Acute Physical Stress Preconditions the Heart Against Ischemia/Reperfusion Injury Through Activation of Sympathetic Nervous System / Estresse Físico Agudo Precondiciona o Coração Contra a Injúria por Isquemia/Reperfusão Através da Ativação do Sistema Nervoso Simpático

Abstract Background: Stress is defined as a complicated state that related to homeostasis disturbances, over-activity of the sympathetic nervous system and hypothalamus-pituitary-adrenal axis responses. Cardiac preconditioning reduces myocardial damages. Objective: This study was designed to assess the cardioprotective effects of acute physical stress against ischemia/reperfusion (I/R) injury through the activation of the sympathetic nervous system. Methods: Thirty-two male Wistar rats were divided into four groups; (1) IR (n = 8): rats underwent I/R, (2) Acute stress (St+IR) (n = 8): physical stress induced 1-hour before I/R, (3) Sympathectomy (Symp+IR) (n = 8): chemical sympathectomy was done 24-hours before I/R and (4) Sympathectomy- physical stress (Symp+St+IR) (n = 8): chemical sympathectomy induced before physical stress and I/R. Chemical sympathectomy was performed using 6-hydroxydopamine (100 mg/kg, sc). Then, the hearts isolated and located in the Langendorff apparatus to induce 30 minutes ischemia followed by 120 minutes reperfusion. The coronary flows, hemodynamic parameters, infarct size, corticosterone level in serum were investigated. P < 0.05 demonstrated significance. Results: Physical stress prior to I/R could improve left ventricular developed pressure (LVDP) and rate product pressure (RPP) of the heart respectively, (63 ± 2 versus 42 ± 1.2, p < 0.05, 70 ± 2 versus 43 ± 2.6, p < 0.05) and reduces infarct size (22.16 ± 1.3 versus 32 ± 1.4, p < 0.05) when compared with the I/R alone. Chemical sympathectomy before physical stress eliminated the protective effect of physical stress on I/R-induced cardiac damages (RPP: 21 ± 6.6 versus 63 ± 2, p < 0.01) (LVDP: 38 ± 4.5 versus 43 ± 2.6, p < 0.01) (infarct size: 35 ± 3.1 versus 22.16 ± 1.3, p < 0.01). Conclusion: Findings indicate that acute physical stress can act as a preconditional stimulator and probably, the presence of sympathetic nervous system is necessary.

Resumo Fundamento: O estresse é definido como um estado complicado de distúrbios da homeostase, hiperatividade do sistema nervoso simpático e das respostas do eixo hipotálamo-hipófise-adrenal. O pré-condicionamento cardíaco diminui os danos do miocárdio. Objetivo: Esse estudo avaliou os efeitos cardioprotetores do estresse físico agudo contra a lesão por isquemia-reperfusão (I/R) através da ativação do sistema nervoso simpático. Métodos: Trinta e dois ratos machos Wistar foram divididos em quatro grupos; (1) IR (n = 8): ratos submetidos a I/R, (2) Estresse agudo (St+IR) (n = 8): estresse físico induzido 1 hora antes da I/R, (3) Simpatectomia (Symp+IR) (n = 8): a simpatectomia química foi realizada 24 horas antes da I/R e (4) Simpatectomia-estresse físico (Symp+St+IR) (n = 8): simpatectomia induzida antes do estresse físico e da I/R. A simpatectomia química foi realizada com 6-hidroxidopamina (100 mg/kg, SC). Em seguida, os corações foram isolados e colocados em aparato de Lagendorff por 30 minutos para induzir isquemia, seguida de reperfusão por 120 minutos. Os fluxos coronarianos, os parâmetros hemodinâmicos, o tamanho do infarto e os níveis de corticosterona plasmática foram investigados. Valores de p < 0,05 foram considerados significativos. Resultados: O estresse físico anterior à I/R pode melhorar a pressão desenvolvida no ventrículo esquerdo (PDVE) e duplo produto (DP), respectivamente, (63 ± 2 versus 42 ± 1,2, p < 0,05, 70 ± 2 versus 43 ± 2,6, p < 0,05) e reduzir o tamanho do infarto (22,16 ± 1,3 versus 32±1,4, p < 0,05) quando comparado com a I/R isoladamente. A simpatectomia química antes do estresse físico eliminou o efeito protetor do estresse físico sobre os danos cardíacos induzidos pela I/R (DP: 21 ± 6,6 versus 63 ± 2, p < 0,01) (PDVE: 38 ± 4,5 versus 43 ± 2,6, p < 0,01) (tamanho do infarto: 35 ± 3,1 versus 22,16 ± 1,3, p < 0,01). Conclusão: Os achados indicam que o estresse físico agudo pode funcionar como um estimulador pré-condicional e, provavelmente, a presença do sistema nervoso simpático é necessária.

