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1.
J Agric Food Chem ; 68(3): 759-768, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31841328

RESUMO

In this study, we investigated the antihypertensive effects in vitro and in vivo of novel angiotensin-converting enzyme inhibitory (ACEI) peptides purified and identified from bovine bone gelatin hydrolysate (BGH). Thirteen ACEI peptides were identified from BGH, and among which, RGL-(Hyp)-GL and RGM-(Hyp)-GF exhibited high ACE inhibition with IC50 values of 1.44 and 10.23 µM. Molecular docking predicted that RGM-(Hyp)-GF and ACE residues of Glu384, His513, and Lys511 formed hydrogen-bonding interactions at distances of 2.57, 2.99, and 2.42 + 3.0 Å. RGL-(Hyp)-GL formed hydrogen bonds with Lys511 and Tyr523 and generated hydrogen-bonding interactions with His387 and Glu411 in the zinc(II) complexation motif at distances of 2.74 and 3.03 + 1.93 Å. The maximal decrements in systolic blood pressure in spontaneously hypertensive rats induced by one-time gavage of RGL-(Hyp)-GL and RGM-(Hyp)-GF at 30 mg/kg were 31.3 and 38.6 mmHg. RGL-(Hyp)-GL had higher enzyme degradation resistance than that of RGM-(Hyp)-GF in vitro incubation in rat plasma, and they were sequentially degraded into pentapeptides and tetrapeptides within 2 h. Our results indicate that BGH can serve as a nutritional candidate to control blood pressure.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/química , Anti-Hipertensivos/química , Osso e Ossos/química , Gelatina/química , Peptídeos/química , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/isolamento & purificação , Pressão Sanguínea/efeitos dos fármacos , Bovinos , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Simulação de Acoplamento Molecular , Peptídeos/administração & dosagem , Peptídeos/isolamento & purificação , Peptidil Dipeptidase A/química , Hidrolisados de Proteína/química , Ratos , Ratos Endogâmicos SHR
2.
J Sci Food Agric ; 100(1): 315-324, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31525262

RESUMO

BACKGROUND: In order to utilize tilapia skin gelatin hydrolysate protein, which is normally discarded as industrial waste in the process of fish manufacture, we study the in vivo and in vitro angiotensin-I-converting enzyme (ACE) inhibitory activity of the peptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP). The aim was to provide a pharmacological basis of the development of minimal side effects of ACE inhibitors by comparative analysis with captopril in molecular docking. RESULTS: This peptide from protein-rich wastes showed excellent ACE inhibitory activity (IC50  = 2.577 µmol L-1 ) and exhibited a mixed noncompetitive inhibitory pattern with Lineweaver-Burk plots. Furthermore, LSGYGP and captopril groups both showed significant decreases in blood pressure after 6 h and maintained good digestive stability over 4 h. Molecular bond interactions differentiate competitive captopril upon hydrogen bond interactions and Zn(II) interaction. The C-terminal Pro generates three interactions (hydrogen bonds, hydrophilic interactions and Van der Waals interactions) in the peptide and effectively interacts with the S1 and S2 pockets of ACE. CONCLUSION: LSGYGP, with an IC50 value of 2.577 µmol L-1 , has an antihypertensive effect in spontaneously hypertensive rats. Through comparison with captopril, this study revealed that LSGYGP may be a potential food-derived ACE inhibitory peptide and could act as a functional food ingredient to prevent hypertension. © 2019 Society of Chemical Industry.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/química , Anti-Hipertensivos/química , Captopril/química , Hipertensão/tratamento farmacológico , Peptídeos/química , Sequência de Aminoácidos , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Captopril/administração & dosagem , Ciclídeos , Digestão , Proteínas de Peixes/química , Trato Gastrointestinal/metabolismo , Humanos , Ligações de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Cinética , Masculino , Simulação de Acoplamento Molecular , Peptídeos/metabolismo , Peptídeos/farmacologia , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Hidrolisados de Proteína/química , Hidrolisados de Proteína/metabolismo , Ratos , Ratos Endogâmicos SHR
3.
Medicine (Baltimore) ; 98(49): e17825, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31804305

