor and behavioural sensitization using speech rate, eye blink rate and self-report. We measured the localization of mGlu5 relative to synaptic markers in mouse striatum using immunofluorescence. Results: We observed amphetamine-induced psychomotor sensitization in mice and humans. We did not see group differences in mGlu5 availability following 3 pre-challenge amphetamine doses, but group differences did develop in mice administered 5 doses. In mice and humans, individual differences in mGlu5 binding after repeated amphetamine administration were negatively correlated with the extent of behavioural sensitization. In drug-naïve mice, mGlu5 was expressed at 67% of excitatory synapses on dendrites of striatal medium spiny neur. Limitations: Correlational results should be interpreted as suggestive because of the limited sample size. We did not assess sex differences. Conclusion: Together, these results suggest that changes in mGlu5 availability are not part of the earliest neural adaptations in stimulant-induced behavioural sensitization, but low mGlu5 binding might identify a higher propensity for sensitization.

Characterization of a Human Point Mutation of VGLUT3 (p.A211V) in the Rodent Brain Suggests a Nonuniform Distribution of the Transporter in Synaptic Vesicles.

The atypical vesicular glutamate transporter type 3 (VGLUT3) is expressed by subpopulations of neurons using acetylcholine, GABA, or serotonin as neurotransmitters. In addition, VGLUT3 is expressed in the inner hair cells of the auditory system. A mutation (p.A211V) in the gene that encodes VGLUT3 is responsible for progressive deafness in two unrelated families. In this study, we investigated the consequences of the p.A211V mutation in cell cultures and in the CNS of a mutant mouse. The mutation substantially decreased VGLUT3 expression (-70%). We measured VGLUT3-p.A211V activity by vesicular uptake in BON cells, electrophysiological recording of isolated neurons, and its ability to stimulate serotonergic accumulation in cortical synaptic vesicles. Despite a marked loss of expression, the activity of the mutated isoform was only minimally altered. Furthermore, mutant mice displayed none of the behavioral alterations that have previously been reported in VGLUT3 knock-out mice. Finally, we used stimulated emission depletion microscopy to analyze how the mutation altered VGLUT3 distribution within the terminals of mice expressing the mutated isoform. The mutation appeared to reduce the expression of the VGLUT3 transporter by simultaneously decreasing the number of VGLUT3-positive synaptic vesicles and the amount of VGLUT3 per synapses. These observations suggested that VGLUT3 global activity is not linearly correlated with VGLUT3 expression. Furthermore, our data unraveled a nonuniform distribution of VGLUT3 in synaptic vesicles. Identifying the mechanisms responsible for this complex vesicular sorting will be critical to understand VGLUT's involvement in normal and pathological conditions.SIGNIFICANCE STATEMENT VGLUT3 is an atypical member of the vesicular glutamate transporter family. A point mutation of VGLUT3 (VGLUT3-p.A211V) responsible for a progressive loss of hearing has been identified in humans. We observed that this mutation dramatically reduces VGLUT3 expression in terminals (∼70%) without altering its function. Furthermore, using stimulated emission depletion microscopy, we found that reducing the expression levels of VGLUT3 diminished the number of VGLUT3-positive vesicles at synapses. These unexpected findings challenge the vision of a uniform distribution of synaptic vesicles at synapses. Therefore, the overall activity of VGLUT3 is not proportional to the level of VGLUT3 expression. These data will be key in interpreting the role of VGLUTs in human pathologies.

Systemic administration of a nitric oxide synthase inhibitor impairs fear sensitization in the plus-maze.

The aim of the present study was to evaluate the occurrence of fear sensitization in rats previously treated with an inhibitor of the NO syntheses and submitted to Trial1/Trial2 plus-maze (PM) procedure. Male Wistar rats received a systemic treatment with N(omega)-nitro-L-Arginine-methyl ester (L-NAME; 5, 10 or 50 mg kg(-1)) and were submitted to PM Trial1. In the following day the animals were re-exposed to the PM with no drug administration (Trial2). Some standards spatial-temporal measures, such as the percentage of entries (% Open arm entries) and time spent (% Open arm time) in the open arms and risk assessment frequency were recorded and used to estimate the animal level of fear sensitization in PM Trial2. The results showed that animals receiving L-NAME (50 mg kg(-1)) displayed increased % Open arm entries and % Open arm time in Trial2 in relation to the group receiving 0.9% saline, which is compatible with impaired fear/anxiety acquisition during Trial1/Trial2 PM procedure. In addition, rats treated with L-NAME (50 mg kg(-1)) exhibited low level of risk assessment in Trial2 in relation to the group treated with 0.9% saline, which indicates low level of fear/anxiety during PM re-exposure. The number of entries into the enclosed arms was not changed by any L-NAME treatment, which suggests no bias of the drug treatments on animal locomotor activity. The data suggest that NO synthesis may mediate the fear sensitization process in the PM.

