Vacuolização neuronal e degeneração espinocerebelar em filhote de Rottweiler / Neuronal vacuolation and spinocerebellar degeneration in a Rottweiller puppy

Background: Spinocerebellar degenerations and neuronal vacuolations are alterations characterized by the formation of vacuoles in the nervous tissue, commonly called status spongiosus. This condition occurs in young Rottweiler dogs causing a disease called Neuronal Vacuolation and Spinocerebellar Degeneration. Clinically, it presents with ataxia of the pelvic limbs, which evolves to generalized ataxia, tetraparesis, and laryngeal paralysis. Histologically, spongiform and vacuolar alterations of the neuropil and neurons are highlighted. This reports a case of neuronal vacuolation and spinocerebellar degeneration in a Rottweiler puppy. Case: Necropsy was performed on the cadaver of a 5-month-old Rottweiler bitch that had been presenting with ataxia for approximately 1 month, in addition to dyspnea, pulmonary crepitations, and microphthalmia. Macroscopic evaluation revealed pale ocular and oral mucosae; marked gastric dilatation and abdominal distension; pulmonary hemorrhage and edema; hepatosplenomegaly; fatty degeneration of the liver; and congestion of meningeal blood vessels. Microscopically, histological evaluation of the spinal cord showed an increase in gray matter cellularity with marked presence of oligodendrocytes and microglia cells; moderate to severe multifocal intracytoplasmic micro- and macrovacuoles with displacement of the neurons' nuclei to the periphery of the cell; central chromatolysis of the neurons adjacent to neurons affected by vacuolation; and mild multifocal necrosis associated with mild multifocal neuronophagia. The white matter exhibited discrete digestion chambers, in addition to marked diffuse congestion of the leptomeninges. In the cerebellum, neurons in the nerve nuclei (emboliform, globose, and fastigial) showed moderate multifocal vacuoles in the cytoplasm, whereas adjacent neurons showed central chromatolysis, necrosis, and mild neuronophagia. Additional histological findings included lymphoid hyperplasia, fatty degeneration of the liver, pulmonary edema, and pulmonary hemorrhage. Discussion: Spongiform and degenerative encephalopathies are diseases recognized worldwide, mainly in cattle and sheep. However, the identification of these changes in new species has led to the need for further investigations. In dogs, the first reports occurred in 1995 and 1997 in Rottweiler animals. This disease affects young dogs, and although its pathogenesis is not completely known, it is believed to be associated with a genetic mutation in the RAB3GAP1 gene. Clinically, it is associated with clinical neurological manifestations, including progressive ataxia of the pelvic limbs, changes in spinal reflex, disordered proprioceptive reactions, laryngeal paralysis, as well as behavioral and gait alterations. In the clinical evaluation, leukoencephalomyelopathy and neuroaxonal dystrophy should be diseases considered as possible differential diagnoses, as they present with similar alterations. However, in histological evaluation, the exclusion of both is basically due to the absence of neuronal vacuolization. Unfortunately, the definitive diagnosis is only made post mortem, through a histopathological evaluation of the nervous tissue. Because it is a disease whose pathogenesis is little known and which shows signs of having a genetic character, histopathological examination for diagnostic purposes in young animals with neurological signs is of great importance.

Lafora's disease in a free-ranging toco toucan (Ramphastos toco) with neurologic disease

Lafora's disease is a genetic disease associated to mutations in genes that encodes laforin and malin, which results in intracellular polyglucan storage. The present report describes a case of Lafora's disease in a toco toucan with episodes of incoordination and myoclonus that resulted in traumatic lesions and fracture of the left hindlimb. The bird was euthanized and submitted to necropsy. Microscopically there were abundant PAS-positive and diastasis-resistant Lafora's inclusion bodies in neurons in the cerebellum, supporting the diagnosis of Lafora's disease.(AU)

Potential of marine compounds in the treatment of neurodegenerative diseases: a review / Potencial de compostos marinhos no tratamento de doenças neurodegenerativas: uma revisão

Neurodegenerative diseases (ND) are characterized, especially, by the progressive loss of neurons, resulting in neuropsychomotor dysfunctions. Even with a high prevalence, NDs are treated with drugs that alleviate the symptoms of patients, but which develop adverse events and still do not inhibit the progression of the disease. Thus, within a new pharmacological perspective, this review aimed to verify the therapeutic potential of natural compounds of marine origin against ND. For this, an integrative review was carried out, according to the PRISMA methodology, which included steps such as: search, pre-selection and inclusion of articles. The results described revealed species such as Acaudina malpodioides, Holothuria scabra and Xylaria sp., which presented important evidence in relation to Alzheimer's, reducing the generation of ROS, presenting neuroprotective effects and reducing the concentration of Aß peptide. Regarding Parkinson's disease (PD), another example of ND, the bioactive compounds from Holothuria scabra and Xylaria sp., showed to be able to reduce the degeneration of dopaminergic neurons, reduce the deposition of alpha synuclein and reduce the formation of Mutant Huntingtin protein (Mhtt). The other marine compounds and bioactive substances are also described in this review. In conclusion, the evaluated studies indicate that compounds of marine origin emerge as a promising source of bioactive compounds, revealing an important therapeutic potential for the treatment of ND.

As doenças neurodegenerativas (ND) são caracterizadas, especialmente, pela perda progressiva de neurônios, resultando em disfunções neuropsicomotoras. Mesmo apresentando uma alta prevalência, as DN são tratadas com medicamentos que aliviam os sintomas dos pacientes, mas que desenvolvem eventos adversos e ainda não inibem a progressão da doença. Assim, dentro de uma nova perspectiva farmacológica, esta revisão teve como objetivo verificar o potencial terapêutico de compostos naturais de origem marinha frente às DN. Para tal, foi realizada uma revisão integrativa, segundo a metodologia PRISMA que compreendeu etapas como: busca, pré-seleção e inclusão dos artigos. Os resultados descritos revelaram espécies como, Acaudina malpodioides, Holothuria scabra e Xylaria sp., que apresentaram importantes evidências em relação ao Alzheimer, reduzindo a geração de ROS, apresentando efeitos neuroprotetores e reduzindo a concentração de peptídeo Aß. Sobre a doença de Parkinson (PD), outro exemplo de ND, os compostos bioativos da Holothuria scabra e da Xylaria sp., mostraram ser capazes de diminuir a degeneração de neurônios dopaminérgicos, reduzir a deposição de alfa sinucleína e reduzir a formação de agregados da proteína Huntingtina mutante (Mhtt). Os outros compostos marinhos e substâncias bioativas também são descritos nesta revisão. Em conclusão, os estudos avaliados indicam que os compostos de origem marinha despontam como uma promissora fonte de compostos bioativos, revelando um importante potencial terapêutico para o tratamento das ND.