Acute exercise inhibits gastric emptying of liquids in rats: influence of the NO-cGMP pathway

We previously found that acute exercise inhibited the gastric emptying of liquid in awake rats by causing an acid-base imbalance. In the present study, we investigated the involvement of the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, vasoactive intestinal peptide (VIP), and corticotropin-releasing factor (CRF) peptide in this phenomenon. Male rats were divided into exercise or sedentary group and were subjected to a 15-min swim session against a load (2.5 or 5% b.w.). The rate of gastric emptying was evaluated after 5, 10, or 20 min postprandially. Separate groups of rats were treated with vehicle (0.9% NaCl, 0.1 mL/100 g, ip) or one of the following agents: atropine (1.0 mg/kg, ip), the NO non-selective inhibitor Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME; 10.0 mg/kg, ip), or the selective cGMP inhibitor 1H-(1,2,4)oxadiazole[4,3-a]quinoxalin-1-one (ODQ; 5.0 mg/kg, ip), the i-NOS non-specific inhibitor (aminoguanidine; 10.0 mg/kg, ip), the corticotropin-releasing factor receptor antagonist (astressin; 100 µg/kg, ip), or the vasoactive intestinal peptide (VIP) receptor antagonist Lys1, Pro2,5, Arg3,4, Tyr6 (100 µg/kg, ip). Compared to sedentary rats, both the 2.5 and 5% exercise groups exhibited higher (P<0.05) values of blood lactate and fractional gastric dye recovery. Corticosterone and NO levels increased (P<0.05) in the 5% exercised rats. Pretreatment with astressin, VIP antagonist, atropine, L-NAME, and ODQ prevented the increase in gastric retention caused by exercise in rats. Acute exercise increased gastric retention, a phenomenon that appears to be mediated by the NO-cGMP pathway, CRF, and VIP receptors.

Social instigation and repeated aggressive confrontations in male Swiss mice: analysis of plasma corticosterone, CRF and BDNF levels in limbic brain areas / Instigação social e confrontos agressivos repetidos em camundongos Swiss machos: análise de corticosterona plasmática e dos níveis de CRF e BDNF em áreas cerebrais límbicas

Abstract Introduction: Agonistic behaviors help to ensure survival, provide advantage in competition, and communicate social status. The resident-intruder paradigm, an animal model based on male intraspecific confrontations, can be an ethologically relevant tool to investigate the neurobiology of aggressive behavior. Objectives: To examine behavioral and neurobiological mechanisms of aggressive behavior in male Swiss mice exposed to repeated confrontations in the resident intruder paradigm. Methods: Behavioral analysis was performed in association with measurements of plasma corticosterone of mice repeatedly exposed to a potential rival nearby, but inaccessible (social instigation), or to 10 sessions of social instigation followed by direct aggressive encounters. Moreover, corticotropin-releasing factor (CRF) and brain-derived neurotrophic factor (BNDF) were measured in the brain of these animals. Control mice were exposed to neither social instigation nor aggressive confrontations. Results: Mice exposed to aggressive confrontations exhibited a similar pattern of species-typical aggressive and non-aggressive behaviors on the first and the last session. Moreover, in contrast to social instigation only, repeated aggressive confrontations promoted an increase in plasma corticosterone. After 10 aggressive confrontation sessions, mice presented a non-significant trend toward reducing hippocampal levels of CRF, which inversely correlated with plasma corticosterone levels. Conversely, repeated sessions of social instigation or aggressive confrontation did not alter BDNF concentrations at the prefrontal cortex and hippocampus. Conclusion: Exposure to repeated episodes of aggressive encounters did not promote habituation over time. Additionally, CRF seems to be involved in physiological responses to social stressors.

Resumo Introdução: Comportamentos agonísticos ajudam a garantir a sobrevivência, oferecem vantagem na competição e comunicam status social. O paradigma residente-intruso, modelo animal baseado em confrontos intraespecíficos entre machos, pode ser uma ferramenta etológica relevante para investigar a neurobiologia do comportamento agressivo. Objetivos: Analisar os mecanismos comportamentais e neurobiológicos do comportamento agressivo em camundongos Swiss machos expostos a confrontos repetidos no paradigma residente-intruso. Métodos: A análise comportamental foi realizada em associação com medidas de corticosterona plasmática em camundongos expostos repetidamente a um rival em potencial próximo, porém inacessível (instigação social), ou a 10 sessões de instigação social seguidas de encontros agressivos diretos. Além disso, o fator de liberação de corticotrofina (CRF) e o fator neurotrófico derivado do cérebro (BNDF) foram medidos no encéfalo desses animais. Camundongos controles não foram expostos à instigação social ou confrontos agressivos. Resultados: Os camundongos expostos a confrontos agressivos exibiram um padrão semelhante de comportamentos agressivos e não agressivos típicos da espécie na primeira e na última sessão. Em contraste com instigação social apenas, confrontos agressivos repetidos promoveram aumento na corticosterona plasmática. Após 10 sessões de confrontos agressivos, os camundongos apresentaram uma tendência não significativa de redução dos níveis de CRF no hipocampo, que se correlacionaram inversamente com os níveis plasmáticos de corticosterona. Por outro lado, sessões repetidas de instigação social ou confronto agressivo não alteraram as concentrações de BDNF no córtex pré-frontal e hipocampo. Conclusão: A exposição a episódios repetidos de encontros agressivos não promoveu habituação ao longo do tempo. Adicionalmente, o CRF parece estar envolvido nas respostas fisiológicas aos estressores sociais.

