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The evaluation of animal locomotor activity is a behavioral tool widely used to measure the mechanisms underlying a particular disease, disorder, or injury, as well as the effects of exposure to a xenobiotic. The elevated beam test is one of the most used tests in rodents to assess balance and motor coordination. Despite being inexpensive and utilizing a simple apparatus, the high beam test requires a long period of animal training and habituation. The development and characterization of an alternative test, namely the gait test, has the potential to circumvent the time and effort required for animal training, deeming it an effective, inexpensive, and fast method for the analysis of behaviors that are comparably assessed by the high beam test. Therefore, the present study focused on determining the effectiveness and feasibility of the gait test for assessing rodent locomotion and balance as a replacement for the elevated beam test. For this purpose, male rats were divided into three groups: one control group exposed to a saline solution (NaCl 0.9%) and two experimental groups exposed to a single dose of either 0.2 or 1.0 mg/kg of ivermectin intraperitoneally for induction of locomotor disturbance. The high beam and gait tests were performed 15 min and 24 h after drug administration. Results show that the experimental groups had difficulty performing the tasks of either test at both time points analyzed compared to the control groups. At the high beam, experimental animals had trouble maintaining balance and walking. At the gait test, experimental animals showed alterations in gait, which were quantitated by: (a) shortening of step length, (b) decrease of stride, (c) altered step symmetry, and (d) altered stride area. Such results are indicative of compensatory efforts and were comparable between both tests. Altogether, the data indicate that the gait test meets all requirements for assessing motor coordination in rodents. The gait test is therefore validated as a complement to the elevated beam test for the study and analysis of neurodegenerative impairment and other disorders involving neuromuscular disturbances.(AU)
A avaliação da atividade locomotora animal é uma ferramenta comportamental bastante utilizada para mensurar os mecanismos subjacentes a uma determinada doença, distúrbio ou lesão e efeitos da exposição a um xenobiótico. Um dos testes mais utilizados em roedores para avaliar o equilíbrio e coordenação motora é o teste da trave elevada que, apesar de ser um teste barato e que exige um aparato simples, é necessário um longo período de treino e habituação dos animais. O desenvolvimento e caracterização de um teste alternativo, chamado de teste da marcha, tem o potencial de contornar o tempo e o esforço necessários ao treino dos animais, considerando-o um método eficaz, barato e rápido para a análise de comportamentos avaliados comparativamente pelo alto teste de feixe. Portanto, o presente estudo concentrou-se em determinar a eficácia e viabilidade do teste de marcha para avaliação da locomoção e equilíbrio de roedores em substituição ao teste da trave elevada. Para isso, ratos machos foram divididos em 3 grupos, sendo 1 grupo controle exposto à solução salina (NaCl 0,9%) e 2 grupos experimentais expostos à dose única de 0,2 e 1,0 mg/kg de ivermectina por via intraperitoneal para indução da alteração locomotora. Os testes de trave elevada e marcha foram realizados 15 min e 24 h após a administração da droga. Os resultados mostram que os grupos experimentais tiveram dificuldade em realizar as tarefas de qualquer teste em ambos os momentos analisados em comparação com os grupos de controle. Na trave elevada, os animais experimentais tiveram dificuldade em manter o equilíbrio e andar. No teste de marcha, os animais experimentais apresentaram alterações na marcha, que foram quantificadas por: (a) encurtamento do comprimento da passada, (b) diminuição da passada, (c) alteração da simetria da passada e (d) alteração da área da passada. Tais resultados são indicativos de esforços compensatórios e foram comparáveis entre os dois testes. Em conjunto, os dados indicam que o teste de marcha atende a todos os requisitos para avaliação da coordenação motora em roedores. O teste de marcha é, portanto, validado como um complementar para o teste da trave elevada e para o estudo e análise de comprometimento neurodegenerativo e outros distúrbios envolvendo distúrbios neuromusculares.(AU)
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Animais , Ratos , Roedores/fisiologia , Doenças Neurodegenerativas/veterinária , Teste de Caminhada/veterinária , Equilíbrio Postural , Locomoção/fisiologiaRESUMO
Ketamine is an anesthetic drug that also has antidepressant properties, with quick action. Despite the great number of studies showing its effectiveness as a treatment for major depression, there is little information about its effects on postpartum depression, as pharmacological treatments bring risks to the health of both mother and child. Thus, this study aimed to evaluate the effects of prolonged treatment with subanesthetic doses of ketamine in a rat model of postpartum depression. Female dams were induced to postpartum depression by the maternal separation model from lactating day (LD) 2 to 12. They were divided into four groups: one control and three experimental groups, which were treated with different doses of ketamine (5, 10 or 20 mg/kg) from LD 2 to 21 i.p. Maternal studies were conducted from LD5 to LD21 and the offspring studies from postnatal day 2 through 90. Ketamine causes poor maternal care, with few neurochemical alterations. However, the highest dose used in this study had an antidepressant effect. Regarding the male offspring, indirect exposure to ketamine through breast milk caused few behavioral changes during infancy, but they were not permanent, as they faded in adulthood. Nevertheless, this exposure was able to cause alterations in their monoaminergic neurotransmission systems that were found in both infancy and adulthood periods.
