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OBJECTIVE: Evaluate autonomic function and low-grade inflammation and characterize the correlation between these variables in schoolchildren with obesity living in the Brazilian northeast region. METHODS: 84 children with obesity and 41 with normal weight were included in this cross-sectional study. Anthropometry, body composition, blood pressure (BP), inflammatory biomarkers, and heart rate variability (HRV) indexes were analyzed in children aged 7 to 11 years. RESULTS: children with obesity had increased systolic (p = 0.0017) and diastolic (p = 0.0131) BP and heart rate (p = 0.0022). The children with obesity displayed significantly lower SDNN, RMSSD, NN50, HF (ms), HF (nu), SD1, SD2, and higher LF (ms), LF (nu), LF/HF, SD1/SD2, DFA-α1, and DFA-α2, compared to normal weight. A lower and higher capacity for producing IL-10 (p = 0.039) and IL-2 (p = 0.009), respectively, were found in children with obesity compared to children with normal weight. Although IL-2, IL-4 and IL17A did not correlate with HRV parameters, IL-6 was positively correlated with SDNN, LF (ms) and SD2, TNF-α was positively correlated with LF/HF and SD1/SD2 ratio, and IFN-γ was positively correlated with SDNN, RMMSSD, NN50, LF (ms), HF (ms), SD1, and SD2. CONCLUSIONS: The findings suggest that children with obesity have impaired autonomic function and systemic low-grade inflammation compared to children within the normal weight range, the inflammatory biomarkers were correlated with HRV parameters in schoolchildren living in the northeastern region of Brazil.
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Interleucina-2 , Obesidade , Criança , Humanos , Brasil/epidemiologia , Estudos Transversais , Inflamação , Frequência Cardíaca/fisiologia , BiomarcadoresRESUMO
Abstract Objective Evaluate autonomic function and low-grade inflammation and characterize the correlation between these variables in schoolchildren with obesity living in the Brazilian northeast region. Methods 84 children with obesity and 41 with normal weight were included in this cross-sectional study. Anthropometry, body composition, blood pressure (BP), inflammatory biomarkers, and heart rate variability (HRV) indexes were analyzed in children aged 7 to 11 years. Results children with obesity had increased systolic (p= 0.0017) and diastolic (p= 0.0131) BP and heart rate (p= 0.0022). The children with obesity displayed significantly lower SDNN, RMSSD, NN50, HF (ms), HF (nu), SD1, SD2, and higher LF (ms), LF (nu), LF/HF, SD1/SD2, DFA-α1, and DFA-α2, compared to normal weight. A lower and higher capacity for producing IL-10 (p= 0.039) and IL-2 (p= 0.009), respectively, were found in children with obesity compared to children with normal weight. Although IL-2, IL-4 and IL17A did not correlate with HRV parameters, IL-6 was positively correlated with SDNN, LF (ms) and SD2, TNF-α was positively correlated with LF/HF and SD1/SD2 ratio, and IFN-γ was positively correlated with SDNN, RMMSSD, NN50, LF (ms), HF (ms), SD1, and SD2. Conclusions The findings suggest that children with obesity have impaired autonomic function and systemic low-grade inflammation compared to children within the normal weight range, the inflammatory biomarkers were correlated with HRV parameters in schoolchildren living in the northeastern region of Brazil.
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Organic nitrates are widely used to restore endogenous nitric oxide (NO) levels reduced by endothelial nitric oxide synthase dysfunction. However, these drugs are associated with undesirable side effects, including tolerance. This study aims to investigate the cardiovascular effects of the new organic nitrate 1,3-diisobutoxypropan-2-yl nitrate (NDIBP). Specifically, we assessed its effects on blood pressure, vascular reactivity, acute toxicity, and the ability to induce tolerance. In vitro and ex vivo techniques showed that NDIBP released NO both in a cell-free system and in isolated mesenteric arteries preparations through a process catalyzed by xanthine oxidoreductase. NDIBP also evoked endothelium-independent vasorelaxation, which was significantly attenuated by 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl 3-oxide (PTIO, 300 µM), a nitric oxide scavenger; 1-H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10 µM), a soluble guanylyl cyclase inhibitor; tetraethylammonium (TEA, 3 mM), a potassium channel blocker; febuxostat (500 nM), a xanthine oxidase inhibitor; and proadifen (10 µM), an inhibitor of cytochrome P450 enzyme. Furthermore, this organic nitrate did not induce tolerance in isolated vessels and presented low toxicity following acute oral administration. In vivo changes on cardiovascular parameters were assessed using normotensive and renovascular hypertensive rats. NDIBP evoked a reduction of blood pressure that was significantly higher in hypertensive animals. Our results suggest that NDIBP acts as a NO donor, inducing blood pressure reduction without having the undesirable effects of tolerance. Those effects seem to be mediated by activation of NO-sGC-cGMP pathway and positive modulation of K+ channels in vascular smooth muscle.
