Behavioral and morphological effects of resveratrol and curcumin in rats submitted to doxorubicin-induced cognitive impairment.

Doxorubicin (DOX) is known to cause cognitive impairments in patients submitted to long-term chemotherapy (deficits also known as chemobrain). Therefore, there is an urgent need for therapeutic strategies capable of returning cancer survivors back to their previous quality of life. The present study investigated whether resveratrol (RSV) or curcumin (CUR) administration could affect mnemonic function and brain morphological changes following DOX administration in rats. Male Wistar rats were divided into 4 groups: DOX group (2.5 mg/kg/week for 4 weeks, i.p., plus distilled water for 28 days, oral gavage - OG), DOX + RSV group (DOX, 2.5 mg/kg/week for 4 weeks, i.p., plus RSV, 10 mg/kg/day for 28 days, OG), DOX + CUR group (DOX, 2.5 mg/kg/week for 4 weeks, i.p., plus CUR, 100 mg/kg/day for 28 days, OG) and control (CTR) group (0.9% saline solution weekly for 4 weeks, i.p., plus distilled water for 28 days, OG). Behavioral analyses (open field - OF - and the novel object recognition test - NORT) were performed. Brains were collected and analyzed by hematoxylin-eosin and luxol fast blue staining techniques and by immunohistochemistry for GFAP (glial fibrillary acidic protein) expression in astrocytes and Iba1 (ionized calcium-binding adaptor molecule 1) expression in microglia. DOX-injected rats presented short-term and long-term memory impairments as seen in the NORT at 3 and 24 h after habituation and increased GFAP and Iba1 expression, respectively, in astrocytes and microglia of the frontal cortex, hypothalamus and hippocampus. Such cognitive deficits were prevented by CUR at both periods and by RSV at 24 h. DOX-induced astrogliosis and microgliosis were avoided by RSV and CUR. No signs of demyelination or neuronal loss were found in any group. Thus, CUR and RSV prevented memory loss, astrogliosis and microgliosis induced by DOX monotherapy.

Short-term systemic methotrexate administration in rats induces astrogliosis and microgliosis.

Methotrexate (MTX), an antifolate drug, is widely used in chemotherapeutic protocols for metastatic and primary brain tumors and some autoimmune diseases. Its efficacy for brain tumors is limited by the high incidence of central nervous system (CNS) complications. This investigation aimed to observe the morphological effects, including astroglial and microglial responses, following systemic short-term MTX administration in adult rats. Male Wistar rats received 5 or 10 mg/kg/day of MTX by intraperitoneal route for 4 consecutive days (respectively, MTX5 and MTX10 groups) or the same volume of 0.9% saline solution (control group). On the 5th day, brain samples were collected for hematoxylin-eosin and luxol fast blue staining techniques, as well as for immunohistochemical staining for glial fibrillary acidic protein (GFAP) expression in astrocytes and Iba1 (ionized calcium binding adaptor molecule 1) for microglia in the frontal cortex, hippocampus, hypothalamus and molecular/granular layers of the cerebellum. Morphometric analyses were performed using Image Pro-Plus software. Brain levels of the proinflammatory cytokines TNF-α and IL-1ß were determined by ELISA. No signs of neuronal loss or demyelination were observed in all groups. Increased GFAP and Iba1 expression was found in all areas from the MTX groups, although it was slightly higher in the MTX10 group compared to the MTX5. Both TNF-α and IL-1ß levels were decreased in the MTX5 group compared to controls. In the MTX10 group, TNF-α decreased, although IL-1ß was increased relative to controls. MTX administration induced microglial reaction and astrogliosis in several CNS areas. In the MTX5 group, it apparently occurred in the presence of decreased proinflammatory cytokines.

Prenatal LPS induces sickness behaviour and decreases maternal and predatory behaviours after an LPS challenge.

