Cerebral infarction and thrombotic meningoencephalitis in a calf due to candidiasis / Infarto cerebral e meningoencefalite trombótica em um bezerro devido a candidíase

We described a case of cerebral infarction and thrombotic meningoencephalitis due to candidiasis in a seven-month-old calf. The death occurred three days after the onset of apathy, fever, and the head's lateral deviation to the left. Macroscopic changes in the brain consisted of asymmetry of telencephalic hemispheres; the right hemisphere was enlarged, causing cerebellar herniation. A focally extensive red area was observed on the surface of the right occipital lobe. At cross-sections of the fixed brain, the lesions revealed to be extensive, red-brown, soft or cavitated areas affecting the white and grey matter from the level of the thalamus to the cerebellum and compressing subjacent structures. Histologically, there was acute, coalescent, multifocal necrosupurative meningoencephalitis, associated with vasculitis, congestion, thrombosis, edema, infarction, and intralesional fungal hyphae. The diagnosis of cerebral infarction and thrombotic meningoencephalitis due to candidiasis was made by the pathological changes, the staining and morphological characteristics of the agent, and immunohistochemistry. The cerebral infarction and thrombotic meningoencephalitis in cattle can result from vascular lesions due to infection by Candida sp.; although uncommon, this case demonstrated that candidiasis should be part of a list of differential diagnoses of severe brain injuries in cattle.

Descreve-se um caso de infarto cerebral e meningoencefalite trombótica devido a candidíase em um bezerro de sete meses de idade. A morte ocorreu três dias após o início de apatia, febre e desvio lateral da cabeça para a esquerda. As alterações macroscópicas no cérebro consistiam em assimetria dos hemisférios telencefálicos; o hemisfério direito estava aumentado, causando herniação cerebelar. Uma extensa área vermelha focal foi observada na superfície do lobo occipital direito. Nos cortes transversais do encéfalo fixado, as lesões revelaram áreas extensas, marrom-avermelhadas, moles ou cavitadas, afetando a substância branca e cinzenta desde o nível do tálamo até o cerebelo e comprimindo as estruturas subjacentes. Histologicamente, havia meningoencefalite necrossupurativa multifocal aguda, coalescente, associada a vasculite, congestão, trombose, edema, infarto e hifas fúngicas intralesionais. O diagnóstico de infarto cerebral e meningoencefalite trombótica devido a candidíase foi feito pelas alterações patológicas, coloração e características morfológicas do agente e imuno-histoquímica. O infarto cerebral e meningoencefalite trombótica em bovinos pode resultar de lesões vasculares devido à infecção por Candida sp.; embora incomum, este caso demonstra que a candidíase deve fazer parte de uma lista de diagnósticos diferenciais de lesões cerebrais graves em bovinos.

Glutamine ameliorates Bungarus multicinctus venom-induced lung and heart injury through HSP70: NF-κB p65 and P53/PUMA signaling pathways involved

Background: Bungarus multicinctus is one of the most dangerous venomous snakes prone to cardiopulmonary damage with extremely high mortality. In our previous work, we found that glutamine (Gln) and glutamine synthetase (GS) in pig serum were significantly reduced after Bungarus multicinctus bite. In the present study, to explore whether there is a link between the pathogenesis of cardiopulmonary injury and Gln metabolic changes induced by Bungarus multicinctus venom. We investigated the effect of Gln supplementation on the lung and heart function after snakebite. Methods: We supplemented different concentrations of Gln to mice that were envenomated by Bungarus multicinctus to observe the biological behavior, survival rate, hematological and pathological changes. Gln was supplemented immediately or one hour after the venom injection, and then changes in Gln metabolism were analyzed. Subsequently, to further explore the protective mechanism of glutamine on tissue damage, we measured the expression of heat-shock protein70 (HSP70), NF-κB P65, P53/PUMA by western blotting and real-time polymerase in the lung and heart. Results: Gln supplementation delayed the envenoming symptoms, reduced mortality, and alleviated the histopathological changes in the heart and lung of mice bitten by Bungarus multicinctus. Additionally, Gln increased the activity of glutamine synthetase (GS), glutamate dehydrogenase (GDH) and glutaminase (GLS) in serum. It also balanced the transporter SLC7A11 expression in heart and lung tissues. Bungarus multicinctus venom induced the NF-κB nuclear translocation in the lung, while the HO-1 expression was suppressed. At the same time, venom activated the P53/PUMA signaling pathway and the BAX expression in the heart. Gln treatment reversed the above phenomenon and increased HSP70 expression. Conclusion: Gln alleviated the glutamine metabolism disorder and cardiopulmonary damage caused by Bungarus multicinctus venom. It may protect lungs and heart against venom by promoting the expression of HSP70, inhibiting the activation of NF-κB and P53/PUMA, thereby delaying the process of snake venom and reducing mortality. The present results indicate that Gln could be a potential treatment for Bungarus multicinctus bite.

Circular RNA protein tyrosine kinase 2 aggravates pyroptosis and inflammation in septic lung tissue by promoting microRNA-766/eukaryotic initiation factor 5A axis-mediated ATP efflux

Purpose: Sepsis is characterized by an acute inflammatory response to infection, often with multiple organ failures, especially severe lung injury. This study was implemented to probe circular RNA (circRNA) protein tyrosine kinase 2 (circPTK2)-associated regulatory mechanisms in septic acute lung injury (ALI). Methods: A cecal ligation and puncture-based mouse model and an lipopolysaccharides (LPS)-based alveolar type II cell (RLE-6TN) model were generated to mimic sepsis. In the two models, inflammation- and pyroptosisrelated genes were measured. Results: The degree of lung injury in mice was analyzed by hematoxylin and eosin (H&E) staining and the apoptosis was by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining. In addition, pyroptosis and toxicity were detected in cells. Finally, the binding relationship between circPTK2, miR-766, and eukaryotic initiation factor 5A (eIF5A) was detected. Data indicated that circPTK2 and eIF5A were up-regulated and miR-766 was down-regulated in LPS-treated RLE-6TN cells and lung tissue of septic mice. Lung injury in septic mice was ameliorated after inhibition of circPTK2. Conclusion: It was confirmed in the cell model that knockdown of circPTK2 effectively ameliorated LPS-induced ATP efflux, pyroptosis, and inflammation. Mechanistically, circPTK2 mediated eIF5A expression by competitively adsorbing miR-766. Taken together, circPTK2/ miR-766/eIF5A axis ameliorates septic ALI, developing a novel therapeutic target for the disease.

