Protective Effects of Kefir Against Unpredictable Chronic Stress Alterations in Mice Central Nervous System, Heart, and Kidney.

Kefir is a probiotic mixture with anxiolytic and antioxidant properties. Chronic stress can lead to anxiety disorders and increase oxidative damage in organs such as the heart and kidney. In this study, we examined whether kefir ameliorates the anxiety-like behavior of mice submitted to chronic unpredictable stress (CUS) by modulating brain-derived neurotrophic factor (BDNF) and corticosterone levels and whether kefir modifies the oxidative parameters in the heart and kidney of mice. Male Swiss mice received kefir (0.3 mL/100 g/day) or milk for 30 days (gavage). On the 10th day, the mice were submitted to CUS. Behavioral analysis was performed using the elevated plus maze and forced swimming tests. BDNF levels were analyzed in brain tissues. Heart and kidney superoxide dismutase (SOD), catalase, glutathione (GSH), thiobarbituric acid reactive substances (TBARS), 3-nitrotyrosine, metalloproteinase-2 (MMP-2), and plasma corticosterone were evaluated. Kefir reverted the CUS-induced decrease in the time spent in the open arms, the increase in grooming frequency, and decrease in the head dipping frequency, but not the reduced immobility time. CUS decreased the cerebellum BDNF levels and increased corticosterone levels, which were restored by Kefir. Neither catalase and SOD activities nor GSH, TBARS, 3-nitrotyrosine, and MMP-2 were modified by CUS in the heart. In the kidney, CUS increased 3-nitrotyrosine and MMP-2. Kefir increased the antioxidant defense in the heart and kidney of control and CUS mice. These results suggest that kefir ameliorated CUS-induced anxiety-like behavior by modulating brain BDNF and corticosterone levels. Kefir also increased the antioxidant defense of mice heart and kidney.

Avaliação da qualidade do sono e níveis séricos de serotonina e cortisol em pacientes com dor crônica / Evaluation of sleep quality and serum levels of serotonin and cortisol in patients with chronic pain / Evaluación de la calidad del sueño y de los niveles séricos de serotonina y cortisol en pacientes con dolor crónico

A dor crônica pode acometer indivíduos de qualquer idade e está atribuída a maior morbidade, declínio cognitivo e imobilidade. Nos pacientes com dor crônica, ocorrem alterações importantes na neurotransmissão, além de alterações endócrinas relacionadas ao estresse. Além do mais, a má qualidade do sono leva a alterações cognitivas, irritabilidade e fadiga durante o dia e está, comumente, presente em pacientes com dor crônica. Assim, o presente estudo avaliou, por meio da aplicação de questionários a indivíduos adultos com diagnóstico de dor crônica, atendidos em ambulatório de reumatologia da microrregião de Alfenas-MG, a qualidade de vida, o padrão da dor e a qualidade do sono, além da análise da dosagem sérica de serotonina e cortisol. Dos 57 pacientes que fizeram parte da amostra, a maioria era composta por mulheres (91,2%), com idade maior de 40 anos (87,7%). Os principais diagnósticos envolvidos foram fibromialgia (35%), osteoartrite (21%) e artrite reumatoide (14%). Os resultados obtidos apontaram moderada intensidade da dor e interferência das atividades diárias, regular estado de saúde geral e má qualidade do sono nestes indivíduos. De acordo com os dados, não houve correlação estatisticamente relevante entre a severidade da dor e a qualidade de sono, tampouco entre a severidade da dor e o estado de saúde geral. Por outro lado, houve correlação positiva moderada entre a severidade da dor e a interferência nas atividades diárias, e correlação negativa moderada entre a severidade da dor e a saúde mental do indivíduo. Também ficou claro que a interferência da dor nas atividades diárias impacta negativamente na saúde mental. Não foi possível constatar uma relação entre a má qualidade do sono e maior intensidade da dor, mas sim entre qualidade de sono e saúde mental, impactando significativamente também no estado geral de saúde. A qualidade do sono impacta ainda na relação das atividades do cotidiano e influencia negativamente a saúde mental. Por fim, no presente estudo não foi evidenciada correlação significativa entre o diagnóstico de dor crônica e alterações de níveis séricos de serotonina e cortisol. Em conclusão, os achados demonstram a complexidade do tratamento de pacientes com dor crônica. Considerando que a dor crônica desencadeia um amplo espectro de alterações orgânicas e cognitivas, torna-se essencial compreender como essas alterações se associam, para que sejam desenvolvidas abordagens preventivas e terapêuticas mais efetivas.

