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1.
Medicine (Baltimore) ; 99(33): e21242, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871984

RESUMO

Currently there is no effective treatment for vascular dementia (VaD). Pharmacological treatment often lead to severe complications and require drug dosage adjustment. This study investigated the effect of scalp electroacupuncture combined with Memantine in VaD. The safety and antioxidative effect of scalp electroacupuncture were also explored.A retrospective study was conducted and data of inpatients of Linyi Central Hospital with VaD between June 2017 and May 2018 were collected and sorted. The patients were divided into scalp electroacupuncture-medication (A), scalp electroacupuncture (B) and medication (control) (C) groups, in which Memantine was prescribed as medication. Cognitive function, activities of daily living and quality of life assessed by Montreal Cognitive Assessment (MoCA), Barthel index and dementia quality of life questionnaire; the contents of superoxide dismutase, lipid peroxide and nitric oxide in blood samples; and adverse reaction were compared.Data from a total of 150 patients were collected (Group A, n = 55; Group B, n = 50; Group C, n = 45). The post-treatment/follow-up Montreal Cognitive Assessment, Barthel index and dementia quality of life questionnaire scores were significantly improved in all groups compared to pre-treatment (groups A and B, P<.01; group C, P<.05). The improvements were significant for groups A vs C, B vs C (P<0.01, both), and group A vs B (P<.05). The post-treatment/follow-up levels of lipid peroxide and nitric oxide decreased significantly while superoxide dismutase increased significantly in groups A and B compared to pre-treatment (P<.01, both). The differences were significant for groups A vs C, and B vs C (P < .01, both), but not significant between groups A and B (P > .05). There were no significant adverse events occurred during the study and follow-up.In combined treatment, scalp electroacupuncture works in parallel with Memantine and significantly increase the therapeutic effect in VaD with no significant adverse events. Scalp electroacupuncture may have the potential to serve as an option or alternative treatment for VaD. Scalp electroacupuncture may alleviate VaD symptoms through its antioxidative mechanism.


Assuntos
Demência Vascular/terapia , Eletroacupuntura , Memantina/uso terapêutico , Nootrópicos/uso terapêutico , Atividades Cotidianas , Idoso , Biomarcadores/sangue , Cognição/efeitos dos fármacos , Terapia Combinada , Demência Vascular/sangue , Eletroacupuntura/efeitos adversos , Eletroacupuntura/métodos , Feminino , Seguimentos , Humanos , Peróxidos Lipídicos/sangue , Masculino , Memantina/efeitos adversos , Óxido Nítrico/sangue , Nootrópicos/efeitos adversos , Qualidade de Vida , Estudos Retrospectivos , Couro Cabeludo , Superóxido Dismutase/sangue , Resultado do Tratamento
2.
Medicine (Baltimore) ; 99(37): e22167, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925783

RESUMO

BACKGROUND: The prevalence of cardiac syndrome X (CSX) is considerable. Some patients show recurrent angina attacks and have a poor prognosis. However, the knowledge of CSX pathophysiological mechanism is still limited, and the treatment fails to achieve a satisfactory suppression of symptoms. Nicorandil has a beneficial effect on improving coronary microvascular dysfunction (CMD). This study aims to evaluate the clinical effects and safety of nicorandil on CSX patients. METHODS: The Cochrane Library, Pubmed, EMBASE, ClinicalTrials.gov and 4 Chinese databases were searched to identify relevant studies. The Cochrane "Risk of bias" tool was used to assess the methodological quality of eligible studies. Meta-analysis was performed by RevMan 5.3 software. The Eggers test and meta-regression were performed by software Stata 14.0. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Twenty four randomized controlled trials (RCTs) involving 2323 patients were included. Most of the included studies were classified as having an unclear risk of bias because of poor reported methodology. The main outcomes are angina symptoms improvement, resting electrocardiogram (ECG) improvement, treadmill test result, and endothelial function. Meta-analysis showed that nicorandil had some benefit on improving angina symptoms (RR 1.24, 95% CI 1.19 to 1.29, I = 20%, P < .00001), resting ECG (RR = 1.24, 95% IC: 1.15 to 1.33, I = 0%, P < .00001), and prolonged the time to 1 mm ST-segment depression in treadmill test result (WMD = 38.41, 95% IC: 18.46 to 58.36, I = 0%, P = .0002). Besides nicorandil could reduce the level of endothelin-1 (ET-1) (SMD = -2.22, 95% IC: -2.61 to -1.83, I = 77%, P < .00001) and increase the level of nitric oxide (NO) (WMD = 27.45, 95% IC: 125.65 to 29.24, I = 81%, P < .00001). No serious adverse drug event was reported. The Eggers test showed that significant statistical publication bias was detected (Eggers test P = .000). The quality of evidence ranged from very low to low. CONCLUSIONS: Nicorandil shows the potential of improving angina symptoms, ECG, and endothelial dysfunction in patients with CSX. However, there is insufficient evidence for the clinical benefits of nicorandil due to the very low-quality evidence.