Trauma decorrente de queda provocada pelo cabo extensor de um bezerreiro tropical / Trauma resulting from a fall caused by the extension cable of a tropical calf

A criação de bezerras é uma das fases mais importantes na bovinocultura leiteira e um manejo profilático em ambientes físicos de alojamento é crucial para evitar acidentes que possam comprometer a vida produtiva dos animais futuramente. O bezerreiro tropical é um dos alojamentos mais comuns utilizados no Nordeste brasileiro em grandes criações, possivelmente devido ao baixo custo. Diante disso, objetivou-se nesse trabalho relatar um acidente provocado por tropeço em fio extensor de superfície do bezerreiro tropical, no qual ocasionou um traumatismo tibial em uma bezerra Girolando de dois meses de idade. O atendimento ocorreu no Hospital Veterinário de Grandes Animais do Centro Universitário Inta (Uninta) em Sobral/CE e o animal foi proveniente de uma fazenda de alta produção leiteira da cidade de Umirim/CE. O exame clínico revelou que a região afetada foi próxima ao jarrete. O exame radiográfico constatou fratura na região epifisária da tíbia proximal. Após avaliação pela equipe clínica e cirúrgica, o paciente foi encaminhado para cirurgia de correção, mas antes foi estabelecida imobilização e bandagens para manter o membro afetado imóvel até a realização do procedimento cirúrgico. O tratamento clínico medicamentoso pós-cirúrgico foi conduzido, além de foram instituídos cuidados diários de limpeza do ferimento cirúrgico com antisséptico local. Após a realização da cirurgia de correção da fratura, estando o paciente estabilizado, este mesmo animal recebeu alta médica 17 dias depois da internação. Desta forma, o bezerreiro tropical está passando por mudanças estruturais e de manejo para evitar mais traumas provocados pelo tropeço, enroscamento e quedas das bezerras.

Calf rearing is one of the most important stages in dairy cattle and, prophylactic management in physical accommodation environments is crucial to avoid accidents that could compromise the productive life of these animals in the future. The tropical calf is one of the most common housings used in the Brazilian Northeast in large creations, possibly due to the low cost. This study aimed to report an accident caused by tripping over surface extender wire of the tropical calf, which caused a tibial trauma in a 2-months-old Girolando heifer. The attendance took place at the Veterinary Hospital for Large Animals of the Inta University Center (Uninta) in Sobral/Ce and the animal came from a high-production dairy farm in the city of Umirim/Ce. The clinical examination revealed that the affected region was close to the knuckle. The radiographic examination showed a fracture in the epiphyseal region of the proximal tibia. After evaluation by the clinical and surgical team, the patient was referred for corrective surgery, but before that, immobilization and bandages were established to keep the affected limb immobile until the surgical procedure was performed. The post-surgical medical treatment was conducted, in addition to the daily care of cleaning the surgical wound with local antiseptic. After the surgery, to correct the fracture with the patient stabilized, the hospital discharge occurred 17 days after hospitalization. Thus, the tropical calf, is undergoing structural and management changes to avoid further trauma caused by stumbling, tangling, and falling.

Protective effect of Guanxin Danshen formula on myocardial ischemiareperfusion injury in rats

Purpose: Myocardial ischemia/reperfusion injury (MIRI) leads to myocardial tissue necrosis, which will increase the size of myocardial infarction. The study examined the protective effect and mechanism of the Guanxin Danshen formula (GXDSF) on MIRI in rats. Methods: MIRI model was performed in rats; rat H9C2 cardiomyocytes were hypoxia-reoxygenated to establish a cell injury model. Results: The GXDSF significantly reduced myocardial ischemia area, reduced myocardial structural injury, decreased the levels of interleukin (IL-1ß, IL-6) in serum, decreased the activity of myocardial enzymes, increased the activity of superoxide dismutase (SOD), and reduced glutathione in rats with MIRI. The GXDSF can reduce the expression of nucleotide- binding oligomerization domain, leucine-rich repeat and pyrin domain containing nod-like receptor family protein 3 (NLRP3), IL-1ß, caspase-1, and gasdermin D (GSDMD) in myocardial tissue cells. Salvianolic acid B and notoginsenoside R1 protected H9C2 cardiomyocytes from hypoxia and reoxygenation injury and reduced the levels of tumor necrosis factor α (TNF-α) and IL-6 in the cell supernatant, decreasing the NLRP3, IL-18, IL-1ß, caspase-1, and GSDMD expression in H9C2 cardiomyocytes. GXDSF can reduce the myocardial infarction area and alleviate the damage to myocardial structure in rats with MIRI, which may be related to the regulation of the NLRP3. Conclusion: GXDSF reduces MIRI in rat myocardial infarction injury, improves structural damage in myocardial ischemia injury, and reduces myocardial tissue inflammation and oxidative stress by lowering inflammatory factors and controlling focal cell death signaling pathways.