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Postpartum depression is a mentally disabling disease with multifactorial etiology that affects women worldwide. It can also influence child development and lead to behavioral and cognitive alterations. Despite the high prevalence, the disease is underdiagnosed and poorly studied. To study the postpartum depression caused by maternal separation model in rats, dams were separated from their litter for 3 h daily starting from lactating day (LD) 2 through LD12. Maternal studies were conducted from LD5 to LD21 and the offspring studies from postnatal day (PND) 2 through PND90. The stress caused by the dam-offspring separation led to poor maternal care and a transient increase in anxiety in the offspring detected during infancy. The female offspring also exhibited a permanent impairment in sociability during adult life. These changes were associated with neurochemical alterations in the prefrontal cortex and hippocampus, and low TSH concentrations in the dams, and in the hypothalamus, hippocampus and striatum of the offspring. These results indicate that the postpartum depression resulted in a depressive phenotype, changes in the brain neurochemistry and in thyroid economy that remained until the end of lactation. Changes observed in the offspring were long-lasting and resemble what is observed in children of depressant mothers.
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Depression is one of the world's most common and mentally disabling illnesses. Post-partum depression is a subtype of depression that affects one in seven women worldwide. Successful pharmacological treatment must consider the consequences for both, since the mother-child bond is fundamental for the well-being of both mother and infant as well as the general development of the newborn. Changes in maternal physiology and/or behavior can significantly influence the development of breastfed infants. Ketamine has been extensively studied for use as an antidepressant due to its mixed mechanisms of action. Safety and efficacy studies in the cardiovascular and urinary systems of a lactating postpartum depression animal model are essential for contributing toward ketamine's clinical use in the respective patient population. Thus, this project aimed to study the implications of postpartum maternal exposure to ketamine during lactation on the cardiovascular system of female rats submitted to the depression induction model by maternal separation. This model promotes depressive effects through stress caused by the interruption of mother-infant bond early in the offspring's life. To achieve depression, each dam was separated from her offspring for 3 h per day, from post-natal day 2 (PND2) to PND12. Experimental groups received daily treatment with either 5, 10, or 20 mg/kg of ketamine intraperitoneally during the lactation period, from PND2 to PND21. Behavioral tests consisted of the maternal and aggressive maternal behavior tests, the olfactory preference test, and the forced swim test. A technique for the detection of catecholamines and indoleamines in the heart muscle was developed for the experimental model groups. The histopathological evaluation was performed on these animals' cardiac muscles and urinary bladders. Our findings suggest that ketamine is safe for use in postpartum depression and does not induce cardiovascular and/or urinary systems toxicity.
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Anticholinesterase pesticides are a main cause of the intentional or accidental poisoning of animals. Anticholinesterases include several substances that cause the overstimulation of both central and peripheral acetylcholine-dependent neurotransmission. Forensic analyses of poisoning cases require high levels of expertise, are costly, and often do not provide reliable quantitative information for unambiguous conclusions. The purpose of the present study was to develop and validate a method of high-performance liquid chromatography with diode array detector (HPLC−DAD) for the identification and quantitation of n-methyl carbamates, organophosphates and respective metabolites from biological samples of animals that were suspected of poisoning. HPLC−DAD is reliable, fast, simplistic and cost-effective. The method was validated for biological samples obtained from stomach contents, liver, vitreous humor and blood from four different animal species. The validation of the method was achieved using the following analytical parameters: linearity, precision, accuracy, selectivity, recovery, and matrix effect. The method showed linearity at the range of 25−500 µg/mL, and the correlation coefficient (r2) values were >0.99 for all matrices. Precision and accuracy were determined by the (a) coefficient of variation (CV), (b) relative standard deviation low-quality control (LQC), (c) medium-quality control (QCM), and (d) high-quality control (QCA). The indicated parameters were all less than 15%. The recovery of analytes ranged from 31 to 71%. The analysis of results showed no significant interfering peaks due to common xenobiotics or matrix effects. The abovementioned method was used to positively identify pesticide analytes in 44 of the 51 animal samples that were suspected of poisoning, demonstrating its usefulness as a forensic tool.