Physiological gait test: an effective method for analyzing balance, locomotion, and neuromuscular disorders in rats and a comparison to the elevated beam test / Teste de marcha fisiológica: um método eficaz para analisar distúrbios de equilíbrio, locomoção e neuromusculares em roedores

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)

Listeria innocua and serotypes of Listeria monocytogenes isolated from clinical cases in small ruminants in the northwest of Uruguay / Listeria innocua e serotipos do Listeria monocytogenes isoladas dos casos clínicos em pequenos ruminantes no noroeste do Uruguai

Listeriosis is an infectious disease caused by bacteria of the genus Listeria, the neurological form being more common in ruminants. There are many reports of listeriosis in small ruminants in the region that includes Brazil, Argentina and Uruguay. However, these diagnoses were mainly based on histological lesions in the central nervous system (CNS) without the isolation and characterization of the involved Listeria strains. The aim of this study was to report sheep and goats listeriosis cases from 2016 to 2021 in northwestern Uruguay. The diagnosis was made according to lesions observed at histopathology, plus Listeria isolation in CNS, identifying it at specie and serotype level. Nine animals (n=9) of three outbreaks and five sporadic cases of listeriosis were studied. Sheep was the species with more cases in relation to goats, and adults were the category most affected. Cases occurred in spring and less frequently in winter. All presented neurological clinical signs and the lesions in the CNS were consistent with suppurative meningoencephalitis and micro-abscesses in the brainstem. In eight of nine CNS samples, Listeria strains were isolated (seven L. monocytogenes and one L. innocua). All the L. monocytogenes isolates carried the inlA gene; serotyping showed that four strains belonged to serotype 1/2b, two isolates belonged to serotype 4b, and one to serotype 1/2a. Considering that listeriosis is a common disease in this region and the fact that isolates are scarcely recovered from small ruminants, it would be important to emphasize the need for Listeria isolation to better characterize the strains that affect animals. Not only to improve knowledge about the epidemiology of disease but also with the objective of developing serotype specific vaccines for animal use.

Listeriose uma doença bacteriana causada pelo gênero Listeria, a forma nervosa é a mais comum em ruminantes. No Brasil, Argentina e Uruguai há vários relatos de listeriose em pequenos ruminantes com diagnóstico baseado na histopatologia do sistema nervoso central (SNC), sem o isolamento e a caracterização do agente. O objetivo deste trabalho foi relatar uma série de casos diagnosticados em ovinos e caprinos no período 2016-2021 no noroeste do Uruguai. O diagnóstico foi feito basado nas lesões observadas na histopatologia, e caracterização das cepas de Listeria recuperadas do SNC quanto à espécie e sorotipo. Nove animais (n=9) do três surtos e cinco casos isolados de listeriose foram estudados. Os ovinos foram a espécie com o maior número de casos em relação aos caprinos, sendo os animais adultos a categoria mais afetada em ambas espécies. A doença ocorreu principalmente na primavera com alguns casos observados no inverno. Todos os casos apresentavam sinais clínicos nervosos e as lesões no SNC caracterizavam-se por meningoencefalite supurativa com presença de microabscessos no tronco encefálico. Em oito de nove amostras do SNC foram isoladas cepas de Listeria (sete L. monocytogenes e uma L. innocua). Todos os isolados de L. monocytogenes continham o gene inlA; a sorotipagem apresentou quatro cepas do serotipo 1/2b, duas cepas serotipo 4b e uma cepa 1/2a. Levando em consideração que nesta região a listeriose é uma doença frequente e que existem poucos isolados recuperados de casos clínicos em pequeño ruminantes, torna-se relevante o isolamento deste agente para caracterização das cepas que afetam os animais. Não só para melhorar o conhecimento sobre a epidemiologia da doença, mas também com o objetivo de desenvolver vacinas sorotipo-especificas para uso animal.

Vitamin A deficiency as a cause of blindness in feedlot calves / Deficiência de vitamina A como causa de cegueira em bezerros confinados

Vitamin A is an essential micronutrient to reproduction, development, normal growth, and function of the nervous system and vision, especially in growing animals. Hypovitaminosis A can affect any of these functions. The aim of this study was to describe the epidemiology, clinical signs, pathological aspects, and diagnostic approach in an outbreak of blindness in feedlot calves fed only grain. Five of 57 ten-month-old calves became blind after eight months at the feedlot. Clinical signs were mydriasis, absent pupillary and menace reflexes, bilaterally. Hypovitaminosis A was suspected and subsequently confirmed by low serum levels of vitamin A. One calf was euthanized and necropsied, and no gross findings were present. Histopathological lesions were restricted to the retina and characterized by degeneration and atrophy of the photoreceptor layer and some retinal scars. The calves were treated with intramuscular vitamin A injection at a dose of 5,000 international units (IU) per kilogram of body weight (kg BW) every 60 days until slaughter. Affected calves did not recover visual capacity, but no other cases occurred.

Vitamina A é um micronutriente essencial para reprodução, desenvolvimento, crescimento normal, além de participar do funcionamento do sistema nervoso central e visão, especialmente em animais em crescimento. Hipovitaminose A pode afetar qualquer uma dessas funções. O objetivo desse artigo é descrever a epidemiologia, sinais clínicos, aspectos patológicos e abordagem diagnóstica em um surto de cegueira em bezerros confinados alimentados apenas com grãos. De 57 bezerros de dez meses de idade, cinco ficaram cegos após oito meses no confinamento. Os sinais clínicos eram midríase, ausência de reflexo pupilar a luz e de ameaça, bilateralmente. Suspeitou-se de hipovitaminose A, que foi subsequentemente confirmada pelos baixos níveis séricos de vitamina A. Um bezerro foi eutanasiado e necropsiado, e alterações macroscópicas não foram encontradas. Lesões histopatológicas estavam restritas a retina e caracterizavam-se por degeneração e atrofia da camada de fotorreceptores, além de cicatrizes na retina. Os bezerros foram tratados com injeção intramuscular de vitamina A, na dose de 5.000 unidades internacionais (UI) por quilograma de peso vivo (Kg PV) a cada 60 dias, até o dia do abate. Os bezerros afetados não recuperaram a capacidade visual, mas novos casos não ocorreram.