Experimental model of nephropathy associated with diabetes mellitus in mice

Purpose: Nontransmissible chronic diseases, such as diabetes mellitus (DM) and nephropathy, affect a significant portion of the population, often treated due to injuries that require healing and regeneration. To create an experimental model of associated comorbidities, for healing and regeneration studies, protocols for induction of nephropathy by ischemia and reperfusion (I/R) and induction of DM by injection of streptozotocin (STZ) were associated. Methods: Sixty-four mice (Mus musculus), female, adult, Swiss strain, weighing approximately 20 g, were divided into four groups: G1: control (n = 24), G2: nephropathy group (N) (n = 7), G3, DM (n = 9), and G4: N+DM (n = 24). Arteriovenous stenosis (I/R) of the left kidney was performed as the first protocol. The animals received a hyperlipidemic diet for 7 days after the injection of STZ (150 mg/kg, via i.p.) and an aqueous glucose solution (10%) for 24 h. The animals in the G3 and G4 groups were observed for 14 days before receiving the diet and STZ. The evolution of nephropathy was observed using a urine test strip and the DM, through the analysis of blood glucose with a reagent strip on a digital monitor. Results: The ischemic induction protocols of nephropathy and DM with STZ, associated, were sustainable, low-cost, and without deaths. There were alterations compatible with initial renal alterations, in the first 14 days, such as increased urinary density, pH alteration, presence of glucose, proteins and leukocytes, when compared to the control group. DM was confirmed by the presence of hyperglycemia 7 days after induction and its evolution after 14 days. The animals in the G4 group showed constant weight loss when compared to the other groups. It was possible to observe morphological alterations in the kidneys submitted to I/R, regarding coloration, during surgery and after the end of the observation period, in the volume and size of the left kidney, when compared to the contralateral kidney. Conclusion: It was possible to induce nephropathy and DM associated in the same animal, in a simple way, confirmed with rapid tests, without losses, providing a basis for future studies.

Naringenin attenuates cerebral ischemia/reperfusion injury by inhibiting oxidative stress and inflammatory response via the activation of SIRT1/FOXO1 signaling pathway in vitro

Purpose: To explore the protection of naringenin against oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cell injury, a cell model of cerebral ischemia/reperfusion (I/R) injury in vitro, focusing on SIRT1/FOXO1 signaling pathway. Methods: Cytotoxicity, apoptosis, reactive oxygen species (ROS) generation, malondialdehyde (MDA) content, 4-hydroxynonenoic acid (4-HNE) level, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were measured by commercial kits. Inflammatory cytokines levels were determined by enzyme-linked immunosorbent assay (ELISA). The protein expressions were monitored by Western blot analysis. Results: Naringenin significantly ameliorated OGD/Rinduced cytotoxicity and apoptosis in HT22 cells. Meanwhile, naringenin promoted SIRT1 and FOXO1 protein expressions in OGD/R-subjected HT22 cells. In addition, naringenin attenuated OGD/R-induced cytotoxicity, apoptosis, oxidative stress (the increased ROS, MDA and 4-HNE levels, and the decreased SOD, GSH-Px and CAT activities) and inflammatory response (the increased tumor necrosis factor-α, interleukin [IL]-1ß, and IL-6 levels and the decreased IL-10 level), which were blocked by the inhibition of the SIRT1/FOXO1 signaling pathway induced by SIRT1-siRNA transfection. Conclusion: Naringenin protected HT22 cells against OGD/R injury depending on its antioxidant and anti-inflammatory activities via promoting the SIRT1/FOXO1 signaling pathway.

Effects of local and remote ischemic postconditioning methods on ischemiareperfusion injury in a young animal model of acute mesenteric ischemia

Purpose: Acute mesenteric ischemia (AMI) is a condition in pediatric surgery that ranges from intestine necrosis to death. Ischemic postconditioning (IPoC) methods were developed to reduce the damage caused by revascularization. This study aimed to evaluate the efficacy of these methods in an experimental weaning rat model. Methods: Thirty-two 21-day-old Wistar rats were allocated into four groups according to the surgical procedure performed: control, ischemia-reperfusion injury (IRI), local (LIPoC) and remote IPoC (RIPoC). At euthanasia, fragments of the intestine, liver, lungs, and kidneys were submitted to histological, histomorphometric, and molecular analyses. Results: In the duodenum, intestines, and kidneys histological alterations promoted by IRI were reversed by remote postconditioning method. In the distal ileum, the histomorphometric alterations could be reversed by the postconditioning methods with more evident effects promoted by the remote method. The molecular analysis found that the levels of expression of Bax (proapoptotic) and Bcl-XL (antiapoptotic) genes in the intestine were increased by IRI. These alterations were equally reversed by the postconditioning methods, with more evident effects of the remote method. Conclusions: IPoC methods positively reduced the damage caused by IRI in weaning rats.

Bioinformatics and expression analysis of the Xeroderma Pigmentosum complementation group C (XPC) of Trypanosoma evansi in Trypanosoma cruzi cells / Análises de bioinformática e da expressão do gene Xeroderma Pigmentosum complementation group C (XPC) de Trypanosoma evansi em células de Trypanosoma cruzi

Nucleotide excision repair (NER) acts repairing damages in DNA, such as lesions caused by cisplatin. Xeroderma Pigmentosum complementation group C (XPC) protein is involved in recognition of global genome DNA damages during NER (GG-NER) and it has been studied in different organisms due to its importance in other cellular processes. In this work, we studied NER proteins in Trypanosoma cruzi and Trypanosoma evansi, parasites of humans and animals respectively. We performed three-dimensional models of XPC proteins from T. cruzi and T. evansi and observed few structural differences between these proteins. In our tests, insertion of XPC gene from T. evansi (TevXPC) in T. cruzi resulted in slower cell growth under normal conditions. After cisplatin treatment, T. cruzi overexpressing its own XPC gene (TcXPC) was able to recover cell division rates faster than T. cruzi expressing TevXPC gene. Based on these tests, it is suggested that TevXPC (being an exogenous protein in T. cruzi) interferes negatively in cellular processes where TcXPC (the endogenous protein) is involved. This probably occurred due interaction of TevXPC with some endogenous molecules or proteins from T. cruzi but incapacity of interaction with others. This reinforces the importance of correctly XPC functioning within the cell.