Purpose: The influence of a challenge dose of lipopolysaccharide (LPS) on the behavioural selection between maternal (MB) and predatory behaviours (PB) of female rats prenatally treated with the same endotoxin or saline solution (F1 generation) were studied.Material and methods: Thus, in adult age, these female rats were mated and, at lactation days 5 or 6, the following groups were formed: (1) LPS + LPS group-female rats prenatally treated with LPS and received an LPS challenge dose; (2) S + LPS group-female rats prenatally treated with saline solution and received a challenge LPS dose (3) S + S group-females rats prenatally treated with saline which received a saline injection. MB, PB to cockroaches, exploratory behaviour, periaqueductal grey (PAG) expression of the astrocytic biomarker glial fibrillary acidic protein (GFAP), and corticosterone and TNF-alpha serum levels were evaluated.Results: Showed that: (1) relative to the S + S group, the LPS + S group showed decreased MB and slightly increased PB, without inducing sickness behaviour; (2) the LPS + LPS group showed decreased MB but few effects on PB; (3) there was increased sickness behaviour associated with increased TNF-alpha serum levels in the LPS + LPS group; (4) a significant increase in GFAP expression was observed in both LPS groups, which was greater in the LPS + LPS group and (5) no differences in the corticosterone of all groups.Conclusions: Prenatal LPS impaired the switch from MB to PB in female rats of the LPS + LPS group by increased sickness behaviour as well as an increase in plasmatic TNF-alpha levels inducing PAG astrogliosis.

Prevalence of Angiostrongylus cantonensis and Angiostrongylus costaricensis in Achatina fulica snails in the municipality of São Bernardo do Campo (SP, Brazil) / Prevalência de Angiostrongylus cantonensis e Angiostrongylus costaricensis em caramujos Achatina fulica na cidade de São Bernardo do Campo (SP, Brasil)

Angiostrongylus cantonensis e Angiostrongylus costaricensis são nematoides parasitas que residem em roedores e usam gastrópodes como hospedeiros intermediários. Achatina fulica, conhecida como caramujo-gigante-africano, é um hospedeiro intermediário que desempenha importante papel na dispersão de A. cantonensis e A. costaricensis, patógenos zoonóticos que causam, respectivamente, meningoencefalite eosinofílica e angiostrongilíase abdominal em humanos. O objetivo deste estudo foi o de coletar caramujos (A. fulica, n=90) de oito regiões diferentes (Rudge Ramos, Baeta Neves, Planalto, Demarchi, Dos Alvarengas, Batistini, Montanhão, Rio Grande) da cidade de São Bernardo do Campo (SP) para detecção molecular de A. cantonensis ou A. costaricensis pela técnica de reação em cadeia da polimerase (PCR). As amostras foram processadas em pools (n=25) segundo a região de coleta. Com exceção da região de Baeta Neves, as demais apresentaram caramujos infectados com larvas de nematoides. Seis regiões apresentaram amostras positivas para A. cantonensis. Quatorze (56%) das 25 amostras em pool apresentaram larvas de nematoides, e 52% delas (13/25) foram positivas para A. cantonensis. Nenhuma amostra positiva para A. costaricensis foi encontrada. A presença de A. fulica naturalmente infectada por A. cantonensis deve servir como um alerta para as autoridades de saúde pública sobre o risco potencial de infecção para humanos.(AU)

Food deprivation in F0 generation and hypercaloric diet in F1 generation reduce F2 generation astrogliosis in several brain areas after immune challenge.

AIMS: The effects of maternal food restriction during gestation in F0 generation followed by hypercaloric diet (HD) during puberty in F1 generation (F1HD) were investigated on astrocyte behavior of F2 generation. Also, the astrocyte behavior, after an immune challenge, was examined by the immunohistochemical expression of glial fibrillary acidic protein (GFAP) in several brain areas. METHODS: The body weight gain (BW) during development and in postnatal day (PND) 90-95, the retroperitoneal fat weight (RPF), and the size of larger and smaller adipocytes in the F1 generation were assessed to observe the effects of HD in female rats. The BW, RPF weight and size of smaller and larger adipocytes was also measured to evaluate the transgenerational effects of F0 and F1 diets on F2 generation, treated or not with lipopolysaccharide (LPS). KEY FINDINGS: The F1HD group exhibited a higher BW gain than the F1 treated with normocaloric diet (ND, group F1ND), from weaning to PND65. In the frontal/parietal cortex, nucleus accumbens, hypothalamic arcuate/periventricular nuclei, molecular/granular layers of the cerebellum areas, excepting the pons, GFAP expression was greater in F1HD group relative to F1ND group. A reduced GFAP expression was observed in both groups born from F1 generation fed with HD (groups F2HDS and F2HDLPS) in relation to F2 generation born from dams fed with ND (groups F2NDS and F2NDLPS), independently of LPS challenge. SIGNIFICANCE: These data show an attenuation of LPS effect on GFAP expression, probably by a transgenerational effect of both maternal food deprivation in F0 generation and HD in F1 generation.

