Murine animal models for in vivo studies of Zika and Chikungunya viruses

Arboviruses are worldwide distributed arthropod-borne viruses representing a constant threat to public health. Among these arboviruses, the Chikungunya (CHIKV) and Zika (ZIKV) viruses have a high prevalence in Brazil being responsible for recent outbreaks resulting mainly in irreparable socioeconomic damages such as the high rate of cases of comorbidities and microcephaly in newborns, respectively. Therefore, it is necessary to understand the biology of these arboviruses and develop effective treatments against them; moreover, appropriate mice animal models are strongly encouraged. Here we reviewed the scientific literature aiming to improve the search for the best murine animal model, specific for the arboviruses, specifically, CHIKV and ZIKV. In this way, we performed a comparison between the various mice models currently available, among them: genetically modified immunosuppressed animals, as the A129 and AG129 which are knockout animals for the α/ß and α/ß/γ receptors, respectively, neonatal immunocompetent models C57BL/6 strains used between 6-8 days old for neuropathogenesis studies or 1 day old for vaccine safety studies and finally immunosuppressed induced by dexamethasone or interferon 1 blocker for pathogenesis studies. Mice models are the first option after in vitro analysis, as they are small animals, which facilitates handling and maintenance, in addition to being more inexpensive and abundantly available in different genetic strains, both wild and modified. If the results of this stage are promising, the studies move forward to the use of models with animals of greater complexity, such as rats, non-human primates and finally humans. For this review, we searched through articles in PubMed, Scopus and ScienceDirect databases using the criteria of date publications, titles, abstracts and complete manuscripts. The correct choice of these models during experimental planning is essential, since increases the confidence and the rational use of animals in experimentation in accordance to current bioethics guidelines.

Changes in ovarian morphology and hormone concentrations associated with reproductive seasonality in wild large Japanese field mice (Apodemus speciosus)

Abstract Wild large Japanese field mice (Apodemus speciosus) responses to cyclic seasonal changes are associated with physiological and behavioral changes. However, the detailed regulation of oogenesis in the ovary during the seasonal reproductive cycle in wild large Japanese field mice has not been studied. We assessed the dynamics and changes in ovarian morphology and hormone concentrations associated with reproductive seasonality throughout the year. The stages of the ovarian morphological breeding cycle of wild large Japanese field mice were classified as breeding, transition, and non-breeding periods during the annual reproductive cycle. Measurement of blood estradiol concentrations throughout the year showed that the levels in September and October were higher than those in other months. It is presumed that follicle development starts from a blood estradiol concentration of 38.4 ± 27.1 pg/mL, which marks a shift from the transitional season to the breeding season, followed by the transition to the non-breeding season at 26.1 ± 11.6 pg/mL. These results suggest that seasonal follicle development in wild rodents is correlated with estradiol regulation. We consider this species to be an alternative animal model for studying seasonal reproductive changes and the effects of environmental changes.

Changes in ovarian morphology and hormone concentrations associated with reproductive seasonality in wild large Japanese field mice (Apodemus speciosus)

Wild large Japanese field mice (Apodemus speciosus) responses to cyclic seasonal changes are associated with physiological and behavioral changes. However, the detailed regulation of oogenesis in the ovary during the seasonal reproductive cycle in wild large Japanese field mice has not been studied. We assessed the dynamics and changes in ovarian morphology and hormone concentrations associated with reproductive seasonality throughout the year. The stages of the ovarian morphological breeding cycle of wild large Japanese field mice were classified as breeding, transition, and non-breeding periods during the annual reproductive cycle. Measurement of blood estradiol concentrations throughout the year showed that the levels in September and October were higher than those in other months. It is presumed that follicle development starts from a blood estradiol concentration of 38.4 ± 27.1 pg/mL, which marks a shift from the transitional season to the breeding season, followed by the transition to the non-breeding season at 26.1 ± 11.6 pg/mL. These results suggest that seasonal follicle development in wild rodents is correlated with estradiol regulation. We consider this species to be an alternative animal model for studying seasonal reproductive changes and the effects of environmental changes.(AU)

Sarcocystidae in wild birds of southeastern Brazil / Sarcocystidae em aves silvestres do sudeste do Brasil

This study aimed to identify members of the Sarcocystidae family in naturally infected wild birds at a rescue center in the state of Minas Gerais, southeastern Brazil. The heart and brain of 44 wild birds were evaluated by bioassay in mice to detect T. gondii, and extracted DNA was used for nested PCR of the 18S ribosomal DNA gene to detect members of the Sarcocystidae family. The positive samples were sequenced, assembled, edited and compared with sequences deposited in GenBank. Toxoplasma gondii was isolated from six (13.6%) out of 44 birds. Toxoplasma gondii DNA was identified in 10/44 (22.7%) of the birds. The amplified sequences exhibited 100% similarity with the DNA of the ME49 strain of T. gondii. Sarcocystis DNA (99% similarity) was identified in 5/44 (11.4%) of the birds. T. gondii and Sarcocystis spp. are common in wild birds in Minas Gerais, Brazil.(AU)