An approach to evaluate the ability of rats to discriminate different levels of illumination in the plus maze test: effects of scopolamine.

Previous research has shown that the visual system is important for rats to establish the arm preference in the elevated plus maze (EPM), an animal model of anxiety. This study aims at evaluating whether a gradient of illumination between the enclosed arms of the maze (E/E(DeltaLux)) could be a reliable approach to detect drugs-induced harmful effect on visual discrimination of rats. Four EPM configurations with different E/E(DeltaLux) (8, 41 and 85lx) were used to demonstrate that as E/E(DeltaLux) increases, rats avoid to explore the light enclosed arm, which characterizes the animal ability to discriminate the most illuminated area within the protected environment of the maze. The establishment of either 41 or 85 E/E(DeltaLux) failed to alter the traditional spatial-temporal variables in the EPM. In addition, systemic treatment with midazolam (MDZ; 1.0mgkg(-1), a classical anxiolytic) induced anxiolysis in rats tested in 41 and 85 E/E(DeltaLux) EPM, with no change in the visual discrimination, when evaluated by the level of light enclosed arm exploration. Systemic treatment with scopolamine (SCP; 1.0, 2.0 and 8.0mgkg(-1)), a drug endowed with harmful properties upon the visual system, did not change either the open arm avoidance or the visual discrimination at the low doses, but induced increased light enclosed arm (visual discrimination deficit) and open arm exploration (anxiolytic like effect) at a higher dose. We propose that the incorporation of an E/E(DeltaLux) in the EPM may reinforce the predict validity of the test since it enables to evaluate whether a visual discrimination deficit can be confounded with an anxiolytic-like effect, thus establishing a false positive detection.

Relative luminosity in the plus maze upon the exploratory behaviour of female Wistar rats.

OBJECTIVE: This study evaluated the provision of two configuration of the Elevated Pluz-Maze (EPM) by analizing the exploratory behaviour of female Wistar rats in different phases of the estrous cycle in EPMs with different gradients of luminosity between the open and enclosed arms (O/E∆Lux). METHODS: Female Wistar rats were treated with Midazolam (MDZ, 1.0 mg.kg-1) and were tested for their exploratory behaviour in either the EPM 10 O/E∆Lux or EPM 96 O/E∆Lux. RESULTS: A multiple regression analysis indicated that the O/E∆Lux is negatively associated with the %Open arm entries and %Open arm time, suggesting that as O/E∆Lux increases, the open arm exploration decreases. The estrous cycle phase did not influence the open-arm exploration in either EPM. MDZ- induced anxiolysis was detected in 96 O/E∆Lux EPM in all phases of the EC. DISCUSSION: Results of this study suggest the importance of the O/E∆Lux to establish the arm preference in the EPM, and to preserve the predictive validity of the EPM.

Comparação da mortalidade para traqueostomia precoce e tardia em pacientes cardiológicos de uma unidade de terapia intensiva no sul do Brasil / Comparing mortality in early and late tracheostomy in cardiologic patients from an intensive care unit in south Brazil

Introdução: Apesar das diversas vantagens atribuídas à traqueostomia em pacientes de unidade de terapia intensiva (UTI) que necessitam de ventilação mecânica, verdadeiros benefícios e o momento ideal da confecção da traqueostomia permanecem controversos. Objetivo: Comparar a evolução dos pacientes cardiológicos entubados com os submetidos à traqueostomia em relação ao período em que foi realizada, quanto ao tempo de internação, de ventilação mecânica, escore APACHE II e a mortalidade. Métodos: Coorte retrospectiva com pacientes da Unidade de Terapia Intensiva do Hospital Nossa Senhora da Conceição, Tubarão-SC. Resultados: Dos 70 pacientes, 16 (22,8%) foram submetidos à traqueostomia, permanecendo maior período na UTI (26,2 dias) quando comparados àqueles que não o foram (p< 0,001). A média do tempo de realização da traqueostomia foi de 11,4 dias de início da ventilação mecânica (VM). Neste estudo, a prevalência de traqueostomia precoce (≤13 dias) foi 11,4% (n=8) e tardia (>13 dias) 11,4% (n=8). Entretanto, os pacientes com traqueostomia precoce e tardia não obtiveram taxas de mortalidade menores do que os entubados. Ainda houve aumento nos tempos de internação na UTI (17,4 (precoce) e 17,4 (tardia) dias) nos dois grupos. Conclusão: Sabe-se que ainda não existem diretrizes para o estabelecimento do período ideal da realização da traqueostomia. Em pacientes cardiológicos, parece que tanto a traqueostomia precoce como a tardia não estiveram associadas com redução da mortalidade, redução de complicações, porém com aumento do tempo de internação.