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Vitiligo is an autoimmune disease characterized by progressive skin depigmentation and the appearance of white patches throughout the body caused by significant apoptosis of epidermal melanocytes. Despite not causing any physical pain, vitiligo can originate several psychosocial disorders, drastically reducing patients' quality of life. Emerging evidence has shown that vitiligo is associated with several genetic polymorphisms related to auto-reactivity from the immune system to melanocytes. Melanocytes from vitiligo patients suffer from excess reactive oxygen species (ROS) produced by defective mitochondria besides a poor endogenous antioxidant system (EAS). This redox imbalance results in dramatic melanocyte oxidative stress (OS), causing significant damage in proteins, lipid membranes, and DNA. The damaged melanocytes secret damage-associated molecular pattern (DAMPs), inducing and increasing inflammatory gene expression response that ultimately leads to melanocytes apoptosis. Vitiligo severity has been also associated with increasing the prevalence and incidence of metabolic syndrome (MetS) or associated disorders such as insulin resistance and hypercholesterolemia. Thus, suggesting that in genetically predisposed individuals, the environmental context that triggers MetS (i.e., sedentary lifestyle) may also be an important trigger for the development and severity of vitiligo disease. This paper will discuss the relationship between the immune system and epidermal melanocytes and their interplay with the redox system. Based on state-of-the-art evidence from the vitiligo research, physical exercise (PE) immunology, and redox system literature, we will also propose chronic PE as a potential therapeutic strategy to treat and prevent vitiligo disease progression. We will present evidence that chronic PE can change the balance of inflammatory to an anti-inflammatory state, improve both EAS and the mitochondrial structure and function (resulting in the decrease of OS). Finally, we will highlight clinically relevant markers that can be analyzed in a new research avenue to test the potential applicability of chronic PE in vitiligo disease.
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Objectives: The herbicide glyphosate, a pesticide used in agriculture to control weeds, both in food crops and in other agricultural areas, has been identified as an endocrine modulator through the inhibition of aromatase activity and the activation of estrogen receptors. The present study examined the effects of a glyphosate-based herbicide (Roundup® (GLY-BH) on sexual dimorphism of rats after perinatal exposure to low and high GLY-BH in males and females offspring. Methods: Two groups of pregnant rats were treated with two doses of GLY-BH (50 or 150 mg/kg) from day 15 of gestation (GD15) to postnatal day 7 (PND7). Play fighting behavior was observed at the juvenile stage and during social and sexual behaviors in adulthood. Results: Perinatal GLY-BH exposure reduced male and female body weight at 28, 75, and 90 days of age. The play fighting behavior was decreased in both sexes, but female rats were more affected. The sexual behaviors were reduced only in females. Conclusions: Perinatal exposure to both doses of GLY-BH promoted sexually dimorphic effects in both juvenile and adulthood stages. These effects were attributed to the inhibition of aromatase activity induced by exposure to GLY-BH in the perinatal period.(AU)
Objetivos: O glifosato é um herbicida não seletivo, usado em muitas culturas alimentares e não alimentares e em áreas não agrícolas, sendo que os produtos a base de glifosato atuam como moduladores das funções endócrinas por meio da inibição da atividade da aromatase e da ativação de receptores de estrógeno. O presente estudo avaliou os efeitos do herbicida Roundup® (GLY-BH) à base de glifosato, em comportamentos sexualmente dimórficos de ratos após exposição perinatal a doses baixas e altas de GLY-BH no período perinatal. Métodos: Ratas prenhas foram tratadas com 50 ou 150 mg/kg de GLY-BH do 15º dia de gestação (GD15) ao 7º dia de lactação (LD7). O comportamento de luta/brincar foi observado na fase juvenil e os comportamentos social e sexual na idade adulta. Resultados: a exposição perinatal a GLY-BH reduziu o peso corporal de machos e fêmeas aos 28, 75 e 90 dias de idade. O comportamento de luta/brincar diminuiu em ambos os sexos, sendo as ratas foram as mais afetadas. O comportamento sexual foi reduzido apenas nas fêmeas. Conclusões: A exposição perinatal a ambas as doses do GLY- BH promoveu tanto na idade juvenil como na idade adulta, efeitos sexualmente dimórficos. Esses efeitos foram atribuídos à inibição da atividade da aromatase induzida exposição perinatal ao GLY-BH.(AU)
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Animais , Masculino , Feminino , Gravidez , Ratos , Comportamento Sexual Animal/fisiologia , Comportamento Social , Inibidores da Aromatase/efeitos adversos , Caracteres Sexuais , Herbicidas/administração & dosagem , Herbicidas/efeitos adversosRESUMO
OBJECTIVE: Obesity is characterized by a state of chronic, low-intensity systemic inflammation frequently associated with insulin resistance and dyslipidemia. METHODS: Given that chronic inflammation has been implicated in the pathogenesis of mood disorders, we investigated if chronic obesity that was initiated early in life - lasting through adulthood - could be more harmful to memory impairment and mood fluctuations such as depression. RESULTS: Here we show that pre-pubertal male rats (30 days old) treated with a high-fat diet (40%) for 8-months gained ~50% more weight when compared to controls, exhibited depression and anxiety-like behaviors but no memory impairment. The prefrontal cortex of the obese rats exhibited an increase in the expression of genes related to inflammatory response, such as NFKb, MMP9, CCl2, PPARb, and PPARg. There were no alterations in genes known to be related to depression. CONCLUSION: Long-lasting obesity with onset in prepuberal age led to depression and neuroinflammation but not to memory impairment.
