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1.
J Appl Oral Sci ; 27: e20180574, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31596365

RESUMO

OBJECTIVES: Hypertension is one of the main causes of premature death in the world; also, it is associated with several bone alterations. Preclinical studies have demonstrated delayed alveolar bone healing in hypertensive rats. However, losartan has been favorable for consolidation of bone grafts and reduction in active periodontitis. Therefore, losartan is suggested to be effective in bone formation stages, as well as in the synthesis of matrix proteins and mineralization. To evaluate the alveolar bone dynamics in hypertensive rats treated with losartan by laser confocal microscopy and histological analysis. METHODOLOGY: Thirty-two rats, 16 spontaneously hypertensive rats (SHR) and 16 Wistar albinus rats, treated or not with losartan (30 mg/kg/day) were used. Calcein fluorochrome at 21 days and alizarin red fluorochrome at 49 days were injected in rats (both 20 mg/kg). The animals were submitted to euthanasia 67 days after treatment, and then the right maxilla was removed for laser confocal microscopy analysis and the left maxilla for histological analysis. RESULTS: This study showed a greater calcium marking in normotensive animals treated with losartan in relation to the other groups. Laser confocal microscopy parameters showed higher values of bone volume formed, mineralized surface, active surface of mineralization and bone formation rate in normotensive animals treated with losartan. However, a smaller mineralized surface was observed in all hypertensive animals. CONCLUSION: Losartan can improve bone mineralization parameters under normal physiological conditions, but the same anabolic effect does not occur under hypertension.


Assuntos
Processo Alveolar/efeitos dos fármacos , Processo Alveolar/fisiopatologia , Anti-Hipertensivos/farmacologia , Hipertensão/fisiopatologia , Losartan/farmacologia , Processo Alveolar/patologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Calcificação Fisiológica/efeitos dos fármacos , Fluoresceínas/análise , Masculino , Microscopia Confocal , Osteogênese/efeitos dos fármacos , Ratos Endogâmicos SHR , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo
3.
Rev Med Suisse ; 15(667): 1882-1886, 2019 Oct 16.
Artigo em Francês | MEDLINE | ID: mdl-31617977

RESUMO

The association of an angiotensin II receptor antagonist and a neprilysin inhibitor (ARNI or Angiotensin Receptor-Neprilysin Inhibitor) is a new actor in the management of heart failure with reduced left ventricular ejection fraction (LVEF). The PARADIGM-HF trial performed in outpatients with a LVEF ≤ 35-40 % demonstrated that sacubitril-valsartan was superior to enalapril in reducing cardiovascular mortality and heart failure hospitalizations. Precautions in the initiation of sacubitril-valsartan, its use as well as its place in the drug management strategy for chronic heart failure are described in the present review. Additional data in patients hospitalized with reduced LVEF, in patients with LVEF > 45 % as well as the effects on blood pressure, renal or cognitive functions are presented.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Neprilisina/antagonistas & inibidores , Aminobutiratos/farmacologia , Aminobutiratos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Cognição/efeitos dos fármacos , Enalapril/farmacologia , Enalapril/uso terapêutico , Insuficiência Cardíaca/metabolismo , Humanos , Rim/efeitos dos fármacos , Neprilisina/metabolismo , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Resultado do Tratamento
5.
J Agric Food Chem ; 67(37): 10313-10320, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31502448