RESUMO

This study tried to investigate the effects of number of medications and age on antihypertensive medication adherence in a real-world setting using a nationwide representative cohort.We obtained data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) of Korea, which is a sample of 2.2% (N = 1,048,061) of total population (N = 46,605,433). Patients aged 20 years or older (N = 150,550) who took antihypertensive medications for at least 1 year were selected. Medication possession ratio (MPR) was used for measuring adherence. The subjects were divided into 5 subgroups according to total number of medications: 1-2, 3-4, 5-6, 7-8, and 9 or more. The mean age and the mean number of medications were 60.3 ±â€Š12.6 years and 4.1 ±â€Š2.2, respectively. The mean MPR was 80.4 ±â€Š23.9%, and 66.9% (N = 100,645) of total subjects were adherent (MPR ≥ 80%). The overall tendency of antihypertensive medication adherence according to the total number of medications displayed an inverted U-shape with a peak at 3-4 drugs. Adherence consistently increased as the age increased until age 69 and started to decrease from age 70. The proportion of adherent patients (MPR ≥ 80%) according to the total number of medications also showed an inverted U-shape with a peak at 3-4 drugs. When the same number of drugs was taken, the proportion of adherent patients according to age featured an inverted U- shape with a peak at 60 to 69 years. Patients taking 9 or more total drugs had the overall odds ratio (95% CI) of non-adherence (MPR < 80%) with 1.17 (1.11-1.24) compared with those taking 1 to 8 total drugs and the odds ratios in the age subgroups of 40 to 49, 50 to 59, 60 to 69 years were 1.57 (1.31-1.87), 1.21 (1.08-1.36), and 1.14 (1.04-1.25), respectively (P < .05).Association between age, total number of medications, and antihypertensive adherence displayed an inverted U-shape with a peak at 3 to 4 total medications and at age 60 to 69 years. When the total number of drugs was 9 or more, adherence decreased prominently, regardless of age.


Assuntos
Anti-Hipertensivos/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Polimedicação , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/administração & dosagem , Feminino , Humanos , Revisão da Utilização de Seguros , Masculino , Pessoa de Meia-Idade , República da Coreia , Estudos Retrospectivos , Fatores Sexuais , Fatores Socioeconômicos
4.
Medicine (Baltimore) ; 98(49): e17963, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31804307

RESUMO

Renin angiotensin aldosterone system inhibitors (RAASi) and diuretics are among the most frequently prescribed anti-hypertensives. Individuals with chronic kidney disease (CKD) are particularly at risk for electrolyte disturbances and kidney injury but the appropriate use of lab monitoring following RAASi or diuretic initiation is uncertain in CKD.We describe the frequency and time interval of lab monitoring during initiation of RAASi and diuretics in CKD and assess whether close lab monitoring associates with one-year risk of emergency department (ED) visit or hospitalization.We evaluated an observational cohort of 8,217 individuals with stage 3-5 non-dialysis CKD newly prescribed a RAASi (52.3%) or diuretic (47.7%) from thirty-six primary care offices affiliated with Brigham and Women's Hospital and Massachusetts General Hospital between 2009 and 2011.Overall, 3306 (40.2%) individuals did not have pre-prescription labs done within 2 weeks, and 5957 (72.5%) did not have post-prescription labs done within 2 weeks which includes 524 (6.4%) individuals without post-prescription within 1 year. Close monitoring occurred in only 1547 (20.1%) and was more likely in individuals prescribed diuretics compared to RAASi (adjusted OR 1.39; 95%CI 1.20-1.62), with CKD stage 4,5 compared with stage 3 (adjusted OR 1.47; 95%CI 1.16-1.86) and with cardiovascular disease (adjusted OR 1.42; 95%CI 1.21-1.66). Close monitoring was not associated with decreased risk of ED visit or hospitalization.Close lab monitoring during initiation of RAASi or diuretics was more common in participants with cardiovascular disease and advanced CKD suggesting physicians selected high-risk individuals for close monitoring. As nearly 80% of individuals did not receive close lab monitoring there may be value in future research on electronic physician decision tools targeted at lab monitoring.


Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Testes de Função Renal/estatística & dados numéricos , Insuficiência Renal Crônica/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Boston , Comorbidade , Diuréticos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Potássio/sangue , Sistema Renina-Angiotensina/efeitos dos fármacos , Índice de Gravidade de Doença , Fatores Socioeconômicos
5.
Medicine (Baltimore) ; 98(49): e18134, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31804323

RESUMO

BACKGROUND: Essential hypertension is one of the most common chronic diseases in the world and a major risk factor for cardiovascular and cerebrovascular diseases. Hypertension often leads to a variety of complications, of which vascular endothelial dysfunction is an important part. Traditional Chinese medicine (TCM) combined with western medicine can significantly improve vascular endothelial function in patients with hypertension, but it has not been systematically evaluated for efficacy and safety of essential hypertension. Therefore, we aim to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of TCM combined with western medicine in improving vascular endothelial function in patients with essential hypertension. METHODS: We will search PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Excerpta Medica Database (EMBASE), China National Knowledge Infrastructure Database (CNKI), Wanfang Database, China Science Journal Database (VIP Database) and China Biomedical Literature Database (CBM). Clinical trial registrations, potential grey literature, related conference abstracts, and reference lists of identified studies will also be retrieved. The electronic database will be searched for literatures published from the beginning to October 2018. Based on the heterogeneity test, data integration is performed using a fixed effect model or a random effects model. Changes in blood pressure and endothelial function will be assessed as primary outcomes. Drug use, disease progression and adverse events will be assessed as secondary outcomes. RevMan V.5.3.5 will be used for meta-analysis. RESULTS: This systematic review and meta-analysis will provide high-quality evidence from a variety of aspects, including efficacy, blood pressure, vascular endothelial function and adverse reactions, to assess the efficacy and safety of TCM combined with western medicine in patients with hypertension. CONCLUSION: This systematic review will determine whether TCM combined with western medicine provides evidence for effective intervention of vascular endothelial function in patients with essential hypertension. ETHICS AND DISSEMINATION: This systematic review and meta-analysis of randomized controlled trials does not require ethical recognition, and the results of this paper will be published in an open access, internationally influential academic journal. PROSPERO REGISTRATION NUMBER: CRD42019140743.


Assuntos
Anti-Hipertensivos/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Hipertensão Essencial/tratamento farmacológico , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
6.
Expert Rev Clin Pharmacol ; 12(12): 1073-1079, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31842637

RESUMO

Introduction: Netarsudil and latanoprost ophthalmic solution (0.02%/0.005%) is indicated for intraocular pressure (IOP) lowering in open-angle glaucoma (OAG) or ocular hypertension (OHTN). The once-daily agent combines the mechanism of action for each of the individual components and provides a new avenue for long-term intraocular pressure control. This review aims to cover the agent's current efficacy and safety data and opine as to its role in glaucoma management.Areas covered: This article will cover Phase II-III clinical efficacy and safety data as well as basic science literature pertaining to the agent's mechanism of action and pharmacodynamics. In selecting articles for inclusion in this review, a literature search using the PubMed database was carried out. Cross-referencing was carried out where applicable. We did not use any date or language restrictions in electronic searches.Expert opinion: Netarsudil and latanoprost ophthalmic solution plays a pivotal role in management of individuals with OAG and OHTN. The agent may be used as first-line therapy to provide substantial IOP-lowering or when additional lowering is indicated and prostaglandins have provided insufficient IOP lowering. The once-daily dosing regimen decreases the risk of inadequate treatment due to nonadherence.


Assuntos
Benzoatos/administração & dosagem , Glaucoma de Ângulo Aberto/tratamento farmacológico , Latanoprosta/administração & dosagem , Hipertensão Ocular/tratamento farmacológico , beta-Alanina/análogos & derivados , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Benzoatos/efeitos adversos , Combinação de Medicamentos , Humanos , Pressão Intraocular , Latanoprosta/efeitos adversos , Soluções Oftálmicas , beta-Alanina/administração & dosagem , beta-Alanina/efeitos adversos
7.
Medicine (Baltimore) ; 98(51): e18471, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31861026

