RESUMO
INTRODUCTION: Brazil is one of the countries with the highest rates of alcohol-related traffic infractions, but little is known about the profile of the drivers who commit them. Identifying the characteristics of impaired drivers is essential for planning preventive actions. OBJECTIVE: To compare drug use and driving behavior profiles of drivers with and without alcohol-related infractions. METHODS: 178 drivers stopped at routine roadblocks were assessed by traffic agents who conducted standard roadblock procedures (document verification; request of a breathalyzer test [BT]). Drug use and driving behavior data were collected through semi-structured interviews. Subjects were divided into three groups: drivers who refused the BT (RDs, n = 72), drivers who tested positive on the BT (PDs, n = 34), and drivers who had committed other infractions (ODs, n = 72). RESULTS: The proportion of alcohol use in the last year was higher among RDs (100%) than in the PD and OD groups (97.1% and 72.2% respectively, p < 0.001). Lifetime prevalence of cannabis and cocaine use for the overall sample was 44.3% and 18.2%, respectively. Fewer individuals in the OD group (31.5%) reported having been stopped at roadblocks in the previous year compared to the PDs (55.9%) and RDs (48.6%, p = 0.03). However, a higher proportion of RDs reported drunk driving in the same period (87.5%; PD 69.7%; OD 26.9%; p < 0.001). CONCLUSION: Essential differences among groups were observed. RDs had a higher proportion of alcohol use and drunk driving in the previous year; drivers who fit into this particular group may be unresponsive or less responsive to social deterrence and enforcement actions.
Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Condução de Veículo/estatística & dados numéricos , Dirigir sob a Influência/fisiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto , Alcoolismo/epidemiologia , Brasil/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PolíciaRESUMO
OBJECTIVE: Traffic fatalities in Brazil still rank among the highest worldwide, with an overall rate of 23.4 deaths/100,000 inhabitants/year. Although alcohol and drug use play an important role in traffic accidents, national data about their relative influence are scarce. Drug screening is not routinely performed by traffic agents because alcohol is the only substance regularly investigated in roadblocks. Therefore, we aimed to describe the initial traffic agent user experience for 4 handheld point-of-collection oral fluid drug testing devices used in routine roadblocks in Brazil, focusing on usage perceptions in hopes of generalizing this approach for other developing countries. METHODS: Four different oral fluid collection devices were evaluated: The DDS2, the DOA MultiScreen, the Dräger DrugTest 5000, and the Multi-Drug Multi-Line Twist Screen Device. Fourteen trained traffic agents obtained oral fluid from 164 drivers and performed 37 qualitative evaluations of the devices. Traffic agents filled out a questionnaire focusing on 9 feasibility criteria: Overall simplicity for roadside operation; operational success; saliva sample collection time; sample analysis time; ease of sample preparation and analysis; agreement with observed clinical signs; overall hygiene and safety; sufficient operating instructions; and hygiene of saliva collection. These were weighted based on an expert panel and yielded an overall composite device experience score that ranged from 1 (poor) to 100 (excellent). RESULTS: Ease of use, operational success, and acceptable collection and analysis time were considered the most important criteria by the expert panel. The results ranged from 27.3 to 88.9% for simplicity of use; 45.5 to 100.0% for operational success; 27.3 to 100% for acceptable collection time; and 36.4 to 100.0% for acceptable analysis time. The final device scores, based on the agents' user experiences, ranked as follows: DOA MultiScreen: 49.3/100; Dräger DrugTest 5000: 82.4/100; Multi-Drug Multi-Line Twist Screen Device: 84.3/100; DDS2: 88.4/100. CONCLUSION: Based on the selected criteria, 3 of the 4 devices were considered useful by traffic agents in routine roadblock operations. The weighted evaluations suggest that their ease of use (handling, sampling analysis, and reliability), as well as their agreement with findings obtained by other means, defined their utility to traffic agents, although such appraisals must be further analyzed in future studies.