RESUMO

A peptide fraction with molecular masses below 3 kDa (PSH-3 kDa) from a peach seed hydrolysate demonstrated high angiotensin converting enzyme (ACE) inhibitory activity (concentration to inhibit 50% ACE (IC50) = 16.4 µg/mL) in our previous work. This work proposes a further study of this highly active fraction. RP-HPLC enabled two fractions (F3 and F4) with high inhibitory activity (IC50 = 2.0 ± 0.5 and 1.2 ± 0.2 µg/mL, respectively) to be isolated. Peptide analysis by LC-Q-TOF-MS/MS using reverse-phase and hydrophilic interaction chromatography enabled 33 peptides within both fractions to be identified. Among them, peptide isoleucine-tyrosine-serine-proline-histidine (IYSPH) showed the highest capacity. The lack of cytotoxicity of peptides was demonstrated in three different cell lines (HeLa, HT-29, and HK-2). Oral administration of PSH-3 kDa fraction or peptide IYSPH caused a significant systolic blood pressure reduction (-30 mmHg) on spontaneously hypertensive rats after 3-6 h treatment.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/química , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/química , Hipertensão/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Prunus persica/química , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Animais , Anti-Hipertensivos/isolamento & purificação , Pressão Sanguínea/efeitos dos fármacos , Humanos , Hipertensão/enzimologia , Hipertensão/fisiopatologia , Masculino , Peptidil Dipeptidase A/metabolismo , Extratos Vegetais/isolamento & purificação , Hidrolisados de Proteína/química , Ratos , Ratos Endogâmicos SHR , Sementes/química
6.
Medicine (Baltimore) ; 98(36): e17081, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490412

RESUMO

OBJECTIVE: The purpose of this study was to assess the efficacy and hypoglycemic risk of sitagliptin versus that of GLP-1 receptor agonists in the management of obese/overweight patients with T2DM. METHODS: EMBASE, PubMed, Cochrane Library, and ClinicalTrials.gov were searched; randomized controlled trials comparing the efficacy of sitagliptin versus that of GLP-1 receptor agonists in obese/overweight patients with T2DM were included. The mean BMI of participants for each study was ≥30 kg/m. We conducted a meta-analysis according to the methods specified in the Cochrane Handbook for Systematic Reviews of Interventions. RevMan 5.1 software was used to perform the meta-analysis. The Cochrane Q test and I statistics were used to estimate the heterogeneity among studies. The results are expressed as the mean difference (MD) or risk ratio (RR) with 95% confidence intervals. RESULTS: A total of 8 eligible studies were included in our meta-analysis. Compared with GLP-1 receptor agonists, sitagliptin was less effective at reducing HbA1c (0.42 [0.27, 0.56]), FPG (0.78 [0.36, 1.19]), PPG (2.61 [1.35, 3.87]), and body weight (1.42 [0.71, 2.14]). Conversely, there were no significant differences in SBP reduction (0.38 [-1.14, 1.89]), DBP reduction (-0.30 [-1.00, 0.39]), and hypoglycemic risk (1.09 [0.50, 2.35]). CONCLUSION: For obese/overweight patients, sitagliptin may exert a less potent effect on HbA1C, FPG, PPG, and weight reduction than GLP-1 receptor agonists, but these drugs had a similar efficacy in reducing blood pressure; furthermore, there was no significant difference in hypoglycemic risk.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Obesidade/complicações , Fosfato de Sitagliptina/uso terapêutico , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/farmacologia , Fosfato de Sitagliptina/farmacologia
7.
Rev Med Suisse ; 15(662): 1608-1613, 2019 Sep 11.
Artigo em Francês | MEDLINE | ID: mdl-31508912

RESUMO

After numerous years of research and development of effective anti-hypertensive drugs, it is regrettable to note that less than half of hypertensive patients reach the blood pressure targets that are known to reduce their cardiovascular risks and mortality. Poor adherence to treatment is one of the main causes of insufficient blood pressure control. Furthermore, non-adherence to anti-hypertensive therapy correlates with higher risks of cardiovascular events. The objective of health professionals is to identify non adherent patients and to offer them appropriate solutions to support their treatment self-management. Innovative approaches like using electronic pillboxes combined with an interprofessional medication adherence support program should allow a more appropriate and effective care.


Assuntos
Anti-Hipertensivos , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/psicologia , Adesão à Medicação , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Humanos , Hipertensão/fisiopatologia
8.
Rev Med Suisse ; 15(662): 1625-1628, 2019 Sep 11.
Artigo em Francês | MEDLINE | ID: mdl-31508914

RESUMO

The salt sensitivity of the blood pressure (SSBP) is defined as a rise or fall in blood pressure induced by a change in sodium intake. There is an interindividual variation and no strong diagnostic criteria exist to date. The SSBP may lead to underestimation of the beneficial effect of sodium restriction in some patients in meta-analyzes. High sodium intake in salt sensitive patients results in an increase in the prevalence of hypertension and target organ damage. The etiology seems to be a failure of one or more natriuretic mechanisms. Some environmental, genetic and epidemiological factors increase its susceptibility. Per se, SSBP cannot be treated, but its identification may help in preventing hypertension and adapt the treatment in some populations.


