Electrical carotid sinus nerve stimulation attenuates experimental colitis induced by acetic acid in rats.

AIMS: The carotid bodies are sensors that detect physiological signals and convey them to the central nervous system, where the stimuli are processed inducing reflexes through efferent pathways. Recent studies have demonstrated that electrical stimulation of the carotid sinus nerve (CSN) triggers the anti-inflammatory reflex under different conditions. However, whether this electrical stimulation attenuates colitis was never examined. This study aimed to evaluate if the electrical CSN stimulation attenuates the experimental colitis induced by intrarectal administration of acetic acid in rats. METHODS: Electrodes were implanted around the CSN to stimulate the CSN, and a catheter was inserted into the left femoral artery to record the arterial pressure. The observation of hypotensive responses confirmed the effectiveness of the electrical CNS stimulation. This maneuver was followed by a 4 % acetic acid or saline administered intrarectally. After 24 h, colons were segmented into distal and proximal parts for macroscopy, histological and biochemical assessment. KEY FINDINGS: As expected, the electrical CSN stimulation was effective in decreasing arterial pressure in saline and colitis rats. Moreover, electrical CSN stimulation effectively reduced colonic tissue lesions, colitis scores, and histopathologic parameters associated with colitis. In addition, the CSN stimulation also reduced the colonic mucosa pro-inflammatory cytokine interleukin-1 beta, and increased the anti-inflammatory interleukin-10, in rats submitted to colitis. SIGNIFICANCE: These findings indicated that electrical CSN stimulation breaks the vicious cycle of local colon inflammation in colitis, which might contribute to its better outcome.

Correlation between heart rate variability and polysomnography-derived scores of obstructive sleep apnea.

Obstructive sleep apnea (OSA) is one of the most common sleep disorders and affects nearly a billion people worldwide. Furthermore, it is estimated that many patients with OSA are underdiagnosed, which contributes to the development of comorbidities, such as cardiac autonomic imbalance, leading to high cardiac risk. Heart rate variability (HRV) is a non-invasive, widely used approach to evaluating neural control of the heart. This study evaluates the relationship between HRV indices and the presence and severity of OSA. We hypothesize that HRV, especially the nonlinear methods, can serve as an easy-to-collect marker for OSA early risk stratification. Polysomnography (PSG) exams of 157 patients were classified into four groups: OSA-free (N = 26), OSA-mild (N = 39), OSA-moderate (N = 37), and OSA-severe (N = 55). The electrocardiogram was extracted from the PSG recordings, and a 15-min beat-by-beat series of RR intervals were generated every hour during the first 6 h of sleep. Linear and nonlinear HRV approaches were employed to calculate 32 indices of HRV. Specifically, time- and frequency-domain, symbolic analysis, entropy measures, heart rate fragmentation, acceleration and deceleration capacities, asymmetry measures, and fractal analysis. Results with indices of sympathovagal balance provided support to reinforce previous knowledge that patients with OSA have sympathetic overactivity. Nonlinear indices showed that HRV dynamics of patients with OSA display a loss of physiologic complexity that could contribute to their higher risk of development of cardiovascular disease. Moreover, many HRV indices were found to be linked with clinical scores of PSG. Therefore, a complete set of HRV indices, especially the ones obtained by the nonlinear approaches, can bring valuable information about the presence and severity of OSA, suggesting that HRV can be helpful for in a quick diagnosis of OSA, and supporting early interventions that could potentially reduce the development of comorbidities.

Short-term effect of ligature-induced periodontitis on cardiovascular variability and inflammatory response in spontaneously hypertensive rats.