Chronic pain can affect individuals of any age and is associated with increased morbidity, cognitive decline, and immobility. In patients with chronic pain, there are important changes in neurotransmission, in addition to stress-related endocrine changes. Moreover, poor sleep quality leads to cognitive changes, irritability, and fatigue during the day and is commonly present in patients with chronic pain. Thus, the present study evaluated, by means of applying questionnaires to adult individuals diagnosed with chronic pain, seen at a rheumatology outpatient clinic in the Alfenas-MG microregion, the quality of life, the pattern of pain and the quality of sleep, in addition to the analysis of serum serotonin and cortisol levels. Of the 57 patients who were part of the sample, most were women (91.2%), aged over 40 years (87.7%). The main diagnoses involved were fibromyalgia (35%), osteoarthritis (21%), and rheumatoid arthritis (14%). The results obtained indicated moderate pain intensity and interference with daily activities, regular general health status, and poor sleep quality in these individuals. According to the data, there was no statistically relevant correlation between pain severity and sleep quality, nor between pain severity and general health status. On the other hand, there was a moderate positive correlation between pain severity and interference with daily activities, and a moderate negative correlation between pain severity and the individual's mental health. It was also clear that pain interference with daily activities negatively impacts mental health. A relationship between poor sleep quality and greater pain intensity could not be found, but rather between sleep quality and mental health, impacting significantly on overall health status as well. Sleep quality also impacts the relationship of activities of daily living and negatively influences mental health. Finally, in the present study no significant correlation was evidenced between the diagnosis of chronic pain and changes in serum levels of serotonin and cortisol. In conclusion, the findings demonstrate the complexity of treating patients with chronic pain. Considering that chronic pain triggers a broad spectrum of organic and cognitive changes, it becomes essential to understand how these changes associate so that more effective preventive and therapeutic approaches can be developed.

dolor crónico puede afectar a individuos de cualquier edad y se asocia a una mayor morbilidad, deterioro cognitivo e inmovilidad. En los pacientes con dolor crónico se producen importantes alteraciones en la neurotransmisión, además de cambios endocrinos relacionados con el estrés. Además, un sueño de mala calidad conduce a alteraciones cognitivas, irritabilidad y fatiga durante el día, y está comúnmente presente en pacientes con dolor crónico. Así, el presente estudio evaluó, mediante la aplicación de cuestionarios a individuos adultos diagnosticados de dolor crónico, atendidos en una consulta externa de reumatología de la microrregión de Alfenas-MG, la calidad de vida, el patrón de dolor y la calidad del sueño, además del análisis del dosaje sérico de serotonina y cortisol. De los 57 pacientes que formaron parte de la muestra, la mayoría eran mujeres (91,2%), mayores de 40 años (87,7%). Los principales diagnósticos fueron fibromialgia (35%), artrosis (21%) y artritis reumatoide (14%). Los resultados obtenidos señalaron una intensidad moderada del dolor y una interferencia de las actividades cotidianas, un estado de salud general regular y una mala calidad del sueño en estas personas. Según los datos, no existía una correlación estadísticamente relevante entre la intensidad del dolor y la calidad del sueño, ni entre la intensidad del dolor y el estado general de salud. Por otro lado, existía una correlación positiva moderada entre la intensidad del dolor y la interferencia en las actividades cotidianas, y una correlación negativa moderada entre la intensidad del dolor y la salud mental del individuo. También quedó claro que la interferencia del dolor en las actividades cotidianas repercute negativamente en la salud mental. No fue posible encontrar una relación entre una mala calidad del sueño y una mayor intensidad del dolor, sino más bien entre la calidad del sueño y la salud mental, lo que también repercute significativamente en el estado general de salud. La calidad del sueño también repercute en la relación de las actividades diarias e influye negativamente en la salud mental. Por último, en el presente estudio no se evidenció una correlación significativa entre el diagnóstico de dolor crónico y las alteraciones en los niveles séricos de serotonina y cortisol. En conclusión, los hallazgos demuestran la complejidad del tratamiento de los pacientes con dolor crónico. Teniendo en cuenta que el dolor crónico desencadena un amplio espectro de alteraciones orgánicas y cognitivas, se hace imprescindible comprender cómo se asocian estas alteraciones, para poder desarrollar abordajes preventivos y terapéuticos más eficaces.

Nicotine exposure through breastfeeding affects brain-derived neurotrophic factor and synaptic proteins levels in the brain of stressed adult female mice.

Nicotine has been used during pregnancy and lactation as a tobacco harm reduction strategy. However, it is unclear whether nicotine exposure during a critical development period negatively impacts stress responses in adulthood. This study investigated how nicotine, administered via breastfeeding, affects the brain-derived neurotrophic factor (BDNF), synaptic proteins levels, and anxiety-like behavior in adult female mice subjected to stress. Female Swiss mice were exposed to saline or nicotine (8 mg/kg/day) through breastfeeding between their fourth and 17th postnatal days (P) via implanted osmotic mini pumps. The unpredictable chronic mild stress (UCMS) protocol was performed during their adulthood (P65) for 10 consecutive days, followed by the elevated plus maze (EPM) test 1 day after the protocol. Animals were euthanized and their blood, collected for plasma corticosterone measurements and their brain structures, dissected for BDNF and synaptic proteins analyses. We found no significant differences in corticosterone levels between groups (Saline/Non-stress, Nicotine/Non-stress, Saline/Stress, and Nicotine/Stress). The UCMS protocol hindered weight gain. Mice exposed to nicotine through breastfeeding with or without the UCMS protocol in adulthood showed higher grooming and head dipping frequency; decreased BDNF levels in cerebellum and striatum; increased postsynaptic density protein 95 (PSD-95), synapsin I, and synaptophysin levels in cerebellum; and decreased PSD-95 and synapsin I levels in brainstem. Our results indicate that nicotine exposure through breastfeeding leads to long-lasting behavioral effects and synaptic protein changes, most of which were independent of the UCMS protocol, even after a long nicotine-free period, highlighting the importance of further studies on nicotine exposure during development.