Assuntos
Variação Biológica Individual , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Cloreto de Sódio na Dieta/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Humanos , Hipertensão/diagnóstico
9.
Medicine (Baltimore) ; 98(34): e16966, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441902

RESUMO

The importance of optimal blood pressure control for preventing or reducing the impairment of vascular and cognitive functions is well known. However, the reversibility of early alterations in vascular and cognitive functions through antihypertensive agents is under-investigated. In this study, we evaluated the influence of 3 months of angiotensin-converting enzyme (ACE) inhibition treatment on the morphological and functional arterial wall and cognitive performance changes in 30 newly diagnosed primary hypertensive patients.Common carotid intima-media thickness (IMT) and brachial artery flow-mediated dilatation (FMD) were detected by ultrasonography. Arterial stiffness indicated by augmentation index (AIx) and pulse wave velocity (PWV) was assessed by arteriography. Cognitive functions were assessed by neuropsychological examination.The executive function overall score was significantly higher at 3-month follow-up than at baseline (median, 0.233 (IQR, 0.447) vs -0.038 (0.936); P = .001). Three-month ACE inhibition did not produce significant improvement in IMT, FMD, AIx and PWV values. Significant negative associations were revealed between IMT and complex attention (r = -0.598, P = .0008), executive function (r = -0.617, P = .0005), and immediate memory (r = -0.420, P = .026) overall scores at follow-up. AIx had significant negative correlations with complex attention (r = -0.568, P = .001), executive function (r = -0.374, P = .046), and immediate memory (r = -0.507, P = .005). PWV correlated significantly and negatively with complex attention (r = -0.490, P = .007).Timely and effective antihypertensive therapy with ACE inhibitors has significant beneficial effects on cognitive performance in as few as 3 months. Early ACE inhibition may have an important role in the reversal of initial impairments of cognitive function associated with hypertension-induced vascular alterations.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Cognição/efeitos dos fármacos , Rigidez Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Adulto , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Artéria Braquial/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Feminino , Seguimentos , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
10.
Adv Exp Med Biol ; 1155: 173-182, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468396

RESUMO

Taurine plays an important role in the modulation of cardiovascular function by acting not only within the brain but also within peripheral tissues. We found that IV injection of taurine to male rats caused hypotension and tachycardia. A single injection of taurine significantly lowered the systolic, diastolic and mean arterial pressure blood pressure in freely moving long Evans control rats. Previousely, we found that the endothelial cells express high levels of taurine transporters and GABAA receptors and showed that taurine activates GABAA receptors. Thus we suggest that the functional implication of GABAA receptors activation is the relaxation of the arterial muscularis, vasodilation and a decrease in blood pressure. Interestingly however, the effects of acute taurine injection were very different that chronic supplementation of taurine. When rats were supplemented taurine (0.05%, 4 weeks) in their drinking water, taurine has significant hypertensive properties. The increase in blood pressure was observed however only in females, males supplemented with taurine did not show an increase in systolic, diastolic or mean arterial pressure. In both genders however, taurine supplementation caused a significant tachycardia. Thus, we suggest that acute administration of taurine may be beneficial to lowering blood pressure. However, our data indicate that supplementation of taurine to females caused a significant increase in blood pressure. It remains to be seen the effect of taurine supplementation on hypertensive rats.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Hipertensão/induzido quimicamente , Fatores Sexuais , Taurina/farmacologia , Animais , Feminino , Hemodinâmica , Masculino , Ratos , Taquicardia/induzido quimicamente
11.
Life Sci ; 234: 116753, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31419445

