Treatment-Resistant Hypertension: An Update in Device Therapy

Resistant hypertension (RH) is a clinical condition in which the hypertensive patient has become resistant to drug therapy and is often associated with increased cardiovascular morbidity and mortality. Several signaling pathways have been studied and related to the development and progression of RH: modulation of sympathetic activity by leptin and aldosterone, primary aldosteronism, arterial stiffness, endothelial dysfunction, and variations in the renin-angiotensin-aldosterone system (RAAS)

Estudo das atividades xilanásicas produzidas pelo fungo Aspergillus caespitosus

A parede celular de planta é constituída por três componentes principais: celulose, hemicelulose e lignina. Entre as hemicelulose, xilana é o heteropolissacarídeo mais comum, e a principal enzima responsável por sua degradação é por Aspergillus caespitosus cultivado em fermentações submersa (FSM) ou semi-sólida (FSS). As xilanases foram purificadas, caracterizadas e testadas no branqueamento da polpa de celulose. Em relação a FSM, o melhor meio de produção xilanásica foi o SR suplementado com 1% de farelo de trigo (FT) ou bagaço de cana-de-açúcar (BCA), mais peptona 0,25% ou 0,1%, respectivamente. As fermentações foram realizadas a 40ºC durante 48 horas em meios com pH iniciais de 8,0 (BCA) ou 6,0 (FT). Não houve ativação enzimática com a adição de íons metálicos, principalmente com as amostras obtidas dos meios com BCA. As xilanases obtidas do meio com BCA foram inativadas termicamente a 55ºC e 65ºC, mais rápido do que as xilanases presentes nos filtrados das culturas com FT. Adição de diferentes concentrações de glicose no meio suplementado com BCA ou FT reduziu a produção de xilanases, mas de diferente modo, considerando que a repressão foi retardada na primeira condição. FSS foram realizadas também com FT ou BCA, mais 4 ou 8 mL de água por grama de substrato, respectivamente, a 30ºC durante 3 ou 6 dias. Os meios contendo FT e BCA foram suplementados com nitrato de amônio ou peptona, respectivamente. Não foi observada repressão catabólica por glicose nessas fermentações. Duas xilanases, xyl 1 e xyl 2, foram purificadas usando Sephadex G-100. Xyl 2 exibiu maior conteúdo de carboidrato (41%) do que xyl 1 (29%), o que pode explicar sua maior estabilidade a temperatura e pH...The plant cell wall is constituted by three main compounds: cellulose, hemicellulose and lignin. Among the hemicelluloses, xylan is the heteropolysaccharide most common, and the principal enzyme responsible for its degradation is xylanase. This study investigated some optimal culture conditions for xylanase production by the filamentous fungus Aspergillus caespitosus cultivated in submerged fermentation (SMF), or solid-state-fermentation (SSF). The xylanases were purified, biochemical characterized and assayed in pulp bleaching. With regard to SMF, several media were tested, but the best results for xylanase production were obtained with SR medium supplemented with 1% (w/v) wheat bran (WB) or sugar cane bagasse (SCB), and with 0.25% (w/v) or 0.1% (w/v) peptone, respectively. Fermentation was carried out at 40oC, for 48 hours, in media with initial pH of 8.0 (SCB) or 6.0 (WB). There was no enzymatic activation by the addition of metallic ions, mainly for the samples obtained from SCB medium. The xylanase obtained from SCB crude extracts was thermally inactivated at 55oC and 65oC, faster than that of the xylanase obtained from WB culture filtrates. Addition of different glucose concentrations to media supplemented with SCB or WB reduced xylanase production, but in a different way, considering that the repression was retarded in the first condition. SSF were carried out also with 2 g WB or SCB, plus 4 mL or 8 mL water, respectively, at 30oC for 3 or 6 days. The WB and SCB media were supplemented with ammonium nitrate or peptone, respectively. It was not observed repression by glucose for these fermentations. Two xylanases, xyl 1 and xyl 2, were purified using Sephadex G-100. Xyl 2 exhibited higher carbohydrate content (41%) than xyl 1 (29%), which might explain its higher stability for temperature and pH. Furthermore, this property probably caused a carbohydrate-carbohydrate... (Compete abstract, click electronic address below)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

The Nitrate-Nitrite-Nitric Oxide Pathway: Potential Role in Mitigating Oxidative Stress in Hypertensive Disorders of Pregnancy

Hypertensive diseases of pregnancy (HDPs) represent a global clinical challenge, affecting 5–10% of women and leading to complications for both maternal well-being and fetal development. At the heart of these complications is endothelial dysfunction, with oxidative stress emerging as a pivotal causative factor. The reduction in nitric oxide (NO) bioavailability is a vital indicator of this dysfunction, culminating in blood pressure dysregulation. In the therapeutic context, although antihypertensive medications are commonly used, they come with inherent concerns related to maternal–fetal safety, and a percentage of women do not respond to these therapies. Therefore, alternative strategies that directly address the pathophysiology of HDPs are required. This article focuses on the potential of the nitrate-nitrite-NO pathway, abundantly present in dark leafy greens and beetroot, as an alternative approach to treating HDPs. The objective of this review is to discuss the prospective antioxidant role of nitrate. We hope our discussion paves the way for using nitrate to improve endothelial dysfunction and control oxidative stress, offering a potential therapy for managing HDPs