Effects of endogenous H2S production inhibition on the homeostatic responses induced by acute high-salt diet consumption.

The gaseous modulator hydrogen sulfide (H2S) is synthesized, among other routes, by the action of cystathionine-γ-lyase (CSE) and importantly participates in body fluid homeostasis. Therefore, the present study aimed to evaluate the participation of H2S in behavioral, renal and neuroendocrine homeostatic responses triggered by the acute consumption of a high Na+ diet. After habituation, adult male Wistar rats were randomly distributed and maintained for seven days on a control [CD (0.27% of Na+)] or hypersodic diet [HD (0.81% of Na+)]. CD and HD-fed animals were treated with DL-Propargylglycine (PAG, 25 mg/kg/day, ip) or vehicle (0.9% NaCl in equivalent volume) for the same period. At the end of the experiment, animals were euthanized for blood and tissue collection. We demonstrated that a short-term increase in dietary Na+ intake, in values that mimic the variations in human consumption (two times the recommended) significantly modified hydroelectrolytic homeostasis, with repercussions in the hypothalamic-neurohypophysial system and hypothalamic-pituitary-adrenal axis function. These findings were accompanied by the development of a clear inflammatory response in renal tubular cells and microvascular components. On the other hand, the inhibition of the endogenous production of H2S by CSE provided by PAG treatment prevented the inflammation induced by HD. In the kidney, PAG treatment induced the overexpression of inducible nitric oxide synthase in animals fed with HD. Taken together, these data suggest, therefore, that HD-induced H2S production plays an important proinflammatory role in the kidney, apparently counter regulating nitric oxide actions in renal tissue.

No effect of prior Dengue virus 1 infection in mouse dams on long-term behavioral profiles in offspring infected with Zika virus during gestation.

Zika virus (ZIKV) is a mosquito-borne Flavivirus structurally and antigenically related to Dengue virus (DENV). Zika virus has been associated with congenital anomalies and most ZIKV outbreaks have occurred in endemic areas of DENV. The present study investigated the effects of prior DENV serotype 1 (DENV1) immunity in immunocompetent female Swiss mice on gestational ZIKV infection in offspring. Physical/reflex development, locomotor activity, anxiety, visual acuity, and brain-derived neurotrophic factor (BDNF) levels were evaluated in offspring during infancy and adolescence. Anti-DENV1 and anti-ZIKV antibodies were detected in sera of the progenitors, whereas no ZIKV genomes were detected in the offspring brain. Pups from dams with only DENV1 immunity presented alterations of physical/reflex development. Pups from all infected dams exhibited time-related impairments in locomotor activity and anxiolytic-like behavior. Offspring from DENV/ZIKV-infected dams exhibited impairments in visual acuity during infancy but not during adolescence, which was consistent with morphometric analysis of the optic nerve. Pups from DENV1-, ZIKV-, and DENV/ZIKV-infected dams exhibited a decrease in BDNF levels during infancy and an increase during adolescence in distinct brain regions. In summary, we found no influence of prior DENV1 immunity on gestational ZIKV infection in offspring, with the exception of alterations of early visual parameters, and an increase in BDNF levels in the hippocampus during adolescence.

Pyrrolidine dithiocarbamate reduces alloxan-induced kidney damage by decreasing nox4, inducible nitric oxide synthase, and metalloproteinase-2.

We examined the effect of the NFκB inhibitor pyrrolidine-1-carbodithioic acid (PDTC) on inducible nitric oxide synthase (iNOS), matrix metalloproteinase-2 (MMP-2) activity, and oxidative and inflammatory kidney damage in alloxan-induced diabetes. Two weeks after diabetes induction (alloxan-130 mg/kg), control and diabetic rats received PDTC (100 mg/kg) or vehicle for 8 weeks. Body weight, glycemia, urea, and creatinine were measured. Kidney changes were measured in hematoxylin/eosin sections and ED1 by immunohistochemistry. Kidney thiobarbituric acid reactive substances (TBARS), superoxide anion (O2-), and nitrate/nitrite (NOx) levels, and catalase and superoxide dismutase (SOD) activities were analyzed. Also, kidney nox4 and iNOS expression, and NFkB nuclear translocation were measured by western blot, and MMP-2 by zymography. Glycemia and urea increased in alloxan rats, which were not modified by PDTC treatment. However, PDTC attenuated kidney structural alterations and macrophage infiltration in diabetic rats. While diabetes increased both TBARS and O2- levels, PDTC treatment reduced TBARS in diabetic and O2- in control kidneys. A decrease in NOx levels was found in diabetic kidneys, which was prevented by PDTC. Diabetes reduced catalase activity, and PDTC increased catalase and SOD activities in both control and diabetic kidneys. PDTC treatment reduced MMP-2 activity and iNOS and p65 NFκB nuclear expression found increased in diabetic kidneys. Our results show that the NFκB inhibitor PDTC reduces renal damage through reduction of Nox4, iNOS, macrophages, and MMP-2 in the alloxan-induced diabetic model. These findings suggest that PDTC inhibits alloxan kidney damage via antioxidative and anti-inflammatory mechanisms.

