Search

ABSTRACT: During pregnancy there are modifications in the metabolic profile of sheep that may predispose to the occurrence of metabolic disorders, of which pregnancy toxaemia (PT) is highlighted. Blood gas analysis is detects changes in acid-base and electrolyte balance effectively. The objectives of this study were to study the acid-base and electrolyte balance of sheep during gestation and in the immediate peripartum (up to 48 hours postpartum), comparing single gestation with twins. Sixty healthy sheep of Dorper breed, two to five years old were raised in a semi-intensive system and were divided in two experimental groups: Group 1: 30 ewes, with ultrasonographic diagnosis of single fetus gestation; Group 2: 30 ewes, with ultrasonographic diagnosis of twin pregnancy. The experimental moments were defined as: MI-immediately after artificial insemination (control); MG30 - 30 days of gestation; MG90 - 90 days of gestation; MG120 - 120 days of gestation; MG130 - 130 days of gestation; MG140 - 140 days of gestation; MP - lambing; MPP1 - 24h postpartum; MPP2 - 48h postpartum. At all times 1mL of blood was collected per jugular vein puncture for blood gas evaluation in a portable equipament (I-Stat®). The pH, carbon dioxide pressure (PCO2), bicarbonate (HCO3-), base excess (BE), sodium (Na+), potassium (K+), chloride (Cl-), ionized calcium (Ca+2), lactate, anion gap (AG) were mensured and strong ion difference (SID) were calculed. This work showed that there were changes in acid-base and electrolyte balance in pregnant ewes, due to the decrease in BE, HCO3-, TCO2 and increase of lactate and AG during gestation, but the pH remained normal and did not present any difference among moments in both groups. Comparing the groups, single-gestation ewes presented higher alkaline expenditure at delivery than twin-gestation, evidenced by lower levels of BE and HCO3-. Lower Na+ levels were observed in prepartum; drop in K+ values with advancing gestation; hyperchloremia and hypocalcemia during gestation according to the reference standards for species; decreased iCa+2 levels in the final third of gestation in both groups. It was concluded that the ewes of this study were healthy until the last moment analyzed (48h postpartum), although have shown greater consumption of the alkaline reserve in the peripartum, being more explicit in the single gestation animals. In addition, this situation can be physiological and result in increased energy demand during gestation, more exacerbated by peripartum.

ABSTRACT: Considering the representativeness of dairy cattle in our country, the concern about the mortality rates of the animals increases each time. Regarding to calf mortality, the Respiratory Distress Syndrome (RDS) has an important relevance during the neonatal period, and it is present in immature lungs. The amniotic fluid is in direct contact with the fetus, and it is able to offer evidence about his maturity. The aim of this study was to standardize the characteristics of the amniotic fluid, color, aspect, viscosity, quantification of lamellar body and surfactant evaluation by the Clements test and cytology, of term-born, mature and healthy calves. There were used 50 Black and White Holstein calves, which mothers were observed at calving in order to collect the amniotic fluid by puncture in the moment of exposure of the fetal membrane through the vaginal canal. Most amniotic fluid had a clear and hazy appearance due to varying degrees of viscosity and the presence or absence of clots. The Clements test could be adapted to the bovine species by the modification consisting in the addition of 3mL of amniotic fluid and 1mL of 95% ethanol. The methodology of the lamellar body count by the automated particle counter is not applicable for the bovine because of the small size of their lamellar body. The Nile Blue staining is unsatisfactory on predicting fetal maturity on the bovine species, different from cytology using Hematoxylin-Shorr stain. The presence of orange cells, increase in large amounts at the end of pregnancy. The cell stained orange counting, cells which are found in great amounts at the end of pregnancy. The present study stablished new parameters for evaluation of fetal and pulmonary maturity in the bovine species.