Assuntos
Angina Microvascular/tratamento farmacológico , Nicorandil/uso terapêutico , Vasodilatadores/uso terapêutico , Eletrocardiografia , Endotelina-1/sangue , Endotélio Vascular/efeitos dos fármacos , Teste de Esforço , Humanos , Óxido Nítrico/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Artigo em Inglês | MEDLINE | ID: mdl-32748882

RESUMO

Chronic cigarette smokers (CCS) are known to have elevated levels of carboxyhemoglobin (COHb). However, it is not known whether increased levels of COHb are associated with endothelial dysfunction (ED), and therefore the development of peripheral arterial disease (PAD). The aim of the study was to investigate the association of blood COHb and plasma nitric oxide (NO) levels, and whether it is an independent risk factor in the development of PAD among CCS at Dr George Mukhari Academic Hospital (DGMAH). A sample of 120 CCS with PAD and a convenience sample of 100 CCS without PAD were recruited into the study. Blood COHb levels were measured using the ABL 90 FLEX CO-oximeter automated spectroscopy. Plasma nitric oxide (NO) levels were measure using ELISA. Logistic regression analysis was used to investigate the association of blood COHb and plasma NO with PAD. Blood COHb levels of CCS with PAD were significantly higher than those of CCS without PAD, and the NO levels of CCS with PAD were significantly lower than those of CCS without PAD. Although both the blood COHb and plasma NO in CCS were significantly associated with PAD in bivariate logistic analysis, only plasma NO was independently associated with PAD in multivariate logistic analysis. This finding is consistent with the hypothesis that COHb is a cause of arterial damage in PAD, leading to reduced NO, and therefore reduced arterial dilation.


Assuntos
Carboxihemoglobina/análise , Fumar Cigarros/sangue , Óxido Nítrico/sangue , Doença Arterial Periférica/sangue , Adulto , Idoso , Artérias , Carboxihemoglobina/metabolismo , Estudos de Casos e Controles , Fumar Cigarros/efeitos adversos , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oximetria , Doença Arterial Periférica/patologia , Fumantes
4.
Medicine (Baltimore) ; 99(27): e20943, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629698

RESUMO

Angiotensin II mediates exercise-induced hypertension (EIH), which adversely impacts future cardiovascular health. There is paucity of data on the association between EIH and angiotensin II in well-trained middle-aged marathoners. Therefore, we investigated the renin-angiotensin-aldosterone-system and total nitric oxide activity in middle-aged marathoners with EIH.Seventy middle-aged marathoners were divided into 3 groups: normal blood pressure ([NBPG] [n = 21]), EIH group ([EIHG] [n = 35]), and complex hypertension group ([CHG] [n = 14]). We defined NBPG as resting systolic BP/diastolic BP (SBP/DBP) of ≤140/90 mm Hg and maximal exercise SBP of ≤210 mm Hg, EIHG as resting SBP/DBP ≤140/90 mm Hg and maximal exercise SBP of ≥210 mm Hg, and CHG as resting SBP/DBP ≥140/90 mm Hg and maximal exercise SBP of ≥210 mm Hg. Renin-angiotensin-aldosterone-system and NO levels were measured before and 30 minutes after the graded exercise test.Renin level was elevated while angiotensin level was reduced after 30 minutes of graded exercise test. There was no change in angiotensin I and angiotensin converting enzyme levels. Comparing the groups, renin level was only elevated in the CHG during recovery, while aldosterone level was higher than the baseline level in the recovery phase in all groups. Angiotensin I level remained unchanged in all groups. Angiotensin II level reduced significantly in the NBPG group but remained at the baseline in the EIHG and CHG groups. NO level was unchanged in the NBPG group but reduced in the EIHG and CHG groups after exercise. At 3 minutes of recovery, SBP was the highest in the NBPG group, followed by the EIHG and CHG groups (P < .05).In conclusion, angiotensin II activity and reduced NO level are associated with EIH in middle-aged long-distance runners. Angiotensin II inhibitors may; therefore, be the more appropriate antihypertensive medication for runners with EIH.


Assuntos
Angiotensina II/sangue , Exercício Físico , Hipertensão/fisiopatologia , Óxido Nítrico/sangue , Corrida , Adulto , Pressão Sanguínea , Humanos , Hipertensão/sangue , Masculino , Pessoa de Meia-Idade , Sistema Renina-Angiotensina
5.
Cardiovasc Pathol ; 49: 107257, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32674046

RESUMO

BACKGROUND: Chronic Chagas disease (CCHD) associated with Systemic Arterial Hypertension (SAH) is frequently found in areas where the disease is endemic. The pathogenesis of patients with both pathologies (CCHD-SAH) is unsettled. Nitric Oxide (NO) and Kinins are important players in the myocardial inflammation process in experimental CCHD. No previous study has addressed this question in patients with CCHD, particularly in those with CCHD-SAH. Accordingly, this study was undertaken in an attempt to contribute to the understanding of the pathogenesis of patients with CCHD-SAH. METHODS: Thirty-seven patients with a positive serology for Chagas disease were enrolled; 15 had CCHD alone, 22 had CCHD-SAH (abnormal ECG/Doppler echocardiogram plus a systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg on admission), and 11 had SAH alone. Thirty healthy individuals matched by age and sex served as controls. Plasma High-molecular (Hkg) and low-molecular weight (LKg) kininogens, plasma kallikrein levels (Pkal and Tcal), Kininase II, and plasma NO were measured. RESULTS: HKg and LKg were lower in CCHD-SAH patients in comparison with other groups (P < .0001). Pkal and Tcal were higher in CCHD-SAH patients in comparison with the other groups (P< .0001). Kininase II levels were similar in SAH, CCHD, and CCHD-SAH patients, but lower in comparison with controls (P< .0001). NO levels were similar in CCHD and CCHD-SAH patients, but higher in comparison with SAH patients and controls (P > .0001). CONCLUSION: Such findings suggest increased Kinin and NO activity in patients with CCHD-SAH, thus contributing to the understanding of the pathogenesis of this condition.