Assuntos
Programas de Rastreamento/métodos , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Acidentes de Trânsito/prevenção & controle , Condução de Veículo , Brasil , Etanol/análise , Humanos , Masculino , Reprodutibilidade dos Testes , Saliva/químicaRESUMO
BACKGROUND: Substance use disorders are associated with the increased risk of driving under the influence (DUI), but little is known about crack-cocaine and its relationship with road traffic crashes (RTC). METHOD: A multicenter sample of 765 crack-cocaine users was recruited in six Brazilian capitals in order to estimate the prevalence of DUI and RTC involvement. Legal, psychiatric, and drug-use aspects related with traffic safety were evaluated using the Addiction Severity Index - 6th version (ASI-6) and the Mini International Neuropsychiatric Interview. RESULTS: Seventy-six (28.3%) current drivers reported accident involvement following crack-cocaine use. Among drivers (n=269), 45.7% and 30.5% reported DUIs in the past 6 months and 30 days, respectively. Drivers reporting DUI's in the past month (n=82) had higher scores in the "psychiatric", "legal", and "family problems" subscales from the ASI-6, and lower scores in the "family social support" subscale in comparison to those without a history of DUIs (n=187). An overall high prevalence of psychiatric comorbidity and substance consumption was observed. Participants with 5+ years of crack-cocaine use were more likely to have been in a RTC (RR=1.52, 95%IC: 1.02-2.75), independently of marijuana use, binge drinking and psychiatric comorbidities. CONCLUSION: The high prevalence of RTC and DUI involvement among crack-using drivers supports the idea that they are at a high risk group regarding traffic safety. Years of crack consumption seem to be associated with RTC involvement. Also, the presence of psychiatric comorbidities, poly-drug use, and cognitive impairment usually associated with crack addiction could yield additional risk of accidents.
Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Condução de Veículo/psicologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Cocaína Crack , Dirigir sob a Influência/estatística & dados numéricos , Acidentes de Trânsito/psicologia , Adulto , Brasil/epidemiologia , Estudos Transversais , Dirigir sob a Influência/psicologia , Feminino , Humanos , Masculino , PrevalênciaRESUMO
Autism spectrum disorders (ASD) are characterized by deficits in social interaction, language and communication impairments and repetitive and stereotyped behaviors, with involvement of several areas of the central nervous system (CNS), including hippocampus. Although neurons have been the target of most studies reported in the literature, recently, considerable attention has been centered upon the functionality and plasticity of glial cells, particularly astrocytes. These cells participate in normal brain development and also in neuropathological processes. The present work investigated hippocampi from 15 (P15) and 120 (P120) days old male rats prenatally exposed to valproic acid (VPA) as an animal model of autism. Herein, we analyzed astrocytic parameters such as glutamate transporters and glutamate uptake, glutamine synthetase (GS) activity and glutathione (GSH) content. In the VPA group glutamate uptake was unchanged at P15 and increased 160% at P120; the protein expression of GLAST did not change neither in P15 nor in P120, while GLT1 decreased 40% at P15 and increased 92% at P120; GS activity increased 43% at P15 and decreased 28% at P120; GSH content was unaltered at P15 and had a 27% increase at P120. These data highlight that the astrocytic clearance and destination of glutamate in the synaptic cleft might be altered in autism, pointing out important aspects to be considered from both pathophysiologic and pharmacological approaches in ASD.
Assuntos
Anticonvulsivantes/efeitos adversos , Astrócitos/efeitos dos fármacos , Transtorno Autístico/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ácido Valproico/efeitos adversos , Animais , Astrócitos/metabolismo , Transtorno Autístico/metabolismo , Transtorno Autístico/fisiopatologia , Modelos Animais de Doenças , Feminino , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos WistarRESUMO
Parkinson's disease (PD) is characterized by a progressive neurodegeneration in the substantia nigra and a striatal dopamine decrease. Striatal extracellular adenosine and ATP modulate the dopaminergic neurotransmission whereas guanosine has a protective role in the brain. Therefore, the regulation of their levels by enzymatic activity may be relevant to the clinical feature of PD. Here it was evaluated the extracellular nucleotide hydrolysis from striatal slices 4 weeks after a unilateral infusion with 6-OHDA into the medial forebrain bundle. This infusion increased ADP, AMP, and GTP hydrolysis by 15, 25, and 41%, respectively, and decreased GDP hydrolysis by 60%. There was no change in NTPDases1, 2, 3, 5, 6, and 5'-nucleotidase transcription. Dopamine depletion changes nucleotide hydrolysis and, therefore, alters the regulation of striatal nucleotide levels. These changes observed in 6-OHDA-lesioned animals may contribute to the symptoms observed in the model and provide evidence to indicate that extracellular purine hydrolysis is a key factor in understanding PD, giving hints for new therapies.