Introduction: Despite the numerous benefits attributed to tracheostomy in patients from the intensive care unit (ICU) requiring mechanical ventilation, and the real benefits of ideal time for tracheostomy realization remains controversial. Objective: To compare the outcome of cardiologic patients intubated with those who underwent early and late tracheostomy regarding the length of hospitalization, mechanical ventilation, APACHE II score and mortality. Methods: Retrospective cohort study with patients in the Intensive Care Unit of Hospital Nossa Senhora da Conceição, Tubarão-SC. Results: Of 70 patients, 16 (22.8%) underwent tracheostomy and remained longest in the ICU (26.2 days) compared to those who were not (p <0.001). The average time of tracheostomy was 11.9 days of mechanical ventilation (MV). In this study, the prevalence of early tracheostomy (≤ 13 days) was 11.4% (n = 8) and late (> 13 days) 11.4% (n = 8). However, patients with early and late tracheostomy had not lower mortality rates than those intubated. Although there was an increase in the time of ICU admission (17.4 (early) and 17.4 (late) days) in both groups. Conclusion: It is known that there are still no guidelines for establishing the optimum period of performing the tracheostomy. In cardiologic patients both the early and late tracheostomy was not associated with reduced mortality, reduced complications but increased length of hospitalization.

Relative luminosity in the plus maze upon the exploratory behaviour of female Wistar rats / Efeito da luminosidade relativa em labirinto em cruz sobre o comportamento exploratório de fêmeas Wistar

Objective This study evaluated the provision of two configuration of the Elevated Pluz-Maze (EPM) by analizing the exploratory behaviour of female Wistar rats in different phases of the estrous cycle in EPMs with different gradients of luminosity between the open and enclosed arms (O/E∆Lux).Methods Female Wistar rats were treated with Midazolam (MDZ, 1.0 mg.kg-1) and were tested for their exploratory behaviour in either the EPM 10 O/E∆Lux or EPM 96 O/E∆Lux.Results A multiple regression analysis indicated that the O/E∆Lux is negatively associated with the %Open arm entries and %Open arm time, suggesting that as O/E∆Lux increases, the open arm exploration decreases. The estrous cycle phase did not influence the open-arm exploration in either EPM. MDZ- induced anxiolysis was detected in 96 O/E∆Lux EPM in all phases of the EC.Discussion Results of this study suggest the importance of the O/E∆Lux to establish the arm preference in the EPM, and to preserve the predictive validity of the EPM.

Objetivo Avaliar a provisão de duas configuracōes do Labirinto Elevado em Cruz (LEC) através do comportamento exploratório de ratas Wistar em diferentes fases do ciclo estral (CE) em LEC com diferentes gradientes de luminosidade entre os braços aberto e fechado (A/F∆Lux).Método Ratas Wistar foram tratadas com Midazolam (MDZ, 1.0 mg.kg-1) e foram testadas no LEC 10 A/F∆Lux ou LEC 96 A/F∆Lux.Resultados A análise de regressão múltipla indicou que o A/F∆Lux está negativamente associado com a % de entrada no braço aberto e % de tempo no braço aberto, sugerindo que no aumento do A/F∆Lux, a exploração do braço aberto diminui. A fase do CE não influenciou a exploração do braço aberto no LEC. A ansiólise induzida pelo MDZ foi demonstrada no 96 LEC A/F∆Lux em todas as fases do CE.Discussão Estes resultados sugerem a importância do A/F∆Lux para estabelecer a preferência da exploração do LEC e preservar a validade do LEC.