O objetivo deste estudo foi identificar membros da família Sarcocystidae em aves silvestres de vida livre naturalmente infectadas e resgatadas no estado de Minas Gerais, Brasil. Coração e cérebro de 44 aves silvestres foram avaliados por bioensaio em camundongos para detecção de T. gondii e extração de DNA para Nested-PCR do gene 18S do DNA ribossomal de membros da família Sarcocystidae. As amostras positivas foram sequenciadas, analisadas, editadas e comparadas com sequências depositadas no GenBank. Toxoplasma gondii foi isolado de seis (13,6%) das 44 aves. DNA de T. gondii foi identificado em 10/44 (22,7%) das 44 aves. As sequências amplificadas exibiram 100% de similaridade com o DNA da cepa ME49 de T. gondii. DNA de Sarcocystis (99% de similaridade) foi identificado em 5/44 (11,4%) das 44 aves. T. gondii e Sarcocystis spp. são encontrados, comumente, em aves silvestres no estado de Minas Gerais, Brasil.(AU)

The protective effect of wild mustard (Sinapis arvensis L) pollen seeds against the toxicity of a solvent (EGME) in Wistar rats

Environmental pollution is the unfavorable alteration of our environment, wholly or mainly as a by-product of human actions, by the direct or indirect effects of changes in energy patterns, radiation levels, the chemical and physical constitution, and the abundance of the organisms. Thus, the environment's pollution is one of the most severe problems humanity and other forms of life face today on our planet, and this population makes severe disruption. The xenobiotic substances responsible for this pollution are numerous and diverse due to multiple human activities that can be the source. However, attention mainly focuses on fertilizers, pesticides, heavy metals, and certain petrochemicals of significant consumption, such as solvents. The purpose of this study is to highlight the reprotoxic and hepatotoxic effects of Ethylene Glycol Monoethyl Ether (EGME) on male Wistar rats. Male Wistar rats were exposed to Ethylene Glycol Monomethyl Etheralone (EGME) (500 mg/kg), combined with the aqueous extract of the pollen grains of Sinapis arvensis (P-EGME) (300mg/kg), in addition to the control (T) and positive control (P) groups for a period of 4 weeks by gavage, to estimate the protective role of this plant against the intoxication of EGME. The results show that EGME can induce reprotoxic effects revealed by a reduction in testes and epididymis mass accompanied by decreased male fertility indicators (sperm concentration). The results also show that treatment with EGME caused a reduction in the red blood cell number, hemoglobin and hematocrit rate, white blood cells in the treated groups compared to the control groups. The present study revealed that treatment with Ethylene Glycol Monoethyl Ether (EGME) under the same experimental conditions could affect several biological markers, especially male fertility. Besides, the protective activity of the wild mustard (Sinapis arvensis) pollen in the face of cellular [...] (AU)

The protective effect of wild mustard (Sinapis arvensis L) pollen seeds against the toxicity of a solvent (EGME) in Wistar rats

Environmental pollution is the unfavorable alteration of our environment, wholly or mainly as a by-product of human actions, by the direct or indirect effects of changes in energy patterns, radiation levels, the chemical and physical constitution, and the abundance of the organisms. Thus, the environment's pollution is one of the most severe problems humanity and other forms of life face today on our planet, and this population makes severe disruption. The xenobiotic substances responsible for this pollution are numerous and diverse due to multiple human activities that can be the source. However, attention mainly focuses on fertilizers, pesticides, heavy metals, and certain petrochemicals of significant consumption, such as solvents. The purpose of this study is to highlight the reprotoxic and hepatotoxic effects of Ethylene Glycol Monoethyl Ether (EGME) on male Wistar rats. Male Wistar rats were exposed to Ethylene Glycol Monomethyl Etheralone (EGME) (500 mg/kg), combined with the aqueous extract of the pollen grains of Sinapis arvensis (P-EGME) (300mg/kg), in addition to the control (T) and positive control (P) groups for a period of 4 weeks by gavage, to estimate the protective role of this plant against the intoxication of EGME. The results show that EGME can induce reprotoxic effects revealed by a reduction in testes and epididymis mass accompanied by decreased male fertility indicators (sperm concentration). The results also show that treatment with EGME caused a reduction in the red blood cell number, hemoglobin and hematocrit rate, white blood cells in the treated groups compared to the control groups. The present study revealed that treatment with Ethylene Glycol Monoethyl Ether (EGME) under the same experimental conditions could affect several biological markers, especially male fertility. Besides, the protective activity of the wild mustard (Sinapis arvensis) pollen in the face of cellular [...]

Ocorrência de casos de raiva em animais silvestres no município de Caicó-RN no período de 2014 a 2019 / Occurrence of rabies cases in the wild animals, in Caicó/RN, from 2014 to 2019

A saúde humana está intimamente ligada à saúde do ambiente e dos animais, sendo de extrema importância a consideração dessa relação nas tomadas de decisão que impliquem em mudanças positivas nos determinantes sociais de saúde. Nesse contexto, a raiva é uma zoonose que tem ocorrido no município de Caicó/RN e tem colocado a cidade entre as primeiras em número de casos em animais silvestres do estado. O presente trabalho objetivou relatar a ocorrência de casos de raiva em animais silvestres nesse município, no período de janeiro de 2014 a julho de 2019. Realizou-se um estudo epidemiológico transversal e descritivo do tipo de série temporal, retrospectivo e quantitativo. Foram utilizados dados secundários, fornecidos pelo LACEN/RN e CCZ, referentes à casuística de raiva em animais silvestres capturados através da vigilância passiva da raiva e submetidos a provas de Imunofluorescência Direta e Inoculação Intracerebral em Camundongos. Foram confirmados 26 casos de raiva em animais silvestres, sendo 21 casos em morcegos (80,76%) e 5 em raposas (19,24%). Apenas essas duas espécies silvestres, morcegos e raposas, foram diagnosticadas positivamente para a doença. Uma variante silvestre comumente encontrada em raposas foi identificada em um cão. A confirmação de casos positivos de raiva em animais silvestres indica que existe a circulação do vírus rábico no município de Caicó, chamando atenção para o risco de exposição de animais domésticos e da população. Diante disso, é de suma importância que o poder público subsidie o funcionamento dos serviços de vigilância para evitar a propagação da doença.