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Comportamento Animal , Depressão , Animais , Ansiedade , Depressão/etiologia , Dieta Hiperlipídica/efeitos adversos , Masculino , Obesidade , RatosRESUMO
ABSTRACT Objective: Obesity is characterized by a state of chronic, low-intensity systemic inflammation frequently associated with insulin resistance and dyslipidemia. Materials and methods: Given that chronic inflammation has been implicated in the pathogenesis of mood disorders, we investigated if chronic obesity that was initiated early in life - lasting through adulthood - could be more harmful to memory impairment and mood fluctuations such as depression. Results: Here we show that pre-pubertal male rats (30 days old) treated with a high-fat diet (40%) for 8-months gained ~50% more weight when compared to controls, exhibited depression and anxiety-like behaviors but no memory impairment. The prefrontal cortex of the obese rats exhibited an increase in the expression of genes related to inflammatory response, such as NFKb, MMP9, CCl2, PPARb, and PPARg. There were no alterations in genes known to be related to depression. Conclusion: Long-lasting obesity with onset in prepuberal age led to depression and neuroinflammation but not to memory impairment.
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Animais , Masculino , Ratos , Comportamento Animal , Depressão/etiologia , Ansiedade , Dieta Hiperlipídica/efeitos adversos , ObesidadeRESUMO
BACKGROUND: More than 3 years since the last Zika virus (ZIKV) outbreak in Brazil, researchers are still deciphering the molecular mechanisms of neurovirulence and vertical transmission, as well as the best way to control spread of ZIKV, a flavivirus. The use of pesticides was the main strategy of mosquito control during the last ZIKV outbreak. METHODS: We used vesicular stomatitis virus (VSV) tagged with green fluorescent protein (GFP) as our prototypical virus to study the impact of insecticide pyriproxyfen (PPF). VZV-GFP infected and uninfected Jurkat, HeLa and trophoblast cells were treated with PPF and compared to untreated cells (control). Cell viability was determined by the MTT assay. Cell morphology, presence of extracellular vesicles (EVs), virus infection/GFP expression as well as active mitochondrial levels/localization were examined by confocal microscopy. RESULTS: PPF, which was used to control mosquito populations in Brazil prior to the ZIKV outbreak, enhances VSV replication and has cell membrane-altering properties in the presence of virus. PPF causes enhanced viral replication and formation of large EVs, loaded with virus as well as mitochondria. Treatment of trophoblasts or HeLa cells with increasing concentrations of PPF does not alter cell viability, however, it proportionately increases Jurkat cell viability. Increasing concentrations of PPF followed by VSV infection does not interfere with HeLa cell viability. Both Jurkats and trophoblasts show proportionately increased cell death with increased concentrations of PPF in the presence of virus. CONCLUSIONS: We hypothesize that PPF disrupts the lipid microenvironment of mammalian cells, thereby interfering with pathways of viral replication. PPF lowers viability of trophoblasts and Jurkats in the presence of VSV, implying that the combination renders immune system impairment in infected individuals as well as enhanced vulnerability of fetuses towards viral vertical transmission. We hypothesize that similar viruses such as ZIKV may be vertically transmitted via EV-to-cell contact when exposed to PPF, thereby bypassing immune detection. The impact of pesticides on viral replication must be fully investigated before large scale use in future outbreaks of mosquito borne viruses.