Gonadotrophic, prolactin, corticosterone, and gonadal hormones levels over 15 months in Giant Amazon River Turtles - Podocnemis expansa (Schweigger, 1812) (Testudines: Podocnemididae), in captive conditions / Gonadotrofinas, prolactina, corticosterona, e as hormonas sexuais durante 15 meses de Tartarugas da Amazônia - Podocnemis expansa (Schweigger, 1812) (Testudines: Podocnemididae), em condições de cativeiro

Abstract In order to achieve successful captive breeding the Podocnemis expansa, it is necessary to study their reproductive endocrinology. The purpose of this research was to evaluate and characterize plasma concentrations in gonadotrophic, gonadic, corticosterone and prolactin hormones from Giant Amazon Turtles under captive conditions. Blood samples were collected over a 15 month period. The samples were assayed by the use of radioimmunoassay, prolactin, corticosterone, LH, FSH, testosterone, 17β-estradiol and progesterone. We verified significant seasonal pattern increase in 17β-estradiol levels and decrease in progesterone levels in the course of a year, which indicates vitellogenesis. This is related to normal ovarian cycles and possibly to the functional integrity of the hypothalamus-pituitary-gonad axis of captive females. There were negative correlations between testosterone and corticosterone in the male samples, suggestive of stress (management stress) on the reproductive system. The plasma concentrations of gonadotrophic, gonadic, prolactin and corticosterone hormones may be used as a reference for further research and possible therapeutic approaches. The data collected during this research are unprecedented for this species and may serve as a reference for future research regarding the reproductive cycle of this turtle, also allowing reproductive management while in captivity. Information about these hormones must be gathered from wild populations during different periods of the year for better clarification of the reproductive physiology of this species.

Resumo Com o objetivo de obter reprodução em cativeiro de Podocnemis expansa, é necessário reunir o conhecimento a respeito de sua endocrinologia reprodutiva. O objetivo deste trabalho foi avaliar e caracterizar as concentrações plasmáticas de hormônios gonadotróficos, gonadais, corticosterona e prolactina em Tartarugas da Amazônia em condições de cativeiro. Amostras de sangue foram coletadas durante 15 meses. As amostras foram ensaiadas pelo uso de um radioimunoensáio, prolactina, corticosterona, LH, FSH, testosterona, 17β-estradiol e progesterona. Verificou-se aumento de padrão sazonal significativo nos níveis de 17β-estradiol e diminuição dos níveis de progesterona ao longo do ano, o que indica o recrutamento folicular. Isto está relacionado com ciclos ovarianos normais e possivelmente para a integridade funcional do eixo hipotálamo-hipófise-gônadas de fêmeas em cativeiro. Houve correlação negativa entre testosterona e corticosterona nas amostras do sexo masculino, sugestivos de efeito do estresse de manejo sobre o sistema reprodutivo. As concentrações plasmáticas de hormônios gonadotrofinas, gonadais, prolactina e hormônios corticosterona pode ser usado como referência para futuras pesquisas e possíveis abordagens terapêuticas. Os dados médios coletados durante a pesquisa são inéditos para a espécie e pode servir como referência para futuras pesquisas sobre o sistema reprodutivo da tartaruga, também permitindo manejo reprodutivo em cativeiro. Informações sobre esses hormônios devem ser recolhidas a partir de natureza selvagem em diferentes períodos do ano para melhor esclarecimento da fisiologia da reprodução desta espécie.

La separación materna durante la lactancia altera los niveles basales del sistema neuroendocrino en ratas adolescentes y adultas / Maternal separation during nursing alters basal neuroendocrine levels in juvenile and adult rats

Introducción. En diversos modelos animales, incluido el de la separación materna durante la lactancia, se ha demostrado que las experiencias tempranas adversas, como el maltrato, el abandono materno y el estrés psicosocial, pueden favorecer el desarrollo de algunas enfermedades mentales, pero no se han descrito completamente varios de los cambios que se producen en el sistema neuroendocrino. Objetivo. Determinar si la separación materna durante la lactancia modificaba los niveles basales de neurohormonas como la corticosterona, la corticotropina (ACTH), la oxitocina y la vasopresina (ADH), en ratas jóvenes (35 días) y adultas (90 días). Materiales y métodos. Se separaron ratas Wistar de sus madres durante dos periodos de tres horas diarias a lo largo de los 21 días de lactancia. A los 35 y 90 días se tomaron muestras de los grupos de las ratas de control y de las separadas de la madre, para obtener el suero y posteriormente medir cada una de las hormonas mediante un ensayo inmunoenzimático. Resultados. Las concentraciones de corticosterona fueron mayores en las hembras adultas de control que en el resto de los grupos, y menores en los machos adultos de control. Las de ACTH fueron mayores en los machos y hembras jóvenes separadas de la madre que en los grupos de adultos. Los niveles de oxitocina fueron significativamente mayores en las hembras adultas separadas de la madre que en los otros grupos y significativamente menores en los machos adultos. En cuanto a la vasopresina, los grupos separados de la madre tuvieron concentraciones menores, en comparación con los grupos de jóvenes y adultos de control. Conclusiones. Estos resultados muestran que el estrés temprano al que fueron sometidas las ratas, produjo cambios en las respuestas del eje hipotálamo-hipófisis-suprarrenal, las cuales variaron según el sexo y la edad.