IL-6, TNF-α, and IL-10 levels/polymorphisms and their association with type 2 diabetes mellitus and obesity in Brazilian individuals

ABSTRACT Objective This study aimed to investigate the association of plasma TNF-α, IL-6, and lL-10 levels and cytokine gene polymorphisms [TNF-α (-308 G→A), IL-6 (-174 C→G) and IL-10 (-1082 A→G, -819 T→C and -592 A→C)] in type 2 diabetes mellitus (T2DM) and obese patients. Subjects and methods One hundred and two T2DM patients and 62 controls were included in this study. Cytokine plasma levels were measured by the Cytometric Bead Array method. Genotyping was carried out by the polymerase chain reaction. Results IL-6 levels were significantly different between T2DM patients and controls. Interestingly, IL-6 levels were higher in T2DM patients with BMI > 30 kg/m2 compared with other patients and obese controls. The genotype and allele frequencies were similar between patients and controls. In the T2DM group, the SNP IL-10 -819 T/C showed a difference between the cytokine level and genotypes: IL-10 level in the TT genotype was significantly higher when compared to CC genotype. Conclusions These results suggest an association between IL-6 levels and obesity, and IL-10 levels and the SNP -819 T/C in T2DM. Knowledge of these variants in T2DM might contribute to a better understanding of the role of inflammation in the etiology and progression of this disease

Monocytes from preeclamptic women previously treated with silibinin attenuate oxidative stress in human endothelial cells

Objective: To investigate whether the supernatant from monocytes of preeclamptic and normotensive pregnant women, cultured in vitro with silibinin, can modulate oxidative stress in HUVEC. Methods: Concentrations of IL-1β, IL-10, and TNF-α in monocyte culture supernatants were determined by ELISA. HUVEC and their supernatant cultures were employed for determination of NO, nitrite and nitrate, lipid peroxidation, and hemeoxygenase-1 (HO-1). Results: HUVEC treatment with supernatant of preeclamptic monocytes cultured with silibinin produced increased levels of nitrite, reduced lipid peroxidation, and increased HO-1. Conclusion: Supernatant of monocytes from preeclamptic women induce oxidative stress in HUVEC which can be reduced by silibinin treatment. Abbreviations: DAF-FMTM, Diaminofluorescein-FM; EDTA, Ethylenediaminetetraacetic acid; HO-1, heme oxygenase-1; HPLC, high-performance liquid chromatography; HUVEC, human umbilical vein endothelial cell; MDA, malondialdehyde; NO, nitric oxide; NT, normotensive; PE, preeclampsia; ROS, reactive oxygen species; Sb, silibinin

Epistasis among eNOS, MMP-9 and VEGF maternal genotypes in hypertensive disorders of pregnancy

Polymorphisms of the endothelial nitric oxide synthase (eNOS), matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) genes were shown to be associated with hypertensive disorders of pregnancy. However, epistasis is suggested to be an important component of the genetic susceptibility to preeclampsia (PE). The aim of this study was to characterize the interactions among these genes in PE and gestational hypertension (GH). Seven clinically relevant polymorphisms of eNOS (T-786C, rs2070744, a variable number of tandem repeats in intron 4 and Glu298Asp, rs1799983), MMP-9 (C-1562T, rs3918242 and -90(CA)(13-25), rs2234681) and VEGF (C-2578A, rs699947 and G-634C, rs2010963) were genotyped by TaqMan allelic discrimination assays or PCR and fragment separation by electrophoresis in 122 patients with PE, 107 patients with GH and a control group of 102 normotensive pregnant (NP) women. A robust multifactor dimensionality reduction analysis was used to characterize gene-gene interactions. Although no significant genotype combinations were observed for the comparison between the GH and NP groups (P>0.05), the combination of MMP-9-1562CC with VEGF-634GG was more frequent in NP women than in women with PE (P<0.05). Moreover, the combination of MMP-9-1562CC with VEGF-634CC or MMP-9-1562CT with VEGF-634CC or-634GG was more frequent in women with PE than in NP women (P<0.05). These results are obscured when single polymorphisms in these genes are considered and suggest that specific genotype combinations of MMP-9 and VEGF contribute to PE susceptibility. Hypertension Research (2012) 35, 917-921; doi:10.1038/hr.2012.60; published online 10 May 2012Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP-Brazil)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq-Brazil)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), BrazilFundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG), Brazi

Existe Alteração em Marcadores Inflamatórios em Estudantes de Medicina após Participação em Programa Mente-Corpo?