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Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Artérias Mesentéricas/efeitos dos fármacos , Nitratos/uso terapêutico , Doadores de Óxido Nítrico/uso terapêutico , Vasodilatadores/uso terapêutico , Animais , Anti-Hipertensivos/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Feminino , Hipertensão/metabolismo , Masculino , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/metabolismo , Canais de Potássio/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Guanilil Ciclase Solúvel/metabolismo , Vasodilatadores/metabolismo , Xantina Desidrogenase/metabolismoRESUMO
This study aimed to evaluate the effects of ingestion of live (9 log CFU mL-1) and ultrasound-inactivated (paraprobiotic, 20 kHz, 40 min) Lacticaseibacillus casei 01 cells for 28 days on healthy parameters (biochemical and cardiovascular) and intestinal microbiota (amplicon sequencing of 16S ribosomal RNA) of rats fed a high-fat diet. Twenty-four male Wistar rats were divided into four groups of six animals: CTL (standard diet), HFD (high-fat diet), HFD-LC (high-fat diet and live L. casei), and HFD-ILC (high-fat diet and inactivated L. casei). The administration of live and ultrasound-inactivated L. casei prevented the increase (p < 0.05) in cholesterol levels (total and LDL) and controlled the insulin resistance in rats fed a high-fat diet. Furthermore, it promoted a modulation of the intestinal microbial composition by increasing (p < 0.05) beneficial bacteria (Lachnospiraceae and Ruminoccocaceae) and decreasing (p < 0.05) harmful bacteria (Clostridiaceae, Enterobacteriaceae, and Helicobacteriacea), attenuating the effects promoted by the HFD ingestion. Only live cells could increase (p < 0.05) the HDL-cholesterol, while only inactivated cells caused attenuation (p < 0.05) of the blood pressure. Results show beneficial effects of live and inactivated L. casei 01 and indicate that ultrasound inactivation produces a paraprobiotic with similar or improved health properties compared to live cells.
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Sistema Cardiovascular , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Lactobacillaceae/fisiologia , Lactobacillaceae/efeitos da radiação , Ondas Ultrassônicas , Animais , Bactérias/classificação , Bactérias/genética , Peso Corporal , Ingestão de Alimentos , Microbioma Gastrointestinal/genética , Resistência à Insulina , Intestinos/microbiologia , Masculino , Probióticos/farmacologia , RNA Ribossômico 16S , Ratos , Ratos WistarRESUMO
BACKGROUND AND AIM: Obese individuals with recommendation for bariatric surgery (BS) exhibit increased cardiovascular risk. The association of obesity with comorbidities, such as arterial hypertension (HTN) and type 2 diabetes mellitus (T2DM) can worsen cardiovascular dysfunction. This study aimed to investigate the effect of HTN on cardiac autonomic function and whether diabetes exacerbates HTN-related impairment of autonomic function in obese subjects. METHODS: Samples (n=63) were allocated to three groups: Obese without HTN and T2DM (n=29), Obese with HTN (OHTN, n=17) and OHTN with T2DM (OHTN+T2DM, n=17), in which anthropometric measures, body composition, blood biochemical parameters, blood pressure (BP) and heart rate variability (HRV) were evaluated. RESULTS: The age was higher in OHTN+T2DM and OHTN than in obese groups (p<0.05). OHTN+T2DM individuals had increased neck circumference and compromised glycemic profile when compared to obese and OHTN groups (p<0.05). Mean values for standard deviation of RR (SDRR), square root of the mean squared differences of successive RR interval (RMSSD) and number of pairs of successive normal-to-normal beat intervals that differed by 50 ms (pRR50) were significantly lower in OHTN+T2DM and OHTN groups when compared to patients with obesity alone (p<0.05). The low frequency (LF), low frequency/high frequency (LF/HF) ratio were higher in the OHTN+T2DM and OHTN than subjects with obesity alone (p<0.05). Nonlinear parameters SD2 and SD1 were also lower in the OHTN+T2DM when compared to the obese group (p<0.05). However, the SD2/SD1 ratio was higher in the OHTN+T2DM and OHTN groups than the obese group. CONCLUSION: T2DM and/or HTN impair the cardiac autonomic function in obese patients. However, the presence of T2DM did not exacerbate the hypertension-related impairment of autonomic function.