O reparo por excisão de nucleotídeos (NER) atua reparando danos no DNA, como lesões causadas por cisplatina. A proteína Xeroderma Pigmentosum complementation group C (XPC) está envolvida no reconhecimento de danos pela via de reparação global do genoma pelo NER (GG-NER) e tem sido estudada em diferentes organismos devido à sua importância em outros processos celulares. Neste trabalho, estudamos proteínas do NER em Trypanosoma cruzi e Trypanosoma evansi, parasitos de humanos e animais, respectivamente. Modelos tridimensionais das proteínas XPC de T. cruzi e T. evansi foram feitos e observou-se poucas diferenças estruturais entre estas proteínas. Durante testes, a inserção do gene XPC de T. evansi (TevXPC) em T. cruzi resultou em crescimento celular mais lento em condições normais. Após o tratamento com cisplatina, T. cruzi superexpressando seu próprio gene XPC (TcXPC) foi capaz de recuperar as taxas de divisão celular mais rapidamente do que T. cruzi expressando o gene TevXPC. Com base nesses testes, sugere-se que TevXPC (sendo uma proteína exógena em T. cruzi) interfere negativamente nos processos celulares em que TcXPC (a proteína endógena) está envolvida. Isso provavelmente ocorreu pois TevXPC é capaz de interagir com algumas moléculas ou proteínas endógenas de T. cruzi, mas é incapaz de interagir com outras. Isso reforça a importância do correto funcionamento de XPC dentro da célula.

Bioinformatics and expression analysis of the Xeroderma Pigmentosum complementation group C (XPC) of Trypanosoma evansi in Trypanosoma cruzi cells / Análises de bioinformática e da expressão do gene Xeroderma Pigmentosum complementation group C (XPC) de Trypanosoma evansi em células de Trypanosoma cruzi

Nucleotide excision repair (NER) acts repairing damages in DNA, such as lesions caused by cisplatin. Xeroderma Pigmentosum complementation group C (XPC) protein is involved in recognition of global genome DNA damages during NER (GG-NER) and it has been studied in different organisms due to its importance in other cellular processes. In this work, we studied NER proteins in Trypanosoma cruzi and Trypanosoma evansi, parasites of humans and animals respectively. We performed three-dimensional models of XPC proteins from T. cruzi and T. evansi and observed few structural differences between these proteins. In our tests, insertion of XPC gene from T. evansi (TevXPC) in T. cruzi resulted in slower cell growth under normal conditions. After cisplatin treatment, T. cruzi overexpressing its own XPC gene (TcXPC) was able to recover cell division rates faster than T. cruzi expressing TevXPC gene. Based on these tests, it is suggested that TevXPC (being an exogenous protein in T. cruzi) interferes negatively in cellular processes where TcXPC (the endogenous protein) is involved. This probably occurred due interaction of TevXPC with some endogenous molecules or proteins from T. cruzi but incapacity of interaction with others. This reinforces the importance of correctly XPC functioning within the cell.(AU)

O reparo por excisão de nucleotídeos (NER) atua reparando danos no DNA, como lesões causadas por cisplatina. A proteína Xeroderma Pigmentosum complementation group C (XPC) está envolvida no reconhecimento de danos pela via de reparação global do genoma pelo NER (GG-NER) e tem sido estudada em diferentes organismos devido à sua importância em outros processos celulares. Neste trabalho, estudamos proteínas do NER em Trypanosoma cruzi e Trypanosoma evansi, parasitos de humanos e animais, respectivamente. Modelos tridimensionais das proteínas XPC de T. cruzi e T. evansi foram feitos e observou-se poucas diferenças estruturais entre estas proteínas. Durante testes, a inserção do gene XPC de T. evansi (TevXPC) em T. cruzi resultou em crescimento celular mais lento em condições normais. Após o tratamento com cisplatina, T. cruzi superexpressando seu próprio gene XPC (TcXPC) foi capaz de recuperar as taxas de divisão celular mais rapidamente do que T. cruzi expressando o gene TevXPC. Com base nesses testes, sugere-se que TevXPC (sendo uma proteína exógena em T. cruzi) interfere negativamente nos processos celulares em que TcXPC (a proteína endógena) está envolvida. Isso provavelmente ocorreu pois TevXPC é capaz de interagir com algumas moléculas ou proteínas endógenas de T. cruzi, mas é incapaz de interagir com outras. Isso reforça a importância do correto funcionamento de XPC dentro da célula.(AU)

Fatal traumatic injuries in free-living wild Passeriformes and Psittaciformes birds in Central Brazil, 2006-2018 / Injúrias traumáticas fatais em aves Passeriformes e Psittaciformes no Brasil Central, 2006-2018

Traumatic injuries are a significant cause of death for birds worldwide, as they are at an increased risk of collisions and other injuries due to man-made environments. This study examined the frequency and morphological characteristics of fatal traumatic injuries in endemic and migratory Passeriformes and Psittaciformes from the Cerrado Biome, a biodiverse but threatened area in Brazil. Results showed that fatal traumatic injuries were found in 21.8% of birds (285/1305), mainly in spring and summer, during the birds' reproductive period. The yellow-chevroned parakeet (Brotogeris chiriri) and Passeriformes from the Thraupidae family were the most affected. Nearly 70% of the fatal injuries observed were to the thoracic, pelvic limbs, and skull, and types of fractures and affected bones were thoroughly evaluated. Blunt traumas were one of the most frequent causes of injuries. Injuries affecting the appendicular skeleton and head represented significant causes of traumatic death for Passeriformes and Psittaciformes. The frequency of these fatal injuries has been increasing in recent years, which may be related to the remarkable environmental changes in the Cerrado Biome and jeopardize the survival of many bird species.