Introduction: Work with different animal models including that of maternal separation during nursing has shown that early adverse experiences such as abuse, maternal abandonment and psychosocial stress may favor the development of various psychopathologies. However, several neuroendocrine changes have not been completely described yet. Objective: To establish whether maternal separation during nursing modifies the basal levels of neurohormones such as corticosterone, ACTH, oxytocin and vasopressin in juvenile and adult rats (aged 35 and 90 days, respectively). Materials and methods: Wistar rats were separated from their mothers for two periods of 3 hours per day during the 21 days of nursing. Once these rats had reached 35 and then 90 days of age, blood samples were taken from both the separated and control groups to obtain serum for immunoenzymatic assays and measure the levels of each of the hormones. Results: Concentrations of corticosterone were higher in control adult females in comparison with the rest of the groups and lower in the control adult males. Those of ACTH were higher in the separated young males and females than in the adult groups. Oxytocin levels were significantly higher in the separated adult females in comparison with the other groups and significantly lower in the adult males. With respect to vasopressin, the separated groups had lower concentrations than the young and adult control groups. Conclusions: These results show that the early stress to which rats were submitted produced changes in the basal responses of the hypothalamic-pituitary-adrenal axis, that these responses were distinct in males and females and that they also differed according to age.

Mesenteric hypoperfusion and inflammation induced by brain death are not affected by inhibition of the autonomic storm in rats

OBJECTIVES: Brain death is typically followed by autonomic changes that lead to hemodynamic instability, which is likely associated with microcirculatory dysfunction and inflammation. We evaluated the role of the microcirculation in the hemodynamic and inflammatory events that occur after brain death and the effects of autonomic storm inhibition via thoracic epidural blockade on mesenteric microcirculatory changes and inflammatory responses. METHODS: Male Wistar rats were anesthetized and mechanically ventilated. Brain death was induced via intracranial balloon inflation. Bupivacaine (brain death-thoracic epidural blockade group) or saline (brain death group) infusion via an epidural catheter was initiated immediately before brain death induction. Sham-operated animals were used as controls (SH group). The mesenteric microcirculation was analyzed via intravital microscopy, and the expression of adhesion molecules was evaluated via immunohistochemistry 180 min after brain death induction. RESULTS: A significant difference in mean arterial pressure behavior was observed between the brain death-thoracic epidural blockade group and the other groups, indicating that the former group experienced autonomic storm inhibition. However, the proportion of perfused small vessels in the brain death-thoracic epidural blockade group was similar to or lower than that in the brain death and SH groups, respectively. The expression of intercellular adhesion molecule 1 was similar between the brain death-thoracic epidural blockade and brain death groups but was significantly lower in the SH group than in the other two groups. The number of migrating leukocytes in the perivascular tissue followed the same trend for all groups. CONCLUSIONS: Although thoracic epidural blockade effectively inhibited the autonomic storm, it did not affect mesenteric hypoperfusion or inflammation induced by brain death. .

Problemas bioéticos en la investigación de nuevas vacunas: ¿obedecen a razones de salud pública? / Bioethical problems in researching new vaccines: Do they respond to public health reasons?

Los problemas éticos de las investigaciones sobre vacunas han crecido en las últimas décadas en frecuencia y magnitud debido a la posición dominante de la industria farmacéutica en el desarrollo de esos estudios. Las tradicionales cuestiones de seguridad y eficacia se han visto agravadas por el conflicto de intereses introducido por la competencia comercial en un mercado a escala global de miles de millones de dólares. La integridad profesional de los investigadores, la responsabilidad moral de los patrocinadores, y la regulación y control por parte de los Estados nacionales, se muestra cuestionada en varios ejemplos. Los resultados de estos cambios son las amenazas a la protección de los derechos de las personas incluidas en estas investigaciones y el discutible progreso que resulta para la salud pública.

The ethical problems in vaccine research have grown in frequency and magnitude in last decades, due to the dominant place of the pharmaceutical industry in the development of such studies. Traditional issues of security and efficacy have been aggravated by the conflicts of interests introduced by commercial competition in a global market worth billions of dollars. We present here a few examples in which the professional integrity of researchers, the moral responsibility of sponsors, and the public regulation and control by national States are put into question. The consequences of these changes represent serious threats to the rights of people included in these studies as well as disputable progress for public health.

The Idealized Brazilian Health System versus the real one: contributions from the nursing field / O Sistema Único de Saúde idealizado versus o realizado: contribuições da Enfermagem / El Sistema Único de Salud idealizado versus el realizado: contribuciones de la Enfermería

OBJECTIVE: to identify the perceptions of professionals working in a facility connected with the Brazilian Unified Health System - SUS in regard to what they know, think and talk about public health policy. METHOD: this exploratory-descriptive study with a qualitative nature was conducted with 28 professionals working in a facility connected with the SUS. Data were collected through interviews with guiding questions and analyzed through the thematic content analysis technique. RESULTS: coded and interpreted data resulted in three thematic axes: The SUS - perfect web that does not work in practice; The recurrent habit of complaining about the SUS; The need to rethink the way of thinking about, acting in and managing the SUS. CONCLUSION: the professionals working for the SUS are aware of the principles and guidelines that govern the Brazilian health system, however, they reproduce a dichotomous and linear model of conception and practice strongly linked to the thinking of society in general. .