Human health is closely linked to the health of the environment and animals, and it is extremely important to consider this relationship in decision-making that imply positive changes in social determinants of health. In this context, rabies is a zoonosis that has occurred in the municipality of Caicó-RN and has placed the city among the first in number of cases in wild animals in the state. This study aimed to report the occurrence of cases of rabies in wild animals in this municipality, from January 2014 to July 2019. A cross-sectional and descriptive epidemiological study of the type of time series, retrospective and quantitative, was carried out. Secondary data provided by LACEN / RN and CCZ regarding rabies casuistry in wild animals captured through passive rabies surveillance and subjected to Direct Immunofluorescence and Intracerebral Inoculation in Mice tests were used. 26 cases of rabies in wild animals were confirmed, 21 cases in bats (80.76%) and 5 in foxes (19.24%). Only these two wild species have been positively diagnosed for the disease. A wild variant commonly found in foxes, has been identified in a dog. The confirmation of positive cases of rabies in wild animals indicates that the circulation of the rabies virus exists in the municipality of Caicó, calling attention to the risk of exposure of domestic animals and the population. In view of this, it is of utmost importance that the public authorities subsidize the operation of surveillance services to prevent the spread of the disease.

Rescue of caprine fetal ovaries, vitrification and follicular development after xenotransplantation in two immunodeficient mice models

Domestic and wild goats are very susceptible animals to predation, specially when pregnancy occurs. This study aimed to evaluate the use of goat fetal ovarian tissue for vitrification followed by xenotransplantation and fresh xenotransplantation in two immunosuppressed mice models (C57BL/6 SCID and Balb-C NUDE). Goat fetus ovaries were collected in slaughterhouses, divided into small cortical pieces and were destined for fresh xenotransplantation (FX) and cryopreservation followed by xenotransplantation (CX). Five recipients from each lineage were used for FX and 10 animals from each lineage for CX. The mice were euthanized after 65 postoperative days, and the transplants were collected for microscopic assessment. The blood plasma was collected for estradiol measurement. Independently of mice strain, all recipients presented complete estrus cycle in FX and 80% after CX groups. Follicles were observed at all development stages without morphological changes. The volume density and total vessel surface observed in the transplants were different (p <0.01) between groups. The estradiol levels in the recipients did not differ (p <0.05) among the treatments. Thus, it is possible to activate the preantral follicles in the ovaries of fetuses by optimizing germplasm utilization and conservation of domestic and endangered wild goats that are in predatory situations, undesirable drowning or accidental death, since provided conditions for xenotransplantation are performed.

Rescue of caprine fetal ovaries, vitrification and follicular development after xenotransplantation in two immunodeficient mice models

Domestic and wild goats are very susceptible animals to predation, specially when pregnancy occurs. This study aimed to evaluate the use of goat fetal ovarian tissue for vitrification followed by xenotransplantation and fresh xenotransplantation in two immunosuppressed mice models (C57BL/6 SCID and Balb-C NUDE). Goat fetus ovaries were collected in slaughterhouses, divided into small cortical pieces and were destined for fresh xenotransplantation (FX) and cryopreservation followed by xenotransplantation (CX). Five recipients from each lineage were used for FX and 10 animals from each lineage for CX. The mice were euthanized after 65 postoperative days, and the transplants were collected for microscopic assessment. The blood plasma was collected for estradiol measurement. Independently of mice strain, all recipients presented complete estrus cycle in FX and 80% after CX groups. Follicles were observed at all development stages without morphological changes. The volume density and total vessel surface observed in the transplants were different (p <0.01) between groups. The estradiol levels in the recipients did not differ (p <0.05) among the treatments. Thus, it is possible to activate the preantral follicles in the ovaries of fetuses by optimizing germplasm utilization and conservation of domestic and endangered wild goats that are in predatory situations, undesirable drowning or accidental death, since provided conditions for xenotransplantation are performed.(AU)

Protocolo de vocalização ultrassônica em camundongos: uma ferramenta para avaliação do comportamento social / Ultrasonic vocalization protocol in mice: a tool for assessing social behavior

O estudo de desarranjos do neurodesenvolvimento, sejam estes herdados ou adquiridos, necessita da integração cada vez mais aprofundada entre pesquisa básica e abordagem clínica. Apesar da análise do comportamental humano ser essencial para caracterizar e motivar a inovação científica nas várias condições clínicas e/ ou de disfunção social, os estudos comportamentais bem controlados utilizando modelos animais favorecem a ponte do conhecimento entre o laboratório e o clínico populacional. No comportamento social fino e adaptado às espécies animais de experimentação científica, estudos de comunicação ultrassônica em camundongos vem sendo de extrema importância para esclarecimento de achados comportamentais de linguagem em correspondentes em condições humanas. O presente estudo busca consolidar um paradigma de investigação comportamental em linguagem utilizando um modelo murino de linhagem selvagem C57/BL6 no contexto de vocalização ultrassônica na separação materna estabelecida em filhotes pré-adolescentes. Além da determinação e aplicação do protocolo experimental aqui relatado, os resultados demonstraram que não houve diferenças nas idades analisadas e corroboram com os dados descritos em literatura uma vez que ocorreu uma inclinação para comunicação de baixa complexidade.