As lesões traumáticas são uma causa significativa de morte nas aves em todo o mundo, pois apresentam um risco maior de colisões e outras lesões devido aos ambientes degradados e criados pelo homem. Este estudo examinou a frequência e as características morfológicas das lesões traumáticas fatais em Passeriformes e Psittaciformes endêmicos e migratórios do Bioma Cerrado, uma área com rica biodiversidade, mas ameaçada no Brasil. Os resultados demostraram que as lesões traumáticas fatais foram observadas em 21,8% das aves (285/1305), principalmente na primavera e verão, durante a época reprodutiva das aves. O periquito-do-encontro-amarelo (Brotogeris chiriri) e Passeriformes da família Thraupidae foram as aves mais frequentemente acometidas. Por volta de 70% das lesões fatais observadas foram nos membros torácicos e pélvicos, e crânio, e os tipos de fraturas e ossos afetados foram minuciosamente avaliados. Os traumas contudentes foram as principais causas das lesões. As injúrias que afetaram o esqueleto apendicular e a cabeça representaram as mais importantes causas de morte traumática para Passeriformes e Psittaciformes. A frequência dessas lesões fatais vem aumentando nos últimos anos, o que pode estar relacionado às mudanças ambientais marcantes no Bioma Cerrado e colocar em risco a sobrevivência de muitas espécies de aves.

Lesão na região metacarpiana do membro torácico esquerdo de bezerra Gir decorrente de contenção para pesagem / Injury in the metacarpinal region of the left thoracic limbs resulting from retention for weighing in a Gir calf

Fraturas ósseas e luxações são mais comuns em animais jovens e, na maioria das vezes, essas fraturas ocorrem devido ao manejo incorreto desses animais, podendo levar a uma queda de produção a curto ou longo prazo, gerando perdas econômicas e produtivas de animais de alto padrão genético. Nesse contexto, o objetivo deste trabalho foi relatar a ocorrência de uma fratura na região metacarpiana do membro torácico esquerdo de uma bezerra Gir de 12 dias de idade, causada por uma contenção ineficaz durante a pesagem. O animal proveniente de uma fazenda em Umirim/CE foi encaminhado ao Hospital Veterinário de Grandes Animais do Centro Universitário INTA em Sobral/CE. Ao passar pelo exame radiográfico, foi constatada a fratura na região metacarpiana do membro torácico esquerdo. O animal foi imobilizado de forma manual, seguindo-se métodos semiológicos para minimizar o estresse. Para a imobilização do membro, foi utilizada a muleta de Thomas modificada e bandagens, associadas ao controle da dor com as drogas Flunixin meglumine (1,1mg/kg) e Fenilbutazona (4,4mg/kg). Depois da imobilização, o animal seguiu internado no HOVET-GA e, após 18 dias, foi realizada uma nova radiografia para ver o progresso a partir do tratamento adotado. Constatou-se a formação de um calo ósseo, com a ossificação da fratura, não sendo necessário o encaminhamento cirúrgico do animal. Assim, o tratamento com muleta de Thomas modificada foi efetivo para a recuperação do membro fraturado, além de ser um tratamento de baixo custo e fácil aplicação, tendo o animal apresentado uma boa resposta ao tratamento terapêutico para controle da dor.

Bone fractures and dislocations are more common in young animals and mostly occur due to incorrect handling of these animals, which can lead to a short or long-term drop in production, generating economic and productive losses of animals of high genetic standard. This study aimed to report the occurrence of a fracture in the metacarpal region of the left thoracic limb of a 12-day-old Gir heifer, caused by an ineffective restraint during weighing. The animal from a farm in Umirim/CE was sent to the Veterinary Hospital of Large Animals of the University Center INTA in Sobral/CE. The radiographic examination found a fracture in the metacarpal region of the left thoracic limb. The animal was manually immobilized following semiological methods to minimize stress. For the limb immobilization, a modified Thomas crutch and bandages associated with pain control with the drugs Flunixin meglumine (1.1mg/kg) and Phenylbutazone (4.4mg/kg) were used. After immobilization, the animal remained hospitalized at HOVET-GA and after 18 days a new radiograph was performed to evaluate the progress achieved with the treatment adopted. It was found the formation of a bone callus with the ossification of the fracture, not requiring the surgical referral of the animal. Thus, the treatment with the modified Thomas crutch was effective for the recovery of the fractured limb, in addition to being a low-cost and easy-to-apply treatment. The animal showed a good response to the therapeutic treatment for pain control.

Cyanidin-3-O-glucoside plays a protective role against renal ischemia/ reperfusion injury via the JAK/STAT pathway

Purpose: To investigate the role of cyanidin-3-O-glucoside (C3G) in renal ischemia/reperfusion (I/R) injury and the potential mechanisms. Methods: Mouse models were established by clamping the left renal vessels, and in vitro cellular models were established by hypoxic reoxygenation. Results: Renal dysfunction and tissue structural damage were significantly higher in the I/R group. After treatment with different concentrations of C3G, the levels of renal dysfunction and tissue structural damage decreased at different levels. And its protective effect was most pronounced at 200 mg/kg. The use of C3G reduced apoptosis as well as the expression of endoplasmic reticulum stress (ERS)-related proteins. Hypoxia/reoxygenation (H/R)-induced apoptosis and ERS are dependent on oxidative stress in vitro. In addition, both AG490 and C3G inhibited the activation of JAK/STAT pathway and attenuated oxidative stress, ischemia-induced apoptosis and ERS. Conclusions: The results demonstrated that C3G blocked renal apoptosis and ERS protein expression by preventing reactive oxygen species (ROS) production after I/R via the JAK/STAT pathway, suggesting that C3G may be a potential therapeutic agent for renal I/R injury.