OBJETIVO: conhecer a percepção de profissionais que atuam em uma instituição conveniada com o Sistema Único de Saúde sobre o que sabem, pensam e falam dessa política pública de saúde. MÉTODO: trata-se de estudo exploratório-descritivo, de caráter qualitativo, realizado com 28 profissionais que atuam em uma instituição conveniada com o Sistema Único de Saúde. Os dados foram coletados por meio de entrevistas com questões norteadoras e analisados pela técnica de análise de conteúdo temática. RESULTADOS: os dados codificados e interpretados resultaram em três eixos temáticos: Sistema Único de Saúde - teia perfeita que não funciona na prática; o recorrente hábito de reclamar do Sistema Único de Saúde; a necessidade de repensar o modo de pensar, atuar e gerir o Sistema Único de Saúde. CONCLUSÃO: os profissionais que atuam no Sistema Único de Saúde têm conhecimento dos princípios e diretrizes que regem o sistema de saúde nacional, no entanto, reproduzem um modelo de concepção e atuação dicotômico, pontual e linear ainda fortemente vigente no pensar da sociedade em geral. .

OBJETIVO: conocer la percepción de profesionales que actúan en una institución que tiene convenio con el Sistema Único de Salud - SUS sobre lo que saben, piensan y hablan de esta política pública de salud. MÉTODO: se trata de un estudio exploratorio descriptivo, de carácter cualitativo, realizado con 28 profesionales que actúan en una institución que tiene convenio con el SUS. Los datos fueron recolectados por medio de entrevistas con preguntas orientadoras y analizados con la técnica de análisis de contenido temático. RESULTADOS: los datos codificados y interpretados resultaron en tres ejes temáticos: SUS - red perfecta que no funciona en la práctica; el recurrente hábito de reclamar del SUS; y la necesidad de repensar el modo de pensar, actuar y administrar el SUS. CONCLUSIÓN: los profesionales que actúan en el SUS tienen conocimiento de los principios y directrices que gobiernan el sistema de salud nacional, sin embargo, reproducen un modelo de concepción y actuación dicotómico, puntual, linear y además fuertemente vigente en el pensar de la sociedad en general. .

Housing under the pyramid reduces susceptibility of hippocampal CA3 pyramidal neurons to prenatal stress in the developing rat offspring.

Mother-offspring interaction begins before birth. The foetus is particularly vulnerable to environmental insults and stress. The body responds by releasing excess of the stress hormone cortisol, which acts on glucocorticoid receptors. Hippocampus in the brain is rich in glucocorticoid receptors and therefore susceptible to stress. The stress effects are reduced when the animals are placed under a model wooden pyramid. The present study was to first explore the effects of prenatal restraint-stress on the plasma corticosterone levels and the dendritic arborisation of CA3 pyramidal neurons in the hippocampus of the offspring. Further, to test whether the pyramid environment would alter these effects, as housing under a pyramid is known to reduce the stress effects, pregnant Sprague Dawley rats were restrained for 9 h per day from gestation day 7 until parturition in a wire-mesh restrainer. Plasma corticosterone levels were found to be significantly increased. In addition, there was a significant reduction in the apical and the basal total dendritic branching points and intersections of the CA3 hippocampal pyramidal neurons. The results thus suggest that, housing in the pyramid dramatically reduces prenatal stress effects in rats.

Effects of chronic stress and high-fat diet on metabolic and nutritional parameters in Wistar rats / Efeitos do estresse crônico e da dieta rica em gordura sobre os parâmetros metabólicos e nutricionais em ratos Wistar

OBJECTIVE: The aim of this study was assess the role of chronic stress on the metabolic and nutritional profile of rats exposed to a high-fat diet. MATERIALS AND METHODS: Thirty-day-old male Wistar rats (70-100 g) were distributed into four groups: normal-diet (NC), chronic stress (St), high-fat diet (HD), and chronic stress/high-fat diet (HD/St). Stress consisted at immobilization during 15 weeks, 5 times per week, 1h per day; and exposure to the high-fat diet lasted 15 weeks. Nutritional and metabolic parameters were assessed. The level of significance was 5%. RESULTS: The HD group had final body weight, total fat, as well as insulin and leptin increased, and they were insulin resistant. The St and HD/St had arterial hypertension and increased levels of corticosterone. Stress blocked the effects of the high-fat diet. CONCLUSION: Chronic stress prevented the appearance of obesity. Our results help to clarify the mechanisms involved in metabolic and nutritional dysfunction, and contribute to clinical cases linked to stress and high-fat diet.

OBJETIVO: Avaliar o papel do estresse crônico sobre parâmetros metabólicos e nutricionais de ratos expostos à dieta rica em gordura. MATERIAIS E MÉTODOS: Ratos Wistar machos (30 dias de idade/70-100 g) foram distribuídos em quatro grupos: dieta-normal (NC), estresse crônico (St), dieta rica em gordura (HD) e estresse crônico/dieta rica em gordura (HD/St). O estresse consistiu em imobilização durante 15 semanas, 5 vezes por semana 1h por dia e a dieta rica em gordura foi oferecida por 15 semanas. Parâmetros nutricionais e metabólicos foram avaliados. O nível de significância foi de 5%. RESULTADOS: HD tiveram peso corpóreo, gordura total e níveis de insulina e leptina aumentados e foram resistentes à insulina. Os grupos St e HD/St manifestaram hipertensão e níveis séricos de corticosterona elevados. O estresse bloqueou os efeitos da dieta. CONCLUSÃO: O estresse impediu o surgimento dela. Nossos resultados ajudam compreender os mecanismos envolvidos na disfunção metabólica e nutricional e contribuem para casos clínicos de estresse e dietas ricas em gorduras.