Assuntos
Adenina/metabolismo , Adrenérgicos/farmacologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Guanina/metabolismo , Oxidopamina/farmacologia , Doença de Parkinson/metabolismo , 5'-Nucleotidase/genética , 5'-Nucleotidase/metabolismo , Hidrolases Anidrido Ácido/genética , Hidrolases Anidrido Ácido/metabolismo , Animais , Modelos Animais de Doenças , Isoenzimas/metabolismo , Masculino , Feixe Prosencefálico Mediano/efeitos dos fármacos , Feixe Prosencefálico Mediano/metabolismo , Fosfatos/metabolismo , Ratos , Ratos WistarRESUMO
In the present study we investigated the effect of in vivo intrastriatal injection of quinolinic acid (QA) on cytoskeletal proteins in astrocytes and neurons of young rats at early stage (30 min) after infusion. QA (150 nmoles/0.5 microL) significantly increased the in vitro phosphorylation of the low molecular weight neurofilament subunit (NFL) and the glial fibrillary acidic protein (GFAP) of neurons and astrocytes, respectively. This effect was mediated by cAMP-dependent protein kinase A (PKA), protein kinase C (PKC) and Ca(2+)/calmodulin-dependent protein kinase II (PKCaMII). In contrast, mitogen activated protein kinases were not activated by QA infusion. Furthermore, the specific N-methyl-D-aspartate (NMDA) antagonist MK-801 (0.25 mg/kg i.p), the antioxidant L-NAME (60 mg\kg\day), and diphenyldisselenide (PheSe)(2) (0.625 mg\kg\day) injected prior to QA infusion totally prevented QA-induced cytoskeletal hyperphosphorylation. We also observed that QA-induced hyperphosphorylation was targeted at the Ser55 phosphorylating site on NFL head domain, described as a regulatory site for NF assembly in vivo. This effect was fully prevented by MK801, by the PKA inhibitor H89 and by (PheSe)(2), whereas staurosporine (PKC inhibitor) only partially prevented Ser55 phosphorylation. The PKCaMII inhibitor (KN93) and the antioxidant L-NAME failed to prevent the hyperphosphorylation of Ser55 by QA infusion. Therefore, we presume that QA-elicited hyperphosphorylation of the neural cytoskeleton, and specially of NFLSer55, achieved by intrastriatal QA injection could represent an early step in the pathophysiological cascade of deleterious events exerted by QA in rat striatum. Our observations also indicate that NMDA-mediated Ca(2+) events and oxidative stress may be related to the altered protein cytoskeleton hyperphosphorylation observed with important implications for brain function.
Assuntos
Astrócitos/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Proteínas de Neurofilamentos/metabolismo , Neurônios/efeitos dos fármacos , Ácido Quinolínico/farmacologia , Análise de Variância , Animais , Astrócitos/metabolismo , Western Blotting , Corpo Estriado/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Maleato de Dizocilpina/farmacologia , Inibidores Enzimáticos/farmacologia , Microinjeções , NG-Nitroarginina Metil Éster/farmacologia , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismoRESUMO
Chemical cues are widely used for intraspecific social communication in a vast majority of living organisms ranging from bacteria to mammals. As an example, mammals release olfactory cues with urine that promote neuroendocrine modulations with changes in behavior and physiology in the receiver. In this work, four-month-old Wistar (regular 4-day cyclic) virgin female rats were utilized in the proestrus-to-estrus phase of the reproductive cycle for experimental exposure. In an isolated room, female rats were exposed for 90 min to male-soiled bedding (MSB). Elevated plus-maze assay, open field test, and light/dark box task were performed to analyze behavioral alterations on females after exposure. For biochemical assays, female rats were killed and the hypothalamus, hippocampus, and frontal cortex were isolated for further analysis. Antioxidant enzyme activities (superoxide dismutase, catalase and glutathione peroxidase), non-enzymatic antioxidant defense measurements (TRAP and TAR), and the oxidative damage parameters (TBARS, Carbonyl and SH content) were analyzed. In behavioral analyses we observe that female rats show decreased anxiety and locomotory/exploratory activities after MSB exposure. In biochemical assays we observed an increase in both enzymatic and non-enzymatic antioxidant defenses in different central nervous system (CNS) structures analyzed 30 and 90 min after MSB exposure. Furthermore, hippocampus and frontal cortex showed diminished free radical oxidative damage at 180 and 240 min after exposure. These results provide the first evidence that oxidative profile of female CNS structures are altered by chemical cues present in the MSB, thus suggesting that pheromonal communication is able to modulate radical oxygen species production and/or clearance in the female brain.