Assuntos
Pressão Arterial , Doença de Chagas/sangue , Hipertensão/sangue , Cininas/sangue , Óxido Nítrico/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Brasil/epidemiologia , Estudos de Casos e Controles , Doença de Chagas/diagnóstico , Doença de Chagas/epidemiologia , Doença de Chagas/fisiopatologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Regulação para Cima
6.
PLoS One ; 15(6): e0235095, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32589680

RESUMO

Our previous studies suggest that physical activity (PA) levels are potentially regulated by endogenous metabolic mechanisms such as the vasodilatory roles of nitric oxide (NO) production via the precursor arginine (ARG) and ARG-related pathways. We assessed ARG metabolism and its precursors [citrulline (CIT), glutamine (GLN), glutamate (GLU), ornithine (ORN), and phenylalanine (PHE)] by measuring plasma concentration, whole-body production (WBP), de novo ARG and NO production, and clearance rates in previously classified low-active (LA) or high-active (HA) mice. We assessed LA (n = 23) and HA (n = 20) male mice by administering a stable isotope tracer pulse via jugular catheterization. We measured plasma enrichments via liquid chromatography tandem mass spectrometry (LC-MS/MS) and body compostion by echo-MRI. WBP, clearance rates, and de novo ARG and NO were calculated. Compared to LA mice, HA mice had lower plasma concentrations of GLU (71.1%; 36.8 ± 2.9 vs. 17.5 ± 1.7µM; p<0.0001), CIT (21%; 57.3 ± 2.3 vs. 46.4 ± 1.5µM; p = 0.0003), and ORN (40.1%; 55.4 ± 7.3 vs. 36.9 ± 2.6µM; p = 0.0241), but no differences for GLN, PHE, and ARG. However, HA mice had higher estimated NO production ratio (0.64 ± 0.08; p = 0.0197), higher WBP for CIT (21.8%, 8.6 ± 0.2 vs. 10.7 ± 0.3 nmol/g-lbm/min; p<0.0001), ARG (21.4%, 35.0 ± 0.6 vs. 43.4 ± 0.7 nmol/g-lbm/min; p<0.0001), PHE (7.6%, 23.8 ± 0.5 vs. 25.6 ± 0.5 nmol/g-lbm/min; p<0.0100), and lower GLU (78.5%; 9.4 ± 1.1 vs. 4.1 ± 1.6 nmol/g lbm/min; p = 0.0161). We observed no significant differences in WBP for GLN, ORN, PHE, or de novo ARG. We concluded that HA mice have an activated whole-body ARG pathway, which may be associated with regulating PA levels via increased NO production.


Assuntos
Arginina/sangue , Atividade Motora , Óxido Nítrico/sangue , Animais , Cromatografia Líquida/métodos , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Condicionamento Físico Animal , Espectrometria de Massas em Tandem/métodos
7.
Tunis Med ; 98(2): 144-149, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32395804

RESUMO

BACKGROUND: Glaucoma is an optic neuropathy induced by many factors. Vascular dysfunction is involved in the mechanism underlying glaucoma. AIM: To determine the involvement of nitric oxide (NO), which is implicated in the regulation of ocular blood flow, in primary open angle glaucoma (POAG). Furthermore, lactate and uric acid (UA) levels were investigated. METHODS: Concentrations of NO, UA and lactate in plasma and aqueous humor (AH) were measured in 214 Tunisian patients (100 patients with POAG and 114 subjects with cataract as control group). NO metabolites, nitrate and nitrite (NOx) production were determined using the Griess reaction. UA and lactate concentrations were measured using enzymatic- colorimetric methods. RESULTS: NOx concentrations in patients with POAG were significantly lower compared to cataract group in plasma (5.23±1.55 µmol/L vs 18.35±6.87 µmol/L, p=0.01) and AH (20.54±7.41 µmol/L vs 45.25±10.92 µmol/L, p=0.02). Plasma and AH levels of lactate and UA were significantly higher in glaucoma patients than in control subjects. CONCLUSIONS: In the present study, decreased NO and increased UA and lactate levels were found in the AH and plasma of POAG patients compared to control subjects. These data suggest a possible involvement of these factors in glaucoma.


Assuntos
Glaucoma de Ângulo Aberto/metabolismo , Óxido Nítrico/metabolismo , Humor Aquoso/química , Humor Aquoso/metabolismo , Análise Química do Sangue , Estudos de Casos e Controles , Catarata/sangue , Catarata/metabolismo , Catarata/patologia , Feminino , Glaucoma de Ângulo Aberto/sangue , Glaucoma de Ângulo Aberto/patologia , Humanos , Ácido Láctico/análise , Ácido Láctico/sangue , Ácido Láctico/metabolismo , Masculino , Óxido Nítrico/análise , Óxido Nítrico/sangue , Tunísia , Ácido Úrico/análise , Ácido Úrico/sangue , Ácido Úrico/metabolismo
8.
Arch Biochem Biophys ; 688: 108408, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32470460

RESUMO

Vascular dysfunction and injurious stimuli such as oxidative stress is closely related to the risk of cardiovascular diseases (CVD). Dietary polyphenols is reported to exert the beneficial effects on reducing the risk of CVD. Black soybean is rich in polyphenols, including isoflavones, anthocyanidins and flavan-3-ols, and its prevention effects on CVD risk were reported in the animal experiments. In this study, we investigated the effect of black soybean consumption on the vascular function and oxidative stress associating with the polyphenol concentrations in healthy women. Lowered vascular age was observed in 33 out of 44 volunteers who completed the 8-week trial. It was observed that improvement of the vascular stiffness, increasing in the urinary NO2 and NO3 level, and decreasing in the oxidative stress markers, 8-hydroxy-2'-deoxyguanosine, hexanoyl-lysine and myeloperoxidase. In addition, concentration of 12 polyphenols in black soybean increased in the plasma and urine. Increased concentration of polyphenols would be involved in the decreased oxidative stress. Thus, black soybean consumption improved the vascular function through an increase in nitric oxide and a decrease in oxidative stress accompanied by increasing the polyphenol concentrations in healthy women.