Antiparkinsoniano para tratamento de sequelas neurológicas causadas pela cinomose / Antiparkinsonian for treatment of neurological sequels caused by canine distemper

Background: Canine distemper (CD) is a highly contagious viral disease caused by the canine distemper virus (CDV). In dogs, CDV infection is characterized by the presentation of systemic and/or neurological signs with viral persistence in some organs, including the central nervous system (CNS). Neurological damages resulting from CD are a defiance for veterinarians, due to occasioned clinical sequels that influence the patient quality of life. The treatment of sequelae should seek to promote the resolution or decrease of the deleterious effects that impede the patient independence. Thus, the present report aims to describe the action of antiparkinsonian medication (levodopa associated with carbidopa) administered to 3 dogs who presented neurological sequels resulting from the canine distemper. Cases: Dog 1. A 9-month-old male mixed breed; Dog 2. A 6-month-old male Shih Tzu. Dog 3. A 8-years-old bitch mixed breed. All animals were referred for neurological care because presented neurological damages after distemper involvement. Only the Dog 2 was vaccinated to CD. Dog 1 (mixed male) had severe myoclonus, lack of proprioception, decreased of muscle tonus and paralysis in both pelvic limbs, associated with a marked thoracolumbar kyphosis. Dog 2 (a puppy Shih Tzu male) presented myoclonus in PL, proprioceptive loss in thoracic and pelvic limbs, absence of withdrawal reflex in thoracic and pelvic limbs, decrease in muscle tonus in pelvic limb and increase in thoracic limb. Dog 3 (adult unneutered bitch) presented intense myoclonus, absence of proprioception, decrease in muscle tonus and paresis of pelvic limb. All patients were treated with antiparkinsonian medication (levodopa 250 mg associated with carbidopa 25 mg) with following dosages: Dog 1 received a commercially available tablet, orally once a day for 30 days, while Dogs 2 and 3 had doses calculated by extrapolation allometric. For the Dog 2 it was prescribed 0.25 mg of levodopa and 0.025 mg of carbidopa daily for 30 days. Dog 3 was treated with 1 mg of levodopa and 0.1 mg of carbidopa patient day for the same period. Thirty days after starting the treatment, the 3 patients were evaluated again, and showed improvement of the motor signs, and the treatment was maintained. At the next return (30 days): Dog 1 showed significant improvement, however, Dog 2 started to present epileptic seizures and nystagmus that were treated with levetiracetam, while the Dog 3 not returned. As Dog 1 had a better prognosis, treatment was maintained for 1 year, with the frequency being changed from 24 h x 24 h to 48 h x 48 h after 30 days and 72x72 h after another 30 days. Unfortunately, Dog 2 had a worsening of epileptic condition and died, while Dog 3 died by road-kill. Discussion: The cases reported are uncommon, because not exist information about the use of antiparksonian to treatment of neurological damages occasioned by canine distemper. Although there are emerging therapies, such as the use of mesenchymal stem cells, that can reduce these sequels, the access is still restricted to a few professionals. Thus, the use of medications for demyelinating diseases, as antiparkinsonian, may be an alternative. In fact, the three reported patients showed recovery of the motor and sensorial damages observed, which corroborates with the possibility of a new treatment using antiparkinsonian or other drugs to demyelinating diseases.

Astragaloside IV alleviates stroke-triggered early brain injury by modulating neuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway

Purpose: Stroke is an acute cerebrovascular disease. Astragaloside IV (AS-IV) is an active ingredient extracted from Astragalus membranaceus with an established therapeutic effect on central nervous system diseases. This study examined the neuroprotective properties and possible mechanisms of AS-IV in stroke-triggered early brain injury (EBI) in a rat transient middle cerebral artery occlusion (MCAO) model. Methods: The neurological scores and brain water content were analyzed. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was utilized to determine the infarct volume, neuroinflammatory cytokine levels, and ferroptosis-related genes and proteins, and neuronal damage and molecular mechanisms were evaluated by terminal deoxynucleotidyl transferase dutp nickend labeling (TUNEL) staining, western blotting, and real-time polymerase chain reaction. Results: AS-IV administration decreased the infarct volume, brain edema, neurological deficits, and inflammatory cytokines TNF-α, interleukin-1ß (IL-1ß), IL-6, and NF-κB, increased the levels of SLC7A11 and glutathione peroxidase 4 (GPX4), decreased lipid reactive oxygen species (ROS) levels, and prevented neuronal ferroptosis. Meanwhile, AS-IV triggered the Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of stroke. Conclusion: Hence, the findings of this research illustrate that AS-IV administration can improve delayed ischemic neurological deficits and decrease neuronal death by modulating nuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway.

Compressive lesions in the central nervous system of buffaloes / Lesões compressivas no sistema nervoso central de bubalinos

This study describes, through a retrospective study, the epidemiological and clinical-pathological findings of compression in the central nervous system (CNS) of buffaloes. The study includes observations made in 15 animals from 1998 to 2021 by reviewing the clinical records of animals with compressive injuries of the CNS treated at the Veterinary Hospital of the Veterinary Medicine Institute of the Federal University of Pará. The animals treated with clinical signs compatible with CNS compressive lesions were subjected to general and specific clinical examinations of the nervous system. Blood samples were collected from four animals for complete blood counts, and cerebrospinal fluid (CSF) samples were collected from three animals for physical evaluation. Thirteen animals were necropsied. The age range of the affected animals ranged from four months to 11 years of age, with a greater frequency over age 12 months (80%, 13/15). The most affected vertebral segment was between T3 and L3 (60%, 9/15), followed by brain injury (20%, 3/15), the L4-S2 segment (13.3%, 2/15) and the C1-C5 segment (6.7%, 1/15). The clinical findings varied according to the location of the lesion. The necropsy findings revealed paraypophyseal abscess in the brainstem and vertebral body, subarachnoid hematoma, lymphoma and vertebral fractures. The performance of a thorough clinical examination of the CNS combined with the necropsy findings was important to characterize the clinical picture and to locate the cause and the affected CNS segments in the buffaloes studied. It is important to include CNS compressive lesions among the neurological diseases of buffaloes.