Assuntos
Infecções por Flavivirus/transmissão , Inseticidas/farmacologia , Piridinas/farmacologia , Vesiculovirus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Aedes/virologia , Animais , Brasil , Sobrevivência Celular/efeitos dos fármacos , Vírus da Dengue/efeitos dos fármacos , Vesículas Extracelulares/efeitos dos fármacos , Vesículas Extracelulares/virologia , Proteínas de Fluorescência Verde/genética , Células HeLa , Humanos , Células Jurkat , Trofoblastos/efeitos dos fármacos , Trofoblastos/virologia , Virulência , Zika virus/efeitos dos fármacosRESUMO
BACKGROUND: Depression is one of the most common mentally debilitating diseases in the world. Ketamine has been recently identified as a potential novel antidepressant. Further animal model evaluations of the use of ketamine as an antidepressant are necessary to determine safety parameters for clinical use. Therefore, the objective of this study was to perform toxicological tests of prolonged treatment using three different doses of ketamine in adult male rats. METHODS: The animals were divided into four groups: three treated with 5, 10 or 20 mg/kg of ketamine and a control group treated with saline solution. Intraperitoneal route of treatment was administered daily for 3 weeks. Body weight, water and food intake were measured once a week, as well as evaluation of the functional observational battery, which includes methodic monitoring of motor activity, motor coordination, behavioral changes, and sensory/motor reflex responses. Upon completion of treatment period, all animals were euthanized by decapitation followed by immediate collection of samples, which included brain structures and blood for neurochemical, hematological and biochemical analyses. RESULTS: Rats treated with the highest tested dosage (20 mg/kg) of ketamine had lower weight gain in the 1st and 2nd weeks of treatment and all experimental groups had measurable alterations in the serotoninergic system. CONCLUSIONS: Our data indicate that the alterations observed are minor and due to a predicted mechanism of action, which implies that ketamine is a promising drug for repurposing as an antidepressant.
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Antidepressivos/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Depressão/tratamento farmacológico , Ketamina/administração & dosagem , Animais , Antidepressivos/farmacologia , Antidepressivos/toxicidade , Depressão/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ketamina/farmacologia , Ketamina/toxicidade , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Wistar , Testes de ToxicidadeRESUMO
Our purpose was to verify the effects of inorganic nitrate combined to a short training program on 10-km running time-trial (TT) performance, maximum and average power on a Wingate test, and lactate concentration ([La-]) in recreational runners. Sixteen healthy participants were divided randomly into two groups: Nitrate (n = 8) and placebo (n = 8). The experimental group ingested 750 mg/day (~12 mmol) of nitrate plus 5 g of resistant starch, and the control group ingested 6 g of resistant starch, for 30 days. All variables were assessed at baseline and weekly over 30 days. Training took place 3x/week. The time on a 10-km TT decreased significantly (p < 0.001) in all timepoints compared to baseline in both groups, but only the nitrate group was faster in week 2 compared to 1. There was a significant group × time interaction (p < 0.001) with lower [La] in the nitrate group at week 2 (p = 0.032), week 3 (p = 0.002), and week 4 (p = 0.003). There was a significant group time interaction (p = 0.028) for Wingate average power and a main effect of time for maximum power (p < 0.001) and [La-] for the 60-s Wingate test. In conclusion, nitrate ingestion during a four-week running program improved 10-km TT performance and kept blood [La-] steady when compared to placebo in recreational runners.
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A preocupação com o bem-estar animal vem aumentando na comunidade científica,principalmente em relação aos animais utilizados em experimentação, uma vez que seu comportamento e fisiologia são influenciados pelo ambiente em que se encontram. Um dos fatores importantes para o bem-estar desses animais é o material utilizado como substrato das gaiolas que possui a função de absorver urina, secar as fezes e fornecer material para confecção de ninhos. Esse estudo teve como objetivo avaliar os principais tipos de substratos utilizados nos biotérios brasileiros, a fim de avaliar o desempenho de ratos em testes comportamentais e identificar o substrato da gaiola depreferência dos animais. Para isto, ratos foram separados em três grupos e mantidos em substratos diferentes: maravalha de Pinus em lâminas, maravalha de Pinus em flocos ou sabugo de milho triturado. Após o período de aclimatação, os animais foram submetidos a testes comportamentais e de preferência. Os resultados mostraram que os diferentes tipos de substrato não tiveram influência no comportamento dos animais. O teste de preferência mostrou que os ratos preferiram a maravalha em lâminas e osabugo de milho triturado como substrato. A maravalha em flocos não agradou osanimais, possivelmente devido ao seu formato que dificulta a execução de comportamentos característicos da espécie.(AU)
Concern about animal welfare has been increasing in the scientific community, especially regarding animals used for research purposes, since their behavior and physiology are influenced by the environment. One important factor for these animals welfare is the material used as substrate of the cages, which is used for absorbing urine, drying the faeces and providing material for nests. This study aimed to evaluate the performanceof rats in behavioral test and to evaluate the main types of substrates used in Brazilian animal facilities in order to determine the material of preference of the animals. Therefore, rats were separated into three groups and kept on different substrates: pine wood shavings, pine wood flake or crushed corn cob. After the acclimation period, the animals were submitted to behavioral and preference tests. The results showed that the differentsubstrate types had no influence on animal behaviors. The preference test showed thatthe rats preferred the pine wood shavings and crushed corn cob as substrate. The pine wood flake did not please the animals, possibly because of its shape which makes it difficult for the animals to perform characteristic behaviors of the species.(AU)