Brief daily postpartum separations from the litter alter dam response to psychostimulants and to stress

Neonatal handling induces several behavioral and neurochemical alterations in pups, including decreased responses to stress and reduced fear in new environments. However, there are few reports in the literature concerning the behavioral effects of this neonatal intervention on the dams during the postpartum period. Therefore, the aim of the current study was to determine if brief postpartum separation from pups has a persistent impact on the dam's stress response and behavior. Litters were divided into two neonatal groups: 1) non-handled and 2) handled [10 min/day, from postnatal day (PND) 1 to 10]. Weaning occurred at PND 21 when behavioral tasks started to be applied to the dams, including sweet food ingestion (PND 21), forced swimming test (PND 28), and locomotor response to a psychostimulant (PND 28). On postpartum day 40, plasma was collected at baseline for leptin assays and after 1 h of restraint for corticosterone assay. Regarding sweet food consumption, behavior during the forced swimming test or plasma leptin levels did not differ between dams briefly separated and non-separated from their pups during the postpartum period. On the other hand, both increased locomotion in response to diethylpropion and increased corticosterone secretion in response to acute stress were detected in dams briefly separated from their pups during the first 10 postnatal days. Taken together, these findings suggest that brief, repeated separations from the pups during the neonatal period persistently impact the behavior and induce signs of dopaminergic sensitization in the dam.

Estresse crônico melhora a função miocárdica sem alterar a atividade do canal-L para Ca+2 em ratos / Chronic stress improves the myocardial function without altering L-type Ca+2 channel activity in rats

FUNDAMENTO: O estresse crônico está associado à remodelação cardíaca; entretanto, os mecanismos permanecem a ser descobertos. OBJETIVO: A proposta deste estudo foi testar a hipótese de que o estresse crônico promove disfunção cardíaca associada a depressão da atividade do canal-L para Ca2+. M MÉTODOS: Ratos Wistar machos com 30 dias de idade (70 - 100 g) foram distribuídos dentro de dois grupos: controle (C) e estresse crônico (St). O estresse consistiu na imobilização durante 15 semanas, cinco vezes por semana, 1 h por dia. A função cardíaca foi avaliada pela performance do ventrículo esquerdo por meio do ecocardiograma e pelo músculo papilar ventricular isolado. A função do músculo papilar foi avaliada em condição basal e com manobras inotrópicas, como: pós-pausa e elevação na concentração extracelular de Ca2+, na presença ou ausência de um bloqueador específico de canal-L para Ca2+. RESULTADOS: O estresse ficou caracterizado por hipertrofia das glândulas adrenais, aumento nos níveis de corticosterona circulante e por hipertensão arterial. Ainda, o estresse crônico gerou hipertrofia ventricular esquerda. O estresse crônico foi capaz de melhorar a resposta no músculo papilar para manobras inotrópicas positivas. A melhora de função não esteve associada com o canal-L para Ca2+. CONCLUSÃO: O estresse produziu hipertrofia cardíaca; entretanto, nos estudos de músculo papilar isolado, as manobras inotrópicas positivas potencializaram a função cardíaca em ratos estressados, sem o envolvimento do canal-L para Ca2+. Assim os mecanismos responsáveis permanecem incertos para alterações no influxo de Ca2+.

BACKGROUND: Chronic stress is associated with cardiac remodeling; however the mechanisms have yet to be clarified. OBJECTIVE: The purpose of this study was test the hypothesis that chronic stress promotes cardiac dysfunction associated to L-type calcium Ca2+ channel activity depression. METHODS: Thirty-day-old male Wistar rats (70 - 100 g) were distributed into two groups: control (C) and chronic stress (St). The stress was consistently maintained at immobilization during 15 weeks, 5 times per week, 1h per day. The cardiac function was evaluated by left ventricular performance through echocardiography and by ventricular isolated papillary muscle. The myocardial papillary muscle activity was assessed at baseline conditions and with inotropic maneuvers such as: post-rest contraction and increases in extracellular Ca2+ concentration, in presence or absence of specific blockers L-type calcium channels. RESULTS: The stress was characterized for adrenal glands hypertrophy, increase of systemic corticosterone level and arterial hypertension. The chronic stress provided left ventricular hypertrophy. The left ventricular and baseline myocardial function did not change with chronic stress. However, it improved the response of the papillary muscle in relation to positive inotropic stimulation. This function improvement was not associated with the L-type Ca2+ channel. CONCLUSION: Chronic stress produced cardiac hypertrophy; however, in the study of papillary muscle, the positive inotropic maneuvers potentiated cardiac function in stressed rats, without involvement of L-type Ca2+ channel. Thus, the responsible mechanisms remain unclear with respect to Ca2+ influx alterations.