BACKGROUND: We previously reported that periodontal disease (PD) induces high arterial pressure variability (APV) consistent with sympathetic overactivity and elicits myocardial inflammation in Balb/c mice. However, it is unknown whether PD can change APV and heart rate variability (HRV) in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. This study aimed to evaluate the hemodynamic level, HRV, and APV associating with myocardial inflammation and plasma concentrations of oxide nitric (NO) in SHR and WKY rats with PD. METHODS: Three weeks after bilateral ligation of the first mandibular molar, or Sham operation, the rats received catheters into the femoral artery and had their arterial pressure (AP) recorded the following day. Subsequently, plasma, heart, and jaw were collected. The NO was quantified by the chemiluminescence method in plasma, and the myocardial IL-1ß concentrations were evaluated by ELISA. In the jaw was evaluated linear alveolar bone loss induced by PD. RESULTS: The linear alveolar bone loss in jaws of SHR with PD was higher than in all other groups. AP and heart rate were higher in SHR than in their WKY counterparts. SHR with PD showed lower AP than control SHR. HRV and APV were different between SHR and WKY rats; however, no differences in these parameters were found between the animals with PD and their control counterparts. Plasma NO and myocardial IL-1ß concentrations were higher in SHR with PD as compared to control WKY. A significant correlation was found between linear alveolar bone loss and plasma NO and myocardial IL-1ß concentrations. CONCLUSION: Our results demonstrated that short-term PD lowered the AP in SHR, which might be due to the higher levels of plasma NO. Even though PD did not affect either HRV or APV, it did induce myocardial inflammation, which can determine cardiovascular dysfunction in long-term PD.

Cardiac sympathetic drive is increased in cafeteria diet-fed rats independent of impairment in peripheral baroreflex and chemoreflex functions.

BACKGROUND AND AIMS: Consumption of a high caloric diet induces autonomic imbalance, which can lead to cardiovascular disease. Impaired arterial baroreflex control is suggested to play an important role in cardiovascular autonomic imbalance, often seen in obesity. We previously demonstrated that cafeteria diets increase the sympathetic drive to white and brown adipose tissue. METHODS AND RESULTS: After feeding a cafeteria diet to rats for 26 days, we evaluated: (i)heart rate (HR) and arterial pressure (AP); (ii)baroreflex and chemoreflex function; and (iii) autonomic modulation of the heart and vessels, measured through pulse interval (PI) and systolic arterial pressure (SAP) variability analyses and following administration of autonomic blockers. The cafeteria diet increased body fat mass and serum insulin, leptin, triacylglycerol and cholesterol levels. Baseline HR (15%) was also increased, accompanied by increased power in the low frequency band (60%) and in the low frequency/high frequency ratio (104%) in the PI spectra. Nonlinear analysis revealed an increased occurrence of 0V (39%) and decreased occurrence of 2UV (18%) patterns. Following administration of autonomic blockers, we observed an increase in cardiac sympathetic tone (425%) in cafeteria diet-fed rats. The cafeteria diet had no effect on AP, SAP variability, baroreflex and chemoreflex control. CONCLUSION: Our findings suggest that consumption of a cafeteria diet increases sympathetic drive to the heart but not to the blood vessels, independent of impairment in baroreflex and chemoreflex functions. Other mechanisms may be involved in the increased cardiac sympathetic drive, and compensatory vascular mechanisms may prevent the development of hypertension in this model of obesity.

Evaluation of the effect of cafeteria diet on the kidney Na,K-ATPase activity, and oxidative stress.

In this study, renal tissue, subdivided into the cortex and medulla of Wistar rats subjected to a cafeteria diet (CAF) for 24 days or to normal diet, was used to analyze whether the renal enzyme Na,K-ATPase activity was modified by CAF diet, as well as to analyze the α1 subunit of renal Na,K-ATPase expression levels. The lipid profile of the renal plasma membrane and oxidative stress were verified. In the Na,K-ATPase activity evaluation, no alteration was found, but a significant decrease of 30% in the cortex was detected in the α1 subunit expression of the enzyme. There was a 24% decrease in phospholipids in the cortex of rats submitted to CAF, a 17% increase in cholesterol levels in the cortex, and a 23% decrease in the medulla. Lipid peroxidation was significantly increased in the groups submitted to CAF, both in the cortical region, 29%, and in the medulla, 35%. Also, a reduction of 45% in the glutathione levels was observed in the cortex and medulla with CAF. CAF showed a nearly two-fold increase in glutathione peroxidase (GPX) activity in relation to the control group in the cortex and a 59% increase in the GPx activity in the medulla. In conclusion, although the diet was administered for a short period of time, important results were found, especially those related to the lipid profile and oxidative stress, which may directly affect renal function.