Contribution of Chinese and French ear acupuncture for the management of chronic back pain: A randomised controlled trial.

AIMS AND OBJECTIVES: To compare the efficacy of Chinese and French ear acupuncture in people with chronic back pain. BACKGROUND: Chronic back pain is a common public health problem worldwide. An intervention for this condition is ear acupuncture. Several approaches are used for ear acupuncture, particularly the Chinese and French guidelines. METHODS: An open, randomised and controlled clinical trial, followed the recommendations of the CONSORT Checklist. One hundred and eleven people were selected and randomised into three groups: Chinese ear acupuncture, French ear acupuncture and Control. Evaluations were performed before the first intervention session (initial), 1 week after the fifth session (final) and after a fifteen-day follow-up period (follow-up), using the Brief Pain Inventory, Rolland Morris Disability Questionnaire, and a thermal imaging camera. For data analysis, the Generalized Estimating Equation Model was applied, with significance level set at 5%. RESULTS: Pain severity was significantly decreased by Chinese ear acupuncture throughout intervention period. Both types of ear acupuncture affected pain interference with daily activities. However, in the comparison between initial and final evaluations, only Chinese ear acupuncture produced statistically significant results. A reduction in physical disability was observed in both ear acupuncture-treated groups during the intervention period and, although Chinese ear acupuncture failed to induce significant changes in tissular temperature at individual time points, a significant increase in cutaneous temperature was detected after the follow-up period in the dorsal region of individuals treated with Chinese ear acupuncture. Importantly, at this time point, the mean difference between Chinese and French ear acupuncture revealed a more benefic effect of Chinese procedure on this parameter. CONCLUSIONS: The individualised treatment based on the Chinese precepts showed, in an overall evaluation, better results for management of chronic back pain in the present study. RELEVANCE TO CLINICAL PRACTICE: Ear acupuncture can be implemented in the nurse's clinical practice to assist the treatment of people with chronic back pain.

Adrenalectomy impairs insulin-induced hypophagia and related hypothalamic changes.

Adrenalectomy (ADX) induces hypophagia and glucocorticoids counter-regulate the peripheral metabolic effects of insulin. This study evaluated the effects of ADX on ICV (lateral ventricle) injection of insulin-induced changes on food intake, mRNA expression of hypothalamic neuropeptides (insulin receptor (InsR), proopiomelanocortin, cocaine and amphetamine-regulated transcript (Cart), agouti-related protein, neuropeptide Y (Npy) in the arcuate nucleus of the hypothalamus (ARC), corticotrophin-releasing factor in the paraventricular nucleus of the hypothalamus) and hypothalamic protein content of insulin signaling-related molecules (insulin receptor substrate (IRS) 1, protein kinase B (AKT), extracellular-signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK), protein tyrosine phosphatase-1B (PTP1B) and T cell protein tyrosine phosphatase (TCPTP)) Compared with sham animals, ADX increased the hypothalamic content of pJNK/JNK, PTP1B and TCPTP, as well as decreased mRNA expression of InsR, and corticosterone (B) treatment reversed these effects. Insulin central injection enhanced hypothalamic content of pAKT/AKT and Cart mRNA expression, decreased Npy mRNA expression and food intake only in sham rats, without effects in ADX and ADX + B rats. Insulin did not alter the hypothalamic phosphorylation of IRS1 and ERK1/2 in the three experimental groups. These data demonstrate that ADX reduces the expression of InsR and increases insulin counter-regulators in the hypothalamus, as well as ADX abolishes hypophagia, activation of hypothalamic AKT pathway and changes in Cart and Npy mRNA expression in the ARC induced by insulin. Thus, the higher levels of insulin counter-regulatory proteins and lower expression of InsR in the hypothalamus are likely to underlie impaired insulin-induced hypophagia and responses in the hypothalamus after ADX.

Effects of auricular acupuncture on chronic pain in people with back musculoskeletal disorders: a randomized clinical trial.

OBJECTIVE: To evaluate the effects of auricular acupuncture on pain intensity, its impact on daily activities, the relief provided by the intervention, and the pain threshold in people with back musculoskeletal disorders. METHODS: Randomized clinical trial carried out with people randomly allocated into three groups: treatment, placebo, and control. Evaluations were performed using the Brief Pain Inventory and a digital algometer before (initial) and after (final) the treatment and after a 15-day follow-up period. RESULTS: The sample was 110 people. There was a decrease in pain intensity in the treatment and placebo groups as revealed by the comparison between the initial and final evaluations (p<0.05), and in the treatment group in the comparison between the initial and follow-up evaluations (p<0.05). A decreased impact of pain on daily activities in the treatment and placebo groups over time was found (p<0.05). At the final evaluation, the impact of pain was lower in the treatment group (p<0.05). Auricular acupuncture did not increase the pain threshold. CONCLUSION: Auricular acupuncture presented positive effects by reducing the chronic pain intensity and its impact on daily activities in people with back musculoskeletal disorders. Brazilian Clinical Trials Registry: RBR-5X69X2.