Assuntos
Antioxidantes/metabolismo , Sinais (Psicologia) , Comportamento Exploratório , Lobo Frontal/metabolismo , Hipocampo/metabolismo , Hipotálamo/metabolismo , Atividade Motora , Comportamento Sexual Animal , Animais , Ansiedade , Feminino , Masculino , Ratos , Ratos WistarRESUMO
The administration of 6-hydroxydopamine (6-OHDA) into the nigrostriatal pathway is a rat model of Parkinson's disease (PD). The footfault test is a behavioural task in which rodents have their motor functions assessed. Here, we observed that unilaterally 6-OHDA-lesioned animals show a context-induced ipsilateral rotational behaviour when placed on the footfault apparatus for 3 min and this may be used as index to detect lesioned animals. Our results showed a sensitivity and specificity of 100% for lesions higher than 94% and 64%, respectively (ROC curve: AUC=0.988). A binary logistic regression model showed an expB=1.116 (95% CI, 1.007-1.236) and C=-9.081+/-4.554 (p=0.046) using the nigral tyrosine hidroxylase immunocontent as standard (each unit represents a 10%-lesion extension). Additionally, the footfault test was more sensitive than apomorphine challenging at 1mg/kg when these tests were carried out days apart and it was less sensitive than methylphenidate at 40 mg/kg (sign test, p<0.05). Therefore, the footfault test may be very useful in the PD animal model for screening animals since it is fast and simple and it does not require a drug to induce rotational activity.
Assuntos
Ciências do Comportamento/métodos , Neurofarmacologia/métodos , Oxidopamina/toxicidade , Transtornos Parkinsonianos/diagnóstico , Transtornos Parkinsonianos/fisiopatologia , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Ciências do Comportamento/instrumentação , Modelos Animais de Doenças , Dopamina/biossíntese , Agonistas de Dopamina/farmacologia , Avaliação Pré-Clínica de Medicamentos/instrumentação , Avaliação Pré-Clínica de Medicamentos/métodos , Marcha/efeitos dos fármacos , Marcha/fisiologia , Transtornos Neurológicos da Marcha/induzido quimicamente , Transtornos Neurológicos da Marcha/diagnóstico , Transtornos Neurológicos da Marcha/fisiopatologia , Masculino , Degeneração Neural/induzido quimicamente , Degeneração Neural/enzimologia , Degeneração Neural/patologia , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Neurônios/patologia , Neurofarmacologia/instrumentação , Transtornos Parkinsonianos/induzido quimicamente , Ratos , Ratos Wistar , Substância Negra/efeitos dos fármacos , Substância Negra/enzimologia , Substância Negra/patologia , Simpatolíticos/toxicidade , Tirosina 3-Mono-Oxigenase/efeitos dos fármacos , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Vitamin A is known to regulate some central nervous system (CNS)-associated functions. Vitamin A at high doses has been demonstrated to be beneficial in the treatment of some diseases, for instance acute promyelocytic leukemia. However, vitamin A and its naturally occurring metabolites (retinoids) are known to alter neuronal function, inducing behavioral disorders. Here we provide an evidence to indicate that vitamin A supplementation, at both therapeutic and excessive doses, induces oxidative stress in the rat substantia nigra. Vitamin A supplementation induced lipid peroxidation, protein carbonylation, and oxidation of protein thiol groups, as well as change in catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activity. Surprisingly, locomotory and exploratory activity of rats were decreased after acute and chronic vitamin A supplementation. Therefore, we may conclude from our results that vitamin A supplementation is prooxidant to the rat substantia nigra and effective in altering behavior.