RESUMO

AIMS: Hypertension is a global disease that has been combating the world health for ages. Peristrophe roxburghiana (PR) is used in traditional medicine to treat hypertension and other ailments. The present study examined phytochemical constituents, antioxidant activities and GC-MS analysis of extracts of PR leaf and also evaluated their anti-hypertensive and anti-lipidemic effects in NG-nitro-L-arginine methyl ester (L-NAME) hypertensive rats. METHODS: Wistar rats were grouped into two groups: control and hypertensive. Hypertension was induced in the hypertensive group by oral gavage of 60 mg/kg b.w of L-NAME for 3 weeks. After induction, the hypertensive group was randomly sub-grouped into hypertensive, hypertensive treated and hypertensive untreated groups. These were orally gavaged respectively with 60 mg/kg b.w of L-NAME, 60 mg/kg b.w/day of L-NAME +200 mg/kg b.w of different extracts of PR (aqueous, ethanolic and methanolic extracts) and 60 mg/kg b.w of L-NAME +20 mg/kg b.w ramipril for 3 weeks. The blood pressure was measured by tail-cuff method at the third and sixth weeks. KEY FINDINGS: The results showed that the extracts of PR significantly decrease blood pressure, pro-atherogenic lipids and atherogenic ratios in L-NAME hypertensive rats. White blood cells count, neutrophil count and creatinine level were also effectively decreased by the extracts. Furthermore, the extracts increase serum nitric oxide (NO) level, anti-atherogenic lipid, glutathione level, lymphocyte and platelet count in the rats. SIGNIFICANCE: Extracts of PR leaf decrease blood pressure and increase NO level in L-NAME hypertensive rats and also corrected the hyperlipidemia and inflammatory response arising from the reduction in NO bioavailability.


Assuntos
Acanthaceae/química , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Anti-Hipertensivos/química , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/sangue , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Hipolipemiantes/química , Lipídeos/sangue , Masculino , NG-Nitroarginina Metil Éster , Óxido Nítrico/sangue , Extratos Vegetais/química , Folhas de Planta/química , Ratos Wistar
12.
Anticancer Res ; 39(8): 4503-4509, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366552

RESUMO

BACKGROUND/AIM: Oral administration of Pantoea agglomerans-derived lipopolysaccharide (LPSp) has been reported to have a preventive effect against various lifestyle-related diseases. Therefore, we examined the preventive effect on high blood pressure, which is a kind of reserve arm for lifestyle-related diseases. MATERIALS AND METHODS: Spontaneous hypertensive rat (SHR) and WKY rat were bred from 6 to 16 weeks of age. SHR were orally administered 100 µg/kg LPSp and 0.1% NaCl, and blood pressure was measured at 6, 10, 13 and 16 weeks. Furthermore, at 16 weeks of age, blood biochemical markers were measured and microbial community composition was analyzed. RESULTS: SHRs developed hypertension with age, which was exacerbated by salt loading. Although there was almost no reduction in blood pressure in SHRs that received LPSp. It was suppressed at 13-16 weeks of age in those with salt loading. CONCLUSION: Oral administration of LPSp showed a preventive effect on salt-loaded hypertension.


Assuntos
Citocinas/genética , Hipertensão/tratamento farmacológico , Lipopolissacarídeos/administração & dosagem , Pantoea/química , Administração Oral , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Hipertensão/genética , Hipertensão/patologia , Lipopolissacarídeos/química , Masculino , Fagocitose/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Sais/toxicidade
13.
N Engl J Med ; 381(8): 716-726, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31433919

RESUMO

BACKGROUND: Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. METHODS: In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 µg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. RESULTS: A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P = 0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P = 0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. CONCLUSIONS: In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.).


Assuntos
Doenças Cardiovasculares/mortalidade , Insuficiência Cardíaca/tratamento farmacológico , Relaxina/uso terapêutico , Vasodilatadores/uso terapêutico , Doença Aguda , Idoso , Pressão Sanguínea/efeitos dos fármacos , Progressão da Doença , Método Duplo-Cego , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Hospitalização , Humanos , Incidência , Infusões Intravenosas , Masculino , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Relaxina/efeitos adversos , Relaxina/farmacologia , Falha de Tratamento , Vasodilatadores/efeitos adversos
14.
Lancet ; 394(10199): 672-683, 2019 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-31448738