Effects of auricular acupuncture on chronic pain in people with back musculoskeletal disorders: a randomized clinical trial / Efectos de la auriculoacupuntura en el dolor crónico en personas con disturbios musculoesqueléticos en la espalda: ensayo clínico randomizado / Efeitos da auriculoacupuntura na dor crônica em pessoas com distúrbios musculoesqueléticos nas costas: ensaio clínico randomizado

ABSTRACT Objective: To evaluate the effects of auricular acupuncture on pain intensity, its impact on daily activities, the relief provided by the intervention, and the pain threshold in people with back musculoskeletal disorders. Methods: Randomized clinical trial carried out with people randomly allocated into three groups: treatment, placebo, and control. Evaluations were performed using the Brief Pain Inventory and a digital algometer before (initial) and after (final) the treatment and after a 15-day follow-up period. Results: The sample was 110 people. There was a decrease in pain intensity in the treatment and placebo groups as revealed by the comparison between the initial and final evaluations (p<0.05), and in the treatment group in the comparison between the initial and follow-up evaluations (p<0.05). A decreased impact of pain on daily activities in the treatment and placebo groups over time was found (p<0.05). At the final evaluation, the impact of pain was lower in the treatment group (p<0.05). Auricular acupuncture did not increase the pain threshold. Conclusion: Auricular acupuncture presented positive effects by reducing the chronic pain intensity and its impact on daily activities in people with back musculoskeletal disorders. Brazilian Clinical Trials Registry: RBR-5X69X2

RESUMEN Objetivo: Evaluar los efectos de la auriculoacupuntura sobre la intensidad del dolor, su interferencia en las actividades cotidianas, el alivio proporcionado por la intervención y el umbral de dolor en personas con disturbios musculoesqueléticos en la espalda. Método: Ensayo clínico randomizado, realizado con personas aleatorizadas en tres grupos: tratado, placebo y control. Las evaluaciones se llevaron a cabo usando el Breve Inventario del Dolor y un algómetro digital antes (inicial) y tras el tratamiento (final), en un período de seguimiento de 15 días (follow-up). Resultados: Participaron 110 personas. Hubo reducción en la intensidad del dolor en los grupos tratado y placebo entre las evaluaciones inicial y final (p<0,05), y en el grupo tratado entre la evaluación inicial y el follow-up (p<0,05). También ocurrió disminución de la interferencia del dolor en las actividades cotidianas en los grupos tratado y placebo a lo largo del tiempo (p<0,05). En la evaluación final, la interferencia del dolor fue menor en el grupo tratado (p<0,05). La auriculoacupuntura no fue suficiente para aumentar el umbral de dolor. Conclusión: La auriculoacupuntura presentó efectos positivos al reducir la intensidad del dolor crónico y su interferencia en las actividades cotidianas en personas con disturbios musculoesqueléticos en la espalda. Registro Brasileño de Ensayos Clínicos: RBR-5X69X2

RESUMO Objetivo: Avaliar os efeitos da auriculoacupuntura sobre a intensidade da dor, a sua interferência nas atividades cotidianas, o alívio proporcionado pela intervenção e o limiar de dor em pessoas com distúrbios musculoesqueléticos nas costas. Método: Ensaio clínico randomizado, realizado com pessoas randomizadas em três grupos: tratado, placebo e controle. As avaliações foram realizadas usando o Inventário Breve de Dor e um algômetro digital antes (inicial) e após o tratamento (final), em um período de seguimento de 15 dias (follow-up). Resultados: Participaram 110 pessoas. Houve redução na intensidade da dor nos grupos tratado e placebo entre as avaliações inicial e final (p<0,05), e no grupo tratado entre a avaliação inicial e o follow-up (p<0,05). Também ocorreu diminuição da interferência da dor nas atividades cotidianas nos grupos tratado e placebo ao longo do tempo (p<0,05). Na avaliação final, a interferência da dor foi menor no grupo tratado (p<0,05). A auriculoacupuntura não foi suficiente para aumentar o limiar de dor. Conclusão: A auriculoacupuntura apresentou efeitos positivos ao reduzir a intensidade da dor crônica e sua interferência nas atividades cotidianas em pessoas com distúrbios musculoesqueléticos nas costas. Registro Brasileiro de Ensaios Clínicos: RBR-5X69X2

Action of ear acupuncture in people with chronic pain in the spinal column: a randomized clinical trial1.