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Hypertension and metabolic disorders evidenced in adults who have been exposed to nutritional insults during early life may be sex-dependent. We evaluated if blood pressure (BP), cardiorespiratory control, and metabolic parameters are affected in female offspring (FO) from dams fed a dyslipidaemic diet during pregnancy and lactation. FO was obtained from dams who received control (CTL) or dyslipidaemic diets during pregnancy and lactation. The effects of a maternal dyslipidaemic diet on BP, cardiorespiratory control, and biochemical parameters were assessed at 30 and 90 days of age. The experimental protocol based on a dyslipidaemic diet intervention was effective in developing maternal dyslipidemia. At 30 days of age, the FO from dyslipidaemic dams displayed disordered respiratory pattern, enhanced ventilatory response to hypercapnia (P < 0.05), and increased serum levels of total cholesterol and triglycerides (P < 0.05) when compared with CTL female offspring. At 90 days of age, FO from dyslipidaemic dams had augmented BP (P < 0.05), exacerbated cardiorespiratory responses to hypercapnia (P < 0.05), enhanced pressor responses to peripheral chemoreflex activation (P < 0.05), impaired baroreflex (P < 0.05), and larger delta variations in arterial pressure after ganglionic blockade (P < 0.05). Furthermore, during oral glucose and insulin tolerance tests, FO from dyslipidaemic dams exhibited altered glucose tolerance and insulin sensitivity (P < 0.05) when compared with FO from CTL dams. Altered breathing linked to enhanced central and peripheral chemosensitivity, impaired baroreflex, and augmented sympathetic tone may be predisposing factors for increased BP and metabolic disorders in female offspring from dyslipidaemic dams.
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Glicemia/metabolismo , Pressão Sanguínea , Fenômenos Fisiológicos Cardiovasculares , Dislipidemias/fisiopatologia , Lactação , Efeitos Tardios da Exposição Pré-Natal , Envelhecimento , Fenômenos Fisiológicos da Nutrição Animal , Animais , Feminino , Homeostase/fisiologia , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Ratos , Ratos Wistar , Triglicerídeos/sangueRESUMO
A particularly phenolic-rich fraction extracted from red wine from the São Francisco valley (Northeastern Brazil) was chemically characterized and its hypotensive and antioxidant effects on spontaneously hypertensive rats were studied both in vitro and in vivo. The liquid-liquid pH dependent fractionation scheme afforded a fraction with high content of bioactive phenolics such as flavonols, flavonol glycosides, phenolic acids and anthocyanins, whose identities were confirmed by liquid chromatography coupled to mass spectrometry analysis. Pretreatment of spontaneously hypertensive rats with this wine fraction at doses of 50 and 100 mg/kg by gavage. for 15 days was able to decrease mean arterial pressure and heart rate as well as decrease serum lipid peroxidation. The fraction at concentrations of 0.01-1000 µg/mL induced concentration-dependent relaxation of isolated rat superior mesenteric artery rings pre-contracted with phenylephrine and this effect was not attenuated by endothelium removal. Our results demonstrate it is possible for phenolic constituents of red wine that are orally bioavailable to exert in vivo hypotensive and antioxidant effects on intact endothelial function.