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Animais , Masculino , Ratos , Bem-Estar do Animal , Substratos para Tratamento Biológico , Comportamento Animal , Pinus , Animais de LaboratórioRESUMO
A preocupação com o bem-estar animal vem aumentando na comunidade científica,principalmente em relação aos animais utilizados em experimentação, uma vez que seu comportamento e fisiologia são influenciados pelo ambiente em que se encontram. Um dos fatores importantes para o bem-estar desses animais é o material utilizado como substrato das gaiolas que possui a função de absorver urina, secar as fezes e fornecer material para confecção de ninhos. Esse estudo teve como objetivo avaliar os principais tipos de substratos utilizados nos biotérios brasileiros, a fim de avaliar o desempenho de ratos em testes comportamentais e identificar o substrato da gaiola depreferência dos animais. Para isto, ratos foram separados em três grupos e mantidos em substratos diferentes: maravalha de Pinus em lâminas, maravalha de Pinus em flocos ou sabugo de milho triturado. Após o período de aclimatação, os animais foram submetidos a testes comportamentais e de preferência. Os resultados mostraram que os diferentes tipos de substrato não tiveram influência no comportamento dos animais. O teste de preferência mostrou que os ratos preferiram a maravalha em lâminas e osabugo de milho triturado como substrato. A maravalha em flocos não agradou osanimais, possivelmente devido ao seu formato que dificulta a execução de comportamentos característicos da espécie.
Concern about animal welfare has been increasing in the scientific community, especially regarding animals used for research purposes, since their behavior and physiology are influenced by the environment. One important factor for these animals welfare is the material used as substrate of the cages, which is used for absorbing urine, drying the faeces and providing material for nests. This study aimed to evaluate the performanceof rats in behavioral test and to evaluate the main types of substrates used in Brazilian animal facilities in order to determine the material of preference of the animals. Therefore, rats were separated into three groups and kept on different substrates: pine wood shavings, pine wood flake or crushed corn cob. After the acclimation period, the animals were submitted to behavioral and preference tests. The results showed that the differentsubstrate types had no influence on animal behaviors. The preference test showed thatthe rats preferred the pine wood shavings and crushed corn cob as substrate. The pine wood flake did not please the animals, possibly because of its shape which makes it difficult for the animals to perform characteristic behaviors of the species.
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Masculino , Animais , Ratos , Bem-Estar do Animal , Comportamento Animal , Substratos para Tratamento Biológico , Animais de Laboratório , PinusRESUMO
Varenicline is a drug used for smoking addiction cessation treatment and acts as a partial agonist of nicotinic cholinergic receptors. Recent clinical trial data support use of varenicline for treatment of conditions/addictions that are not related to smoking cessation. Considering the importance of this issue and the need for new studies on its effects, especially on behavior, more studies using animal models are necessary. Thus, the aim of this study was to evaluate the effects of prolonged exposure to varenicline in anxiety-like behavior and memory, as well as in cerebral neurochemistry of rats. Male rats received three different doses of varenicline: 0.03 (therapeutic dose for humans), 0.1 and 0.3?mg/kg orally (gavage) for 30?days. Animal behavior was analyzed through open field, elevated plus maze, light/dark box, social interaction, Barnes maze and novel object recognition tests. Neurotransmitter levels and their metabolites in different brain structures (hippocampus, striatum and frontal cortex) were measured. Results showed that prolonged exposure of rats to varenicline: 1) did not interfere in motor activity, but caused an anxiogenic effect on elevated plus maze, light/dark box and social interaction testes; 2) did not alter memory; and 3) promoted alterations on serotoninergic system in the striatum and frontal cortex. In conclusion, compilation of the data indicates that prolonged exposure of rats to varenicline promoted anxiogenic effects and alteration in serotonergic system, which corroborated behavioral findings.
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The current study aimed to determine the effects of sildenafil-associated aerobic exercise training (ET) on the physical performance, hemodynamic, autonomic and inflammatory parameters of rats. Male Wistar rats were randomly assigned to: sedentary rats placebo-treated (SP); sedentary rats sildenafil-treated (SS); trained rats placebo-treated (TP); and trained rats sildenafil-treated (TS). Sildenafil treatment consisted of 8 weeks of daily oral gavage (1.5 mg/kg), one hour before the session of ET (60-75% of maximal running speed, 5 days/week, for 8 weeks). After ET period, physical capacity, hemodynamic, autonomic and skeletal muscle inflammatory profile were assessed. Chronic sildenafil treatment causes an additional increase of physical capacity in aerobically trained rats. However, these beneficial effects were accompanied by unwanted alterations, as increased of arterial pressure and peripheral sympathetic modulation, as well as exacerbated inflammatory status on skeletal muscle of rats. Taken together, these data suggest the positive and negative effects of sildenafil chronic administration, associated to aerobic ET, at doses used in clinical practice. This report stresses the importance of paying greater attention to the indiscriminate use of this substance in high-performance sports.