OBJECTIVES: to assess the action of ear acupuncture on disability and tissue temperature in people with chronic pain in the spinal column. METHOD: a clinical trial with a sample of 110 people, randomized into three groups: Treatment, Placebo and Control. The assessment instruments were the Rolland Morris Disability Questionnaire (RMDQ) and a thermographic camera, administered before the first treatment session, one week after and 15 days after (follow-up) the fifth session of ear acupuncture. In the analysis of the data, the Kruskal Wallis, Student-Newman Keuls and Wilcoxon tests were applied. RESULTS: there was a significant reduction in disability in the Treatment and Placebo groups between the initial and final assessments (p<0.05) and between the initial assessments and follow-up (p<0.05). In the final assessment, the Treatment group presented improvement of disability when compared with the Placebo and Control groups (p<0.05). There was an increase in mean tissue temperature of the dorsal region between the initial and follow-up assessments in Treatment and Control groups (p<0.05), and between the final assessments and follow-up in the Treatment and Placebo groups (p<0.05). CONCLUSION: ear acupuncture was efficacious in reducing disability and increasing tissue temperature in people with chronic pain in the spinal column. Brazilian Register of Clinical Trials (RBR-5X69X2).

Glucocorticoid receptor gene expression in a CLP-induced ARDS-like rat model treated with dexamethasone and metyrapone.

Glucocorticoids (GCs) are used for acute respiratory distress syndrome (ARDS) to improve or prevent lung injury. The mechanisms underlying the effects of GCs involve inadequate GC-receptor (GR)-mediated downregulation of pro-inflammatory factors despite elevated levels of cortisol. Within this context, knowledge of the transcriptional pattern of the GR gene in response to variations in physiological parameters may shed light on this issue. We addressed this problem by measuring plasmatic corticosterone (CCT) levels and assessing GR expression at transcript and protein levels in rats with caecal ligation and puncture (CLP)-induced ARDS-like syndrome treated with dexamethasone and metyrapone. Seventy male rats were randomized into three main groups: Naïve (any treatment), Sham (caecum-exposed) and CLP. CLP animals were divided into three groups according to pretreatments performed before surgery: CLP sal (0.9% NaCl ip), CLP metyrapone (50 mg.kg-1 ip) and CLP dexamethasone (0.5 mg.kg-1 ip). Our results showed that CLP sal promotes elevation in CCT levels, which are significantly reduced with metyrapone to levels comparable to untreated animals when dexamethasone is used. In this hormonal milieu, the GR gene transcript levels of both variants, GRα and GRß, are produced in comparable levels and in response to caecum-exposing surgery. Nonetheless, the expression of the GRα variant demonstrated positive sensitivity to variations in CCT levels and was downregulated in animals treated with dexamethasone. Moreover, nuclear translocation of GR protein decreased with high levels of plasma CCT and higher GR translocation was found in animals with moderate CCT levels; in either case, the process seemed to be positively associated with the CLP procedure.

Action of ear acupuncture in people with chronic pain in the spinal column: a randomized clinical trial / Ação da auriculoacupuntura em pessoas com dor crônica na coluna vertebral: ensaio clínico randomizado / Acción de la auriculoacupuntura en personas con dolor crónico en la columna vertebral: ensayo clínico aleatorio

ABSTRACT Objectives: to assess the action of ear acupuncture on disability and tissue temperature in people with chronic pain in the spinal column. Method: a clinical trial with a sample of 110 people, randomized into three groups: Treatment, Placebo and Control. The assessment instruments were the Rolland Morris Disability Questionnaire (RMDQ) and a thermographic camera, administered before the first treatment session, one week after and 15 days after (follow-up) the fifth session of ear acupuncture. In the analysis of the data, the Kruskal Wallis, Student-Newman Keuls and Wilcoxon tests were applied. Results: there was a significant reduction in disability in the Treatment and Placebo groups between the initial and final assessments (p<0.05) and between the initial assessments and follow-up (p<0.05). In the final assessment, the Treatment group presented improvement of disability when compared with the Placebo and Control groups (p<0.05). There was an increase in mean tissue temperature of the dorsal region between the initial and follow-up assessments in Treatment and Control groups (p<0.05), and between the final assessments and follow-up in the Treatment and Placebo groups (p<0.05). Conclusion: ear acupuncture was efficacious in reducing disability and increasing tissue temperature in people with chronic pain in the spinal column. Brazilian Register of Clinical Trials (RBR-5X69X2).

RESUMO Objetivos: avaliar a ação da auriculoacupuntura na incapacidade e na temperatura tissular de pessoas com dor crônica na coluna vertebral. Método: ensaio clínico com amostra de 110 pessoas, randomizadas em três grupos: Tratado, Placebo e Controle. Os instrumentos de avaliação foram o Questionário de Incapacidade de Rolland Morris e uma câmera termográfica, aplicados antes da primeira sessão de tratamento, uma semana após e 15 dias após (follow up) à quinta sessão de auriculoacupuntura. Na análise dos dados, aplicaram-se os testes Kruskal-Wallis, Student-Newman-Keuls e Wilcoxon. Resultados: houve redução significativa da incapacidade nos grupos Tratado e Placebo entre as avaliações inicial e final (p<0,05) e entre as avaliações inicial e follow up (p<0,05). Na avaliação final, o grupo Tratado apresentou melhora da incapacidade se comparado ao Placebo e ao Controle (p<0,05). Houve aumento na temperatura média tissular da região dorsal entre as avaliações inicial e follow up no Tratado e Controle (p<0,05). Entre as avaliações final e follow up no Tratado e Placebo (p<0,05). Conclusão: a auriculoacupuntura foi eficaz para reduzir a incapacidade e aumentar a temperatura tissular em pessoas com dor crônica na coluna vertebral. Registro Brasileiro de Ensaios Clínicos (RBR-5X69X2).