Assuntos
Antioxidantes/farmacologia , Vasos Sanguíneos/efeitos dos fármacos , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/farmacologia , Soja/química , Administração Oral , Adulto , Idoso , Animais , Antioxidantes/administração & dosagem , Antioxidantes/análise , Biomarcadores/sangue , Biomarcadores/metabolismo , Biomarcadores/urina , Pressão Sanguínea , Feminino , Humanos , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Óxido Nítrico/urina , Fotopletismografia , Polifenóis/administração & dosagem , Polifenóis/sangue , Polifenóis/urina , Adulto Jovem
9.
Int J Mol Sci ; 21(7)2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32276345

RESUMO

Gastric ulcer (GU), a prevalent digestive disease, has a high incidence and is seriously harmful to human health. Finding a natural drug with a gastroprotective effect is needed. Ocotillol, the derivate of ocotillol-type saponins in the Panax genus, possesses good anti-inflammatory activity. The study aimed to investigate the gastroprotective effect of ocotillol on acetic acid-induced GU rats. The serum levels of endothelin-1 (ET-1) and nitric oxide (NO), the gastric mucosa levels of epidermal growth factor, superoxide dismutase and NO were assessed. Hematoxylin and eosin staining of gastric mucosa for pathological changes and immunohistochemical staining of ET-1, epidermal growth factor receptors and inducible nitric oxide synthase were evaluated. A UPLC-QTOF-MS-based serum metabolomics approach was applied to explore the latent mechanism. A total of 21 potential metabolites involved in 7 metabolic pathways were identified. The study helps us to understand the pathogenesis of GU and to provide a potential natural anti-ulcer agent.


Assuntos
Anti-Inflamatórios/farmacologia , Ginsenosídeos/farmacologia , Metabolômica , Úlcera Gástrica/prevenção & controle , Ácido Acético/toxicidade , Animais , Anti-Inflamatórios/uso terapêutico , Antiulcerosos/farmacologia , Endotelina-1/sangue , Ginsenosídeos/uso terapêutico , Masculino , Óxido Nítrico/sangue , Ratos , Ratos Wistar , Úlcera Gástrica/sangue , Úlcera Gástrica/induzido quimicamente
10.
Medicine (Baltimore) ; 99(11): e19292, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176054

RESUMO

BACKGROUND: The aim of the study was to provide a theoretical basis for the early diagnosis and prediction of acute altitude sickness, to provide a better entry mode for healthy people from plain areas to plateau areas, and to preliminarily clarify the possible mechanism of this approach. METHODS: We measured endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA), vascular endothelial growth factor (VEGF), nitric oxide (NO), and hypoxia-inducible factor 1 (HIF-1) levels in each sample and determined flow-mediated dilation (FMD) values using a portable OMRON color Doppler with a 7.0- to 12.0-MHz linear array probe. We used the Lewis Lake score to diagnose acute mountain sickness (AMS) and to stratify the disease severity. RESULTS: We found no cases of AMS at any of the studied elevation gradients. We found significant differences in FMD values between individuals when at 400 m above sea level and when at 2200, 3200, and 4200 m above sea level (P < .05) but found no significant differences among those at 2200, 3200, and 4200 m. Our variance analysis showed that serum ET-1, VEGF, ADMA, NO, and HIF-1 levels in individuals at ≥3000 m and those at subplateau and plain areas (<3000 m) significantly differed (P < .05). The level of these factors also significantly differed between individuals at elevation gradients of plateau areas (3260 m vs 4270 m) (P < .05). We found no significant differences in serum ET-1, VEGF, and ADMA levels between individuals at the plateau (2260 m) and plain (400 m) areas (P > .05). NO and HIF-1 levels were significantly different in serum samples from individuals between the plateau (2260 m) and plain (400 m) areas (P < .05). However, with increasing altitude, the NO level gradually increased, whereas ET-1, ADMA, VEGF, and HIF-1 levels showed a decreasing trend. With the increase of altitude, there is no correlation between the trend of FMD and hematologic-related factors such as VEGF, NO, and HIF-1. CONCLUSION: A healthy young male population ascending to a high-altitude area experiences a low incidence of AMS. Entering an acute plateau exposure environment from different altitude gradients may weaken the effect of acute highland exposure on vascular endothelial dysfunction in healthy individuals. Changes in serum ET-1, VEGF, ADMA, NO, and HIF-1 levels in healthy young men may be related to the body's self-regulation and protect healthy individuals from AMS. A short stay in a subplateau region may initiate an oxygen-free preconditioning process in healthy individuals, thereby protecting them from AMS. Noninvasive brachial artery endothelial function test instead of the detection of invasive hematologic-related factors for early diagnosis and prediction of the occurrence and severity of acute high-altitude disease is still lack of sufficient theoretical basis.