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Sistema Nervoso Autônomo/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Inflamação/fisiopatologia , Músculo Esquelético/efeitos dos fármacos , Substâncias para Melhoria do Desempenho/farmacologia , Inibidores da Fosfodiesterase 5/farmacologia , Condicionamento Físico Animal/fisiologia , Citrato de Sildenafila/farmacologia , Animais , Sistema Nervoso Autônomo/fisiologia , Barorreflexo/efeitos dos fármacos , Peso Corporal , Masculino , Ratos WistarRESUMO
Varenicline is a synthetic chemical substance produced from the alkaloid cytisine, used for smoking treatment, which acts as a partial agonist for α4ß2 and α3ß4 nicotinic cholinergic receptors and as a total agonist for α7 receptor. While there are studies regarding varenicline's non-smoking-related effects, as in treatment for drug dependence, there are no studies in the literature evaluating the long-term toxicity of varenicline through a physiological approach. Thus, the aim of this study was to evaluate possible toxicity through haematological, biochemical and anatomopathological parameters of prolonged exposure (30 days) to varenicline in rats. Three doses of varenicline were used: 0.03 (therapeutic dose for human beings), 0.1 and 0.3 mg/kg orally (gavage). Body-weight, water and food intake were measured weekly during treatment. On the 30th treatment day, blood and various organs were collected for haematological, biochemical and anatomopathological evaluations. The results show a decrease in some biochemical parameters in animals from the 0.1 and 0.3 mg/kg group, although the values are within the normal range of the species. There were no changes in the other evaluations performed. Together, these data indicate that prolonged exposure of rats to different doses of varenicline was not able to alter haematological, biochemical and anatomopathological parameters.
Assuntos
Agonistas Nicotínicos/efeitos adversos , Dispositivos para o Abandono do Uso de Tabaco/efeitos adversos , Vareniclina/efeitos adversos , Administração Oral , Animais , Relação Dose-Resposta a Droga , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Energia/efeitos dos fármacos , Coração/efeitos dos fármacos , Hematopoese/efeitos dos fármacos , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Miocárdio/citologia , Miocárdio/metabolismo , Agonistas Nicotínicos/administração & dosagem , Especificidade de Órgãos , Ratos Wistar , Reprodutibilidade dos Testes , Testes de Toxicidade Subaguda , Vareniclina/administração & dosagem , Aumento de Peso/efeitos dos fármacosRESUMO
O Paraquate (1,1'-dimetil-4,4'-bipiridina-dicloreto) é herbicida amplamente utilizado em vários países para diferentes culturas. O objetivo é determinar a concentração de Paraquate em batatas comercializadas em diferentes estabelecimentos da zona leste de São Paulo. Foram coletadas 12 (doze) amostras de batatas adquiridas no comércio varejista (sacolões, ou seja, do de frutas, verduras e legumes; supermercados e feiras livres) da zona leste do município de São Paulo. A quantificação do Paraquate foi baseada na reação de complexação com o ditionito de sódio, gerando composto de cor azulada, cuja absorvância foi lida em espectrofotômetro em comprimento de onda de 600nm. Foi construída a curva padrão e a determinada a equação da reta (y = 1,6448x e R2= 0,9945). O limite de tolerância do herbicida em alimentos é de 0,2 partes por milhão ou 0,2 mg/kg, enquanto que a ingestão diária aceitável (IDA) é de 0,004 mg/kg de peso corpóreo. Assim, pode-se observar que os valores encontrados em três amostras estão acima do limite máximo permitido, enquanto quatro apresentaram concentrações muito próximas ao limite. Os resultados permitem inferir que existe a necessidade de intensificação na fiscalização nos locais de comercialização de alimentos produzidos com a utilização de agrotóxicos.(AU)
Paraquat (1,1'-dimethyl-4,4'- bipyridine-dichloríde) is herbicide widely used in several countries in different plantations. The objective is to determine the concentration of Paraquat in potatoes, marketed in different establishments in the eastern zone of São Paulo. Twelve (12) samples of potatoes purchased from the retail trade ("sacolões", ie fruit, vegetable and vegetable markets, supermarkets and free markets) were collected from the eastern part of the city of São Paulo. The quantification of Paraquat was based on the reaction of complexation with the sodium dithionite, generating compound of blue color, whose absorbance was read in a spectrophotometer at wavelength of 600 nm. The standard curve was constructed and the equation of the tine was determined (y=1,6448x e R2=0,9945). The tolerance limit of the herbicide infoods is 0.2 parts per million or 0.2 mg/kg, while the acceptable daily intake (ADI) is 0.004 mg/kg body weight. Thus, it can be observed that the values found in three samples are above the maximum allowed limit, while four of them presented concentrations very close to the limito The results allow inferring that there is a need for intensification in the inspection in the commercial places of food produced with the use of pesticides.(AU)