RESUMO

BACKGROUND: A fixed-dose combination therapy (polypill strategy) has been proposed as an approach to reduce the burden of cardiovascular disease, especially in low-income and middle-income countries (LMICs). The PolyIran study aimed to assess the effectiveness and safety of a four-component polypill including aspirin, atorvastatin, hydrochlorothiazide, and either enalapril or valsartan for primary and secondary prevention of cardiovascular disease. METHODS: The PolyIran study was a two-group, pragmatic, cluster-randomised trial nested within the Golestan Cohort Study (GCS), a cohort study with 50 045 participants aged 40-75 years from the Golestan province in Iran. Clusters (villages) were randomly allocated (1:1) to either a package of non-pharmacological preventive interventions alone (minimal care group) or together with a once-daily polypill tablet (polypill group). Randomisation was stratified by three districts (Gonbad, Aq-Qala, and Kalaleh), with the village as the unit of randomisation. We used a balanced randomisation algorithm, considering block sizes of 20 and balancing for cluster size or natural log of the cluster size (depending on the skewness within strata). Randomisation was done at a fixed point in time (Jan 18, 2011) by statisticians at the University of Birmingham (Birmingham, UK), independent of the local study team. The non-pharmacological preventive interventions (including educational training about healthy lifestyle-eg, healthy diet with low salt, sugar, and fat content, exercise, weight control, and abstinence from smoking and opium) were delivered by the PolyIran field visit team at months 3 and 6, and then every 6 months thereafter. Two formulations of polypill tablet were used in this study. Participants were first prescribed polypill one (hydrochlorothiazide 12·5 mg, aspirin 81 mg, atorvastatin 20 mg, and enalapril 5 mg). Participants who developed cough during follow-up were switched by a trained study physician to polypill two, which included valsartan 40 mg instead of enalapril 5 mg. Participants were followed up for 60 months. The primary outcome-occurrence of major cardiovascular events (including hospitalisation for acute coronary syndrome, fatal myocardial infarction, sudden death, heart failure, coronary artery revascularisation procedures, and non-fatal and fatal stroke)-was centrally assessed by the GCS follow-up team, who were masked to allocation status. We did intention-to-treat analyses by including all participants who met eligibility criteria in the two study groups. The trial was registered with ClinicalTrials.gov, number NCT01271985. FINDINGS: Between Feb 22, 2011, and April 15, 2013, we enrolled 6838 individuals into the study-3417 (in 116 clusters) in the minimal care group and 3421 (in 120 clusters) in the polypill group. 1761 (51·5%) of 3421 participants in the polypill group were women, as were 1679 (49·1%) of 3417 participants in the minimal care group. Median adherence to polypill tablets was 80·5% (IQR 48·5-92·2). During follow-up, 301 (8·8%) of 3417 participants in the minimal care group had major cardiovascular events compared with 202 (5·9%) of 3421 participants in the polypill group (adjusted hazard ratio [HR] 0·66, 95% CI 0·55-0·80). We found no statistically significant interaction with the presence (HR 0·61, 95% CI 0·49-0·75) or absence of pre-existing cardiovascular disease (0·80; 0·51-1·12; pinteraction=0·19). When restricted to participants in the polypill group with high adherence, the reduction in the risk of major cardiovascular events was even greater compared with the minimal care group (adjusted HR 0·43, 95% CI 0·33-0·55). The frequency of adverse events was similar between the two study groups. 21 intracranial haemorrhages were reported during the 5 years of follow-up-ten participants in the polypill group and 11 participants in the minimal care group. There were 13 physician-confirmed diagnoses of upper gastrointestinal bleeding in the polypill group and nine in the minimal care group. INTERPRETATION: Use of polypill was effective in preventing major cardiovascular events. Medication adherence was high and adverse event numbers were low. The polypill strategy could be considered as an additional effective component in controlling cardiovascular diseases, especially in LMICs. FUNDING: Tehran University of Medical Sciences, Barakat Foundation, and Alborz Darou.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Combinação de Medicamentos , Prevenção Secundária/métodos , Adulto , Idoso , Anticolesterolemiantes/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Aspirina/administração & dosagem , Atorvastatina/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/efeitos dos fármacos , Diabetes Mellitus/epidemiologia , Enalapril/administração & dosagem , Feminino , Humanos , Hidroclorotiazida/administração & dosagem , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Valsartana/administração & dosagem
15.
Lancet ; 394(10203): 1011-1021, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31378394