Analysis of nuclear maturation, DNA damage and repair gene expression of bovine oocyte and cumulus cells submitted to ionizing radiation'

Radiotherapy causes destruction of tumor cells, but also threatens the integrity and survival of surrounding normal cells. Then, woman submitted to irradiation for cancer treatment may present permanent ovary damage, resulting in impaired fertility. The objective of this study was to investigate the effects of therapeutic doses of ionizing radiation (IR), used for ovarian cancer treatment in humans, on bovine cumulus-oocyte complexes (COCs) as experimental model. Bovine ovaries were exposed to 0.9 Gy, 1.8 Gy, 3.6 Gy or 18.6 Gy IR, and then COCs were collected and used to evaluate: (a) oocyte nuclear maturation; (b) presence of phosphorylated H2A.X (γH2AX), as an indicator of DNA double-strand breaks (DSBs); and (c) expression of genes involved in DNA repair (TP53BP1, RAD52, ATM, XRCC6 and XRCC5) and apoptosis (BAX). The radiation doses tested in this study had no detrimental effects on nuclear maturation and did not increase γH2AX in the oocytes. However, IR treatment altered the mRNA abundance of RAD52 (RAD52 homolog, DNA repair protein) and BAX (BCL2-associated X protein). We conclude that although IR doses had no apparent effect on oocyte nuclear maturation and DNA damage, molecular pathways involved in DNA repair and apoptosis were affected by IR exposure in cumulus cells.(AU)

Puerarin alleviated oxidative stress and ferroptosis during renal fibrosis induced by ischemia/reperfusion injury via TLR4/Nox4 pathway in rats

Purpose: To investigate the role of puerarin on renal fibrosis and the underlying mechanism in renal ischemia and reperfusion (I/R) model. Methods: Rats were intraperitoneally injected with puerarin (50 or 100 mg/kg) per day for one week before renal I/R. The level of renal collagen deposition and interstitial fibrosis were observed by hematoxylin and eosin and Sirius Red staining, and the expression of α-smooth muscle actin (α-SMA) was examined by immunohistochemical staining. The ferroptosis related factors and TLR4/Nox4-pathway-associated proteins were detected by Western blotting. Results: Puerarin was observed to alleviate renal collagen deposition, interstitial fibrosis and the α-SMA expression induced by I/R. Superoxide dismutase (SOD) activities and glutathione (GSH) level were decreased in I/R and hypoxia/reoxygenation (H/R), whereas malondialdehyde (MDA) and Fe2+ level increased. However, puerarin reversed SOD, MDA, GSH and Fe2+ level changes induced by I/R and H/R. Besides, Western blot indicated that puerarin inhibited the expression of ferroptosis related factors in a dose-dependent manner, which further demonstrated that puerarin had the effect to attenuate ferroptosis. Moreover, the increased expression of TLR/Nox4-pathway-associated proteins were observed in I/R and H/R group, but puerarin alleviated the elevated TLR/Nox4 expression. Conclusions: Our results suggested that puerarin inhibited oxidative stress and ferroptosis induced by I/R and, thus, delayed the progression of renal fibrosis, providing a new target for the treatment of renal fibrosis.

Integrative analysis in toxicological assessment of the insecticide Malathion in Allium cepa L. system / Análise integrativa na avaliação toxicológica do inseticida Malation no sistema Allium cepa L

Abstract For many centuries human populations have been suffering and trying to fight with disease-bearing mosquitoes. Emerging and reemerging diseases such as Dengue, Zika, and Chikungunya affect billions of people around the world and recently has been appealing to control with chemical pesticides. Malathion (MT) is one of the main pesticides used against mosquitoes, the vectors of these diseases. This study aimed to assess cytotoxicity and mutagenicity of the malathion for the bioindicator Allium cepa L. using a multivariate and integrative approach. Moreover, an appendix table was compiled with all available literature of insecticides assessed by the Allium cepa system to support our discussion. Exposures during 48h to 0.5 mg mL-1 and 1.0 mg mL-1 MT were compared to the negative control (distilled water) and positive control (MMS solution at 10 mg L-1). The presence of chromosomal aberrations, micronuclei frequency, and mitotic index abnormalities was evaluated. Anaphase bridges were the alterations with higher incidence and presented a significantly elevated rate in the concentration of 0.5 mg mL-1, including when compared to the positive control. The integrative discriminant analysis summarizes that MT in assessed concentrations presented effects like the positive control, corroborating its potential of toxicity to DNA. Therefore, it is concluded that MT in its pure composition and in realistic concentrations used, has genotoxic potential in the biological assessment of A. cepa cells. The multivariate integrative analysis was fundamental to show a whole response of all data, providing a global view of the effect of MT on DNA.