Identification of Suitable Reference Genes for Quantitative Gene Expression Analysis in Innervated and Denervated Adipose Tissue from Cafeteria Diet-Fed Rats.

Our previous studies show that cafeteria diet increases body adiposity, plasma insulin levels, and sympathetic activity to brown adipose tissue (BAT) and white adipose tissue (WAT) of Wistar rats, leading to rapid and progressive changes in the metabolic profile. The identification of suitable reference genes that are not affected by the experimental conditions is a critical step in accurate normalization of the reverse transcription quantitative real-time PCR (qRT-PCR), a commonly used assay to elucidate changes in the gene expression profile. In the present study, the effects of the cafeteria diet and sympathetic innervation on the gene expression of adrenoceptor beta 3 (Adrb3) from BAT and WAT were assessed using one of the most stable and one of the least stable genes as normalizers. Rats were fed the cafeteria diet and on the 17th day, interscapular BAT or retroperitoneal WAT was denervated and, 7 days after surgery, the contralateral innervated tissue was used as control. Ten reference genes were evaluated (18S, B2m, Actb, CypA, Gapdh, Hprt1, Rpl32, Tbp, Ubc, and Ywhaz) and ranked according to their stability using the following algorithms: geNorm, NormFinder, BestKeeper, and comparative delta threshold cycle (ΔC t ) method. According to the algorithms employed, the normalization of Adrb3 expression by the least stable genes produced opposite results compared with the most stable genes and literature data. In cafeteria and control diet-fed rats, the three most stable genes were Hprt1, Tbp, and Rpl32 for interscapular BAT and Tbp, B2m, and Hprt1 for retroperitoneal WAT, while the least stable genes were 18S, Actb, and Gapdh for both tissues.

Insulin as a hormone regulator of the synthesis and release of leptin by white adipose tissue.

Leptin and its receptor are widely distributed in several tissues, mainly in white adipose tissue. The serum leptin is highly correlated with body mass index in rodents and humans, being documented that leptin levels reduces in the fasting state and increase during refeeding, similarly to insulin release by pancreatic islets. Insulin appears to increase leptin mRNA and protein expression and its release by adipocytes. Some studies have suggested that insulin acts through the activation of the transcription factors: sterol regulatory element binding protein 1 (SREBP1), CCAAT enhancer binding protein-α (C/EBP-α) and specificity protein 1 (Sp1). Insulin stimulates the release of preformed and newly synthesized leptin by adipocytes through its signaling cascade. Its effects are blocked by inhibitors of the insulin signaling pathway, as well as by inhibitors of protein synthesis and agents that increase the intracellular cAMP. The literature data suggest that chronic hyperinsulinemia increases serum leptin levels in humans and rodents. In this review, we summarized the most updated knowledge on the effects of insulin on serum leptin levels, presenting the cell mechanisms that control leptin synthesis and release by the white adipose tissue.

Role of calcitonin gene-related peptide in energy metabolism.