Neurodevelopmental disorders can be inherited or acquired and requires deeper integration between basic and clinical research. The access and analysis of human behavior patterns are essential to push for scientific innovation in various clinical conditions and/or social dysfunction, but clinical and psychological approach can be challenging to achieve in these conditions. Thus, behavioral studies using animal models in experimental settings favor and advance the understanding of neurodevelopmental disarrangements in human population. In this regard, social behavior testing in fine and elaborate cognitive skills such as ultrasonic vocalization in mice have been extremely important to study behavioral findings of language dysfunction in human condition. Therefore, the present study seeks to consolidate a behavioral investigation paradigm in language using a murine model of wild line C57/BL6 in the context of ultrasonic vocalization in the maternal separation established in pre-adolescent subjects. Besides the establishment and application of the experimental design reported here, the results showed a trend for low complexity communication manifested by the pre-adolescent offspring with no differences regarding age or sex in tested animals.

Protocolo de vocalização ultrassônica em camundongos: uma ferramenta para avaliação do comportamento social / Ultrasonic vocalization protocol in mice: a tool for assessing social behavior

O estudo de desarranjos do neurodesenvolvimento, sejam estes herdados ou adquiridos, necessita da integração cada vez mais aprofundada entre pesquisa básica e abordagem clínica. Apesar da análise do comportamental humano ser essencial para caracterizar e motivar a inovação científica nas várias condições clínicas e/ ou de disfunção social, os estudos comportamentais bem controlados utilizando modelos animais favorecem a ponte do conhecimento entre o laboratório e o clínico populacional. No comportamento social fino e adaptado às espécies animais de experimentação científica, estudos de comunicação ultrassônica em camundongos vem sendo de extrema importância para esclarecimento de achados comportamentais de linguagem em correspondentes em condições humanas. O presente estudo busca consolidar um paradigma de investigação comportamental em linguagem utilizando um modelo murino de linhagem selvagem C57/BL6 no contexto de vocalização ultrassônica na separação materna estabelecida em filhotes pré-adolescentes. Além da determinação e aplicação do protocolo experimental aqui relatado, os resultados demonstraram que não houve diferenças nas idades analisadas e corroboram com os dados descritos em literatura uma vez que ocorreu uma inclinação para comunicação de baixa complexidade.(AU)

Neurodevelopmental disorders can be inherited or acquired and requires deeper integration between basic and clinical research. The access and analysis of human behavior patterns are essential to push for scientific innovation in various clinical conditions and/or social dysfunction, but clinical and psychological approach can be challenging to achieve in these conditions. Thus, behavioral studies using animal models in experimental settings favor and advance the understanding of neurodevelopmental disarrangements in human population. In this regard, social behavior testing in fine and elaborate cognitive skills such as ultrasonic vocalization in mice have been extremely important to study behavioral findings of language dysfunction in human condition. Therefore, the present study seeks to consolidate a behavioral investigation paradigm in language using a murine model of wild line C57/BL6 in the context of ultrasonic vocalization in the maternal separation established in pre-adolescent subjects. Besides the establishment and application of the experimental design reported here, the results showed a trend for low complexity communication manifested by the pre-adolescent offspring with no differences regarding age or sex in tested animals.(AU)

Biomodelos e a covid-19: estado da arte e tendências de uso / Biomodels and covid-19: state-of-the-art and usage trends

A COVID-19 é uma nova coronovirose que demonstrou seu potencial pandêmico a partir de um surto observado em dezembro de 2019 na cidade de Wuhan, na China e, atualmente, já está sendo compreendida como uma síndrome de disfunção múltipla de órgãos, além dos pulmões. Até o momento, há ainda muito a se conhecer sobre o vírus, suas interações e potencial de transmissão, bem como a patogênese da doença; o desenvolvimento das candidatas a vacinas, terapias, diagnósticos mais precisos e ferramentas de controle da doença. Um dos principais desafios encontrados atualmente na pesquisa em COVID-19 é a disponibilização de modelos animais que mimetize a fisiopatogênese da doença humana. Sendo assim, este artigo objetiva fazer uma revisão não só do estado da arte em estudos pré-clínicos desenvolvidos para entendimento e enfrentamento da COVID-19 com a participação de diversos modelos animais de experimentação no aprimoramento de terapias imunes, mas também trazer à discussão a participação de espécies animais selvagens na origem da pandemia, ciclo de transmissão e manutenção da doença. De acordo com a revisão dos trabalhos publicados, foi possível observar que algumas espécies, como primatas não humanos e camundongos têm potencial de uso em múltiplas formas de experimentação, enquanto outras se limitam a um tipo de observação. Desta forma, a avaliação contínua de bons modelos animais para estudo da COVID-19 consolida a importância da investigação em animais e dos estudos pré-clínicos para solucionar esta e próximas pandemias que possam vir a ocorrer na história da saúde pública mundial.