Changes in prolactin secretion in the short- and long-term after adrenalectomy / Efeito da evolução temporal da adrenalectomia na secreção de prolactina

OBJECTIVE: To evaluate the modulation of the hypothalamus-pituitary-adrenal axis (HPA) on prolactin secretion in rats after adrenalectomy (ADX). MATERIALS AND METHODS: Plasma corticosterone, ACTH, and prolactin concentrations were measured by radioimmunoassay in rats after bilateral ADX in the short- (3 hours and 1day) and long-term (3, 7, and 14 days). RESULTS: Animals that underwent ADX showed undetectable corticosterone levels and a triphasic ACTH response with a transient increase (3h), a decrease (1d), and further increase in the long-term after ADX. Sham animals showed a marked increase in corticosterone and ACTH levels three hours after surgery, with a decrease to basal levels thereafter. Plasma prolactin levels were not changed after ADX. CONCLUSION: There are different points of equilibrium in the HPA axis after the glucocorticoid negative feedback is removed. Prolactin plasma secretion is not altered in the short or long- term after ADX, suggesting that the peptidergic neurons essential for prolactin release are not activated after ADX.

OBJETIVO: Avaliar a modulação do eixo hipotálamo-hipófise-adrenal (HHA) sobre a secreção de prolactina após adrenalectomia (ADX). MATERIAIS E MÉTODOS: Quantificamos por RIE corticosterona, ACTH e prolactina plasmáticos em ratos após curtos (3 horas e 1 dia) e longos (3, 7 e 14 dias) períodos de ADX bilateral. RESULTADOS: Animais ADX mostraram níveis indetectáveis de corticosterona. As concentrações plasmáticas de ACTH apresentaram resposta trifásica: aumento transitório (3h), diminuição (1d) e novo aumento após longos períodos de ADX. Animais Sham mostraram aumento de corticosterona/ACTH após três horas de cirurgia, diminuindo posteriormente aos níveis basais. As concentrações plasmáticas de prolactina não se alteraram após ADX. CONCLUSÃO: Existem diferentes pontos de equilíbrio do eixo HHA após a remoção da retroalimentação negativa exercida pelos glicocorticoides. A secreção de prolactina não se alterou após curtos/longos períodos de ADX, sugerindo que os neurônios peptidérgicos essenciais para a liberação de prolactina não estão ativados durante os diferentes períodos de ADX.

Effects of heat stress on endocrine functions & behaviour in the pre-pubertal rat.

Background & objectives: Heat stress related hyperthermia may cause damage to various organ systems. There are very few studies on the effects of hyperthermia on the endocrine system. We therefore, investigated effects of exogenously induced hyperthermia on adrenal, testicular and thyroid functions and behavioural alterations in pre-pubertal male Sprague-Dawley rats. Methods: Three groups of 30-day old rats (n=7 per group) were used. Body temperature was increased to 39°C (Group I) and 41°C (Group II) in a hyperthermia induction chamber for 30 min. The rats in the Group III served as control (36 °C). All animals received saline and were decapitated 48 h after the experiments. Serum free triiodothyronin (fT3), free thyroxine (fT4), total testosterone and dehydroepiandrosterone sulphate (DHEA-S) levels were determined by chemiluminescence assay, and corticosterone by enzyme immunoassay. Testes, pituitary and adrenal glands were dissected out and processed for histopathological examination. To assess activity and anxiety of the animals, the open field test and elevated-0-maze test, respectively, were used in all groups 24 h before (day 29) and after (day 31) hyperthermia induction. Results: Serum corticosterone levels (3.22±1.3) were significantly reduced in the 39°C (1.3±0.9) and 41°C (1.09±0.7) hyperthermia groups (P<0.01) compared to controls. Serum levels of thyroid hormones did not significantly differ among the groups. DHEA-S and testosterone values were below the limit of detection in all groups. Histopathological examination revealed that there was mild hydropic degeneration in the pituitary and adrenal glands. Apoptotic germ cells were seen in the seminiferous tubules of pre-pubertal male rats exposed to hyperthermia (41°C). Progression time in the open field test was significantly decreased and anxiety test scores increased in animals exposed to 39°C compared to the control group (P<0.01). These parameters were more pronounced in the 41°C hyperthermia group. Interpretation & conclusions: Our results show that heat exposure-induced stress may cause delayed reduction in serum corticosterone levels which may be associated with behavioural deficits in pre-pubertal male rats.

Paradoxical effects of brain death and associated trauma on rat mesenteric microcirculation: an intravital microscopic study

OBJECTIVE: Experimental findings support clinical evidence that brain death impairs the viability of organs for transplantation, triggering hemodynamic, hormonal, and inflammatory responses. However, several of these events could be consequences of brain death-associated trauma. This study investigated microcirculatory alterations and systemic inflammatory markers in brain-dead rats and the influence of the associated trauma. METHOD: Brain death was induced using intracranial balloon inflation; sham-operated rats were trepanned only. After 30 or 180 min, the mesenteric microcirculation was observed using intravital microscopy. The expression of Pselectin and ICAM-1 on the endothelium was evaluated using immunohistochemistry. The serum cytokine, chemokine, and corticosterone levels were quantified using enzyme-linked immunosorbent assays. White blood cell counts were also determined. RESULTS: Brain death resulted in a decrease in the mesenteric perfusion to 30 percent, a 2.6-fold increase in the expression of ICAM-1 and leukocyte migration at the mesentery, a 70 percent reduction in the serum corticosterone level and pronounced leukopenia. Similar increases in the cytokine and chemokine levels were seen in the both the experimental and control animals. CONCLUSION: The data presented in this study suggest that brain death itself induces hypoperfusion in the mesenteric microcirculation that is associated with a pronounced reduction in the endogenous corticosterone level, thereby leading to increased local inflammation and organ dysfunction. These events are paradoxically associated with induced leukopenia after brain damage.