Resumo Por muitos séculos, as populações humanas sofrem e tentam combater os mosquitos transmissores de doenças. Doenças emergentes e reemergentes como Dengue, Zika e Chikungunya afetam bilhões de pessoas em todo o mundo e, recentemente, vem apelando ao controle com pesticidas químicos. O Malation (MT) é um dos principais pesticidas usados ​​contra mosquitos, vetores dessas doenças. O objetivo deste estudo foi avaliar a citotoxicidade e a mutagenicidade do MT para o bioindicador Allium cepa L. usando uma abordagem multivariada e integrativa. Além disso, uma tabela suplementar foi compilada com toda a literatura disponível de inseticidas avaliada pelo sistema Allium cepa para apoiar nossa discussão. Exposições ao MT durante 48h a 0,5 mg mL-1 e 1,0 mg mL-1 foram comparadas a um controle negativo (água destilada) e um controle positivo (10 mg L-1 de MMS). Foram avaliadas a presença de aberrações cromossômicas, frequência de micronúcleos e anormalidades no índice mitótico. As pontes anafásicas foram as alterações com maior incidência e apresentaram uma taxa significativamente elevada na concentração de 0,5 mg mL-1, inclusive quando comparadas ao controle positivo. A análise discriminante integrativa resume que o MT nas concentrações avaliadas apresentou efeitos semelhantes ao controle positivo, corroborando seu potencial de toxicidade para o DNA. Portanto, conclui-se que o MT, em sua composição pura e nas concentrações realistas utilizadas, possui potencial genotóxico na avaliação biológica de células de A. cepa. A análise integrativa multivariada foi fundamental para mostrar uma resposta completa de todos os dados, fornecendo uma visão global do efeito da MT no DNA.

Effects of Gundelia tournefortii L. on biochemical parameters, antioxidant activities and DNA damage in a rat model of experimental obesity / Efeitos de Gundelia tournefortii L. em parâmetros bioquímicos, atividades antioxidantes e danos ao DNA em um modelo de obesidade experimental de rato

Abstract The present study was designed to investigate the effects of Gundelia tournefortii L. plant extract on different tissues in terms of DNA damage, biochemical and antioxidant parameter values in rats with high-calorie diets. With this aim, Wistar albino male rats were divided into 4 groups containing 6 rats each and the study was completed over 12 weeks duration. At the end of the implementation process over the 12 weeks, rats were sacrificed and blood and tissue samples were obtained. Analyses were performed on blood and tissue samples. According to results for DNA damage (8-OHdG), in brain tissue the OG2 group was significantly reduced compared to the NC group. For MDA results in liver tissue, OG1 and OG2 groups were determined to increase by a significant degree compared to the control group, while the OG2 group was also increased significantly compared to the obese group. In terms of the other parameters, comparison between the groups linked to consumption of a high calorie diet (HCD) and administration of Gundelia tournefortii L. in terms of antioxidant activities and serum samples obtained statistically significant results. Gundelia tournefortii L. plant extracts had effects that may be counted as positive on antioxidant parameter activity and were especially identified to improve DNA damage and MDA levels in brain tissues. Additionally, consumption of Gundelia tournefortii L. plant extract in the diet may have antiobesity effects; thus, it should be evaluated for use as an effective weight-loss method and as a new therapeutic agent targeting obesity.

Resumo O presente estudo foi desenhado para investigar os efeitos do extrato da planta Gundelia tournefortii L. em diferentes tecidos em termos de danos ao DNA, valores de parâmetros bioquímicos e antioxidantes em ratos com dietas hipercalóricas. Com esse objetivo, ratos Wistar albinos machos foram divididos em 4 grupos contendo 6 ratos cada e o estudo foi concluído ao longo de 12 semanas de duração. No final desse processo de implementação, os ratos foram sacrificados e amostras de sangue e tecido foram obtidas. As análises foram realizadas em amostras de sangue e tecido. De acordo com os resultados para danos ao DNA (8-OHdG), no tecido cerebral o grupo OG2 foi significativamente reduzido em comparação com o grupo NC. Para os resultados de MDA no tecido hepático, os grupos OG1 e OG2 aumentaram significativamente em comparação ao grupo controle, enquanto o grupo OG2 também aumentou significativamente em comparação ao grupo obeso. Quanto aos demais parâmetros, a comparação entre os grupos ligados ao consumo de dieta hipercalórica (DC) e à administração de Gundelia tournefortii L. em termos de atividades antioxidantes e amostras de soro obteve resultados estatisticamente significativos. Os extratos de plantas de Gundelia tournefortii L. tiveram efeitos que podem ser considerados positivos na atividade dos parâmetros antioxidantes e foram especialmente identificados para melhorar os danos ao DNA e os níveis de MDA nos tecidos cerebrais. Além disso, o consumo de extrato vegetal de Gundelia tournefortii L. na dieta pode ter efeitos antiobesidade; portanto, deve ser avaliado para uso como um método eficaz de perda de peso e como um novo agente terapêutico voltado para a obesidade.

Bioinformatics and expression analysis of the Xeroderma Pigmentosum complementation group C (XPC) of Trypanosoma evansi in Trypanosoma cruzi cells / Análises de bioinformática e da expressão do gene Xeroderma Pigmentosum complementation group C (XPC) de Trypanosoma evansi em células de Trypanosoma cruzi

Abstract Nucleotide excision repair (NER) acts repairing damages in DNA, such as lesions caused by cisplatin. Xeroderma Pigmentosum complementation group C (XPC) protein is involved in recognition of global genome DNA damages during NER (GG-NER) and it has been studied in different organisms due to its importance in other cellular processes. In this work, we studied NER proteins in Trypanosoma cruzi and Trypanosoma evansi, parasites of humans and animals respectively. We performed three-dimensional models of XPC proteins from T. cruzi and T. evansi and observed few structural differences between these proteins. In our tests, insertion of XPC gene from T. evansi (TevXPC) in T. cruzi resulted in slower cell growth under normal conditions. After cisplatin treatment, T. cruzi overexpressing its own XPC gene (TcXPC) was able to recover cell division rates faster than T. cruzi expressing TevXPC gene. Based on these tests, it is suggested that TevXPC (being an exogenous protein in T. cruzi) interferes negatively in cellular processes where TcXPC (the endogenous protein) is involved. This probably occurred due interaction of TevXPC with some endogenous molecules or proteins from T.cruzi but incapacity of interaction with others. This reinforces the importance of correctly XPC functioning within the cell.