COVID-19 is a new virus disease that demonstrated its pandemic potential from an outbreak observed in December 2019, in Wuhan, China and it is now considered as a multiple organ dysfunction syndrome, in addition to the lungs. So far, there is still much to know about the virus, its interactions and potential for transmission, as well as the pathogenesis of the disease; the development of vaccines candidates, therapies, more accurate diagnoses and disease control tools. One of the main challenges currently found in research in COVID-19 is the availability of animal models that mimic the pathophysiology of human disease. Therefore, this article aims to review not only the state of the art in preclinical studies developed to understand and confront COVID-19 with participation of several animal models of experimentation in the improvement of immune therapies, but also to bring to discussion the participation of wild animal species in the origin of the pandemic, transmission cycle and maintenance of the disease. According to this review, it was possible to observe that some species, such as non-human primates and mice, have potential for use in multiple forms of experimentation, while others are limited to one type of observation. Thus, the continuous evaluation of good animal models for COVID-19 studies consolidates the importance of animal research and preclinical studies to solve this and the next pandemics that may occur in the history of public health worldwide.

Biomodelos e a covid-19: estado da arte e tendências de uso / Biomodels and covid-19: state-of-the-art and usage trends

A COVID-19 é uma nova coronovirose que demonstrou seu potencial pandêmico a partir de um surto observado em dezembro de 2019 na cidade de Wuhan, na China e, atualmente, já está sendo compreendida como uma síndrome de disfunção múltipla de órgãos, além dos pulmões. Até o momento, há ainda muito a se conhecer sobre o vírus, suas interações e potencial de transmissão, bem como a patogênese da doença; o desenvolvimento das candidatas a vacinas, terapias, diagnósticos mais precisos e ferramentas de controle da doença. Um dos principais desafios encontrados atualmente na pesquisa em COVID-19 é a disponibilização de modelos animais que mimetize a fisiopatogênese da doença humana. Sendo assim, este artigo objetiva fazer uma revisão não só do estado da arte em estudos pré-clínicos desenvolvidos para entendimento e enfrentamento da COVID-19 com a participação de diversos modelos animais de experimentação no aprimoramento de terapias imunes, mas também trazer à discussão a participação de espécies animais selvagens na origem da pandemia, ciclo de transmissão e manutenção da doença. De acordo com a revisão dos trabalhos publicados, foi possível observar que algumas espécies, como primatas não humanos e camundongos têm potencial de uso em múltiplas formas de experimentação, enquanto outras se limitam a um tipo de observação. Desta forma, a avaliação contínua de bons modelos animais para estudo da COVID-19 consolida a importância da investigação em animais e dos estudos pré-clínicos para solucionar esta e próximas pandemias que possam vir a ocorrer na história da saúde pública mundial.(AU)

COVID-19 is a new virus disease that demonstrated its pandemic potential from an outbreak observed in December 2019, in Wuhan, China and it is now considered as a multiple organ dysfunction syndrome, in addition to the lungs. So far, there is still much to know about the virus, its interactions and potential for transmission, as well as the pathogenesis of the disease; the development of vaccines candidates, therapies, more accurate diagnoses and disease control tools. One of the main challenges currently found in research in COVID-19 is the availability of animal models that mimic the pathophysiology of human disease. Therefore, this article aims to review not only the state of the art in preclinical studies developed to understand and confront COVID-19 with participation of several animal models of experimentation in the improvement of immune therapies, but also to bring to discussion the participation of wild animal species in the origin of the pandemic, transmission cycle and maintenance of the disease. According to this review, it was possible to observe that some species, such as non-human primates and mice, have potential for use in multiple forms of experimentation, while others are limited to one type of observation. Thus, the continuous evaluation of good animal models for COVID-19 studies consolidates the importance of animal research and preclinical studies to solve this and the next pandemics that may occur in the history of public health worldwide.(AU)

In vivo effect of essential oil of Mentha x villosa and its active compound against Schistosoma mansoni (Sambon, 1907) / Efeito in vivo do óleo essencial de Mentha x villosa e seu composto ativo sobre Schistosoma mansoni (Sambon, 1907)

Schistosomiasis treatment is dependent on a single drug, praziquantel (PZQ). The development of resistance of PZQ has drawn the attention of many researchers to alternative drugs. One viable and promising treatment is the study of medicinal plants as a new approach to the experimental treatment for Schistosomiasis. The present work aimed to evaluate in vivo antischistosomal activity of effect of Mentha x villosa Oil Essential (Mv-EO) and rotundifolone (ROT) against Schistosoma mansoni. Thirty-day-old female Swiss webster mice (Mus musculus) weighing 50 grams were used. Mice were infected with 80 cercariae of S. mansoni (BH strain) and orally administered Mv-EO (50, 100 and 200 mg/Kg) and ROT (35.9, 70.9 and 141.9 mg/Kg) at 45-days post infection for 5 consecutive days. All mice were euthanized 60 days after infection. Praziquantel was the positive control in the experiment. Doses of 200 mg/kg (Mv-EO) and ROT (141.9 mg/Kg) resulted in a significant reduction in fluke burden (72.44% and 74.48%, respectively). There was also marked reduction in liver, intestinal and faecal and changed oogram pattern, compared to infected untreated mice. Considering the results obtained, further biological studies are required in order to elucidate the mechanism of schistosomicidal action on against adult S. mansoni.(AU)