RESUMO

This study aimed to compare the Hamilton anxiety rating/Hamilton depression rating (HAMA/HAMD) scale scores and blood pressure (BP) goal achievement associated with the use of valsartan-amlodipine single-pill combinations (SPCs) versus valsartan and amlodipine combination in adult hypertensive patients.A total of 476 hypertensive patients were randomly assigned into the SPC (valsartan-amlodipine) and control (valsartan and amlodipine combination) groups. All patients had an uncontrolled BP (160-179/100-109 mm Hg). BP goal was <140/90 mm Hg. Cox proportional hazards regression analysis was used to analyze the likelihood of HAMA/HAMD scales, SPCs, control group, and daily dosage number. Kaplan-Meier analysis was used to estimate the rates of BP goal achievement over time among the 2 groups.A total of 476 patients were included in the study, and 439 patients completed the follow-up and received the index drug therapy. There was a significant difference in BP between the 2 groups on days 28, 42, and 56. Patients who received SPCs had a significantly higher rate of BP goal achievement over time (P = .000). The average HAMD scores in the SPC and control groups were 5.54 and 5.49 and 6.06 and 6.21 on days 28 and 56, respectively. The average HAMA scores in the SPC and control groups were 7.41 and 7.13 and 7.90 and 8.01 on days 28 and 56, respectively. The means of HAMD and HAMA scores were 5.826 and 7.614, respectively. The higher the HAMA/HAMD scores, the lower was the BP goal achievement. The number of drugs taken by the patients was associated with the HAMA and HAMD scores. There was no significant difference between HAMA scores of patients taking 1 tablet daily (7.22 ±â€Š1.885) and those taking two-tablets daily (7.38 ±â€Š1.953) (P = .408). However, when these scores were compared to those of patients taking 4 tablets daily (8.08 ±â€Š2.285), a significant difference was observed (P = .000, P = .000).Hypertensive patients treated with valsartan-amlodipine SPCs were significantly more likely to achieve BP goal and have lesser HAMA/HAMD scores compared to patients treated with valsartan and amlodipine combination.


Assuntos
Combinação Anlodipino e Valsartana/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Ansiedade/prevenção & controle , Depressão/prevenção & controle , Hipertensão/tratamento farmacológico , Combinação Anlodipino e Valsartana/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Feminino , Humanos , Hipertensão/psicologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Lakartidningen ; 1162019 Dec 23.
Artigo em Sueco | MEDLINE | ID: mdl-31873937

RESUMO

Night-time blood pressure is an independent prognostic marker for cardiovascular disease. Evening dosing of antihypertensive agents can reduce night-time blood pressure and restore night-time blood pressure dipping pattern. In the Hygia Chronotherapy Trial, evening dosing of antihypertensive agents was compared to morning dosing, with dramatic effects on cardiovascular events and total mortality. We review possible limitations of the Hygia trial, including aspects of randomization, allocation concealment, outcome reporting and imbalance between groups. Based on these limitations, the trial should be interpreted with caution and future studies should be awaited before changing clinical practice.


Assuntos
Anti-Hipertensivos , Hipertensão , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea , Determinação da Pressão Arterial , Ensaios Clínicos como Assunto , Relação Dose-Resposta a Droga , Humanos , Hipertensão/tratamento farmacológico
9.
Rom J Ophthalmol ; 63(3): 249-256, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687627

RESUMO

Introduction. The topical medications containing benzalkonium chloride (BAK) as preservative is known to induce corneal toxicity and ocular surface disease (OSD) in glaucoma patients. Newer preservatives like SofZia or polyquaternium-1 (Polyquad) have been developed to replace BAK in many medications. The present study aimed at comparing the OSD in glaucoma patients receiving BAK preserved travoprost versus travoprost with polyquad as preservative and controls not receiving any medications. Methods. This prospective, controlled, observational study was conducted on patients of primary open angle glaucoma (POAG) on medications for more than 6 months. The first group comprised of 40 patients receiving BAK preserved travoprost, the second group included 40 patients receiving polyquad preserved travoprost and 30 of control group not receiving any medical treatment. Ocular Surface Disease Index (OSDI) scores using Ocular Surface Disease Index (OSDI) Questionnaire were assessed and compared in all subjects. Results. The mean OSDI score was 29.09 ± 13.45 in BAK group, 12.4 ± 5.085 in polyquad group and 10.93 ± 7.36 in controls. The mean difference in OSDI scores between BAK and polyquad group 16.63 (p < 0.05) and between the BAK and control group was 18.96 (p < 0.05). The mean difference in OSDI scores between the polyquad and control group was 1.53 (p > 0.05). The mean IOP in the BAK group was 19.2 ± 3.5 and in polyquad group was 20.1 ± 4.2. The IOP measured at 12 months of treatment was 13.2 ± 2.1 in BAK group and 12.8 ± 3.3 in polyquad group. The IOP measured at baseline and 12 months showed statistically significant difference in both the groups (p