Assuntos
Comportamento Exploratório/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Substância Negra/metabolismo , Vitamina A/uso terapêutico , Animais , Biomarcadores , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Masculino , Carbonilação Proteica/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Wistar , Substância Negra/efeitos dos fármacos , Compostos de Sulfidrila/metabolismo , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Vitamina A/administração & dosagemRESUMO
Although vitamin A has been reported to be essential to brain homeostasis, some central nervous system (CNS)-associated deleterious effects may be induced by vitamin A or by its metabolites. In this work, we investigated the effects of acute and chronic vitamin A supplementation at therapeutic (1,000 or 2,500 IU/kg/day) or excessive (4,500 or 9,000 IU/kg/day) doses on the redox state of the rat striatum. We found a 1.8- to 2.7-fold increase of lipid peroxidation in the striatum after acute or chronic supplementation (TBARS method). Therapeutic doses induced a 1.6- to 2.2-fold increase of protein carbonylation (dinitrophenylhydrazine (DNPH) derivatization). Vitamin A supplementation induced a 1.2- to 1.4-fold decrease of protein thiol content acutely and chronically. Superoxide dismutase (SOD) activity, assessed through the inhibition of epinephrine's autoxidation, was increased in a dose-dependent manner chronically. Acutely, both therapeutic and excessive vitamin A doses induced a 1.8- to 2.2-fold decrease of catalase (CAT) activity, as determined through the rate of decrease of hydrogen peroxide (H(2)O(2)). Glutathione peroxidase (GPx) activity did not change in this experimental model. Some vitamin A doses decreased the non-protein thiol content only chronically. Vitamin A supplementation decreased the striatal non-enzymatic antioxidant defenses (TRAP assay). Furthermore, our results show that vitamin A supplementation impaired the SOD/CAT ratio. Moreover, we observed a 1.6- to 2.0-fold decrease of locomotion and exploration in an open field after vitamin A supplementation. Therefore, our results suggest that vitamin A supplementation induces oxidative stress in the rat striatum and that it may be related to a metabolic impairment in such brain area.
Assuntos
Doenças dos Gânglios da Base/induzido quimicamente , Encefalopatias Metabólicas/induzido quimicamente , Corpo Estriado/efeitos dos fármacos , Discinesia Induzida por Medicamentos/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Vitamina A/toxicidade , Animais , Antioxidantes/metabolismo , Doenças dos Gânglios da Base/metabolismo , Doenças dos Gânglios da Base/fisiopatologia , Encefalopatias Metabólicas/metabolismo , Encefalopatias Metabólicas/fisiopatologia , Catalase/efeitos dos fármacos , Catalase/metabolismo , Corpo Estriado/metabolismo , Corpo Estriado/fisiopatologia , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Esquema de Medicação , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Oxirredução , Estresse Oxidativo/fisiologia , Carbonilação Proteica/efeitos dos fármacos , Carbonilação Proteica/fisiologia , Ratos , Ratos Wistar , Compostos de Sulfidrila/metabolismo , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologiaRESUMO
Vitamin A participates in the maintenance of normal hippocampal function during embryonic and postnatal stages of the vertebrate life. Some works demonstrated that vitamin A metabolites impair learning and induce a depression-like behavior in mice, among other effects. Since vitamin A has prooxidant effects on other experimental models, we decided to investigate whether vitamin A can induce oxidative stress in the adult rat hippocampus. We analyzed the sub acute effects of therapeutic (1000 and 2500 I.U./kg) or excessive (4500 and 9000 I.U./kg) vitamin A doses on the hippocampal redox state, as well as on levels of anxiety, and locomotory and exploratory activity. Vitamin A supplementation induced lipid peroxidation, protein carbonylation, and oxidation of the protein thiol content in the rat hippocampus in all periods analyzed. Increased superoxide dismutase (SOD) activity and decreased catalase (CAT) activity were also observed, which gives rise to an imbalance in the principal cellular enzymatic antioxidant system. Then, our results show, for the first time, that vitamin A induced oxidative stress in the adult rat hippocampus, is anxiogenic, and decreases locomotion in and exploration of an open field.