Esse trabalho descreve, através de estudo retrospectivo, os achados epidemiológicos e clínico-patológicos de compressão no sistema nervoso central (SNC) de bubalinos. O estudo compreendeu as observações realizadas em 15 animais, durante os anos de 1998 a 2021, por meio da revisão dos arquivos de fichas clínicas de animais com lesões compressivas no SNC atendidos pelo Hospital Veterinário do Instituto de Medicina Veterinária da Universidade Federal do Pará. Os animais atendidos com sinais clínicos compatíveis com lesões compressivas no SNC foram submetidos a exames clínicos geral e específico do sistema nervoso. Foram coletadas amostras de sangue de quatro animais para realização de hemograma e amostras de líquido cefalorraquidiano (LCR) de três animais para avaliação física. Foram necropsiados 13 animais. A faixa etária dos animais acometidos variou de quatro meses a 11 anos de idade, com maior frequência na faixa acima de 12 meses (80%, 13/15). O segmento vertebral mais acometido foi entre T3-L3 (60%, 9/15), seguida por lesão no encéfalo (20%, 3/15), pelo segmento L4-S2 (13,3%, 2/15) e pelo segmento C1-C5 (6,7%, 1/15). Os achados clínicos variaram de acordo com a localização da lesão. Os achados de necropsia revelaram abscesso parahipofisário, no tronco encefálico e no corpo da vértebra, hematoma subaracnoidea, linfoma e fraturas vertebrais. A realização de um minucioso exame clínico do SNC associado aos achados de necropsia foram importantes para caracterizar o quadro clínico e localizar a causa e os seguimentos acometidos do SNC nos búfalos estudados. Torna-se importante incluir as lesões compressivas do SNC entre as enfermidades neurológicas dos bubalinos.

Compressive lesions in the central nervous system of cattle: a retrospective study of 50 cases in the Amazon biome / Lesões compressivas no sistema nervoso central de bovinos: um estudo retrospectivo de 50 casos no bioma amazônico

The present study gathered epidemiological and clinical-pathological information about cattle with compressive lesions in the central nervous system (CNS). The retrospective study included observations made in 50 cattle from 1998 to 2021 by reviewing the clinical records of animals with compressive lesions in the CNS treated at the Veterinary Hospital of the Veterinary Medicine Institute of the Federal University of Pará. The animals had clinical signs and were subjected to general and specific clinical examination of the nervous system. Blood samples were collected from 13 animals for complete blood counts, and cerebrospinal fluid (CSF) samples were collected from four animals for physical evaluation. Twenty-nine cattle underwent necropsy. The most affected sites were the T3-L3 (46%, 23/50), C1-C5 (22%, 11/50), C6-T2 (14%, 7/50), sacrococcygeal vertebrae, (4%, 2/50), L4-S2 (2%, 1/50), brain (8%, 4/50) and cerebellum (4%, 2/50). The age of the affected cattle ranged from 20 days to 16 years, with a higher occurrence in animals younger than 12 months (56%, 28/50). More Females were affected (58%, 29/50) than males (42%, 21/50). The clinical signs varied according to the location of the lesion and were mainly represented by ataxia, paresis or paralysis of the limbs, inability to stand and walk, postural changes, hyperesthesia in the extremities, and loss of skin sensitivity at the location of the lesion. The necropsy findings revealed changes such as abscesses in the vertebral body; intervertebral space in the medullary canal, pituitary and cerebellum; granuloma in the arch of the vertebra; fractures of the body of the vertebrae; subarachnoid haematoma; congenital bone alteration causing spinal cord compression; and spondylitis. Detailed anamnesis and clinical examination of the CNS, associated with necropsy findings, were important to determine the cause of the disease, correlate with the clinical picture and locate the affected segments of the CNS in the cattle. It is important to include these diseases in the list of differential diagnoses in cattle with nervous symptoms.

O presente trabalho reúne informações epidemiológicas e clínicopatológicas de bovinos com lesões compressivas no sistema nervoso central (SNC). O estudo retrospectivo compreendeu as observações realizadas em 50 bovinos durante os anos de 1998 a 2021, por meio da revisão dos arquivos de fichas clínicas de animais com lesões compressivas no SNC atendidos pelo Hospital Veterinário do Instituto de Medicina Veterinária da Universidade Federal do Pará. Os animais atendidos com sinais clínicos foram submetidos a exame clínico geral e específico do sistema nervoso. Foram coletadas amostras de sangue de 13 animais para realização de hemograma e amostras de líquido cefalorraquidiano de quatro animais para avaliação física. Foram submetidos à necropsia 29 bovinos. Os locais mais acometidos foram as vértebras T3-L3 (46%, 23/50), C1-C5 (22%, 11/50), C6-T2 (14%, 7/50), sacrococcígea (4%, 2/50) e L4-S2 (2%, 1/50); cérebro (8%, 4/50) e cerebelo (4%, 2/50). A idade dos bovinos afetados variou de 20 dias a 16 anos, com maior ocorrência em animais com menos de 12 meses (56%, 28/50). As fêmeas foram mais acometidas (58%, 29/50) do que os machos (42%, 21/50). Os sinais clínicos variaram de acordo com a localização da lesão e foram representados principalmente por ataxia, paresia ou paralisia dos membros, incapacidade de se levantar e de ficar em estação, alterações posturais, hiperestesia nas extremidades, além de perda da sensibilidade cutânea relacionada com a localização da lesão. Os achados de necropsia revelaram alterações como abscessos no corpo vertebral, no espaço intervertebral, no canal medular, para-hipofisário e no cerebelo; granuloma no arco da vértebra, fraturas do corpo das vértebras; hematoma subaracnoide; alteração óssea congênita causando compressão medular e espondilite. Anamnese detalhada e exame clínico do SNC, associados aos achados de necropsia foram importantes para determinar a causa da doença, correlacionar com o quadro clínico e localizar os segmentos acometidos do SNC dos bovinos. Torna-se importante incluir estas enfermidades na lista de diagnósticos diferenciais em bovinos que apresentem sintomatologia nervosa.