PURPOSE: Calcitonin gene-related peptide (CGRP) is a neuropeptide produced by alternative tissue-specific splicing of the primary transcript of the CALC genes. CGRP is widely distributed in the central and peripheral nervous system, as well as in several organs and tissues. The presence of CGRP in the liver and brown and white adipose tissue suggests an effect of this neuropeptide on regulation of energy homeostasis. METHODS: In this review, we summarize the current knowledge of the effect of CGRP on the control of energy metabolism, primarily focusing on food intake, thermoregulation and lipid metabolism in adipose tissue, liver and muscle. RESULTS: CGRP induces anorexia, stimulating anorexigenic neuropeptide and/or inhibiting orexigenic neuropeptide expression, through cAMP/PKA pathway activation. CGRP also induces energy expenditure, increasing the skin temperature and brown adipose tissue thermogenesis. It has been also suggested that information related to peripheral lipid stores may be conveyed to the brain via CGRP-sensory innervation from adipose tissue. More recently, it was demonstrated that mice lacking αCGRP are protected from obesity induced by high-fat diet and that CGRP regulates the content of lipid in liver, muscle and adipose tissue. CONCLUSIONS: It is unclear the receptor responsible by CGRP effects, as well as whether this neuropeptide acts directly or indirectly in liver, muscle and adipose tissue.

Frequency of metabolic syndrome in children and adolescents from public schools of Divinópolis, Minas Gerais, Brazil, according to three international diagnostic criteria / Frequência de síndrome metabólica em crianças e adolescentes de escolas públicas de Divinópolis, Minas Gerais, Brasil, conforme três critérios diagnósticos internacionais

AIMS: To assess the frequency of metabolic syndrome in children and adolescents according to three international diagnostic criteria determining the level of agreement between these different criteria. METHODS: Waist circumference, blood pressure, blood glucose, high-density lipoprotein cholesterol, and serum triglycerides were evaluated in students from public schools of different regions of Divinópolis, MG, Brazil. Children and adolescents aged between 10 and 17 years were selected. Criteria adapted from the World Health Organization (WHO), National Cholesterol Education Program ­ Adult Treatment Panel III (NCEP/ATPIII), and International Diabetes Federation (IDF) were used for the diagnosis of metabolic syndrome. The kappa coefficient was used to evaluate the level of agreement among the three criteria. RESULTS: The study evaluated 202 students (86 boys and 116 girls). The frequency of metabolic syndrome was 1.16% for boys and none of the girls presented with metabolic syndrome, according to WHO criteria. According to the NCEP/ATPIII and IDF criteria, metabolic syndrome was not detected in the studied sample. Low blood levels of high-density lipoprotein cholesterol was the most frequent metabolic alteration in all teenagers according to the NCEP/ATPIII and IDF criteria, while body mass index was the most frequent one according to WHO criteria. The level of agreement for one altered parameter was poor when comparing WHO and NCEP/ATP/III, moderate when comparing WHO and IDF and high when comparing the NCEP/ATP/III and IDF criteria. CONCLUSIONS: Significant differences between the frequencies of individual metabolic syndrome parameters were found in the studied sample of children and adolescents, depending on the criteria used. According to WHO criteria, metabolic syndrome was found at a low frequency and only in boys, while the NCEP/ATPIII and IDF criteria did not diagnose metabolic syndrome. The present findings suggest the need to reach a consensus on the cut-off points for risk factors and a single diagnostic definition of metabolic syndrome in children and adolescents.

Esquizofrenia e o uso de álcool e outras drogas: perfil epidemiológico / Schizophrenia and the use of alcohol and other drugs: epidemiological profile

Este estudo teve como objetivo caracterizar o perfil sociodemográfico e clínico de pacientes esquizofrênicos e dependentes de álcool e outras drogas usuários de um Centro de Atenção Psicossocial III do Centro-Oeste de Minas Gerais, Brasil, no período julho de 1997 a julho de 2013. Configura-se como estudo epidemiológico descritivo, observacional e retrospectivo. A amostra foi composta por 1.618 pacientes e os principais resultados encontrados foram: prevalência do sexo masculino (60,4%) e da faixa etária de 21 a 30 anos (48,2%), abuso mais expressivo de álcool (35,6%) e de canabinóides (29,5%) e diagnóstico mais frequente de esquizofrenia paranoide (41,7%). Compreender os fatores associados a coexistência dessas duas patologias pode fornecer subsídios para a criação de estratégias intervencionistas que visem melhorar o prognóstico desses pacientes.