Abstract: There is no standardization in the literature of kidney length in sheep at different ages, as there are few studies about the access with the Doppler triplex ultrasound for the renal vascularization in this species. Eighty healthy sheep of three age groups of Ile de France and White Dorper breed were used: 20 lambs, 30 yearlings and 30 adults (8 rams and 22 ewes). Renal healthiness of the animals was confirmed by serum biochemical tests of urea and creatinine, and by observation of renal architecture with conventional ultrasound, besides measurement of vital parameters. A portable ultrasound (My LabTM30 Vet Gold Esaote®, Esaote Healthcare) device was used, with a convex transducer with 3.5MHz frequency. After identification of the kidneys in two-dimensional mode, the measurement of length in the sagittal section was performed in all sheep (n=80). Then color Doppler was activated for visualization of renal and interlobar arteries of the right kidney, and the resistivity index (RI) of the yearlings (n=30) and ewes (n=22) was measured. Biochemical tests remained within normal limits and renal architecture was preserved. The values of the right and left renal length were different between the groups, increasing with age (4.34cm and 4.31cm in lambs; 6.08cm and 6.23cm in yearlings; 7.57cm and 7.37cm in adults, respectively). Median values of RI of the renal artery were statistically different (p

Abstract: The veterinary cardiology has growing importance in equine medicine. There are studies of standardization of electrocardiographic parameters of many races, according to their stature and ability. However, no studies are in the literature with the American Miniature Horse. To evaluate the electrocardiogram (ECG) tracing configuration of this breed at rest and to verify the influence of age and sex on ECG parameters, 203 horses including 143 females and 60 males were divided into four age groups (foals, yearlings, adults and elderly). Electrocardiographic parameters were performed by computerized electrocardiogram (TEB), and the parameters were evaluated in six leads of frontal plane (Lead I, II, III, aVR, aVL and aVF) and base-apex (BA). Heart rates (HR) decreased with increasing age were higher in males than in females. Sinus tachycardia followed by sinus arrhythmia was dominant in both sexes. The cardiac axis was higher in males and ranged between 120° and 150° for foals, 30° and 60° for yearlings and adults, and 60° and 90° for the elderly. The P wave was bifid in several animals. The P-wave amplitude and T-wave duration from lead II and BA were larger in males than in females. The majority of the animals exhibited ST segment depression and a negative T-wave. The most common QRS complex morphology was Qr. Differences were observed between the electrocardiographic tracings of males and females, and age influenced the ECG parameters. Therefore, this study established the ECG patterns for the American Miniature Horse breed and could be used to determine the influence of age and sex on several of the studied variables.

Abstract: The present paper reports blood gas analysis, hematologic and micro bacteriologic information on four female Red-billed curassows, rescued from illegal wild animal trading, that were undergoing habilitation for reintroduction into the wild through Projeto Centrofauna/Botucatu-SP. There is a lack of physiological data on this species, endemic to the region of Atlantic Forest (Mata Atlântica), now under threat of extinction. This lack of information makes the clinical evaluation of these birds very difficult and has a direct and adverse effect on any of these birds received for medical treatment in hospitals, veterinary clinics and centers for research and conservation, as well as in reintroduction centers.

Resumo: A acidificação urinária com cloreto de amônio (CA) é um método preventivo eficiente em urolitíase obstrutiva em ovinos. Os objetivos deste estudo com ovinos confinados, que receberam dieta concentrada com elevado teor proteico, foram: verificar o efeito da dieta sobre a formação de urólitos e o desenvolvimento da doença; analisar as características macroscópicas e histopatológicas do sistema urinário; relacionar os achados clínicos, laboratoriais e necroscópicos com a presença de urólitos. Utilizaram-se 60 ovinos machos: grupo CA (n=40), 400 mg/kg CA/dia, tratados via oral, por 42 dias consecutivos; grupo-controle (n=20), não tratado. Determinaram-se sete momentos de colheita de amostras com intervalos de sete dias, no total de 56 dias de confinamento. Encontraram-se microcálculos na pelve renal em cinco animais de ambos os grupos. As lesões renais microscópicas mais relevantes foram congestão vascular e necrose tubular. Concluiu-se que a dieta rica em concentrado provocou lesão renal em ambos os grupos, embora sem alterar a função renal, o que foi comprovado em testes pela ureia e creatinina séricas. O cloreto de amônio fornecido ao grupo CA não impediu a calculogênese, mas reduziu sua prevalência em relação ao grupo-controle. Os ovinos do grupo-controle tiveram maior comprometimento renal, pela alta incidência de cristalúria e pela necrose tubular, induzidas pelo consumo da dieta rica em grãos.