Assessment of melatonin-alpha adrenergic receptor complexes by molecular docking analysis / Avaliação dos complexos melatonina-receptores alfa-adrenérgicos por análises de docagem molecular

The pineal melatonin (N-acetyl-5-methoxytryptamine) is a molecule associated in a way or another with probably all physiological systems, aiming to fulfil its functional integrative roles in central nervous system activity, sleep and wakefulness cycles, energy metabolism and thermoregulation, immune, reproductive, endocrine, cardiovascular, respiratory and excretory systems. Within this context, the present study aimed to assess in silico the formation of complexes between ligand melatonin and other potential receptor proteins by molecular docking analyses. The main steps established in this experimental procedure were: a) search and selection of the 3D structure of the melatonin from DrugBank; b) search and selection of 3D structures of other target receptor proteins using STRING, protein BLAST and database PDB; and c) formation of the complexes between melatonin and receptors selected using AutoDock4.0 server by molecular docking analyses. High reliability score and significant similarity were only identified between type 1B melatonin and alpha-2A adrenergic receptor. Thus, molecular docking assays were carried out using ligand melatonin and crystallographic structures of the alpha-2A adrenergic receptor coupled to an antagonist (ID PDB 6kux) and a partial agonist (ID PDB 6kuy) available in the database PDB. Binding energy values of -6.79 and -6.98 kcal/mol and structural stability by non-covalent intermolecular interactions were predicted during the formation of complexes between melatonin and alpha-2A adrenergic receptor 6kux and 6kuy, respectively. In this way, the findings described in current study may indicate strong interactions between melatonin and adrenoceptors, suggesting its possible partial agonist effect on the activation of the alfa-2A adrenergic receptor.(AU)

A melatonina pineal (N-acetil-5-metoxitriptamina) é uma molécula associada de um modo ou outro com provavelmente todos os sistemas fisiológicos, visando cumprir seus papéis funcionais integradores na atividade do sistema nervoso central, ciclos de sono e vigília, metabolismo energético e termorregulação, sistemas imunológico, reprodutivo, endócrino, cardiovascular, respiratório e excretor. Assim, o presente estudo objetivou avaliar in silico a formação de complexos entre o ligante melatonina e outras proteínas potenciais receptoras por meio de análises de docagem molecular. As principais etapas estabelecidas neste procedimento experimental foram: a) busca e seleção da estrutura 3D da melatonina a partir do banco de dados DrugBank; b) busca e seleção de estruturas 3D de outras proteínas receptoras-alvo utilizando STRING, proteína BLAST e o banco de dados PDB; e c) avaliação da formação dos complexos entre melatonina e receptores selecionados a partir do servidor AutoDock4.0 para análises de docagem molecular. Alto escore de confiabilidade e similaridade significativa foram identificados apenas entre a melatonina do tipo 1B e o receptor alfa-2A adrenérgico. Valores de energia de ligação de -6,79 e -6,98 kcal/mol e estabilidade estrutural pela presença de interações intermoleculares não covalentes foram preditos durante a formação de complexos entre o ligante melatonina e os receptores adrenérgico alfa-2A 6kux e 6kuy, respectivamente. Dessa forma, os achados descritos no presente estudo podem indicar fortes interações entre melatonina e adrenoceptores, sugerindo seu possível efeito agonista parcial na ativação do receptor alfa-2A adrenérgico.(AU)

Listeriosis outbreak in sheep raised in feedlots in the Southern Region of Rio Grande do Sul state, Brazil

Background: A listeriosis outbreak in a sheep fattening feedlot in the Southern Region of Rio Grande do Sul State, Brazilis described. This disease is caused by Listeria monocytogenes and represents a risk to public health since it affects notonly ruminants but also humans. This agent is widely spread in the environment, such as in the soil and water. It is alsofound in decaying vegetable matter and the feces and fluids of domestic animals. The aim of this study was to describe alisteriosis outbreak in sheep raised in feedlots, its epidemiology, and to establish the importance of this disease in this typeof sheep management system, evaluate the possible sources of infection, and suggest ways to control it.Cases: Sheep were kept in a 2-sector shed, one with east solar orientation and the other with west solar orientation, thelatter with free access to domestic birds. Sheep were fed silage and concentrate. Seven sheep were affected, 5 died and 2recovered. Clinically, the sheep displayed loss of balance, excessive drooling, and tremors; one exhibited circling, headdeviation, apathy, nystagmus, lateral recumbency, paddling, and labored breathing. At necropsy, macroscopic lesions werenot found, and histologically several micro-abscesses and perivascular cuffs with lymphocytes, macrophages, and neutrophils were present in the brain stem. Listeria monocytogenes suspected colonies were observed in the microbiologicalculture, and the bacteria was identified by biochemical analysis. The immunohistochemistry test in brain stem sectionswas positive for the antibody BD DifcoTM Listeria O Antiserum Poly Serotypes 1 and 4.Discussion: A listeriosis outbreak in a feedlot sheep was confirmed through epidemiological findings, histological lesions,bacterial culture, and immunohistochemistry analysis. This infection is frequent...

Listeriosis outbreak in sheep raised in feedlots in the Southern Region of Rio Grande do Sul state, Brazil

Background: A listeriosis outbreak in a sheep fattening feedlot in the Southern Region of Rio Grande do Sul State, Brazilis described. This disease is caused by Listeria monocytogenes and represents a risk to public health since it affects notonly ruminants but also humans. This agent is widely spread in the environment, such as in the soil and water. It is alsofound in decaying vegetable matter and the feces and fluids of domestic animals. The aim of this study was to describe alisteriosis outbreak in sheep raised in feedlots, its epidemiology, and to establish the importance of this disease in this typeof sheep management system, evaluate the possible sources of infection, and suggest ways to control it.Cases: Sheep were kept in a 2-sector shed, one with east solar orientation and the other with west solar orientation, thelatter with free access to domestic birds. Sheep were fed silage and concentrate. Seven sheep were affected, 5 died and 2recovered. Clinically, the sheep displayed loss of balance, excessive drooling, and tremors; one exhibited circling, headdeviation, apathy, nystagmus, lateral recumbency, paddling, and labored breathing. At necropsy, macroscopic lesions werenot found, and histologically several micro-abscesses and perivascular cuffs with lymphocytes, macrophages, and neutrophils were present in the brain stem. Listeria monocytogenes suspected colonies were observed in the microbiologicalculture, and the bacteria was identified by biochemical analysis. The immunohistochemistry test in brain stem sectionswas positive for the antibody BD DifcoTM Listeria O Antiserum Poly Serotypes 1 and 4.Discussion: A listeriosis outbreak in a feedlot sheep was confirmed through epidemiological findings, histological lesions,bacterial culture, and immunohistochemistry analysis. This infection is frequent...(AU)