O tratamento da esquistossomose é dependente de uma única droga, praziquantel (PZQ). O desenvolvimento da resistência de PZQ tem atraído atenção de muitos pesquisadores por medicamentos alternativos. Um tratamento viável e promissor é o estudo das plantas medicinais como uma nova abordagem para o tratamento experimental para esquistossomose. O presente trabalho objetivou avaliar a atividade esquistossomicida in vivo óleo essencial de Mentha x villosa (OE-Mv) e rotundifolona (ROT) contra Schistosoma mansoni. Foram utilizados camundongos Swiss webster (Mus musculus) fêmea de trinta dias de idade pesando 50 gramas. Os camundongos foram infectados com 80 cercárias de S. mansoni (cepa BH) e administrado por via oral OE-Mv (50, 100 e 200 mg/Kg) e ROT (35,9, 70,9 e 141,9 mg/Kg) apos 45 dias de infecção durante 5 dias consecutivos. Todos os animais foram eutanasiados 60 dias após a infecção. Praziquantel foi o controle positivo no experimento. O tratamento dos camundongos infectados com doses de 200 mg/kg (OE-Mv) e rotundifolona (141,9 mg/Kg) resultaram em redução significativa dos vermes (72.44% e 74.48%, respectivamente). Foi observado também redução no fígado, intestino e fecal e alteração no padrão do oograma, em comparação aos camundongos infectados e não tratados. Considerando os resultados obtidos, mais estudos biológicos são necessários a fim de elucidar o mecanismo de ação esquistossomicida contra adultos de S. mansoni.(AU)

The liver injury following ischemia and reperfusion is worse in experimental knockout heterozygote mouse model for expression of connexin 43

Purpose:To evaluate that Connexin (Cx43) plays a role in lesions after hepatic ischemia/reperfusion (IR) injury.Methods:We use Cx43 deficient model (heterozygotes mice) and compared to a wild group. The groups underwent 1 hour ischemia and 24 hours reperfusion. The heterozygote genotype was confirmed by PCR. We analyzed the hepatic enzymes (AST, ALT, GGT) and histology.Results:The mice with Cx43 deficiency showed an ALT mean value of 4166 vs. 307 in the control group (p<0.001); AST mean value of 7231 vs. 471 in the control group (p<0.001); GGT mean value of 9.4 vs. 1.7 in the control group (p=0.001); histology showed necrosis and inflammation in the knockout group.Conclusions:This research demonstrated that the deficiency of Cx43 worses the prognosis for liver injury. The topic is a promising target for therapeutics advancements in liver diseases and procedures.(AU)

Wild mouse & laboratory mouse historical aspects, genetic selection and welfare / Camundongo selvagem & camundongo de laboratório aspectos históricos, seleção genética e bem estar

The mouse is the most used animal model in biomedical pre clinical trials. Its phylogeny descends from the genus Mus, subgenus Mus and species Mus musculus. The origin of this animal as an experimental model is due to the capture of wild subspecies mainly Mus musculus domesticus, Mus musculus musculus, Mus musculus castaneus and the hybrid subspecie Mus musculus molosinus. For centuries, diverse breeders with diverse geographical locations have been breeding and swapping selected individuals from among them, which has promoted very large genetic variability and difficulty in accurately recording subspecies that gave rise to both isogenic strains and outbred stocks individuals. The couple Abbie Lathrop and Leo Loeb in Massachusetts (United States of America) are the most cited in this activity. But it was documented, mainly at the origin of the inbred lineages, however, Swiss outbred stock that other unknownsuppliers were selecting albino mice and supplying to research institutes. Currently, we believe in the theory of the subspecies Mus musculus laboratorius existence in house facilities. Because through years suffering artificial evolutionary and selective pressuresthe extreme adaptability of this animal (which made it possible to be captured in the wild and reproduce in captivity) also made the restriction of space in the laboratory enviroment. However, we must take into consideration, with great respect for this animal, that despite its adaptability, its welfare is linked to the expression of its intrinsic natural behavior to the species M. musculus. Thus we have the obligation to provide mating and management directed at reducing the aggressiveness of adult males; searchingfor equipment and materials to the mouse preference; avoiding abrupt changes inenvironment and routine and proper handling...

O camundongo é o modelo animal mais utilizado em ensaios biomédicos. Sua filogenia descende do gênero Mus, subgênero Mus e espécie Mus musculus. A origem desse animal como modelo experimental, deve-se a captura de subespécies selvagens como as Mus musculus domesticus, Mus musculus musculus, Mus musculus castaneuse do híbrido Mus musculus molosinus. Durante séculos, diversos criadores, comdiversas localizações geográficas, realizaram o acasalamento e troca de indivíduos selecionados entre eles, o que promoveu uma variabilidade genética muito grande e uma dificuldade de precisão de registros das subespécies que deram origem tanto as linhagens isogênicas e os indivíduos outbred stocks. O casal Abbie Lathrop e Leo Loebem Massachusetts nos Estados Unidos são os mais citados nessa atividade. Porém sua origem foi documentada, principalmente em relação à linhagem inbred, contudo em relação ao Swiss outbred stock os relatos sugerem que outros fornecedores desconhecidos realizavam a seleção de camundongos albinos e forneciam a instituosde pesquisa. Atualmente, acreditamos na teoria da existência da subespécie Musmusculus laboratorius, pois através de anos sofrendo pressões evolutivas e seletivas artificiais, a extrema capacidade de adaptabilidade desse animal (que o possibilitou ser capturado na natureza e se reproduzir em cativeiro) também tornou adaptado à restrição de espaço em biotério. Contudo, devemos levar em consideração, com muito respeito a esse animal, que apesar dessa adaptabilidade, o seu bem estar é inerente a expressão do comportamento natural intrínsseco da espécie M. musculus. Dessa forma temos a obrigação de propiciar acasalamento e manejo direcionado a redução da agressividade de indivíduos machos adultos, busca por equipamentos emateriais que sejam de preferência do animal, evitar mudanças abruptas de ambiente e rotina e manipulação adequada...