Resumo O reparo por excisão de nucleotídeos (NER) atua reparando danos no DNA, como lesões causadas por cisplatina. A proteína Xeroderma Pigmentosum complementation group C (XPC) está envolvida no reconhecimento de danos pela via de reparação global do genoma pelo NER (GG-NER) e tem sido estudada em diferentes organismos devido à sua importância em outros processos celulares. Neste trabalho, estudamos proteínas do NER em Trypanosoma cruzi e Trypanosoma evansi, parasitos de humanos e animais, respectivamente. Modelos tridimensionais das proteínas XPC de T. cruzi e T. evansi foram feitos e observou-se poucas diferenças estruturais entre estas proteínas. Durante testes, a inserção do gene XPC de T. evansi (TevXPC) em T. cruzi resultou em crescimento celular mais lento em condições normais. Após o tratamento com cisplatina, T. cruzi superexpressando seu próprio gene XPC (TcXPC) foi capaz de recuperar as taxas de divisão celular mais rapidamente do que T. cruzi expressando o gene TevXPC. Com base nesses testes, sugere-se que TevXPC (sendo uma proteína exógena em T. cruzi) interfere negativamente nos processos celulares em que TcXPC (a proteína endógena) está envolvida. Isso provavelmente ocorreu pois TevXPC é capaz de interagir com algumas moléculas ou proteínas endógenas de T.cruzi, mas é incapaz de interagir com outras. Isso reforça a importância do correto funcionamento de XPC dentro da célula.

Annexin A1 peptide Ac2-26 mitigates ventilator-induced lung injury in acute respiratory distress syndrome rats and partly depended on the endothelial nitric oxide synthase pathway

Purpose: Although mechanical ventilation is an essential support for acute respiratory distress syndrome (ARDS), ventilation also leads to ventilator-induced lung injury (VILI). This study aimed to estimate the effect and mechanism of Annexin A1 peptide (Ac2-26) on VILI in ARDS rats. Methods: Thirty-two rats were randomized into the sham (S), mechanical ventilation (V), mechanical ventilation/Ac2-26 (VA), and mechanical ventilation/Ac2-26/L-NIO (VAL) groups. The S group only received anesthesia, and the other three groups received endotoxin and then ventilation for 4 h. Rats in the V, VA and VAL groups received saline, Ac2-26, and A c2-26/N5-(1-iminoethyl)-l-ornithine (L-NIO), respectively. Results: All indexes deteriorated in the V, VA and VAL groups compared with the S group. Compared with V group, the PaO2/FiO2 ratio was increased, but the wet-to-dry weight ratio and protein levels in bronchoalveolar lavage fluid were decreased in the VA group. The inflammatory cells and proinflammatory factors were reduced by Ac2-26. The oxidative stress response, lung injury and apoptosis were also decreased by Ac2-26 compared to V group. All improvements of Ac2-26 were partly reversed by L-NIO. Conclusions: Ac2-26 mitigates VILI in ARDS rats and partly depended on the endothelial nitric oxide synthase pathway.

Tratamiento de la reacción inflamatoria cerebral después de un accidente vascular cerebral (acv) y traumatismo cerebral (tec) en un perro / Treatment of inflammatory brain reaction after brain vascular accident (cva) and traumatic brain injury (tbi) in a dog / Tratamento de reação inflamatória cerebral após acidente vascular encefálico (ave) e trauma cranioencefálico (tce) em cão

El presente reporte de caso tiene como objetivo describir la aparición de una condición neurológica tardía, posterior a un traumatismo craneoencefálico en un paciente canino, atendido en una clínica veterinaria privada. El animal fue evaluado clínicamente, con alteraciones neurológicas severas de ataxia vestibular, marcha compulsiva, paresia, pérdida de propiocepción en las cuatro extremidades, miosis bilateral, anisocoria, entre otras. El diagnóstico fue presuntivo, ayudado por resonancia magnética y basado en una historia clínica detallada. El tratamiento clínico se determinó empíricamente, a base de dexametasona comercial, asociada a metionina, nicotinamida y piridoxina. El paciente presentó una rápida mejoría clínica, sin cuadro neurológico.

The present case report aims to describe the occurrence of a late neurological condition, after traumatic brain injury in a canine patient, treated at a private veterinary clinic. The animal was clinically evaluated, with severe neurological alterations of vestibular ataxia, compulsive gait, paresis, loss of proprioception in all four limbs, bilateral miosis, anisocoria, among others. Diagnosis was presumptive, aided by MRI, and based on detailed history. Clinical treatment was empirically determined, based on commercial dexamethasone, associated with methionine, nicotinamide and pyridoxine. The patient showed rapid clinical improvement, with no neurological picture.

O presente relato de caso tem por objetivo descrever a ocorrência de quadro neurológico tardio, pós-trauma cranioencefálico em um paciente canino, atendido em clínica veterinária particular. O animal foi avaliado clinicamente, com alterações neurológicas intensas de ataxia vestibular, andar compulsivo, paresia, perda de propriocepção nos quatro membros, miose bilateral, anisocoria, entre outros. O diagnóstico foi presuntivo, auxiliado por ressonância magnética, e baseado no histórico detalhado. O tratamento clínico foi determinado empiricamente, a base de dexametasona comercial, associada a metionina, nicotinamida e piridoxina. O paciente apresentou melhora clínica rápida, diminuindo inflamação encefálica e desaparecimento de quadro neurológico.