Canine hypothyroidism with neurological disorders

Background: Hypothyroidism is characterized by hypofunction of the thyroid gland. It results in deficient production of thyroid hormones. Neurological disorders resulting from hypothyroidism are rare, which highlights the importance of this study. This study reports a case of hypothyroidism in a dog with neurological clinical signs, that was treated at the Universidade Estadual de Santa Cruz's Veterinary Hospital (HV-UESC). Case: A 4-year-old male intact Dogo Argentino breed dog, weighing 64 kg, presenting obesity, anorexia, prostration, walking in circles, and chronic dermatopathy was presented at HV-UESC. Upon physical examination, the animal presented a deficit of proprioception in the 4 limbs, with preserved superficial and deep pain. No alteration was observed in the ears, that could explained the clinical signs. In terms of dermatopathy, the animal presented symmetrical alopecia in the lateral region of the thighs and tail. Blood samples were collected for a complete blood count and biochemical tests of urea, creatinine, ALT, AST and cholesterol. Imaging radiography and ultrasonography were performed, which ruled out thoracic and abdominal changes that could be related to the case. Prior to receiving the blood test results, idiopathic encephalitis was suspected and enrofloxacin and prednisone were prescribed for 7 days. During the medication period, previous exams were provided, which indicated only increased cholesterol (500 mg/dL). The animal showed no improvement with the prescribed medication. In view of the clinical signs presented by the patient and the results of the additional tests, hormonal disease was suspected, compatible with hypothyroidism. Thus, hormonal tests of total T4, free T4, and TSH were requested, leading to verification of reduced total T4 (0.3 ng/dL) and free T4 (0.15 ng/dL) levels, and confirming the dysfunction of the thyroid gland. The previous treatment was suspended and thyroid hormone replacement was initiated. After 3 days of treatment, the neurological signs regressed and the animal became more active; after 30 days, the areas of alopecia decreased. Although the patient did not receive the recommended clinical follow-up for such cases, it was possible to establish the ideal levothyroxine dosage for the dog after appropriate adjustments, which permitted thyroid hormone levels to return to normal. Discussion: This report refers to a case of hypothyroidism in a giant dog breed. The dog in the report showed clinical signs of a dermatological, metabolic, and neurological nature, which is consistent with a lack of thyroid hormone. The main signs presented by the animal were neurological, such as walking in circles and a deficit of proprioception in the four limbs. These clinical signs are rarely mentioned in the literature associated with hypothyroidism. Laboratory abnormalities are correlated with the severity and chronicity of the disease. The animal showed a decrease in total T4 and free T4, which is to be expected in a hypothyroid animal. As a result, levothyroxine replacement treatment was initiated. The dose used for the dog, which is the recommended dose in the literature, greatly increased its total T4 levels. As a result, the dose was readjusted after a new clinical evaluation. The rate of metabolism and absorption of levothyroxine varies widely and is independent of weight. The patient showed quickly improvement in neurological signs, activity level, and serum cholesterol rate. Regarding dermatological signs and body condition, there was a more gradual improvement. This corroborates what is mentioned in the literature, which indicates that improvements can take many months

Polioencephalomalacia in sheep - clinical and magnetic resonance imaging findings

Background: Polioencephalomalacia (PEM) is a neurological disease in ruminants, which is characterized by malacia of brain gray matter. Thiamine deficiency and sulfur intoxication are the most common causes of PEM in sheep. Affected animals present signs of cerebrocortical syndrome, including amaurosis, ataxia, head pressing, mental depression, seizures, and opisthotonus. The neurological examination aims to determine the neurolocalization of the lesions and advanced imaging techniques are useful for confirming the affected area(s) in the central nervous system. The aim of this study is to describe clinical features and ante-mortem diagnosis using magnetic resonance imaging (MRI) in a sheep with PEM. Case: A 18-month-old male Dorper sheep from a flock started receiving concentrate 7 days before. According to the owner, no clinical signs of abnormality were observed on the previous morning. However, in the afternoon, the animal became selfisolated and did not follow the flock to the sheepfold. The following day, he was found in recumbency. Physical examination revealed lateral recumbency, rectal temperature 39.5ºC, 52 bpm, 120 bpm, congested mucous membranes, capillary refill time 1 s, ruminal (4/5 min) and intestinal hypomotility. The assessment of the central nervous system revealed a decreased level of consciousness, focal seizures, opisthotonus, and absence of menace response. The following differential diagnoses were listed: PEM, head trauma, focal symmetrical encephalomalacia, bacterial encephalitis, and rabies. Treatment was composed of dexamethasone [0.2 mg/kg - i.v., SID (1st-3rd day), 0.1 mg/kg, i.v., SID (4th-6th day), and 0.05 mg/kg, i.v., SID (7th-9th day)]; mannitol [1 g/kg - i.v. and diazepam 0.4 mg/kg, i.v. single dose at admission]; vitamin B1 [10 mg/kg - i.m., SID], furosemide [1 mg/kg - i.v., SID for 3 days] and sulfadoxine/trimethoprim [30 mg/kg - i.m., SID for 10 days]. After the initial treatment, the patient showed mild clinical improvement; however, the amaurosis was still present. Magnetic resonance imaging of the brain was performed on the 2nd day of hospitalization, showing a symmetrical hypersignal in the parietal and occipital cortices, in the axial and sagittal sequences weighted in T2 and FLAIR. Discussion: This study aimed to describe the clinical signs and MRI findings in a sheep with PEM. In this case, the sudden change to the feed composition probably led to ruminal dysbiosis, inhibition of thiamine-producing microorganisms and proliferation of bacteria that synthesize thiaminase. Thiamine therapy proved to be effective and capable of reverting the clinical signs. The decrease in the level of consciousness, cortical blindness, and opisthotonus are due to alterations in the parietal cortex, in the occipital cortex, and in the cerebellum, respectively, which were demonstrated by hypersignal areas in the MRI. Therefore, the neurolocalization of the lesion based on neurologic examination and the MRI findings were related. The physicochemical and cytological evaluations of the cerebrospinal fluid, and dosage of thiamine and the concentration of hydrogen sulphide in the rumen were not performed. However, the response to thiamine treatment associated with the neurologic examination and MRI findings helped in determining the diagnosis. Additionally, MRI can be used as a useful tool for the ante mortem diagnosis of PEM.