A high corticosterone/DHEA-s ratio in young rats infected with Trypanosoma cruzi is associated with increased susceptibility

We have previously established that young male rats are more susceptible to the effects of Trypanosoma cruzi infection than adult rats. To explore underlying age-associated differences in disease outcome, we simultaneously assessed hormone levels and cytokine release throughout the acute infection period in young and adult rats infected with T. cruzi. Young rats were inoculated with 1 x 10(6) and adult rats with 7 x 10(6) blood trypomastigotes, according to their relative body weight. At zero, seven, 14, 21 and 28 days after infection, blood was collected for the determination of gonadal and adrenal hormones, tumor necrosis factor α (TNF-α), interleukin (IL)-10 and specific IgM and IgG subtypes. Young animals displayed significantly higher parasitaemia values and an endocrine pattern that was characterised by elevated values in corticosterone (CT) and the CT/dehydroepiandrosterone-sulfate ratio, which favours immunosuppression and susceptibility. In contrast, adult male rats were able to restrict the parasite burden, which likely resulted from increased IgG antibody synthesis and oestradiol levels. Adult rats also showed a reduced TNF-α/IL-10 ratio and less tissue damage. We conclude that young animals exhibited increased vulnerability to T. cruzi infection compared with adults and this is associated with an unsuitable immunoendocrine milieu.

Differential behavioral outcomes of 3,4-methylenedioxymethamphetamine (MDMA-ecstasy) in anxiety-like responses in mice

Anxiolytic and anxiogenic-like behavioral outcomes have been reported for methylenedioxymethamphetamine (MDMA or ecstasy) in rodents. In the present experiment, we attempted to identify behavioral, hormonal and neurochemical outcomes of MDMA treatment to clarify its effects on anxiety-related responses in 2-month-old Balb/c male mice (25-35 g; N = 7-10 mice/group). The behavioral tests used were open field, elevated plus maze, hole board, and defensive behavior against predator odor. Moreover, we also determined striatal dopamine and dopamine turnover, and serum corticosterone levels. MDMA was injected ip at 0.2, 1.0, 5.0, 8.0, 10, or 20 mg/kg. MDMA at 10 mg/kg induced the following significant (P < 0.05) effects: a) a dose-dependent increase in the distance traveled and in the time spent moving in the open field; b) decreased exploratory activity in the hole board as measured by number of head dips and time spent in head dipping; c) increased number of open arm entries and increased time spent in open arm exploration in the elevated plus maze; d) increased time spent away from an aversive stimulus and decreased number of risk assessments in an aversive odor chamber; e) increased serum corticosterone levels, and f) increased striatal dopamine level and turnover. Taken together, these data suggest an anxiogenic-like effect of acute MDMA treatment, despite the fact that behavioral anxiety expression was impaired in some of the behavioral tests used as a consequence of the motor stimulating effects of MDMA.

comparison of the effects of acute swimming stress on plasma corticosterone and leptin concentration in male and female rats

The aim of this study was to investigate the effect of acute swimming stress on plasma corticosterone and leptin levels in female and male rats. Thirty- seven adult male [n=20] and female [n=20] Sprague Dawley rats [200-250 g weight] were used. The leptin and corticosterone levels were measured following swimming stress [10 minutes] or no stress. Plasma leptin and corticosterone were measured by ELISA system. The plasma leptin and corticosterone levels were significantly increased in female and male rats by swimming stress. Plasma leptin level was not correlated significantly with plasma corticosterone in all groups. There were no sex differences in leptin level among stressed and non stressed rats. The results suggest that changes in plasma leptin level could not be associated with stimulation of corticosterone secretion from adrenal glands and leptin secretion is not sex dependent

effect of morphine consumption on plasma corticosteron concentration and placenta development in pregnant rats

Previous studies have shown that morphine consumption during pregnancy may delay embryo development or cause abnormal nervous system function. The present study focused on the effect of maternal morphine consumption on development of placenta and blood corticosteron concentration in addictive pregnant mothers. 24 female rats, 170-200g weight, were used. The experimental groups after pregnancy received an oral dose of 0.05 mg/ml of morphine by tap water while the control group received only tap water. On 10[th] and 14[th] day of pregnancy, rats were anesthetized and placenta removed surgically, 1ml blood was collected from each pregnant mother from retro-orbital sinus, the concentration of blood corticosteron was determined by corticosteron Elisa kit after centrifugation. The fixed tissue was processed, sectioned and stained with hematoxylin and eosin. Placenta was studied microscopically according to the thickness of layers, area of blood cisterns, and the number of cells. Comparing the plasma corticosteron concentration of the treatment and the control groups, not only a severe increase in the treatment group was detected, but also the thickness of maternal and embryonic portions of the placenta at day 10th and 14th of gestation was different significantly [p