Wild mouse & laboratory mouse historical aspects, genetic selection and welfare / Camundongo selvagem & camundongo de laboratório aspectos históricos, seleção genética e bem estar

The mouse is the most used animal model in biomedical pre clinical trials. Its phylogeny descends from the genus Mus, subgenus Mus and species Mus musculus. The origin of this animal as an experimental model is due to the capture of wild subspecies mainly Mus musculus domesticus, Mus musculus musculus, Mus musculus castaneus and the hybrid subspecie Mus musculus molosinus. For centuries, diverse breeders with diverse geographical locations have been breeding and swapping selected individuals from among them, which has promoted very large genetic variability and difficulty in accurately recording subspecies that gave rise to both isogenic strains and outbred stocks individuals. The couple Abbie Lathrop and Leo Loeb in Massachusetts (United States of America) are the most cited in this activity. But it was documented, mainly at the origin of the inbred lineages, however, Swiss outbred stock that other unknownsuppliers were selecting albino mice and supplying to research institutes. Currently, we believe in the theory of the subspecies Mus musculus laboratorius existence in house facilities. Because through years suffering artificial evolutionary and selective pressuresthe extreme adaptability of this animal (which made it possible to be captured in the wild and reproduce in captivity) also made the restriction of space in the laboratory enviroment. However, we must take into consideration, with great respect for this animal, that despite its adaptability, its welfare is linked to the expression of its intrinsic natural behavior to the species M. musculus. Thus we have the obligation to provide mating and management directed at reducing the aggressiveness of adult males; searchingfor equipment and materials to the mouse preference; avoiding abrupt changes inenvironment and routine and proper handling...(AU)

O camundongo é o modelo animal mais utilizado em ensaios biomédicos. Sua filogenia descende do gênero Mus, subgênero Mus e espécie Mus musculus. A origem desse animal como modelo experimental, deve-se a captura de subespécies selvagens como as Mus musculus domesticus, Mus musculus musculus, Mus musculus castaneuse do híbrido Mus musculus molosinus. Durante séculos, diversos criadores, comdiversas localizações geográficas, realizaram o acasalamento e troca de indivíduos selecionados entre eles, o que promoveu uma variabilidade genética muito grande e uma dificuldade de precisão de registros das subespécies que deram origem tanto as linhagens isogênicas e os indivíduos outbred stocks. O casal Abbie Lathrop e Leo Loebem Massachusetts nos Estados Unidos são os mais citados nessa atividade. Porém sua origem foi documentada, principalmente em relação à linhagem inbred, contudo em relação ao Swiss outbred stock os relatos sugerem que outros fornecedores desconhecidos realizavam a seleção de camundongos albinos e forneciam a instituosde pesquisa. Atualmente, acreditamos na teoria da existência da subespécie Musmusculus laboratorius, pois através de anos sofrendo pressões evolutivas e seletivas artificiais, a extrema capacidade de adaptabilidade desse animal (que o possibilitou ser capturado na natureza e se reproduzir em cativeiro) também tornou adaptado à restrição de espaço em biotério. Contudo, devemos levar em consideração, com muito respeito a esse animal, que apesar dessa adaptabilidade, o seu bem estar é inerente a expressão do comportamento natural intrínsseco da espécie M. musculus. Dessa forma temos a obrigação de propiciar acasalamento e manejo direcionado a redução da agressividade de indivíduos machos adultos, busca por equipamentos emateriais que sejam de preferência do animal, evitar mudanças abruptas de ambiente e rotina e manipulação adequada...(AU)

Knockdown of transglutaminase-2 prevents early age-induced vascular changes in mice

Purpose:To determine whether the absence of transglutaminase 2 enzyme (TG2) in TG2 knockout mice (TG2-/-) protect them against early age-related functional and histological arterial changes.Methods:Pulse wave velocity (PWV) was measured using non-invasive Doppler and mean arterial pressure (MAP) was measured in awake mice using tail-cuff system. Thoracic aortas were excised for evaluation of endothelial dependent vasodilation (EDV) by wire myography, as well as histological analyses.Results:PWV and MAP were similar in TG2-/-mice to age-matched wild type (WT) control mice. Old WT mice exhibited a markedly attenuated EDV as compared to young WT animals. The TG2-/-young and old mice had enhanced EDV responses (p<0.01) as compared to WT mice. There was a significant increase in TG2 crosslinks by IHC in WT old group compared to Young, with no stain in the TG2-/-animals. Optical microscopy examination of Old WT mice aorta showed thinning and fragmentation of elastic laminae. Young WT mice, old and young TG2-/-mice presented regularly arranged and parallel elastic laminae of the tunica media.Conclusion:The genetic suppression of TG2 delays the age-induced endothelial dysfunction and histological modifications.(AU)

Isolation and genetic characterization of Toxoplasma gondii from free-ranging and captive birds and mammals in Pernambuco state, Brazil