Resumo: A incidência da urolitíase obstrutiva em ovinos é elevada, principalmente em machos confinados, tanto para produção de carne, quanto reprodutores de alto valor genético. A acidificação urinária é um dos métodos para prevenção desta enfermidade e pode ser realizada de forma eficaz com a suplementação de cloreto de amônio (CA) na dieta. Utilizaram-se 100 ovinos, machos não castrados, mestiços (Ile de France X White Dorper), confinados, com idade aproximada de três meses. Constituíram-se três grupos experimentais: Grupo 21CA (n=40) que recebeu 400mg/kg/PV de cloreto de amônio/animal/dia, por 21 dias consecutivos; Grupo 42CA (n=40) que foi suplementado com 400mg/kg/PV de cloreto de amônio/animal/dia, por 42 dias consecutivos; Grupo controle (n=20), que não recebeu CA. A alimentação consistiu de ração total, composta por 15% de feno triturado e 85% de concentrado, água e sal mineral ad libitum. Após 14 dias de adaptação à alimentação e ao ambiente, os Momentos (M) de avaliação clínica, colheita de sangue e exame ultrassonográfico foram realizados com intervalo de sete dias, sendo M0 (imediatamente antes do início do tratamento com cloreto de amônio), M1 (sete dias após), M2 (14 dias após), M3 (21 dias após o início do tratamento e suspensão do cloreto de amônio em Grupo 21CA), M4 (28 dias após), M5 (35 dias após) e M6 (42 dias após), totalizando 56 dias de confinamento. As dosagens de ureia e creatinina não evidenciaram alteração na função renal, embora a ureia estivesse acima dos valores de referência para espécie ovina. Observaram-se imagens ultrassonográficas compatíveis com cálculos vesicais e dilatação de pelve renal. No Grupo 21CA, 15% (6/40) dos animais apresentaram cálculos vesicais; no Grupo 42CA, 5% (2/40); e no Grupo controle, 20% (4/20) dos cordeiros. Visibilizaram-se também imagens sugestivas de sedimentos e cristais em 31% (31/100) dos animais examinados. A ultrassonografia permitiu a visibilização de alterações renais e vesicais, porém não relacionados ao quadro clínico de urolitíase obstrutiva, revelando-se como um exame complementar de grande relevância para o diagnóstico precoce de alterações no sistema urinário de ovinos.

A incidência da urolitíase obstrutiva em ovinos é elevada, principalmente em machos confinados, tanto para produção de carne, quanto reprodutores de alto valor genético. A acidificação urinária é um dos métodos para prevenção desta enfermidade e pode ser realizada de forma eficaz com a suplementação de cloreto de amônio na dieta, que pode propiciar a instalação de acidose metabólica. A hemogasometria avalia o equilíbrio ácido-básico sanguíneo de forma prática e fácil. Neste trabalho, avaliou-se o efeito do cloreto de amônio sobre o equilíbrio ácido-básico e eletrolítico de ovinos em confinamento para quantificar a acidose metabólica desenvolvida. Utilizaram-se 100 ovinos, machos, confinados, com idade aproximada de três meses. Constituíram-se três grupos experimentais: Grupo I (n=40), recebeu 400mg/kg/PV de cloreto de amônio/animal/dia por 21 dias consecutivos, momento da interrupção da administração do acidificante urinário (M3) e continuidade do acompanhamento clinico até o final do experimento (M6); Grupo II (n=40), 400mg/kg/PV de cloreto de amônio/animal/dia por 42 dias consecutivos; Grupo III (n=20), não recebeu cloreto de amônio durante todo o período do experimento. Os Momentos (M) de colheita de amostras e avaliação clínica foram estabelecidos com intervalo de sete dias, sendo M0 (imediatamente antes do início do tratamento com cloreto de amônio), M1 (sete dias após), M2, M3, M4, M5 e M6, totalizando 56 dias de confinamento. A alimentação consistiu de ração total, composta por 15% de feno triturado e 85% de concentrado, água e sal mineral ad libitum. Após adaptação de 15 dias à dieta de confinamento, colheram-se de todos os animais amostras de urina para mensuração do pH, e sangue venoso para hemogasometria, nos diferentes momentos. A acidificação urinária foi mantida enquanto houve a administração de cloreto de amônio nos grupos GI e GII. Os valores de Na+ e K+ permaneceram dentro da normalidade para a espécie. O cloreto de amônio provocou acidose metabólica hiperclorêmica compensada nos grupos GI e GII, comprovada pelos valores reduzidos de HCO3-, EB e SID, pelos valores elevados de Cl- e pelo pH normal. Concluiu-se que o cloreto de amônio apesar de provocar diminuição da reserva alcalina no organismo, não interferiu com o desenvolvimento dos animais, podendo ser empregado como agente preventivo da urolitíase obstrutiva em ovinos.