Meningioma intracraniano em cão - tratamento com radioterapia / Intracranial meningioma in a dog - treatment with radiotherapy

Background: The most common primary brain neoplasm is meningioma. Dolichocephalic breeds are predisposed and there is no sexual predilection. Clinical signs depend on the location and size of the tumor and have a progressive course. Primary treatement includes surgery, radiotherapy or both. This study aimed to describe the treatment of a dog with suspected intracranial meningioma with definitive radiotherapy, which resulted in significant clinical improvement and prolonged survival. Case: A 9-year-old Shetland Shepherd bitch was diagnosed with a head tilt to the left side that progressed over a few weeks. She previously received corticosteroid therapy, which resulted a clinical improvement that worsened after treatment was discontinued. Computed tomography revealed an extra-axial brain mass in the caudal fossa, lateralized to the right, welldelimited, and measuring approximately 1.5 × 1.4 × 1.7 cm, suggestive of intracranial meningioma. The patient was treated with radiotherapy using Cobalt-60 equipment, with 18 daily fractions of 2.5 Gy at a total dose of 45 Gy using parallel and opposite technique fields. A new tomography performed 30 days after treatment showed a remission of 85% of the initial brain mass measuring approximately 0.9 × 1.0 × 0.5 cm, as well as complete resolution of the clinical signs initially presented. After 14 months, the patient presented with signs of lethargy and ataxia and was medicated with hydroxyurea at a dose of 50 mg/kg 3 times a week and corticosteroid therapy. However, the patient's neurological condition deteriorated, and she was subjected to reirradiation using the same protocol used previously, which resulted in clinical improvement and a 54% reduction in tumor volume on magnetic resonance. As a late side effect, only permanent alopecia in the irradiated region was observed. The patient died of disease 330 days after the second course of radiotherapy, with a total survival time of 1087 days. Discussion: Meningiomas are extra-axial neoplasms of the central nervous system that grow inside the dura mater. The literature shows that meningiomas are more common in dolichocephalic races with a mean age of 9 years, which supports our findings. Meningiomas most commonly affect the cortical thalamus and cerebellopontine region in dogs, which are normally associated with vestibular symptoms, as seen in this case. Diencephalic damage can result in vestibular signals since the thalamus functions as a relay station for vestibular afferent stimuli that are relayed to the cerebral cortex. In addition to the vestibular syndrome, common clinical signs associated with meningiomas in dogs include seizures, behavioral changes, and walking in circles, which are frequently misinterpreted due to tumor-induced side effects, such as cerebral edema, obstructive hydrocephalus, and cerebral hernia. Advanced imaging techniques should be used to diagnose intracranial neoplasms. In this case, computed tomography was critical for diagnosis and treatment planning. Meningioma treatment may comprise palliative measures, surgery, and radiotherapy. Radiotherapy as a single treatment can improve the quality of life with a decrease in clinical signs and a median survival time of approximately 250-536 days, as reported in the literature. Hydroxyurea can be a therapeutic option in inoperable cases and for patients with clinical limitations to undergo successive anesthesia during radiotherapy. Its most serious side effect is progressive myelosuppression. It can cause temporary partial tumor remission and improvement in clinical signs. As previously stated, radiotherapy can be an effective primary treatment option for treating intracranial meningiomas in dogs, with significant improvement in neurological clinical signs and mild side effects.

4-hydroxy-2-nonenal as a marker of the oxidative stress in brains of dogs with canine distemper / 4-hidroxi-2-nonenal como marcador de estresse oxidativo no cérebro de cães com cinomose

Canine Distemper is a disease caused by Canine morbillivirus (CM), a pantropic virus that can affect the central nervous system (CNS), causing demyelination. However, the pathogenesis of this lesion remains to be clarified. Brain samples of 14 naturally infected dogs by CM were analyzed to evaluate the presence of oxidative stress and demyelination. RT-PCR assay was performed to confirm a diagnosis of canine distemper in the brain, immunohistochemistry anti-CM was used to localize the viral proteins in the tissue, and anti-4-hydroxy-2-nonenal (4-HNE) was a marker of a product of lipid peroxidation. The results showed the presence of viral proteins in the demyelinated area with the presence of 4-HNE. Our results suggest that the CM virus infection causes oxidative stress leading to lipid peroxidation, which causes tissue damage and demyelination. In conclusion, oxidative stress plays a significant role in canine distemper pathogenesis in the CNS.(AU)

A cinomose canina é uma doença causada pelo Morbilivírus canino (CM), um vírus pantrópico que pode afetar o sistema nervoso central (SNC), causando desmielinização. No entanto, a patogênese dessa lesão não está totalmente esclarecida. RT-PCR e imuno-histoquímica foram realizadas para confirmação do diagnóstico de cinomose em amostras de encéfalo de 14 cães naturalmente infectados. Após confirmação, foi realizada uma avaliação do estresse oxidativo por imuno-histoquímica com uso de anti-4-hidroxi-nonenal (4HNE) como marcador de produtos resultantes da peroxidação lipídica. Os resultados sugerem que a infecção pelo CM causa estresse oxidativo no tecido, levando a peroxidação lipídica, a qual causa danos ao tecido, culminando com desmielinização. Conclui-se que o estresse oxidativo tem papel importante na patogênese da cinomose canina no sistema nervoso central.(AU)

Clinical and pathological aspects of an outbreak of Streptococcus suis serotype 9 infection in pigs / Aspectos clínicos e patológicos de um surto de infecção por Streptococcus suis sorotipo 9 em suínos

Streptococcus suis is a Gram-positive pathogen that inhabits the upper respiratory tract and can cause severe systemic inflammatory disease in pigs, mainly during the nursery phase. Streptococcus suis is a reemergent pathogen, and outbreaks of its inducing disease represent significant economic losses for the pig industry worldwide. In this study, we described the clinical, pathological, and molecular aspects of an outbreak of S. suis infection with atypically high mortality. The outbreak occurred in nursery farms integrated into a cooperative in the state of Paraná, Brazil. Of the 30 nurseries, 10 were severely affected by the pathogen and had high economic losses. Clinical signs usually started approximately 10 days after weaning and were mainly characterized by acute nervous and locomotor disorders. The mortality of the affected batches usually ranged between 8% and 10%, but in some cases, it reached 18%. Nine piglets were submitted to post mortem examination. Macroscopically, the synovial joints were enlarged and contained fibrinous exudates. In the central nervous system, there was hyperemia of the leptomeningeal vessels associated with deposition of fibrin and purulent exudate in the leptomeninges. In three piglets, there was thickening of the choroid plexus associated with dilation of the lateral ventricles. Microscopic lesions were characterized mainly by fibrinosuppurative inflammation, which involved the synovial membranes, leptomeninges of the brain, and spinal cord. Furthermore, it also affects the choroid plexus, ependyma, nerve roots, and central canal of the spinal cord. S. suis was isolated from the cerebrospinal fluid, meningeal swabs, and/or synovial fluid of 8/9 piglets, and typified as serotype 9 by multiplex PCR.