Assuntos
Doença da Altitude/sangue , Altitude , Endotelina-1/sangue , Fator 1 Induzível por Hipóxia/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Doença Aguda , Adulto , Doença da Altitude/diagnóstico , Análise de Variância , Biomarcadores/sangue , China , Diagnóstico Precoce , Voluntários Saudáveis , Humanos , Masculino , Militares , Óxido Nítrico/sangue , Valores de Referência , Sensibilidade e Especificidade , Adulto Jovem
11.
Gene ; 737: 144479, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32068124

RESUMO

BACKGROUND: Cardiac and renal dysfunction are often co-morbid pathologies leading to worsening prognosis resulting in difficulty in therapy of left ventricular hypertrophy (LVH). The aim of the current study was to determine the changes in expression of human ortholog genes of hypertension, vascular and cardiac remodeling and hypertensive nephropathy phenotypes under normal, disease and upon treatment with gasotransmitter including H2S (hydrogen sulphide), NO (nitric oxide) and combined (H2S + NO). METHODS: A total of 72 Wistar Kyoto rats (with equivalent male and female animals) were recruited in the present study where LVH rat models were treated with H2S and NO individually as well as with both combined. Cardiac and renal physical indices were recorded and relative gene expression were quantified. RESULTS: Both cardiac and renal physical indices were significantly modified with individual as well as combined H2S + NO treatment in control and LVH rats. Expression analysis revealed, hypertension, vascular remodeling genes ACE, TNFα and IGF1, mRNAs to be significantly higher (P ≤ 0.05) in the myocardia and renal tissues of LVH rats, while individual and combined H2S + NO treatment resulted in lowering the gene expression to normal/near to normal levels. The cardiac remodeling genes MYH7, TGFß, SMAD4 and BRG1 expression were significantly up-regulated (P ≤ 0.05) in the myocardia of LVH where the combined H2S + NO treatment resulted in normal/near to normal expression more effectively as compared to individual treatments. In addition individual as well as combined H2S and NO treatment significantly decreased PKD1 expression in renal tissue, which was up-regulated in LVH rats (P ≤ 0.05). CONCLUSIONS: The reduction in hemodynamic parameters and cardiac indices as well as alteration in gene expression on treatment of LVH rat model indicates important therapeutic potential of combined treatment with H2S + NO gasotransmitters in hypertension and cardiac hypertrophy when present as co-morbidity with renal complications.


Assuntos
Expressão Gênica/efeitos dos fármacos , Sulfeto de Hidrogênio/farmacologia , Hipertensão Renal/genética , Hipertensão/genética , Hipertrofia Ventricular Esquerda/genética , Nefrite/genética , Óxido Nítrico/farmacologia , Remodelação Vascular/genética , Remodelação Ventricular/genética , Animais , Progressão da Doença , Feminino , Humanos , Sulfeto de Hidrogênio/sangue , Masculino , Óxido Nítrico/sangue , Ratos , Ratos Endogâmicos WKY , Canais de Cátion TRPP/genética
12.
Oxid Med Cell Longev ; 2020: 7504521, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31998441

RESUMO

Serotonin is involved in the pathological processes of several liver diseases via the regulation of inflammatory response and oxidative stress. We aimed to investigate the role of serotonin in Concanavalin A- (Con A-) induced acute liver injury (ALI). ALI was induced in C57B/6 wild-type (WT) mice and tryptophan hydroxylase 1 (TPH1) knockout mice through tail vein injection of Con A (15 mg/kg body weight). Another group of TPH1 knockout ALI mice was supplied with 5-hydroxytryptophan (5-HTP) in advance to recover serotonin. The blood and liver tissues of mice were collected in all groups. Markedly increased serum levels of serotonin were identified after the injection of Con A. Increased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and stronger hepatic tissue pathology were detected, suggesting that serotonin could mediate Con A-induced liver damage. Serotonin significantly facilitated the release of serum and intrahepatic inflammatory cytokines, including interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-17A (IL-17A), interferon-gamma (IFN-γ), and tumor necrosis-alpha (TNF-α), after the administration of Con A. In addition, serotonin significantly increased the intrahepatic levels of oxidative stress markers malonaldehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) and decreased antioxidant stress indicator glutathione (GSH) in Con A-treated mice. Additionally, serotonin promoted hepatocyte apoptosis and autophagy based on B-cell lymphoma-2 (Bcl-2), Bcl-2-asociated X protein (Bax), and Beclin-1 levels and TUNEL staining. More importantly, serotonin activated nuclear factor kappa B (NF-κB) and upregulated the hepatic expressions of high mobility group protein B1 (HMGB1), toll-like receptor-4 (TLR4), and downstream molecules in Con A-mediated liver injury. Serotonin 2A receptor was upregulated in liver tissue after Con A injection, and serotonin 2A receptor antagonist Ketanserin protected against Con A-induced hepatitis. These results indicated that serotonin has the potential to aggravate Con A-induced ALI via the promotion of inflammatory response, oxidative stress injury, and hepatocyte apoptosis and the activation of hepatic HMGB1-TLR signaling pathway and serotonin 2A receptor.