Dermatosparaxia em animais é uma doença autossômica recessiva do tecido conjuntivo caracterizada por fragilidade e hiperextensibilidade cutânea. A doença em ovinos White Dorper é provocada pela mutação c.421G>T no gene ADAMmetalopeptidase com trombospondina tipo 1 motif, 2 (ADAMTS2). O objetivo deste estudo foi descrever os achados clínicos, moleculares e histopatológicos da dermatosparaxia em ovinos White Dorper de um rebanho localizado no Centro-Oeste Paulista. O rebanho era composto por nove animais, sendo um reprodutor, quatro matrizes e seus respectivos borregos. Dos nove animais examinados, dois apresentavam sinais clínicos compatíveis com dermatosparaxia. O exame histopatológico de amostras cutâneas das lesões destes dois animais revelou também achados compatíveis com dermatosparaxia, sendo caracterizados por epiderme e anexos cutâneos preservados e sem características atípicas; colágeno displásico arranjado em feixes pequenos, fragmentados e com focos de degeneração, anexos cutâneos proeminentes e na região da derme foco hemorrágico intenso associado a moderado infiltrado neutrofílico na derme profunda. Com o objetivo de realizar o diagnóstico molecular da enfermidade, uma PCR foi padronizada utilizando primers específicos desenhados para amplificar a região do gene ADAMTS2 que continha a mutação c.421G>T e o DNA obtido de amostras de sangue de todos os animais do rebanho. O sequenciamento direto dos produtos da PCR, comprovou que os dois animais clinicamente afetados possuíam a mutação responsável pela dermatosparaxia. A metodologia descrita neste estudo possibilitou o diagnóstico definitivo da doença. Segundo a literatura consultada, esta é a primeira vez que a dermatosparaxia é descrita em ovinos White Dorper no Brasil. A metodologia aqui descrita poderá ser empregada em estudos futuros que avaliem a prevalência desta mutação no Brasil, possibilitando a adoção de medidas que previnam a disseminação dessa mutação no rebanho brasileiro de ovinos White Dorper.

O presente trabalho estudou a intoxicação acidental por arsênico em um lote de 24 vacas Girolando, as quais tiveram acesso a pasto pulverizado com herbicida à base de metano arsonato ácido monossódico (MSMA). Os bovinos apresentaram apatia, anorexia e diarreia profusa. Foram necropsiados na fazenda dois animais de 14 que morreram. Os principais achados macroscópicos foram úlceras abomasais e congestão renal. No exame microscópico, as principais lesões observadas foram abomasite e omasite necro-hemorrágica multifocal acentuada e, nos rins, necrose tubular difusa. As concentrações médias de arsênico em vacas com sinais clínicos foram 1,19±0,40, 10,52±2,16 e 76,06±48,37ppm no sangue, leite e fezes, respectivamente. Os níveis de arsênico encontrados em dois animais necropsiados foram 25,58 e 23,85ppm em fígado, e 28,71 e 35,94ppm em rins, respectivamente. No feto de uma vaca necropsiada, os níveis de arsênico mensurados no fígado e rim foram 9,0 e 8,92ppm, respectivamente. A concentração de arsênico no capim do piquete pulverizado foi 111,58ppm. No Brasil, o uso MSMA na composição de pesticidas e herbicidas é permitido somente para uso agrícola, mas não pecuário. A utilização desse ou de outros produtos à base de arsênico na pecuária pode causar altos índices de mortalidade no rebanho, além de diminuição da produção e contaminação de produtos de origem animal.