Haematological reference of snakes: Amazon tree boa (Corallus hortulanus, Linnaeus, 1758) and Burmenese Python (Python bivittatus, Kuhl, 1820) in captive

Hematology has become important for making clinical diagnoses in snakes because maintenance techniques in captivity have been improving and increasing their life expectancy. The emergence of diseases in captivity requires the creation of parameters to understand the species in their healthy state. The possible association between the onset of neoplasia, immunosuppression, and viral infection are also important factors to consider. Thus, hematology is a fundamental tool for observing the responses of animals to diseases and treatments. The present study aims to study hematology between two species of snakes and compare the profiles observed with published results. Blood samples were collected from 16 male and female snakes: seven Corallus hortulanus from the family Boidae and nine Python bivittatus from the family Pythonidae belonging to the Biological Museum of the Butantan Institute, Sao Paulo, Brazil. Complete blood count results including blood smear, total erythrocyte count, leukocytes, and differential leukocyte count were evaluated. The data obtained in this study could help with the diagnosis, the treatment of snakes in captive conditions and in of nature conservation programs.

Haematological reference of snakes: Amazon tree boa (Corallus hortulanus, Linnaeus, 1758) and Burmenese Python (Python bivittatus, Kuhl, 1820) in captive

Hematology has become important for making clinical diagnoses in snakes because maintenance techniques in captivity have been improving and increasing their life expectancy. The emergence of diseases in captivity requires the creation of parameters to understand the species in their healthy state. The possible association between the onset of neoplasia, immunosuppression, and viral infection are also important factors to consider. Thus, hematology is a fundamental tool for observing the responses of animals to diseases and treatments. The present study aims to study hematology between two species of snakes and compare the profiles observed with published results. Blood samples were collected from 16 male and female snakes: seven Corallus hortulanus from the family Boidae and nine Python bivittatus from the family Pythonidae belonging to the Biological Museum of the Butantan Institute, Sao Paulo, Brazil. Complete blood count results including blood smear, total erythrocyte count, leukocytes, and differential leukocyte count were evaluated. The data obtained in this study could help with the diagnosis, the treatment of snakes in captive conditions and in of nature conservation programs.

Haematological reference of snakes: Amazon tree boa (Corallus hortulanus, Linnaeus, 1758) and Burmenese Python (Python bivittatus, Kuhl, 1820) in captive / Parâmetros hematológicos das serpentes: suaçuboia (Corallus hortulanus, Linnaeus, 1758) e píton birmanesa (Python bivittatus, Kuhl, 1820) em cativeiro

Hematology has become important for making clinical diagnoses in snakes because maintenance techniques in captivity have been improving and increasing their life expectancy. The emergence of diseases in captivity requires the creation of parameters to understand the species in their healthy state. The possible association between the onset of neoplasia, immunosuppression, and viral infection are also important factors to consider. Thus, hematology is a fundamental tool for observing the responses of animals to diseases and treatments. The present study aims to study hematology between two species of snakes and compare the profiles observed with published results. Blood samples were collected from 16 male and female snakes: seven Corallus hortulanus from the family Boidae and nine Python bivittatus from the family Pythonidae belonging to the Biological Museum of the Butantan Institute, São Paulo, Brazil. Complete blood count results including blood smear, total erythrocyte count, leukocytes, and differential leukocyte count were evaluated. The data obtained in this study could help with the diagnosis, the treatment of snakes in captive conditions and in of nature conservation programs.(AU)

A hematologia das serpentes tem se tornado algo de grande importância para o diagnóstico clínico, visto que as técnicas de manutenção em cativeiro vêm aumentando a expectativa de vida. O surgimento de doenças em cativeiro leva à necessidade de criar parâmetros para conhecer as espécies em seu estado hígido. A possível associação entre o surgimento de neoplasias, imunossupressão e infecção viral também é um importante fator a ser considerado. Assim, a hematologia é uma ferramenta fundamental para se observarem as respostas dos animais diante das doenças e dos tratamentos. Nesse contexto, o presente estudo tem como objetivo o estudo hematológico entre duas espécies de serpentes e a comparação dos perfis encontrados com a literatura atual. Foi coletado sangue de 16 serpentes de ambos os sexos da família Boidae: sete Corallus hortulanus, e da família Pythonidae: nove Python bivittatus, pertencentes ao Museu Biológico do Instituto Butantan, São Paulo, Brasil. Foram avaliados o hemograma completo com esfregaço sanguíneo, a contagem total de eritrócitos, os leucócitos e a contagem diferencial de leucócitos. Os dados obtidos neste estudo poderão auxiliar no diagnóstico e no tratamento de serpentes em cativeiro e em programas de conservação da natureza.(AU)

Transgenerational effects of a hypercaloric diet.