Assuntos
Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/sangue , Concanavalina A/efeitos adversos , Serotonina/sangue , Transdução de Sinais/efeitos dos fármacos , Animais , Biomarcadores/sangue , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/patologia , Concanavalina A/farmacologia , Citocinas/sangue , Citocinas/genética , Masculino , Malondialdeído/sangue , Camundongos , Camundongos Knockout , Óxido Nítrico/sangue , Óxido Nítrico/genética , Peroxidase/sangue , Peroxidase/genética , Receptor 5-HT2A de Serotonina/genética , Receptor 5-HT2A de Serotonina/metabolismo , Serotonina/genética , Triptofano Hidroxilase/genética , Triptofano Hidroxilase/metabolismo
13.
BMC Cardiovasc Disord ; 20(1): 13, 2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931715

RESUMO

BACKGROUND: Liver disorders may be associated with normal pulmonary hemodynamic, hepatopulmonary syndrome (HPS), or portopulmonary hypertension (POPH). In this study, we aimed to investigate the effect of the severity of liver dysfunctions on blood-borne variables, and pulmonary hemodynamic during repeated ventilation with hyperoxic and hypoxic gases. METHODS: Female Sprague Dawley rats were assigned into four groups of Sham (n = 7), portal vein ligation (PPVL, n = 7), common bile duct ligation (CBDL, n = 7), and combination of them (CBDL+ PPVL, n = 7). Twenty-eight days later, right ventricular systolic pressure (RVSP) and systemic blood pressure were recorded in anesthetized animals subjected to repeated maneuvers of hyperoxia (O2 50%) and hypoxia (O2 10%). Besides, we assessed blood parameters and liver histology. RESULTS: Liver histology score, liver enzymes, WBC and plasma malondialdehyde in the CBDL+PPVL group were higher than those in the CBDL group. Also, the plasma platelet level in the CBDL+PPVL group was lower than those in the other groups. On the other hand, the serum estradiol in the CBDL group was higher than that in the CBDL+PPVL group. All the above parameters in the PPVL group were similar to those in the Sham group. During ventilation with hyperoxia gas, RVSP in the CBDL+PPVL group was higher than the ones in the other groups, and in the CBDL group, it was more than those in the PPVL and Sham groups. Hypoxic pulmonary vasoconstriction (HPV) was not detected in both CBDL+PPVL and CBDL groups, whereas, it retained in the PPVL group. CONCLUSION: Severe liver damage increases RVSP in the CBDL+PPVL group linked to the high level of ROS, low levels of serum estradiol and platelets or a combination of them. Furthermore, the high RVSP at the noted group could present a reliable animal model for POPH in female rats.


Assuntos
Hemodinâmica , Síndrome Hepatopulmonar/fisiopatologia , Hiperóxia/fisiopatologia , Hipóxia/fisiopatologia , Hepatopatias/fisiopatologia , Circulação Pulmonar , Anestesia Geral , Animais , Biomarcadores/sangue , Pressão Sanguínea , Ducto Colédoco/cirurgia , Modelos Animais de Doenças , Estradiol/sangue , Feminino , Síndrome Hepatopulmonar/sangue , Síndrome Hepatopulmonar/patologia , Hiperóxia/sangue , Hipóxia/sangue , Ligadura , Fígado/patologia , Hepatopatias/sangue , Hepatopatias/patologia , Malondialdeído/sangue , Óxido Nítrico/sangue , Veia Porta/cirurgia , Ratos Sprague-Dawley , Respiração Artificial , Índice de Gravidade de Doença , Função Ventricular Direita , Pressão Ventricular
14.
Genet Test Mol Biomarkers ; 24(1): 10-16, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31880470

RESUMO

Aims: To investigate the expression levels of serum interleukin-17 (IL-17) and interleukin-27 (IL-27) in children with bronchial asthma and to correlate these expression levels with lung function indicators. Methods: A total of 106 children with bronchial asthma (observation group: 76 in the acute attack phase, 30 in remission) and 60 healthy children (control group) aged 1-10 years were enrolled. Results: Levels of IL-17, IL-27, and fractional exhaled nitric oxide (FeNO) in the peripheral blood of children with bronchial asthma were higher compared to the control group. In addition, blood IL-17, IL-27, and FeNO levels in the children in the acute stage of bronchial asthma were higher compared with those in remission. The respiratory rate of children in the remission stage was lower compared with those in the acute stage, however, the other indicators were higher. IL-17, IL-27, and FeNO levels positively correlated with the respiratory rate and were negatively correlated with inspiratory time, expiratory time, peak time, and time to reach peak tidal expiratory flow/total expiratory time (TPTEF/TE; all p < 0.05). Conclusion: IL-17 and IL-27 levels are associated with the incidence and the development of bronchial asthma in children, and could be useful diagnostic markers. They may also effectively improve the specificity of FeNO for diagnosing the extent of lung injury in children.


Assuntos
Asma/imunologia , Interleucina-17/genética , Interleucinas/genética , Asma/genética , Asma/metabolismo , Criança , Pré-Escolar , China , Feminino , Volume Expiratório Forçado , Expressão Gênica/genética , Humanos , Lactente , Interleucina-17/análise , Interleucina-17/sangue , Interleucinas/análise , Interleucinas/sangue , Masculino , Óxido Nítrico/análise , Óxido Nítrico/sangue , Testes de Função Respiratória/métodos , Escarro/metabolismo
15.
Br J Nutr ; 123(2): 182-189, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31870463