Abstract Recent genetic population studies on Toxoplasma gondii in Brazil have shown large genetic variability. The objective of the present study was to isolate and genotypically characterize T. gondii from free-ranging and captive wild mammals and birds in Pernambuco state, Brazil. Fragments of heart, brain, skeletal muscle and diaphragm tissue from 71 birds and 34 mammals, which were either free-ranging or captive, were collected. Samples from 32 of these animals were subjected to bioassays in mice. Samples from the remaining 73 animals underwent biomolecular diagnosis, using PCR technique, targeting a repetitive DNA fragment of 529 bp in T. gondii. A non-virulent isolate (TgButstBrPE1) was obtained from a free-ranging striated heron (Butorides striata) and, based on primary samples, seven animals were found to be positive. The primary samples and the isolate obtained were subjected to PCR-RFLP using the markers SAG1, 53SAG2, alt.SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, Apico and CS3. ToxoDB-RFLP genotype /13 from the striated heron isolate and Type BrIII genotype from a captive otter ( Lontra longicaudis) (PS-TgLonloBrPE1) were obtained. The present study describes the first isolation and genotypic characterization of T. gondii in free-ranging striated heron, and the first genotypic characterization of T. gondii in a captive otter.

Resumo Recentes estudos genéticos nas populações deste parasita no Brasil têm mostrado grande variabilidade genética. O objetivo do presente estudo foi isolar e caracterizar genotipicamente T. gondii de aves e mamíferos de vida livre e de cativeiro no estado de Pernambuco, Brazil. Fragmentos de tecido do coração, cérebro, músculo esquelético e diafragma de 71 aves e 34 mamíferos de vida livre ou cativeiro foram colhidos. Amostras de 32 destes animais foram submetidas a bioensaios em camundongos. As amostras dos 73 animais restantes foram submetidas a diagnóstico biomolecular usando a técnica de PCR, tendo como alvo o fragmento repetitivo de 529 pb do DNA de T. gondii. Dentre os 32 bioensaios conduzidos, obteve-se um isolado não-virulento (TgButstBrPE1) de um socozinho (Butorides striata ) de vida livre, e dentre as amostras primárias, sete animais foram positivos. As amostras primárias e o isolado foram submetidos a PCR-RFLP usando os marcadores SAG1, 53SAG2, alt.SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, Apico e CS3. Foram obtidos o genótipo ToxoDB-RFLP /13 do isolado do socozinho e o genótipo Type BrIII de uma lontra (Lontra longicaudis) de cativeiro (PS-TgLonloBrPE1). O presente estudo descreve o primeiro isolamento e caracterização genotípica de T. gondii em socozinho de vida livre, e a primeira caracterização genotípica de T. gondii em lontra em cativeiro.

Isolation and genetic characterization of Toxoplasma gondii from free-ranging and captive birds and mammals in Pernambuco state, Brazil / Isolamento e caracterização genética de Toxoplasma gondii de aves e mamíferos de vida livre e cativeiro em Pernambuco

Recent genetic population studies on Toxoplasma gondii in Brazil have shown large genetic variability. The objective of the present study was to isolate and genotypically characterize T. gondii from free-ranging and captive wild mammals and birds in Pernambuco state, Brazil. Fragments of heart, brain, skeletal muscle and diaphragm tissue from 71 birds and 34 mammals, which were either free-ranging or captive, were collected. Samples from 32 of these animals were subjected to bioassays in mice. Samples from the remaining 73 animals underwent biomolecular diagnosis, using PCR technique, targeting a repetitive DNA fragment of 529 bp in T. gondii. A non-virulent isolate (TgButstBrPE1) was obtained from a free-ranging striated heron (Butorides striata) and, based on primary samples, seven animals were found to be positive. The primary samples and the isolate obtained were subjected to PCR-RFLP using the markers SAG1, 53SAG2, alt.SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, Apico and CS3. ToxoDB-RFLP genotype/13 from the striated heron isolate and Type BrIII genotype from a captive otter (Lontra longicaudis) (PS-TgLonloBrPE1) were obtained. The present study describes the first isolation and genotypic characterization of T. gondii in free-ranging striated heron, and the first genotypic characterization of T. gondii in a captive otter.(AU)

Recentes estudos genéticos nas populações deste parasita no Brasil têm mostrado grande variabilidade genética. O objetivo do presente estudo foi isolar e caracterizar genotipicamente T. gondii de aves e mamíferos de vida livre e de cativeiro no estado de Pernambuco, Brazil. Fragmentos de tecido do coração, cérebro, músculo esquelético e diafragma de 71 aves e 34 mamíferos de vida livre ou cativeiro foram colhidos. Amostras de 32 destes animais foram submetidas a bioensaios em camundongos. As amostras dos 73 animais restantes foram submetidas a diagnóstico biomolecular usando a técnica de PCR, tendo como alvo o fragmento repetitivo de 529 pb do DNA de T. gondii. Dentre os 32 bioensaios conduzidos, obteve-se um isolado não-virulento (TgButstBrPE1) de um socozinho (Butorides striata) de vida livre, e dentre as amostras primárias, sete animais foram positivos. As amostras primárias e o isolado foram submetidos a PCR-RFLP usando os marcadores SAG1, 53SAG2, alt.SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, Apico e CS3. Foram obtidos o genótipo ToxoDB-RFLP/13 do isolado do socozinho e o genótipo Type BrIII de uma lontra (Lontra longicaudis) de cativeiro (PS-TgLonloBrPE1). O presente estudo descreve o primeiro isolamento e caracterização genotípica de T. gondii em socozinho de vida livre, e a primeira caracterização genotípica de T. gondii em lontra em cativeiro.(AU)