RESUMEN Objetivos: evaluar la acción de la auriculoacupuntura en la incapacidad y en la temperatura del tejido de personas con dolor crónico en la columna vertebral. Método: ensayo clínico con muestra de 110 personas, asignadas aleatoriamente en tres grupos: Tratado, Placebo y Control. Los instrumentos de evaluación fueron el Cuestionario de Incapacidad de Rollad Morris y una cámara termográfica, aplicados antes de la primera sesión de tratamiento, una semana después y quince días después (follow up) de la quinta sesión de auriculoacupuntura. En el análisis de los datos se aplicaron las pruebas Kruskal-Wallis, Student-Newman Keuls y Wilcoxon. Resultados: hubo reducción significativa de la incapacidad en los grupos Tratado y Placebo, entre las evaluaciones inicial y final (p<0,05) y entre las evaluaciones inicial y follow up (p<0,05). En la evaluación final, el grupo Tratado presentó mejoría de la incapacidad si comparado al Placebo y al Control (p<0,05). Hubo aumento en la temperatura media del tejido de la región dorsal entre las evaluaciones inicial y follow up en el Tratado y Control (p<0,05), y entre las evaluaciones final y follow up en el Tratado y Placebo (p<0,05). Conclusión: la auriculoacupuntura fue eficaz en reducir la incapacidad y en aumentar la temperatura del tejido en personas con dolor crónico en la columna vertebral. Registro Brasileño de Ensayos Clínicos (RBR-5X69X2).

Corticotrophin-releasing factor receptor 2 mediates the enhanced activation of satiety-related responses through oxytocin neurons in the paraventricular nucleus of the hypothalamus after adrenalectomy.

Adrenalectomy (ADX)-induced hypophagia is associated with increased activation of corticotrophin-releasing factor (CRF) and oxytocin (OT) neurons in the paraventricular nucleus of the hypothalamus (PVN) after refeeding. CRF2- and OT-receptor antagonists abolish the hypophagia and the augmented activation of the nucleus of the solitary tract neurons induced by feeding after ADX. In addition, OT-receptor antagonist reversed CRF-induced anorexia. We evaluated the effect of intracerebroventricular pretreatment with CRF2-receptor antagonist, antisauvagine-30 (AS30), on the activation of OT neurons of the PVN in response to refeeding of sham, adrenalectomized (ADX) and ADX rats replaced with corticosterone (ADX+B). In vehicle-pretreated animals, refeeding increased the number of Fos+OT double labeled neurons in the posterior parvocellular subdivision of the PVN (PaPo) of sham, ADX and ADX+B animals, with higher Fos expression and OT neuronal activation in the ADX group. AS30 reversed refeeding-induced increased activation of OT and non-OT neurons in the PaPo in the ADX group. In the medial parvocellular subdivision of the PVN (PaMP) of vehicle-pretreated animals, the number of Fos- and Fos+OT-immunoreactive neurons was increased after refeeding in ADX group. AS30 in the ADX group attenuated the enhanced Fos expression but not the number of Fos+OT double labeled neurons in the PaMP. In conclusion, CRF2-receptor antagonist reverses the increased activation of OT neurons in the PaPo induced by feeding in ADX animals, suggesting that OT neurons might be downstream mediators of CRF effects on satiety-related responses after ADX.

Neuroendocrine Regulation of Hydromineral Homeostasis.

Since the crucial evolutionary change from an aqueous to a terrestrial environment, all living organisms address the primordial task of equilibrating the ingestion/production of water and electrolytes (primarily sodium) with their excretion. In mammals, the final route for the excretion of these elements is mainly through the kidneys, which can eliminate concentrated or diluted urine according to the requirements. Despite their primary role in homeostasis, the kidneys are not able to recover water and solutes lost through other systems. Therefore, the selective stimulation or inhibition of motivational and locomotor behavior becomes essential to initiate the search and acquisition of water and/or sodium from the environment. Indeed, imbalances affecting the osmolality and volume of body fluids are dramatic challenges to the maintenance of hydromineral homeostasis. In addition to behavioral changes, which are integrated in the central nervous system, most of the systemic responses recruited to restore hydroelectrolytic balance are accomplished by coordinated actions of the cardiovascular, autonomic and endocrine systems, which determine the appropriate renal responses. The activation of sequential and redundant mechanisms (involving local and systemic factors) produces accurate and self-limited effector responses. From a physiological point of view, understanding the mechanisms underlying water and sodium balance is intriguing and of great interest for the biomedical sciences. Therefore, the present review will address the biophysical, evolutionary and historical perspectives concerning the integrative neuroendocrine control of hydromineral balance, focusing on the major neural and endocrine systems implicated in the control of water and sodium balance.