Uso de álcool e tabaco por gestantes em maternidade do sul de Santa Catarina / Alcohol and tobacco use by pregnant women in a maternity from the south Santa Satarina

Objetivo: Estimar perfil epidemiológico do consumo de álcool e tabaco durante a gravidez entre mulheres atendidas em maternidade de Santa Catarina. Métodos: Entrevistaram-se 157 mulheres, foram coletados dados sócio-demográficos e gestacionais, bem como informações sobre uso de álcool (incluindo questionário T-ACE) e tabaco (incluindo Questionário de Tolerância de Fagerström-QTF). Empregaram-se os testes qui-quadrado de Pearson ou Fisher (quando pertinente) e U de Mann-Whitney com nível de significância 95%, seguido de análise multivariada através de regressão logística. Resultados: O consumo alcoólico foi 36,9%. Na avaliação do T-ACE 22,9% foram positivas. A prática religiosa foi fator protetor para o álcool, as demais variáveis não. Não associaram-se fatores com resultado T-ACE. O hábito tabagístico foi de 14% e no QTF, 41,1% apresentaram dependência leve, 29,4% moderada ou grave. Menor escolaridade e ausência de prática religiosa associaram-se ao tabagismo. Houve consumo simultâneo das duas drogas. Conclusões: O consumo de álcool e tabaco no período gestacional não se caracterizou como evento incomum neste estudo. Praticar religião foi fator protetor para consumo de ambos, porém o tabagismo também esteve relacionado a menor escolaridade. Havendo, portanto indicativo de disseminação do álcool de forma mais homogênea e democrática nas diferentes classes sociais.

Objective: Estimate the epidemic profile of the consumption of alcohol and tobacco during the pregnancy period among women assisted at a maternity in Santa Catarina. Methods: Social-demographic and pregnancy data were collected from 157 women , as well as information on use of alcohol (including questionnaire T-ACE) and tobacco (including Questionary of Tolerance of Fagerström-QTF). The tests Qui-square of Pearson or Fisher were used (as pertinent) and U of Mann-Whitney with significance level of 95%, following by multi-sorted analysis through the regression logistics. Results: The alcoholic consumption was 36,9%. In T-ACE the evaluation of 22,9% was positive. The religious practice went protecting factor to alcohol, the other variables not. They didn't associate factors with resulted T-ACE. The habit of tabagism was of 14% and in QTF, 41,1% demonstrated light dependence, 29,4% moderate or serious. Low education level and absence of religious practicing were associated to the tabagism. There was simultaneous consumption of the two drugs. Conclusions: The consumption of the alcohol and the tobacco in the pregnancy period was not characterized as uncommon event in this study. To have a religion went protecting factor to consumption of both, however the tabagism was also related to the lowest education, therefore being an indicative of spread of the alcohol in a more homogeneous and democratic way in the different social classes.

Sintomas associados à exposição aos agrotóxicos entre rizicultores em uma cidade no sul de Santa Catarina.

Introdução: A Região do sul do Brasil tem na agricultura um dos pilares de sua economia. A quantidade de pessoas envolvidas com o uso de agrotóxicos é expressiva, e caso estes sejam utilizados de maneiraincorreta podem desencadear um grave problema de saúde pública, pelos riscos ambientais e intoxicações. Objetivo: Verificar cuidados e descrever sintomas associados ao uso de agrotóxicos organofosforados e/ou carbamatos em riziculturas. Métodos: estudo transversal com 59 agricultores no município de Jaguaruna, sul de Santa Catarina. A regiãocaracteriza-se por pequenas e médias propriedades dedicadas ao cultivo de arroz. Para coleta dos dados foi utilizado instrumento contendo questões relacionadas aos aspectos sócio-demográficos, à aplicação e cuidados referentes à utilização de agrotóxicos e os sintomasprovenientes deste uso. As variáveis foram descritas através de proporções, medidas de tendência central e dispersão. O teste exato de Fisher foi aplicado nas associações entre as variáveis no nível de confiança de 95%. Resultados: Toda amostra era do sexo masculinocom a idade média de 46,98 anos e baixa escolaridade (69,4% nunca estudaram). O uso de EPI foi de 93,2%, dentre estes 83,1% utilizavam máscara. Dentre os sintomas relacionados ao uso de agrotóxicos, a cefaléia foi a mais freqüente com 40,7%, seguida de náuseascom 23,7%, vertigem 16,9%, irritação da pele 15,3%, secura na garganta 13,6%, nervosismo 10,2%, sonolência 10,2%, entre outros. Os agricultores que afirmaram utilizar EPI apresentaram 70% menos sintomas quando comparados aos que não o utilizavam. Discussão: Grande parte da amostra dos produtores era orientada por engenheiro agrônomo. A prevalência de sintomas associados ao uso de agrotóxicos foi de 64,4%.