Estudou-se a broncopneumonia de ocorrência natural em bezerros e a influência da administração de acetato de DL-α-tocoferol na profilaxia e tratamento desta enfermidade. Foram avaliados 60 bezerros machos, com idade máxima de 10 dias, divididos em dois grupos experimentais: GSV (grupo sem vitamina) e GCV (grupo com vitamina). A suplementação com dose única de 4.500 UI de acetato de DL-α-tocoferol por via intramuscular (IM) foi precedida por exame físico, perfil hematológico, determinação de proteínas séricas, globulinas, gamaglutamiltransferase e citologia do lavado traqueobrônquico (D0) para verificar a sanidade e homogeinização dos grupos. Os bezerros foram mantidos em bezerreiro e distribuídos aleatoriamente, 2 a 2 em baias individuais de 2,40m², onde permaneceram até o 21º dia (D0 ao D21). Foram avaliados por exame físico diário e, na presença de sinais clínicos indicativos de broncopneumonia (DX), retirados do bezerreiro, avaliados por hemograma e citologia do lavado traqueobrônquico, e tratados com enrofloxacina (5mg/kg, IM). Durante o tratamento, o exame físico foi realizado diariamente, e o hemograma e a citologia do lavado traqueobrônquico repetidos uma semana após seu término (DY). Nos bezerros sadios foram repetidos hemograma e citologia do lavado traqueobrônquico, no último dia (D21) do experimento. Não houve diferença significativa quanto às variáveis gamaglutamiltrasfrase (p=0,09), proteínas séricas (p=0,27) e globulinas (p=0,10) e a idade dos bezerros (p=0,15) entre os grupos. Os bezerros do grupo GSV e GCV levaram em média 11 e 12 dias para adoecerem, respectivamente. Contudo, não houve diferença estatística significativa entre os grupos (p=0,68). Em 34 bezerros (56,66%) foi diagnosticado broncopneumonia, sendo que 17 destes bezerros (50%) pertenciam ao grupo GCV e 17 (50%) ao grupo GSV. Com relação aos sinais clínicos, não houve diferença significativa entre os grupos em nenhum dos momentos estudados. Dos 34 bezerros que adoeceram 73,52% morreram pela doença, sendo 64,7% do GCV e 82,35% do GSV. A citologia do lavado traqueobrônquico não apresentou diferença significativa entre os grupos em nenhum dos momentos estudados (D0, DX, DY e D21). A suplementação com vitamina E não teve influência na profilaxia e no tratamento de broncopneumonia de bezerros.

ABSTRACT: Pulsed Doppler ultrasound was used to evaluate portal blood flow, portal velocity and portal congestion index in 24 healthy sheep divided into groups (lambs, yearlings and ewes), according to age. Measurements were performed at the 11th right intercostal space using ideal insonation angle and uniform insonation method. Mean values obtained in each group were compared with one-way ANOVA, followed by Tukey post-hoc test. Portal velocity and portal blood flow were statistically similar between the groups (P>0.05). Mean portal velocity were 17.75; 17.13 and 16.75; while mean portal blood flow were 26.65; 31.04 and 24.32 for lambs, yearlings and ewes, respectively. Portal congestion index was statistically distinct between the groups and values for lambs, yearlings and ewes were 0.009; 0.058 and 0.09, respectively (P

RESUMO: A urolitíase é uma doença importante de cordeiros confinados. A acidificação da urina, pela ingestão de cloreto de amônio, é o método preventivo mais frequentemente empregado. Devido à falta de informação específica em ovinos, este estudo foi realizado para avaliar as alterações que ocorrem nos eletrólitos urinários de cordeiros, que receberam cloreto de amônio na dieta. Foram utilizados 100 cordeiros, com 3 meses de idade, que foram mantidos em confinamento durante 56 dias, e distribuídos em 3 grupos: G1 (n=40) que receberam 400mg/kg de peso vivo (PV) de cloreto de amônio/dia, durante 21 dias; G2 (n=40) que receberam 400mg/kg de PV de cloreto de amônio/dia durante 42 dias; e G3 (n=20) que não receberam cloreto de amônio. Os cordeiros foram examinados e as amostras de sangue e urina foram colhidas a cada 7 dias: 0 (antes do início da ingestão de cloreto de amônio), 7, 14, 21, 28, 35, e 42 dias. As concentrações séricas e urinárias de sódio (Na+), potássio (K+), cloreto (Cl-), e de creatinina foram mensuradas em todos os momentos de colheita. A excreção fracionada urinária (EFu) de eletrólitos e a diferença de íons fortes (SID) na urina [(Na+ + K+) - Cl] foram calculadas. A EFu de Na+, K+ e Cl- não variou ao longo do tempo em G3, provando que a dieta de confinamento, por si só, não influenciou a excreção urinária destes eletrólitos. A ingestão de cloreto de amônio, pelo grupo G1 e G2, influenciou a EFu sobre o tempo de confinamento. A SID urinária foi mais precisa do que a EFu de Cl- para demonstrar que a concentração de Cl- aumentou na urina, o que destacou a relevância desta variável.