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Anti-Hipertensivos/farmacologia , Antioxidantes/farmacologia , Polifenóis/farmacologia , Vinho/análise , Animais , Antocianinas/análise , Antocianinas/farmacologia , Anti-Hipertensivos/análise , Antioxidantes/análise , Pressão Sanguínea , Brasil , Flavonóis/análise , Flavonóis/farmacologia , Concentração de Íons de Hidrogênio , Hidroxibenzoatos/análise , Hidroxibenzoatos/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Polifenóis/análise , Ratos , Ratos Endogâmicos SHR , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Nutritional intervention with antioxidants rich foods has been considered a strategy to minimize the effects of overtraining in athletes. This experimental, randomized, and placebo-controlled study evaluated the effects of consumption of sesame (Sesamum indicum L.) on muscle damage markers, oxidative stress, systemic inflammation, and aerobic performance in male semi-professional soccer players. Twenty athletes were randomly assigned to groups that received 40 g (two tablespoons) per day of sesame or a placebo during 28 days of regular training (exposed to routine training that includes loads of heavy training in the final half of the season). Before and after intervention, creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), C-reactive protein (hs-CRP), and aerobic capacity were evaluated. Before intervention, a physiologic imbalance was noted in both groups related to CK and LDH levels. Sesame intake caused a reduction of CK (19%, p < 0.05), LDH (37%, p < 0.05), MDA (55%, p < 0.05) and hs-CRP (53%, p < 0.05) and increased SOD (14%, p < 0.05), vitamin A (25%, p < 0.05), and vitamin E (65%, p < 0.05) in the experimental group. These phenomena were accompanied by increased aerobic capacity (17%, p < 0.05). The placebo group showed an increase in CK (5%, p < 0.05) and no significant change in LDH, SOD or vitamin A. MDA levels decreased (21%, p < 0.05) and vitamin E increased (14%, p < 0.05) in the placebo group, but to a much lesser extent than in the experimental group. These results show that sesame consumption may reduce muscle damage and oxidative stress while improving the aerobic capacity in soccer players.
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The follow-up of phytochemical and pharmacological studies of Sida rhombifolia L. (Malvaceae) aims to strengthen the chemosystematics and pharmacology of Sida genera and support the ethnopharmacological use of this species as hypotensive herb. The present work reports phytoconstituents isolated and identified from aerial parts of S. rhombifolia by using chromatographic and spectroscopic methods. The study led to the isolation of scopoletin (1), scoporone (2), ethoxy-ferulate (3), kaempferol (4), kaempferol-3-O-ß-d-glycosyl-6''-α-d-rhamnose (5), quindolinone (6), 11-methoxy-quindoline (7), quindoline (8), and the cryptolepine salt (9). The alkaloids quindolinone (6) and cryptolepine salt (9) showed vasorelaxant activity in rodent isolated mesenteric arteries.
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Alcaloides/química , Anti-Hipertensivos/química , Malvaceae/química , Fenóis/química , Compostos Fitoquímicos/química , Vasodilatadores/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Anti-Hipertensivos/isolamento & purificação , Anti-Hipertensivos/farmacologia , Cumarínicos/química , Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , Relação Dose-Resposta a Droga , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Humanos , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiologia , Fenóis/isolamento & purificação , Fenóis/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Ratos , Técnicas de Cultura de Tecidos , Vasodilatadores/isolamento & purificação , Vasodilatadores/farmacologiaRESUMO
Renal artery stenosis is frequently associated with resistant hypertension, which is defined as failure to normalize blood pressure (BP) even when combined drugs are used. Inhibition of PDE5 by sildenafil has been shown to increase endothelial function and decrease blood pressure in experimental models. However, no available study evaluated the baroreflex sensitivity nor autonomic balance in renovascular hypertensive rats treated with sildenafil. In a translational medicine perspective, our hypothesis is that sildenafil could improve autonomic imbalance and baroreflex sensitivity, contributing to lower blood pressure. Renovascular hypertensive 2-kidney-1-clip (2K1C) and sham rats were treated with sildenafil (45 mg/Kg/day) during 7 days. At the end of treatment, BP and heart rate (HR) were recorded in conscious rats after a 24-h-recovery period. Spontaneous and drug-induced baroreflex sensitivity and autonomic tone were evaluated; in addition, lipid peroxidation was measured in plasma samples. Treatment was efficient in increasing both spontaneous and induced baroreflex sensitivity in treated hypertensive animals. Inhibition of PDE5 was also capable of ameliorating autonomic imbalance in 2K1C rats and decreasing systemic oxidative stress. Taken together, these beneficial effects resulted in significant reductions in BP without affecting HR. We suggest that sildenafil could be considered as a promising alternative to treat resistant hypertension.