RESUMO

BACKGROUND: Hypertension is the most common medical disorder in pregnancy, complicating one in ten pregnancies. Treatment of severely increased blood pressure is widely recommended to reduce the risk for maternal complications. Regimens for the acute treatment of severe hypertension typically include intravenous medications. Although effective, these drugs require venous access and careful fetal monitoring and might not be feasible in busy or low-resource environments. We therefore aimed to compare the efficacy and safety of three oral drugs, labetalol, nifedipine retard, and methyldopa for the management of severe hypertension in pregnancy. METHODS: In this multicentre, parallel-group, open-label, randomised controlled trial, we compared these oral antihypertensives in two public hospitals in Nagpur, India. Pregnant women were eligible for the trial if they were aged at least 18 years; they were pregnant with fetuses that had reached a gestational age of at least 28 weeks; they required pharmacological blood pressure control for severe hypertension (systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥110 mm Hg); and were able to swallow oral medications. Women were randomly assigned to receive 10 mg oral nifedipine, 200 mg oral labetalol (hourly, in both of which the dose could be escalated if hypertension was maintained), or 1000 mg methyldopa (a single dose, without dose escalation). Masking of participants, study investigators, and care providers to group allocation was not possible because of different escalation protocols in the study groups. The primary outcome was blood pressure control (defined as 120-150 mm Hg systolic blood pressure and 70-100 mm Hg diastolic blood pressure) within 6 h with no adverse outcomes. This study is registered with ClinicalTrials.gov, number NCT01912677, and the Clinical Trial Registry, India, number ctri/2013/08/003866. FINDINGS: Between April 1, 2015, and Aug 21, 2017, we screened 2307 women for their inclusion in the study. We excluded 1413 (61%) women who were ineligible, declined to participate, had impending eclampsia, were in active labour, or had a combination of these factors. 11 (4%) women in the nifedipine group, ten (3%) women in the labetalol group, and 11 (4%) women in the methyldopa group were ineligible for treatment (because they had only one qualifying blood pressure measurement) or had treatment stopped (because of delivery or transfer elsewhere). 894 (39%) women were randomly assigned to a treatment group and were included in the intention-to-treat analysis: 298 (33%) women were assigned to receive nifedipine, 295 (33%) women were assigned to receive labetalol, and 301 (33%) women were assigned to receive methyldopa. The primary outcome was significantly more common in women in the nifedipine group than in those in the methyldopa group (249 [84%] women vs 230 [76%] women; p=0·03). However, the primary outcome did not differ between the nifedipine and labetalol groups (249 [84%] women vs 228 [77%] women; p=0·05) or the labetalol and methyldopa groups (p=0·80). Seven serious adverse events (1% of births) were reported during the study: one (<1%) woman in the labetalol group had an intrapartum seizure and six (1%) neonates (one [<1%] neonate in the nifedipine group, two [1%] neonates in the labetalol group, and three [1%] neonates in the methyldopa group) were stillborn. No birth had more than one adverse event. INTERPRETATION: All oral antihypertensives reduced blood pressure to the reference range in most women. As single drugs, nifedipine retard use resulted in a greater frequency of primary outcome attainment than labetalol or methyldopa use. All three oral drugs-methyldopa, nifedipine, and labetalol-are viable initial options for treating severe hypertension in low-resource settings. FUNDING: PREEMPT (University of British Columbia, Vancouver, BC, Canada; grantee of Bill & Melinda Gates Foundation).