RESUMO

A higher intake of food rich in flavonoids such as quercetin can reduce the risk of CVD. Enzymatically modified isoquercitrin (EMIQ®) has a bioavailability 17-fold higher than quercetin aglycone and has shown potential CVD moderating effects in animal studies. The present study aimed to determine whether acute ingestion of EMIQ® improves endothelial function, blood pressure (BP) and cognitive function in human volunteers at risk of CVD. Twenty-five participants (twelve males and thirteen females) with at least one CVD risk factor completed this randomised, controlled, crossover study. In a random order, participants were given EMIQ® (2 mg aglycone equivalent)/kg body weight or placebo alongside a standard breakfast meal. Endothelial function, assessed by flow-mediated dilatation (FMD) of the brachial artery was measured before and 1·5 h after intervention. BP, arterial stiffness, cognitive function, BP during cognitive stress and measures of quercetin metabolites, oxidative stress and markers of nitric oxide (NO) production were assessed post-intervention. After adjustment for pre-treatment measurements and treatment order, EMIQ® treatment resulted in a significantly higher FMD response compared with the placebo (1·80 (95 % CI 0·23, 3·37) %; P = 0·025). Plasma concentrations of quercetin metabolites were significantly higher (P < 0·001) after EMIQ® treatment compared with the placebo. No changes in BP, arterial stiffness, cognitive function or biochemical parameters were observed. In this human intervention study, the acute administration of EMIQ® significantly increased circulating quercetin metabolites and improved endothelial function. Further clinical trials are required to assess whether health benefits are associated with long-term EMIQ® consumption.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/epidemiologia , Cognição/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Quercetina/análogos & derivados , Administração Oral , Idoso , Artéria Braquial/efeitos dos fármacos , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Estresse Oxidativo/efeitos dos fármacos , Quercetina/administração & dosagem , Fatores de Risco , Voluntários
16.
Carbohydr Polym ; 229: 115405, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31826414

RESUMO

The fruit of Alpinia oxyphylla is often used in traditional Chinese medicine to treat dementia and memory defects. In this study, we isolated a novel acidic polysaccharide (AOP70-2-1) from A. oxyphylla fruit. Structural analysis showed that AOP70-2-1 consists of ß-D-GlcAp-(1→, →2,3,6)-α-D-Galp-(1→, α-L-Araf-(1→, →2,5)-α-L-Araf-(1→, →4)-α-D-Glcp-(1→, →3,4)-α-D-Xylp-(1→, →3,6)-ß-D-Manp-(1→, and α-L-Rhap-(1→. Morphological analysis indicated that AOP70-2-1 had an irregular sheet structure. The crude polysaccharide (AOP70) from A. oxyphylla significantly improved learning and memory ability of Alzheimer's disease (AD) mice, and AOP70 exhibited comparable or even better effects than huperzine A. Most important, AOP70 reduced NO, IL-1ß, TNF-α, and PGE-2 concentrations to normal levels. AOP70-2-1 significantly inhibited NO production in lipopolysaccharide stimulated BV2 microglial cells. Note that the effect of 2.6 µM AOP70-2-1 was superior to indomethacin. AOP70-2-1 also remarkably decreased the values of IL-6 and TNF-α. AOP70-2-1 may be a bioactive component of AOP70 and has the potential for the treatment of AD.


Assuntos
Alpinia , Doença de Alzheimer/tratamento farmacológico , Anti-Inflamatórios , Fármacos Neuroprotetores , Polissacarídeos , Doença de Alzheimer/sangue , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Linhagem Celular , Dinoprostona/sangue , Frutas , Interleucina-1beta/sangue , Masculino , Camundongos , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico/sangue , Polissacarídeos/química , Polissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/sangue
17.
Biol Pharm Bull ; 42(12): 2076-2082, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31787722

RESUMO

The cyclitol bornesitol is the main constituent of the leaves from the antihypertensive medicinal plant Hancornia speciosa. This study aimed to investigate the ability of bornesitol to reduce blood pressure and its mechanism of action. Normotensive Wistar rats were divided into control group and bornesitol groups treated intravenously with bornesitol (0.1, 1.0 and 3.0 mg/kg). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded in non-anesthetized awake animals. Nitric oxide (NO) and angiotensin-converting enzyme (ACE) were measured in plasma by using colorimetric methods. Vascular reactivity study was performed in rat aorta rings and the involvement of nitric oxide synthase (NOS), calcium-calmodulin complex and phosphatidylinositol-3-kinase (PI3K)/Akt pathway in the vasodilator effect was investigated. Administration of bornesitol significantly reduced the SBP, increased the plasmatic level of nitrite, and decreased ACE activity in normotensive rats. In the rat aorta, bornesitol induced endothelium-dependent vasodilatation, which was abolished by NOS blockade. While calcium-calmodulin complex inhibition decreased the vasodilator effect of bornesitol, the inhibition of PI3K/Akt pathway did not alter it. Bornesitol reduced the blood pressure by a mechanism involving an increased production or bioavailability of NO, inhibition of ACE, and by an endothelium- and NO-dependent vasodilator effect. The present results support the use of bornesitol as an active marker for the cardiovascular activity of Hancornia speciosa.