The effects of a maternal hypercaloric diet (HD) during puberty and early adulthood on neuroimmune aspects in offspring were investigated. In female rats of the F0 generation and male rats of the F1 generation, bodyweight (BW) gain, retroperitoneal fat (RPF) weight, the number of hypodermic adipocytes (HAs) and expression of glial fibrillary acidic protein (GFAP) were measured in hypothalamic astrocytes. On Postnatal Day 50, the F1 pups were challenged with lipopolysaccharide (LPS, 100µgkg-1, s.c.) or an equal volume of saline (S), and behaviour in the open field test was evaluated, as were plasma neuropeptide and cytokine concentrations. The maternal HD caused the female F0 rats to become overweight. The F1 offspring of dams fed the HD and challenged with saline (HDS group) exhibited increases in BW gain, RPF weight and in the number of large HAs and a decrease in GFAP immunoreactivity. F1 offspring of dams fed the HD and challenged with LPS (HDLPS group) exhibited decreases in BW gain, RPF weight and GFAP immunoreactivity, but no differences were observed in the number of larger and small HAs. Plasma tumour necrosis factor-α concentrations were high in the HDS and HDLPS groups. Thus, the maternal HD during puberty and early adulthood caused the F1 generation to become overweight despite the fact that they received a normocaloric diet. These results indicate a transgenerational effect of the HD that may occur, in part, through permanent changes in immune system programming. The attenuation of neuroinflammation biomarkers after LPS administration may have resulted in a decrease in the number of adipocytes, which, in turn, reduced cytokine, adipokine and chemokine levels, which are able to recruit inflammatory cells in adipose tissue.

Maternal food restriction in rats of the F0 generation increases retroperitoneal fat, the number and size of adipocytes and induces periventricular astrogliosis in female F1 and male F2 generations.

The present study investigated whether male offspring (F2 generation) from female rats (F1 generation) whose mothers (F0 generation) were food restricted during gestation inherit a phenotypic transgenerational tendency towards being overweight and obese in the juvenile period, in the absence of food restriction in the F1/F2 generations. Dams of the F0 generation were 40% food restricted during pregnancy. Bodyweight, the number and size of larger and small hypodermal adipocytes (HAs), total retroperitoneal fat (RPF) weight and the expression of glial fibrillary acidic protein (GFAP) in periventricular hypothalamic astrocytes (PHAs), as determined by immunohistochemistry, were evaluated in both generations. In the female F1 generation, there was low bodyweight gain only during the juvenile period (30-65 days of age), a decrease in the size of small adipocytes, an increase in the number of small adipocytes, an increase in RPF weight and an increase in GFAP expression in PHAs at 90-95 days of age. In males of the F2 generation at 50 days of age, there was increased bodyweight and RPF weight, and a small number of adipocytes and GFAP expression in PHAs. These data indicate that the phenotypic transgenerational tendency towards being overweight and obese was observed in females (F1) from mothers (F0) that were prenatally food restricted was transmitted to their male offspring.

Addressing conflicts of interest in the research paper: a societal demand in contemporary science?

In the last decade, dialogue between science and society has found a forum in an increasing number of publications on topics such as public engagement with science and public trust in science. Concerning the latter, issues that include cases of research misconduct, accountability in research, and conflicts of interest (COIs) have shaped global discussions on the communication of science. In the publication setting, the perception that hiding COIs and/or not managing them well may affect public trust in the research record has grown among editors. We conducted a search for editorials addressing COIs between 1989 and 2011, using four major databases: Medline/PubMed, Embase, Scopus, and Web of Knowledge. We explored the content of these editorials and the relationship they established between COIs and the public trust in science. Our results demonstrate that the relationship between disclosure of COIs and public trust in science has become a major concern among editors. We, thus, argue that COIs should be discussed more openly and frequently in graduate courses in the sciences, around the globe, not only in biomedical but also in non-biomedical areas. This is a critical issue in contemporary science, as graduate students are the future voices and decision-makers of the research community. Therefore, COIs, especially in the broader context of science and society, merit closer attention from policymakers, researchers, and educators. At times of great expectations for public engagement with science, mishandling of COIs may have undesirable consequences for public engagement with science and confidence in the scientific endeavor.