Gaseous modulators in the control of the hypothalamic neurohypophyseal system.

Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) are gaseous molecules produced by the brain. Within the hypothalamus, gaseous molecules have been highlighted as autocrine and paracrine factors regulating endocrine function. Therefore, in the present review, we briefly discuss the main findings linking NO, CO, and H2S to the control of body fluid homeostasis at the hypothalamic level, with particular emphasis on the regulation of neurohypophyseal system output.

The CB1 cannabinoid receptor mediates glucocorticoid-induced effects on behavioural and neuronal responses during lactation.

It has been shown that glucocorticoids can modulate oxytocin (OT) secretion and disrupt maternal behaviour. Because the CB1 receptor (CB1R) has been implicated in some rapid glucocorticoid-induced actions, the present study aimed to evaluate the possible involvement of CB1Rs in maternal behaviour and neuronal activation during lactation. For this purpose, lactating female rats were pre-treated with dexamethasone (DEX) or saline, followed by treatment with AM251, a CB1R antagonist, or vehicle 90 min later. All of the experiments were performed 30 min after the administration of AM251 or vehicle. To evaluate maternal behaviour, the pups were returned to their home cages to the side of the cage opposite the previous nest after 12 h of separation and were filmed for the next 30 min. Aggressive behaviour was evaluated for 10 min following the placement of a male rat in the home cage. For the evaluation of behavioural performance, lactating rats were subjected to a T-maze and open-field tests. The amount of weight gained by the pups was evaluated 15 min after the onset of suckling to determine the amount of milk that they had obtained from the dam. In the central nervous system of lactating rats, c-Fos-positive nuclei were counted in the medial preoptic area, in both the ventral (v) and dorsal (d) parts of the median preoptic nucleus and in the bed nucleus of the stria terminalis (BNST). The number of neurons that were double-labelled for c-Fos/OT was counted in the medial magnocellular subdivision of the paraventricular nucleus, in the periventricular hypothalamic nucleus and in the supraoptic nucleus of the lactating rats. The results show that DEX had the following effects: (1) decreased the amount time the dam spent licking the pups, the amount of time the dam spent in an arched-nursing position and full maternal behaviour; (2) increased the latency to the first attack and decreased front attacks; (3) increased anxiety-like behaviour; and (4) decreased weight gain in the pups. In addition, DEX decreased neuronal activation in all of the investigated hypothalamic and forebrain areas. AM251 administration reversed these parameters, indicating that the behavioural effects and neuronal responses produced by DEX in lactating rats are likely to be mediated by CB1Rs.

Hypophagia induced by glucocorticoid deficiency is associated with an increased activation of satiety-related responses.

Glucocorticoids have major effects on food intake, demonstrated by the decrease of food intake following adrenalectomy. Satiety signals are relayed to the nucleus of the solitary tract (NTS), which has reciprocal projections with the arcuate nucleus (ARC) and paraventricular nucleus (PVN) of the hypothalamus. We evaluated the effects of glucocorticoids on the activation of hypothalamic and NTS neurons induced by food intake in rats subjected to adrenalectomy (ADX) or sham surgery 7 days before the experiments. One-half of ADX animals received corticosterone (ADX+B) in the drinking water (B: 25 mg/l). Fos/tyrosine hydroxylase (TH), Fos/corticotrophin-releasing factor (CRF) and Fos immunoreactivity were assessed in the NTS, PVN, and ARC, respectively. Food intake and body weight were reduced in the ADX group compared with sham and ADX+B groups. Fos and Fos/TH in the NTS, Fos, and Fos/CRF immunoreactive neurons in the PVN and Fos in the ARC were increased after refeeding, with higher number in the ADX group, compared with sham and ADX+B groups. CCK administration showed no hypophagic effect on ADX group despite a similar increase of Fos/TH immunoreactive neurons in the NTS compared with sham and ADX+B groups, suggesting that CCK alone cannot further increase the anorexigenic effect induced by glucocorticoid deficiency. The present data indicate that glucocorticoid withdrawal reduced food intake, which was associated with higher activation of ARC, CRF neurons of the PVN, and catecholaminergic neurons of the NTS. In the absence of glucocorticoids, satiety signals elicited during a meal lead to an augmented activation of brain stem and hypothalamic pathways.

Role of nitric oxide in lipopolysaccharide-induced release of vasopressin in rats.

This study evaluated the role of nitric oxide (NO) in vasopressin (AVP) release induced by intravenous lipopolysaccharide (LPS) in rats previously treated with intracerebroventricular (i.c.v.) saline, L-NAME, L-arginine or sodium nitroprusside (SNP). In control rats given i.c.v. saline, L-NAME, L-arginine or SNP, AVP levels did not change from baseline. After LPS, plasma AVP increased, reaching a peak at 60 min, and returning to basal levels 4 h later in all i.c.v. pre-treated groups (P<0.05). The LPS administration in rats previously treated with L-NAME induced higher AVP levels (P<0.05) that remained elevated throughout the period of the experiment (P<0.05). These findings confirm the inhibitory role of NO in AVP secretion induced by LPS.