Assuntos
Anti-Hipertensivos/farmacologia , Apocynaceae , Ciclitóis/farmacologia , Vasodilatadores/farmacologia , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Brasil , Masculino , Óxido Nítrico/sangue , Nitritos/sangue , Peptidil Dipeptidase A/sangue , Folhas de Planta , Plantas Medicinais , Ratos Wistar
18.
BMC Neurol ; 19(1): 323, 2019 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-31837702

RESUMO

BACKGROUND: In recent years, the role of neuroinflammation and oxidative stress in migraine pathogenesis has achieved considerable interest; however, to date findings are equivocal. Thus, the objective of this study was to investigate biomarkers of oxidative stress in episodic and chronic migraineurs (EM and CM patients) and controls. METHODS: Forty-four patients with EM, 27 individuals with CM and 19 age-sex-matched controls were enrolled. After collecting data on demographic and headache characteristics, blood samples were collected and analyzed to detect serum levels of oxidative stress biomarkers (malondialdehyde (MDA) and nitric oxide (NO)); total antioxidant capacity using Trolox equivalent antioxidant capacity (TEAC) assay; and antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase-1 (GPx-1)). RESULTS: Serum levels of CAT and SOD were significantly lower in the CM group than the EM group and controls. However, serum GPx-1 levels of the CM patients were slightly higher than the EM patients and controls (P-value≤0.001). CM patients had lower mean TEAC values than EM patients and controls. In addition, serum levels of NO and MDA were significantly elevated among subjects with CM compared to EM and control individuals (P-value≤0.001). Pearson correlation analysis revealed negative correlations between the number of days of having headaches per month and serum concentrations of the two antioxidant enzymes CAT (r = - 0.60, P-value< 0.001) and SOD (r = - 0.50, P-value< 0.001) as well as TEAC values (r = - 0.61, P-value< 0.001); however, there were positive correlations between headache days and serum GPx-1 levels (r = 0.46, P-value< 0.001), NO (r = 0.62, P-value< 0.001), and MDA (r = 0.64, P-value< 0.001). CONCLUSION: Present findings highlighted that chronic migraineurs had lower total non-enzymatic antioxidant capacity and higher oxidative stress than episodic migraineurs and control individuals. Although more studies are needed to confirm these data, applying novel prophylactic medications or dietary supplements with antioxidant properties could be promising in migraine therapy.


Assuntos
Biomarcadores/sangue , Transtornos de Enxaqueca/sangue , Estresse Oxidativo/fisiologia , Adulto , Estudos de Casos e Controles , Catalase/sangue , Feminino , Glutationa Peroxidase/sangue , Humanos , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Capacidade de Absorbância de Radicais de Oxigênio , Superóxido Dismutase/sangue
19.
Food Funct ; 10(12): 7707-7713, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31746877

RESUMO

Berry fruits contain a variety of bioactive polyphenolic compounds that exhibit potent antioxidant and anti-inflammatory activities. We have shown that consumption of freeze-dried whole berry powder, equivalent to 1 cup per day of blueberry (BB) or 2 cups per day of strawberry (SB), can differentially improve some aspects of cognition in healthy, older adults, compared to placebo-supplemented controls. We investigated whether fasting and postprandial serum from BB- or SB-supplemented older adults (60-75 years), taken at baseline or after 45 or 90 days of supplementation, would reduce the production of inflammatory and oxidative stress markers compared to serum from a placebo group, in LPS-stressed HAPI rat microglial cells, in vitro. Serum from both BB- and SB-supplemented participants reduced nitrite production, iNOS and COX-2 expression, and TNF-alpha release relative to serum from placebo controls (p < 0.05). Protection was greatest with serum from the 90-day time-point, suggesting that ongoing supplementation may provide the most health benefits. Serum was protective in both fasted and postprandial conditions, indicating that the effects are not only acute and that the meal did not challenge subjects' ability to regulate oxidative and inflammatory stress. These results suggest that berry metabolites, present in the circulating blood following ingestion, may be mediating the anti-inflammatory effects of dietary berry fruit.


Assuntos
Envelhecimento/sangue , Mirtilos Azuis (Planta)/metabolismo , Fragaria/metabolismo , Estresse Oxidativo , Idoso , Envelhecimento/imunologia , Animais , Método Duplo-Cego , Feminino , Frutas/metabolismo , Humanos , Masculino , Microglia/imunologia , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo II/sangue , Período Pós-Prandial , Ratos , Fator de Necrose Tumoral alfa/sangue
20.
Mediators Inflamm ; 2019: 5091630, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772504

RESUMO

Infection with the protozoan Trypanosoma cruzi causes Chagas disease and consequently leads to severe inflammatory heart condition; however, the mechanisms driving this inflammatory response have not been completely elucidated. Nitric oxide (NO) is a key mediator of parasite killing in T. cruzi-infected mice, and previous studies have suggested that leukotrienes (LTs) essentially regulate the NO activity in the heart. We used infected 5-lipoxygenase-deficient mice (5-LO-/-) to explore the participation of nitric oxide synthase isoforms, inducible (iNOS) and constitutive (cNOS), in heart injury, cytokine profile, and oxidative stress during the early stage of T. cruzi infection. Our evidence suggests that the cNOS of the host is involved in the resistance of 5-LO-/- mice during T. cruzi infection. iNOS inhibition generated a remarkable increase in T. cruzi infection in the blood and heart of mice, whereas cNOS inhibition reduced cardiac parasitism (amastigote nests). Furthermore, this inhibition associates with a higher IFN-γ production and lower lipid peroxidation status. These data provide a better understanding about the influence of NO-interfering therapies for the inflammatory response toward T. cruzi infection.


Assuntos
Araquidonato 5-Lipoxigenase/sangue , Doença de Chagas/sangue , Doença de Chagas/enzimologia , Animais , Antioxidantes/metabolismo , Citocinas/sangue , Camundongos , Camundongos Knockout , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo II/sangue , Trypanosoma cruzi/patogenicidade
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