Assuntos
Herbicidas , Solanum tuberosum , Controle de Qualidade , Controle de Plantas Daninhas , AgroquímicosRESUMO
O Paraquate (1,1'-dimetil-4,4'-bipiridina- dicloreto) é herbicida amplamente utilizado em vários países para diferentes culturas. O objetivo é determinar a concentração de Paraquate em batatas comercializadas em diferentes estabelecimentos da zona leste de São Paulo. Foram coletadas 12 (doze) amostras de batatas adquiridas no comércio varejista (sacolões, ou seja, do de frutas, verduras e legumes; supermercados e feiras livres) da zona leste do município de São Paulo. A quantificação do Paraquate foi baseada na reação de complexação com o ditionito de sódio, gerando composto de cor azulada, cuja absorvância foi lida em espectrofotômetro em comprimento de onda de 600nm. Foi construída a curva padrão e a determinada a equação da reta (y = 1,6448x e R2= 0,9945). O limite de tolerância do herbicida em alimentos é de 0,2 partes por milhão ou 0,2 mg/kg, enquanto que a ingestão diária aceitável (IDA) é de 0,004 mg/kg de peso corpóreo. Assim, pode-se observar que os valores encontrados em três amostras estão acima do limite máximo permitido, enquanto quatro apresentaram concentrações muito próximas ao limite. Os resultados permitem inferir que existe a necessidade de intensificação na fiscalização nos locais de comercialização de alimentos produzidos com a utilização de agrotóxicos.(AU)
Paraquat (1,1'-dimethyl-4,4'- bipyridine-dichloride) is herbicide widely used in several countries in different plantations. The objective is to determine the concentration of Paraquat in potatoes, marketed in different establishments in the eastern zone of São Paulo. Twelve (12) samples of potatoes purchased from the retail trade ("sacolões", ie fruit, vegetable and vegetable markets, supermarkets and free markets) were collected from the eastern part of the city of São Paulo. The quantification of Paraquat was based on the reaction of complexation with the sodium dithionite, generating compound of blue color, whose absorbance was read in a spectrophotometer at wavelength of 600 nm. The standard curve was constructed and the equation of the line was determined (y = 1,6448x e R2 = 0,9945). The tolerance limit of the herbicide in foods is 0.2 parts per million or 0.2 mg/kg, while the acceptable daily intake (ADI) is 0.004 mg/kg body weight. Thus, it can be observed that the values found in three samples are above the maximum allowed limit, while four of them presented concentrations very close to the limit. The results allow inferring that there is a need for intensification in the inspection in the commercial places of food produced with the use of pesticides.
Assuntos
Humanos , Paraquat/administração & dosagem , Paraquat/análise , Solanum tuberosum , Resíduos de Praguicidas , Amostras de Alimentos , Herbicidas/toxicidadeRESUMO
Animal cruelty is a known behavior of psychopaths, and although the serial killing of humans is widely acknowledged worldwide, this type of crime against animals is seldom discussed. This report describes the necropsy and toxicological findings of 37 dogs and cats, which were found dead in plastic bags in Sao Paulo, Brazil. The animals had all been in the care of an alleged animal rescuer and were to be referred for adoption before being found dead. In the necropsy, the animals showed varying degrees of putrefaction, indicating different periods of death, as well as single or multiple perforations on the thorax. The perforations reached the heart, lungs or large thoracic vessels, culminating in hemopericardium and hemothorax that led to death by circulatory failure and cardiac tamponade. Blood from the heart and thoracic cavity was analyzed by gas chromatography coupled with mass spectrometry (GC-MS) and tested positive for ketamine, a dissociative anesthetic. The suspect declared that she had killed only five of the animals and that they had all been fatally sick. The necropsy proved that all 37 animals were killed in the same way, that none of the animals had any terminal diseases and that a restricted drug was used. The suspect was sentenced to 12 years, 6 months and 14days of prison for the killing of the 37 animals. This was the first conviction for the crime of animal cruelty in Brazil. The combined role of police, forensic veterinary pathologists and prosecutors were essential to the conviction, which was a great historical occasion in the fight against animal cruelty.