ABSTRACT: In order for successful extra-uterine adaptation to occur, it is necessary for the neonate to be able to establish its respiratory functions effectively, guaranteeing efficient oxygenation and good vitality. Respiratory disorders are the major cause of death during the neonatal period in cattle, and this mortality is even more significant when it comes to calves originated by in vitro fertilization (FIV) or animal cloning (CA). Blood gas analysis assesses acid-base balance changes effectively, and when associated with the neonate’s clinical examination, provides subsidies for accurate diagnosis and early treatment of neonatal maladaptation. The objective of this study was to study neonates born from artificial insemination (IA) and to compare them to calves conceived by FIV and CA, regarding blood gas and clinical examination. For that, 20 AI calves, 15 FIV calves, and 15 cloned calves were evaluated immediately after calving and at 6, 12, 24 and 48 hours of life. At all experimental times, venous blood samples were collected for blood gas and clinical examination was performed. In the postpartum evaluation, Apgar score and column length and respiratory amplitude measurements were used. IVF animals showed no alterations, resembling Group IA calves. The calves from CA showed more pronounced acidosis postpartum than expected physiological acidosis mixed for neonates, with decreasing values of bicarbonate (HCO3-), and base excess (BE) and the increase in carbon dioxide pressure (PCO2) when compared to the other groups. This disorder may have reflected lower mean values of Apgar scores and increased heart and respiratory rates. Intensive follow-up of these neonates is suggested, with monitoring by clinical and hemogasometric examination for early diagnosis of this condition and treatment based on oxygen therapy and bicarbonate replacement.

RESUMO: Os objetivos deste estudo foram descrever a frequência cardíaca (FC) e os índices de variabilidade da frequência cardíaca (VFC) materna e fetal no terço final da gestação, bem como descrever a evolução do desenvolvimento do sistema nervoso autônomo durante o período fetal e neonatal. Foram avaliados 20 animais de cada categoria, cujos exames eletrocardiográficos, maternos e fetais, foram realizados aos 15 e sete dias pré-parto. Quanto ao eletrocardiograma neonatal, os momentos avaliados foram ao nascimento até as primeiras 48 horas de vida, e posteriormente, uma vez por semana até os 35 dias de idade. Ocorreram diferenças significativas na frequência cardíaca fetal (FCF) no período avaliado, porém os índices de VFC fetais não se alteraram. Não foram encontradas diferenças significativas nos índices de VFC materna. A média da FCF diminuiu significativamente dos 15 para sete dias do pré-parto (95,6±11,4 bpm; 83,1±12,6, respectivamente), entretanto os índices de VFC fetal não diminuíram. Os resultados obtidos da VFC fetal e neonatal deste estudo, quando comparados aos maternos, indicaram predomínio parassimpático durante a fase fetal e, simpático durante a neonatal, até a terceira e/ou quarta semanas de idade, momento no qual se inicia o equilíbrio entre os dois sistemas.

Snake venom metalloproteinases (SVMP) are involved in local inflammatory reactions observed after snakebites. Based on domain composition, they are classified as PI (pro-domain + proteolytic domain), PII (PI + disintegrin-like domains), or PIII (PII + cysteine-rich domains). Here, we studied the role of different SVMPs domains in inducing the expression of adhesion molecules at the microcirculation of the cremaster muscle of mice. We used Jararhagin (Jar)—a PIII SVMP with intense hemorrhagic activity, and Jar-C—a Jar devoid of the catalytic domain, with no hemorrhagic activity, both isolated from B. jararaca venom and BnP-1—a weakly hemorrhagic P1 SVMP from B. neuwiedi venom. Toxins (0.5 µg) or PBS (100 µL) were injected into the scrotum of mice, and 2, 4, or 24 h later, the protein and gene expression of CD54 and CD31 in the endothelium, and integrins (CD11a and CD11b), expressed in leukocytes were evaluated. Toxins induced significant increases in CD54, CD11a, and CD11b at the initial time and a time-related increase in CD31 expression. In conclusion, our results suggest that, despite differences in hemorrhagic activities and domain composition of the SVMPs used in this study, they behave similarly to the induction of expression of adhesion molecules that promote leukocyte recruitment.