Assuntos
Anti-Hipertensivos/administração & dosagem , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Labetalol/administração & dosagem , Metildopa/administração & dosagem , Nifedipino/administração & dosagem , Administração Oral , Adulto , Pressão Sanguínea/efeitos dos fármacos , Feminino , Humanos , Índia/epidemiologia , Recém-Nascido , Gravidez , Resultado da Gravidez/epidemiologia , Resultado do Tratamento , Adulto Jovem
16.
Rom J Ophthalmol ; 63(2): 142-145, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31334392

RESUMO

Purpose: To quantitatively evaluate the cardiopulmonary effects of various topical antiglaucoma drugs. Material & method: In this study, forty consecutive cases of newly diagnosed primary open angle glaucoma were recruited. After taking a detailed history, an ophthalmological examination and a systemic examination including resting pulse rate, blood pressure, ECG, auscultation of the chest and spirometry were performed. Then the patients were randomly divided into four groups and one of the four topical anti glaucoma medication (Timolol, Latanoprost, Brimonidine, and Dorzolamide) prescribed. Patients were reviewed 4 weeks later and the same ocular and systemic examinations were performed. Result: Timolol therapy reduced all the spirometry parameters that are statistically significant difference with the P value of less than 0.1. Timolol therapy resulted in the mean reduction of pulse rate by 3.2 beats/ minute and a mean reduction of systolic and diastolic blood pressure by 5.8 mmHg and 5.6 mmHg, respectively all the spirometry & cardiovascular parameters remained unchanged in the other three groups after 4 weeks of treatment. Conclusion: Timolol significantly affects the cardiopulmonary status. Therefore, we could advice the assessment of cardiopulmonary status mandatory in patients receiving topical beta-blockers. Bronchospasm may be of clinical significance in the elderly, who commonly have undiagnosed reversible airway obstruction.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Glaucoma de Ângulo Aberto/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Respiração/efeitos dos fármacos , Timolol/administração & dosagem , Administração Tópica , Antagonistas Adrenérgicos beta/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas , Estudos Prospectivos , Espirometria
20.
Br J Anaesth ; 123(4): 430-438, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31255290

RESUMO

BACKGROUND: Vasopressor agents are used to prevent intraoperative hypotension and ensure adequate perfusion. Vasopressors are usually administered as intermittent boluses or manually adjusted infusions, but this practice requires considerable time and attention. We have developed a closed-loop vasopressor (CLV) controller to correct hypotension more efficiently. Here, we conducted a proof-of-concept study to assess the feasibility and performance of CLV control in surgical patients. METHODS: Twenty patients scheduled for elective surgical procedures were included in this study. The goal of the CLV system was to maintain MAP within 5 mm Hg of the target MAP by automatically adjusting the rate of a norepinephrine infusion using MAP values recorded continuously from an arterial catheter. The primary outcome was the percentage of time that patients were hypotensive, as defined by a MAP of 5 mm Hg below the chosen target. Secondary outcomes included the total dose of norepinephrine, percentage of time with hypertension (MAP>5 mm Hg of the chosen target), raw percentage "time in target" and Varvel performance criteria. RESULTS: The 20 subjects (median age: 64 years [52-71]; male (35%)) underwent elective surgery lasting 154 min [124-233]. CLV control maintained MAP within ±5 mm Hg of the target for 91.6% (85.6-93.3) of the intraoperative period. Subjects were hypotensive for 2.6% of the intraoperative period (range, 0-8.4%). Additional performance criteria for the controller included mean absolute performance error of 2.9 (0.8) and mean predictive error of 0.5 (1.0). No subjects experienced major complications. CONCLUSIONS: In this proof of concept study, CLV control minimised perioperative hypotension in subjects undergoing moderate- or high-risk surgery. Further studies to demonstrate efficacy are warranted. TRIAL REGISTRY NUMBER: NCT03515161 (ClinicalTrials.gov).


Assuntos
Infusões Intravenosas/instrumentação , Norepinefrina/administração & dosagem , Procedimentos Cirúrgicos Operatórios/métodos , Vasoconstritores/efeitos adversos , Idoso , Anestesia , Pressão Sanguínea/efeitos dos fármacos , Procedimentos Cirúrgicos Eletivos , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Humanos , Hipertensão/induzido quimicamente , Hipotensão/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Norepinefrina/uso terapêutico , Resultado do Tratamento , Vasoconstritores/uso terapêutico
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