Addressing conflicts of interest in the research paper: a societal demand in contemporary science?

In the last decade, dialogue between science and society has found a forum in an increasing number of publications on topics such as public engagement with science and public trust in science. Concerning the latter, issues that include cases of research misconduct, accountability in research, and conflicts of interest (COIs) have shaped global discussions on the communication of science. In the publication setting, the perception that hiding COIs and/or not managing them well may affect public trust in the research record has grown among editors. We conducted a search for editorials addressing COIs between 1989 and 2011, using four major databases: Medline/PubMed, Embase, Scopus, and Web of Knowledge. We explored the content of these editorials and the relationship they established between COIs and the public trust in science. Our results demonstrate that the relationship between disclosure of COIs and public trust in science has become a major concern among editors. We, thus, argue that COIs should be discussed more openly and frequently in graduate courses in the sciences, around the globe, not only in biomedical but also in non-biomedical areas. This is a critical issue in contemporary science, as graduate students are the future voices and decision-makers of the research community. Therefore, COIs, especially in the broader context of science and society, merit closer attention from policymakers, researchers, and educators. At times of great expectations for public engagement with science, mishandling of COIs may have undesirable consequences for public engagement with science and confidence in the scientific endeavor.

Semi-quantitative analysis of the effects of cyclosporine on remyelination following gliotoxic injection in the brainstem / Análise semiquantitativa dos efeitos da ciclosporina na remielinização após injeção gliotóxica no tronco encefálico

The use of cyclosporine (CsA) has shown to induce an increase in the density of oligodendrocytes near remyelinating areas following the injection of ethidium bromide (EB), a demyelinating agent, in the rat brainstem. This study was designed in order to evaluate if CsA has the capacity of increasing remyelination. In this context, a comparison between the final balance of myelin repair in CsA treated and non-treated rats was assessed using a semi-quantitative method developed for documenting the extent and nature of remyelination in gliotoxic lesions. Wistar rats were submitted to intracisternal injection of 10 microliters of 0.1 percent EB. Some were treated during 31 days with CsA (group III - 10 mg/kg/day by 7 days and, thereafter, 3 times a week, with a minimal interval of 48 hours) by intraperitonial route. Others were not treated with CsA (group I). A control group was planned receiving into the cisterna pontis 10 microliters of 0.9 percent saline solution and following after that the same CsA administration protocol (group II). Results clearly demonstrate that in vivo administration of CsA after EB-demyelinating lesions stimulated oligodendrocyte remyelination (mean remyelination scores of 3.72±0.25 for oligodendrocytes and 1.04±0.39 for Schwann cells) compared to non-treated animals (3.13±0.71 and 1.31±0.62, respectively), although the mechanisms by which this positive CsA effect occurs are unclear.

O uso de ciclosporina (CsA) mostrou induzir um aumento na densidade de oligodendrócitos próximos a áreas de remielinização após injeção de brometo de etídio (EB), um agente desmielinizante, no tronco encefálico de ratos. Este estudo foi desenvolvido a fim de avaliar se a CsA possui a capacidade de acelerar a remielinização. Neste contexto, foi feita uma comparação entre o balanço final de reparo mielínico em ratos tratados ou não com CsA usando-se um método semiquantitativo desenvolvido para documentação da extensão e natureza da remielinização em lesões gliotóxicas. Ratos Wistar foram submetidos à injeção intracisternal de EB a 0,1 por cento. Alguns foram tratados durante 31 dias com CsA (grupo III - 10 mg/kg/dia por 7 dias e, após, 3 vezes por semana, com um intervalo mínimo de 48 horas entre as aplicações) por via intraperitoneal. Outros não foram tratados com CsA (grupo I). Um grupo controle foi desenvolvido recebendo, na cisterna pontina, 10 microlitros de solução salina e seguindo após o mesmo protocolo de administração de CsA (grupo II). Os resultados mostram claramente que a administração in vivo de CsA após lesões desmielinizantes induzidas pelo EB estimulou a remielinização por oligodendrócitos (escores médios de remielinização de 3,72±0,25 para oligodendrócitos e 1,04±0,39 para células de Schwann) em comparação aos animais não-tratados (3,13±0,71 e 1,31±0,62, respectivamente), embora os mecanismos pelos quais este efeito positivo da CsA ocorre sejam desconhecidos.