In South America, accidental contact with Lepidoptera larvae can produce a diversity of reactions that vary from dermatological problems to severe hemorrhagic syndromes, such as those caused by contact with caterpillars of the genus Lonomia (Saturniidae). Lonomia venom can alter the hemostatic system and lead to renal failure, internal and brain bleeding, and in severe cases, death. The only specific treatment available for these envenomations is the Lonomia Antivenom (LAV) produced by the Butantan Institute, in Brazil, using an extract of Lonomia obliqua scoli as the antigen. LAV has been used to treat exposure to other Lonomia species across South America. However, no experimental studies have been performed to test the efficacy of LAV in neutralizing the venom of species other than L. obliqua found in Southern Brazil. In this study, we tested the effectiveness of LAV in reversing the hemostatic disturbances induced by injecting Lonomia casanarensis (Lca) and Lonomia orientoandensis (Lor) scolus extracts into rats and compared the effects to the case of L. obliqua (Lob) scolus extract-induced envenomation. Lca and Lor caterpillars were collected in Colombia, and some of them were reared to adults for identification. The Minimum Defibrinating Doses (MDD) of Lca and Lor were estimated. Rats were injected (i.d.) with a dose of 3 MDD per rat of each scolus extract and treated (i.v.) with 1.5 mL of LAV or 1.5 mL of saline. Twenty-four hours after the treatment, the fibrinogen levels and platelet counts had recovered to the hemostatic levels in the groups treated with LAV. The groups treated with the saline solution had fibrinogen levels and platelet counts at non-hemostatic levels. Thromboelastometric analyses confirmed these results. In conclusion, the results showed that LAV is effective at neutralizing the envenomation induced by Lca and Lor spine extracts in rats and restoring hemostasis.

The venom of the snake Bothrops asper, the most important poisonous snake in Central America, evokes an inflammatory response, the mechanisms of which are not well characterized. The objectives of this study were to investigate whether B. asper venom and its purified toxins – phospholipases and metalloproteinase – activate the complement system and the contribution of the effect on leucocyte recruitment. In vitro chemotaxis assays were performed using Boyden's chamber model to investigate the ability of serum incubated with venom and its purified toxins to induce neutrophil migration. The complement consumption by the venom was evaluated using an in vitro haemolytic assay. The importance of complement activation by the venom on neutrophil migration was investigated in vivo by injecting the venom into the peritoneal cavity of C5-deficient mice. Data obtained demonstrated that serum incubated with crude venom and its purified metalloproteinase BaP–1 are able to induce rat neutrophil chemotaxis, probably mediated by agent(s) derived from the complement system. This hypothesis was corroborated by the capacity of the venom to activate this system in vitro. The involvement of C5a in neutrophil chemotaxis induced by venom-activated serum was demonstrated by abolishing migration when neutrophils were pre-incubated with antirat C5a receptor antibody. The relevance of the complement system in in vivo leucocyte mobilization was further demonstrated by the drastic decrease of this response in C5-deficient mice. Pre-incubation of serum with the soluble human recombinant complement receptor type 1 (sCR 1) did not prevent the response induced by the venom, but abolished the migration evoked by metalloproteinase-activated serum. These data show the role of the complement system in bothropic envenomation and the participation of metalloproteinase in the effect. Also, they suggest that the venom may contain other component(s) which can cause direct activation of C5a.