Introduction: Agriculture is one of the most important economic activities in South Brazil region. The amount of people involved with the use of pesticides is expressive, and these, when wrongly manipulated, cantrigger a severe health problem, due to environmental risks and intoxications. Objective: To verify health care and to describesymptoms associated with the use of pesticides (organophosphorus and/or carbamates) in rice rural workers in a city in South Santa Catarina ? Brazil. Methods: cross-sectional study with 59 rural workers from Jaguaruna, South Brazil. This region is characterized by small and medium properties dedicated to cultivate rice. Data was collected with a questionnaire with social demographic aspects, to the application, care and symptoms referent to the use of pesticides. Variables was described by proportions, central tendency measures and dispersion. Fisher?s exact test was applied to the associations at the 95% confidence level.Results: The entire sample was male with mean age of 46.98 years old and low school level (69,4% have never studied). Equipments protection was used in 93.2%, in which 83.1% utilized mask. Among symptomsrelated to the pesticides use, headache was in first place with 40.7%, nausea in 23.7%, dizziness 16.9%, skin irritation 15.3%, dryness in the throat 13.6%, nervousness 10.2%, drowsiness 10.2%, and other symptoms. Rural workers that affirms to use equipments protection had70% less symptoms then those did not utilized them. Discussion: Mostly of the producers sample was oriented by agricultural engineer. Prevalence rate of symptoms associated to the pesticides use was 64.4%.

Estado nutricional e prevalência de dislipidemias em idosos

Introdução: O envelhecimento populacional aumentacada vez mais a necessidade de conhecimento dos fatoresque incidem sobre a prevalência das doenças crônicodegenerativasassociadas à idade, e, dentre estas, estãoas dislipidemias.Objetivo: O estudo objetivou verificar a relação entreestado nutricional e prevalência de dislipidemias numapopulação de idosos atendidos no município de Criciúma(SC).Métodos: Realizou-se uma pesquisa retrospectiva,descritiva em 99 prontuários escolhidos de formasistemática e aleatória de pacientes idosos atendidos entresetembro de 2002 e setembro de 2007. O estudo ocorreumediante à análise dos exames bioquímicos referentesàs lipoproteínas (triglicerídeos, colesterol total, LDL-C eHDL-C) e de peso e altura. O diagnóstico nutricional foirealizado através do índice de massa corporal e osresultados classificados segundo os pontos de corte paraindivíduos idosos propostos por KAMIMURA. Para odiagnóstico bioquímico foram considerados portadoresde dislipidemias os idosos que apresentaram resultadossuperiores ao intervalo referencial para adultos propostospela IV Diretriz Brasileira Sobre Dislipidemias ePrevenção da Aterosclerose da Sociedade Brasileira deCardiologia.Resultados: O peso médio dos idosos foi de 77,1kg,a altura de 1,60m e o IMC de 30,2kg/m2. Quanto aoestado nutricional, 70% dos idosos encontravam-se acimado peso ideal; 29% apresentavam-se eutróficos e 1%com baixo peso. Não apresentarem nenhuma dislipidemia9,23% das mulheres e 17,65% dos homens. A maiorprevalência de dislipidemia foi encontrada entre as idosasobesas.Conclusão: Relacionando o estado nutricional comas dislipidemias constatou-se uma maior prevalênciaentre as idosas obesas.

Introduction: Elderly population is rising andincreases the necessity of knowledge about risk factorsof chronic-degenerative diseases associated with age,including dyslipidemias.Objectives: To verify the relation between nutritionalstatus and the prevalence of dyslipidemias in an elderlypopulation in Criciúma city, South Brazil.Methods: A transversal study was carried out with99 randomly chosen medical records of elderly patientsbetween september 2002 and september 2007. Themedical records were analyzed in terms of lipoprotein(triglycerides, total cholesterol, LDL-C and HDL-C),weight and height. Nutritional diagnosis was conductedthrough body mass index and results were classified byKamimura cutpoint. Biochemistry diagnosis was onlyconsidered dyslipidemic elderly people with results aboveIV Brazilian Guideline for Dyslipidemia andAtherosclerosis Prevention of Brazilian Society ofCardiology.Results: In average, the weight of the elderly peoplewas 77,1kg, height 1,60m and BMI 30,2kg/m2. Aboutnutritional status, 70% were above ideal weight, 29%were eutrofics and 1% with were low-weight. In thisstudy, only 9,23% of women and 17,65% of men did notpresent any kind of dyslipidemia, and the highestprevalences were found among obese elderly women.Conclusion: Relating nutritional status withdyslipidemias, it was observed, in this study, a higherprevalence among obese elderly women.