Streptococcus suis é um patógeno Gram positivo que habita o trato respiratório superior e pode causar doença inflamatória sistêmica grave em suínos, principalmente durante a fase de creche. Streptococcus suis é um patógeno reemergente e surtos representam perdas econômicas significativas a suinocultura mundial. Neste estudo descrevemos os aspectos clínicos, patológicos e moleculares de um surto de infecção por S. suis com mortalidade atipicamente alta. O surto ocorreu em creches integradas a uma cooperativa do estado do Paraná, Brasil. Das 30 creches, 10 foram severamente afetadas pelo patógeno e apresentavam elevadas perdas econômicas. Os sinais clínicos iniciavam em torno de 10 dias após o desmame e eram caracterizados principalmente por sinais clínicos nervosos e locomotores agudos. A mortalidade dos lotes afetados variava entre 8% e 10%, mas em alguns casos ultrapassava 18%. Nove leitões foram submetidos ao exame post mortem. Macroscopicamente, as articulações sinoviais estavam aumentadas e continham exsudato fibrinoso. No sistema nervoso central havia hiperemia dos vasos leptomeníngeos associada a deposição de fibrina e exsudato purulento nas leptomeninges. Em três leitões havia espessamento do plexo coroide associado a dilatação dos ventrículos laterais. As lesões microscópicas eram caracterizadas principalmente por inflamação fibrinossupurativa que envolvia as membranas sinoviais, as leptomeninges do cérebro e medula espinhal. Além disso, também afetava o plexo coroide, epêndima, raízes nervosas e canal central da medula espinhal. S. suis foi isolado do líquido cefalorraquidiano, suabe de meninge e/ou líquido sinovial de 8/9 leitões e tipificado como sorotipo 9 por PCR multiplex.

Objective lameness assessment in horses used for equine-assisted therapy in Rio Grande do Sul state, Brazil / Avaliação objetiva da claudicação em cavalos de equoterapia no Rio Grande do Sul, Brasil

Equine-assisted therapy is a method used since ancient times to rehabilitate individuals. The biomechanics provided by horses and the friction between their back and the riders' saddle generate impulses that are transmitted to riders' central nervous system; thus, these horses must be healthy enough to enable the desired therapeutic effect. The aim of the current study is to investigate lameness prevalence and intensity in equine-assisted therapy horses in Rio Grande do Sul State. The adopted methodology consisted of the objective evaluation of lameness based on Lameness Locator® wireless inertial sensors, which were placed in the 21 horses assessed in six equestrian centers in Rio Grande do Sul State. Results have shown that 90.1% of the assessed horses presented lameness in the hind (54.2%) and forelimbs (45.8%), as well as that 72% of them with presented mild lameness degree. This outcome has evidenced the need, and significance, of assessing these horses' locomotor system. To support effective therapy and protect equine welfare, it is essential that veterinarians should regularly monitor these animals in order to treat and prevent disease. Even subtle lameness can influence the generated stimuli; thus, it is an important factor to be taken into consideration when selecting equine-assisted therapy.

A equoterapia é um método de terapia, utilizada para reabilitação do praticante desde a antiguidade. A biomecânica proporcionada pelo cavalo e o atrito entre o dorso do cavalo e a sela do praticante geram impulsos que são transmitidos ao sistema nervoso central do mesmo, por isso a importância desse cavalo estar em condições aptas para promover o efeito terapêutico desejado. Nosso objetivo foi identificar a prevalência e intensidade da claudicação em equinos de equoterapia no estado do Rio Grande do Sul. A metodologia utilizada foi a avaliação objetiva da claudicação com base na utilização de sensores inerciais sem fio Lameness Locator® em seis centros equestres do Rio Grande do Sul, totalizando 21 equinos avaliados. Foi constatado que 90,1% dos equinos avaliados apresentavam claudicação, 54,2% do membro pélvico e 45,8% do membro torácico, quanto a intensidade 72% foram leves. A partir desse resultado, verifica-se a necessidade e a importância da avaliação no sistema locomotor destes animais. Para uma terapia eficaz e proteger o bem-estar dos equinos, é essencial o acompanhamento periódico por um médico veterinário para tratamento e prevenção de afecções. Claudicações, mesmo sutis, podem interferir nos estímulos gerados, sendo um importante fator de escolha do cavalo apto para a equoterapia.

ß-micrustoxin (Mlx-9), a PLA2 from Micrurus lemniscatus snake venom: biochemical characterization and anti-proliferative effect mediated by p53

Background: Endogenous phospholipases A2 (PLA2 ) play a fundamental role in inflammation, neurodegenerative diseases, apoptosis and cellular senescence. Neurotoxins with PLA2 activity are found in snake venoms from the Elapidae and Viperidae families. The mechanism of action of these neurotoxins have been studied using hippocampal and cerebellar neuronal cultures showing [Ca2+]i increase, mitochondrial depolarization and cell death. Astrocytes are rarely used as a model, despite being modulators at the synapses and responsible for homeostasis and defense in the central nervous system. Preserving the cell division ability, they can be utilized to study the cell proliferation process. In the present work cultured astrocytes and glioblastoma cells were employed to characterize the action of ß-micrustoxin (previously named Mlx-9), a PLA2 isolated from Micrurus lemniscatus snake venom. The ß-micrustoxin structure was determined and the cell proliferation, cell cycle phases and the regulatory proteins p53, p21 and p27 were investigated. Methods: ß-micrustoxin was characterized biochemically by a proteomic approach. Astrocytes were obtained by dissociation of pineal glands from Wistar rats; glioblastoma tumor cells were purchased from ATCC and Sigma and cultured in DMEM médium. Cell viability was evaluated by MTT assay; cell proliferation and cell cycle phases were analyzed by flow cytometry; p53, p21 and p27 proteins were studied by western blotting and immunocytochemistry. Results: Proteomic analysis revealed fragments on ß-micrustoxin that aligned with a PLA2 from Micrurus lemniscatus lemniscatus previously identified as transcript ID DN112835_C3_g9_i1/m.9019. ß-micrustoxin impaired the viability of astrocytes and glioblastoma tumor cells. There was a reduction in cell proliferation, an increase in G2/M phase and activation of p53, p21 and p27 proteins in astrocytes. Conclusion: These findings indicate that ß-micrustoxin from Micrurus lemniscatus venom could inhibit cell proliferation through p53, p21 and p27 activation thus imposing cell cycle arrest at the checkpoint G2/M.(AU)