We investigated morphological alterations induced by s.c. injection of 2.5 μg of Bothrops jararaca venom in rats. Intense disorganisation of collagen fibres was observed 1 min after the venom injection, particularly at regions near vessels and nerves. Mast cells were degranulated, and erythrocytes were seen leaving venules throughout the endothelial junctions. At this time, damaged endothelial cells were not observed. In rats envenomed as above, but immediately after cardiorespiratory failure induced by deep ether anaesthesia, alterations in the connective tissue structures, as previously described, were not observed. The mediation of this haemorrhage was investigated by injecting the venom into the foot pad of mice and compared to the mediation of oedema. Local haemorrhage was significantly reduced in mice pre-treated with capsaicin or guanethidine or submitted to a surgical section of sciatic and saphenous nerves. In these animals, oedema was not affected. Groups treated with methysergide or morphine showed both haemorrhage and oedema significantly reduced. Indomethacin or dexamethasone pre-treatments significantly reduced the oedema, but not the haemorrhage. Moreover, in animals treated with promethazine or mepyramine, oedema and haemorrhage were not affected. These data suggest that local haemorrhage induced by Bothrops jararaca venom is partially controlled by serotonin and neurohumoral mediators. Furthermore, results indicate that haemorrhage and oedema are mediated by different pharmacological systems.

In recent years, extensive research has delved into the pathophysiology of local reactions triggered by Bothrops snake venoms. Even though antivenom works well at reducing death and systemic effects, it is still not very effective in treating local reactions because it cannot counteract damage that has already been triggered. This limitation might be attributed to certain molecules that amplify the venom-induced innate response. While evidence suggests endogenous mediators at the venom site play a role in this envenomation, in Brazil, the concurrent use of anti-inflammatory agents or other drugs alongside antivenom remains uncommon. This study evaluated the pharmacological mediation of alterations in leukocyte–endothelium interactions following the experimental envenomation of mice with Bothrops jararaca venom, the main culprit of snake-related accidents in Southeast Brazil. We treated envenomed mice with inhibitors of different pharmacological pathways and observed the cremaster muscle microcirculation with intravital microscopy. We found that eicosanoids related to cyclooxygenase pathways and nitric oxide significantly contributed to B. jararaca venom-induced alterations in leukocyte–endothelium interactions. Conversely, lipoxygenase-mediated eicosanoids, histamine, and serotonin had minimal participation. Notably, dexamethasone and antivenom treatment diminished B. jararaca venom–induced alterations in leukocyte–endothelium interactions. The limited efficacy of the antivenom in managing Bothrops venom-induced local reactions emphasizes the critical need for supplementary treatments to enhance therapeutic outcomes.

Introduction: Alzheimer’s disease (AD) is the main type of dementia, caused by the accumulation of amyloid plaques, formed by amyloid peptides after being processed from amyloid precursor protein (APP) by γ- and ß-secretases (BACE-1). Although amyloid peptides have been well established for AD, they have been found in other neurodegenerative diseases, such as Parkinson’s disease, Lewy body dementia, and amyotrophic lateral sclerosis. Inhibitors of BACE-1 have been searched and developed, but clinical trials failed due to lack of efficacy or toxicity. Nevertheless, it is still considered a good therapeutic target, as it was proven to remove amyloid peptides and improve memory.Methods: In this work, we designed a peptide based on a sequence obtained from the marine fish Merluccius productus and evaluated it by molecular docking to verify its binding to BACE-1, which was tested experimentally by enzymatic kinetics and cell culture assays. The peptide was injected in healthy mice to study its pharmacokinetics and toxicity.Results: We could obtain a new sequence in which the first N-terminal amino acids and the last one bound to the catalytic site of BACE-1 and showed high stability and hydrophobicity. The synthetic peptide showed a competitive inhibition of BACE-1 and Ki = 94 nM, and when injected in differentiated neurons, it could reduce Aβ42o production. In plasma, its half-life is ∼1 h, clearance is 0.0015 μg/L/h, and Vss is 0.0015 μg/L/h. The peptide was found in the spleen and liver 30 min after injection and reduced its level after that, when it was quantified in the kidneys, indicating its fast distribution and urinary excretion. Interestingly, the peptide was found in the brain 2 h after its administration. Histological analysis showed no morphological alteration in any organ, as well as the absence of inflammatory cells, indicating a lack of toxicity.Discussion: We obtained a new BACE-1 inhibitor peptide with fast distribution to the tissues, without accumulation in any organ, but found in the brain, with the possibility to reach its molecular target, BACE-1, contributing to the reduction in the amyloid peptide, which causes amyloid-linked neurodegenerative diseases.