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Cardiovascular diseases can be considered the most important cause of death in diabetic population and diabetes can in turn increase the risk of cardiovascular events. Inflammation process is currently recognized as responsible for the development and maintenance of diverse chronic diseases, including diabetes and atherosclerosis. Considering that adipose tissue is an important source of adipokines, which may present anti and proinflammatory effects, the aim of this review is to explore the role of the main adipokines in the pathophysiology of diabetes and atherosclerosis, highlighting the therapeutic options that could arise from the manipulation of these signaling pathways both in humans and in translational models.
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The objective of this study was to develop a pharmaceutical O/W emulsion containing plant-derived polyphenol extracts and evaluate its stability and antioxidant activity. O/W emulsions were prepared using ionic surfactant polysorbate 80 (Tween 80®). The odorwas adjusted with few drops of blue sea fragrance. DPPH (1,1-diphenyl-2-picrylhydrazyl) assay was used to evaluate the antioxidant activity of the plant extracts alone and emulsions containing these extracts. Physical stability was assessed by submitting the emulsions to storage at 8 ºC, 25 ºC, 40 ºC and 40 ºC + 70% RH (relative humidity) for two months. Various physical characteristics of emulsions monitored, include color, creaming, liquefaction, centrifugation and pH. Brookfield rotational rheometer was used to determined viscosities and rheological behavior of emulsions. Different types of emulsion were determined microscopically, while pH values of emulsions were measured by a pH meter. Electrical conductivity data confirmed that the outer phase was water. Samples presented an acceptable pH value for an external topical use. Shear thinning behaviour was observed for all emulsions. The polyphenol-rich-plant-derived extracts alone and the extract containing emulsions showed good antioxidant activities. This research confirmed that the method used was suitable for preparing emulsions with Hippophae rhamnoids and Cassia fistula extracts, suggesting that those emulsions are suitable for topical use.
O presente estudo objetivou o desenvolvimento de uma emulsão farmacêutica óleo-água contendo extratos de plantas ricos em polifenóis, a comparação à sua formulação-controle e a avaliação de sua estabilidade, assim como de sua capacidade antioxidante. Extrato concentrado de Hippophae rhamnoids e Cassia fistula foi encapsulado no interior da fase oleosa da emulsão O/W. As emulsões foram preparadas usando o tensoativo iônico monooleato sorbital de polioxietileno (Tween 80®). O odor foi ajustado pela adição de algumas gotas de fragrância azul do mar. O ensaio do DPPH (1,1-difenil-2-picrilidrazil) foi utilizado para avaliar a atividade antioxidante dos extratos de plantas sozinhos e nas emulsões contendo os extratos. A estabilidade física foi avaliada submetendo os cremes a diferentes temperaturas de estocagem, como a 8 ºC, 25 ºC e 40 ºC e a 40% + 70% de umidade relativa por um período de 2 meses. As características físicas das emulsões foram monitoradas por 2 meses incluindo cor, cremosidade, liquefação, centrifugação e pH. O reômetro rotacional de Brookfield foi utilizado para determinar a viscosidade e o comportamento reológico das emulsões. O programa Rheocalc Brookfield foi utilizado para análise dos dados. As características organolépticas também foram avaliadas. O tipo de emulsão foi determinado microscopicamente, enquanto o pH das emulsões foi avaliado por meio de um pHmetro. A estabilidade farmacêutica esperada das emulsões foi alcançada dentro dos dois meses de estudo. Os resultados da condutividade elétrica confirmaram que a fase externa da emulsão era composta de água. O pH das amostras estava dentro da normalidade para uso tópico. A emulsão apresentou boa fragrância e pode ser retirada da pele com água após a aplicação, características desejáveis em emulsões O/W. Os extratos vegetais ricos em polifenóis isolados ou nas emulsões apresentaram boa atividade antioxidante. Nossos estudos confirmaram que o método utilizado foi adequado para preparar a emulsão semi-sólida contendo extratos de Hippophae rhamnoids e Cassia fistula. Nossos achados sugerem que emulsões contendo extratos de Hippophae rhamnoids e Cassia fistula são adequados para o uso tópico.