RESUMO Introdução Estudantes do curso de Medicina estão expostos a carga elevada de estresse, desencadeada por terem que lidar com adoecimento e morte dos pacientes, extensa carga horária, privação de sono, competitividade, cobrança, responsabilidade e medo de errar, entre outros fatores. Algumas técnicas e práticas como a meditação têm sido utilizadas para auxiliar no manejo e redução de estresse, já sendo utilizadas em escolas médicas. O estresse pode ativar componentes do sistema inflamatório, desencadeando uma série de doenças. As desordens causadas pelo estresse podem ser mensuradas por meio de marcadores sorológicos, sendo que os biológicos são os principais utilizados. Objetivo Avaliar os efeitos de um programa de práticas mente-corpo, Redução de Estresse e Desenvolvimento da Empatia na Medicina (Redemed©), nos níveis dos marcadores pró- e anti-inflamatórios de estudantes de medicina. Metodologia Trata-se de um estudo quase-experimental, composto por 86 estudantes, sendo 44 do grupo intervenção, que participaram do programa Redemed© com oito encontros semanais, englobando técnicas de meditação e exercícios de vivências interpessoais, e 42 estudantes do grupo controle. Ambos os grupos, antes e após o curso, coletaram sangue para análise dos marcadores: proteína C reativa (PCR), fator de necrose tumoral-alfa (TNF-alfa), interleucina 06 (IL06) e interleucina 10 (IL10). Resultados Neste estudo, não foi observada alteração estatisticamente significativa nas citocinas pró-inflamatórias: PCR, TNF-α e IL06. No entanto, a IL-10, que é uma citocina anti-inflamatória, apresentou uma variação positiva e estatisticamente significativa (p: 0,009). Ela tem sido utilizada em estudos com práticas integrativas e complementares a fim de demonstrar seus benefícios. Conclusão O programa Redemed© parece beneficiar os estudantes de Medicina por meio da modulação inflamatória e como grupo de acolhimento no qual eles puderam compartilhar seu estresse e treinar estratégias de enfrentamento. Este estudo, mesmo não tendo encontrado diferença estatística significativa nos marcadores pesquisados, com exceção da IL10, traz à tona este tema importante do grande estresse vivenciado por estudantes de Medicina e a necessidade de as escolas médicas terem maior cuidado com seus alunos, acolhendo e trabalhando o estresse desses estudantes de forma a reduzir e gerenciar melhor este fator de adoecimento em suas vidas

Características clínicas e laboratoriais de gestantes com pré-eclâmpsia versus hipertensão gestacional

Purpose: To compare clinical and laboratory characteristics, obstetric and perinatal outcomes of patients with pre-eclampsia versus gestational hypertension. Methods: A retrospective study was carried out to analyze medical records of patients diagnosed with pre-eclampsia and gestational hypertension whose pregnancies were resolved within a period of 5 years, for a total of 419 cases. We collected clinical and laboratory data, obstetric and perinatal outcomes. Comparisons between groups were performed using the test suitable for the variable analyzed: unpaired t test, Mann-Whitney U test or χ2test, with the level of significance set at p<0.05. Results: Were evaluated 199 patients in the gestational hypertension group (GH) and 220 patients in the pre-eclampsia group (PE). Mean body mass index was 34.6 kg/m2 in the GH group and 32.7 kg/m2 in the PE group, with a significant difference between groups. The PE group showed higher systolic and diastolic blood pressure and higher rates of abnormal values in the laboratory tests, although the mean values were within the normal range. Cesarean section was performed in 59.1% of cases of PE and in 47.5% of the GH group; and perinatal outcomes in terms of gestational age and birth weight were significantly lower in the PE group. Conclusion: Women with gestational hypertension exhibit epidemiological characteristics of patients at risk for chronic diseases. Patients with pre-eclampsia present clinical and laboratory parameters of greater severity, higher rates of cesarean delivery and worse maternal and perinatal outcomes.Objetivo: Comparar as características clínicas e laboratoriais, os resultados maternos e perinatais de gestantes com pré-eclâmpsia versushipertensão gestacional. Métodos: Análise retrospectiva dos prontuários médicos de pacientes com diagnóstico de pré-eclâmpsia e hipertensão gestacional, cujas gestações foram resolvidas em um período de cinco anos. Foram coletadas informações laboratoriais, resultados obstétricos e perinatais. As comparações entre os grupos foram realizadas com o uso do teste adequado para a variável analisada: testet não pareado, teste U de Mann-Whitney, ou teste do χ2. Consideramos p<0,05 como nível de significância estatística. Resultados: Foram avaliadas 199 pacientes no grupo com hipertensão gestacional (HG) e 220 pacientes no grupo com pré-eclâmpsia (PE). No grupo HG o índice de massa corpórea médio foi 34,6 kg/m2 e no grupo PE, 32,7 kg/m2, com diferença significativa. O grupo PE apresentou valores de pressão arterial sistólica superiores ao grupo HG. Em relação aos exames laboratoriais, a média de valores denotou, de uma forma geral, maior gravidade no grupo PE. Pacientes submetidas à cesárea foram 59,1% dos casos no grupo PE e 47,5% no grupo HG. Em relação aos resultados perinatais, a idade gestacional e o peso ao nascer foram significativamente inferiores no grupo PE. Cconclusão: As mulheres com hipertensão gestacional apresentam características epidemiológicas de pacientes com risco de doenças crônicas. As pacientes com pré-eclâmpsia apresentam parâmetros clínicos e laboratoriais de maior gravidade, taxas superiores de cesárea e piores resultados maternos e perinatais