Assuntos
Compostos de Benzalcônio/farmacologia , Túnica Conjuntiva/patologia , Córnea/patologia , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma/tratamento farmacológico , Polímeros/farmacologia , Travoprost/administração & dosagem , Administração Tópica , Anti-Hipertensivos/administração & dosagem , Túnica Conjuntiva/efeitos dos fármacos , Córnea/efeitos dos fármacos , Seguimentos , Glaucoma/diagnóstico , Glaucoma de Ângulo Aberto/diagnóstico , Humanos , Pressão Intraocular/efeitos dos fármacos , Pressão Intraocular/fisiologia , Conservantes Farmacêuticos/farmacologia , Estudos Prospectivos
10.
Undersea Hyperb Med ; 46(5): 611-618, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31683358

RESUMO

Background: Immersion can cause immersion pulmonary edema (IPE) in previously healthy subjects. We performed a case-control study to better identify IPE risk factors. Methods: We prospectively included recreational scuba divers who had presented signs of IPE and control divers who were randomly chosen among diving members of the French Underwater Federation. We sent an anonymous questionnaire to each diver, with questions on individual characteristics, as well as the conditions of the most recent dive (controls) or the dive during which IPE occurred. Univariate logistic regressions were performed for each relevant factor. Then, multivariate logistic regression was performed. Results: Of the 882 questionnaires sent, 480 (54%) were returned from 88 cases (90%) and 392 control divers (50%). Multivariate analysis identified the following independent risk factors associated with IPE: being aged over 50 years ((OR) 3.30, (95%CI) 1.76-6.19); female sex (OR 2.20, 95%CI 1.19-4.08); non-steroidal anti-inflammatory drug (NSAID) intake before diving (OR 24.32, 95%CI 2.86-206.91); depth of dive over 20 m (OR 2.00, 95%CI 1.07-3.74); physical exertion prior to or during the dive (OR 5.51, 95%CI 2.69-11.28); training dive type (OR 5.34, 95%CI 2.62-10.86); and daily medication intake (OR 2.79, 95%CI 1.50-5.21); this latter factor appeared to be associated with hypertension in the univariate analysis. Conclusion: To reduce the risk of experiencing IPE, divers over 50 years of age or with hypertension, especially women, should avoid extensive physical effort, psychological stress, deep dives and NSAID intake before diving.


Assuntos
Mergulho , Edema Pulmonar/etiologia , Adulto , Fatores Etários , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Estudos de Casos e Controles , Feminino , França , Humanos , Hipertensão/tratamento farmacológico , Imersão/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Esforço Físico , Estudos Prospectivos , Recreação , Fatores de Risco , Fatores Sexuais , Inquéritos e Questionários/estatística & dados numéricos
11.
Int J Nanomedicine ; 14: 6555-6574, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31616143

RESUMO

Introduction: The intention of this work was to load olmesartan medoxomil (OLM), a sparsely water soluble antihypertensive bioactive with low oral bioavailability (26%), into PEGylated bilosomes (PBs) for augmenting its transdermal delivery. PBs contain PEGylated single chain edge activator besides the components of traditional bilosomes (Span 60, cholesterol and bile salts). The PEG gives further resilience to vesicle membrane and is speculated to augment both permeability and bioavailability of OLM. Methods: A 24 factorial experiment was constructed to inspect the impact of diverse variables on vesicles' features and sort out the optimal formula adopting Design Expert® software utilizing thin film hydration technique. Vesicles' evaluation was done by finding out entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and amount of drug released after 6 hrs (Q6h). The optimal formula was selected and characterized for further investigations. Results: The optimal formula (PB15) showed spherical vesicles with EE% of 72.49±0.38%, PS of 559.30±10.70 nm, PDI of 0.57±0.15, ZP of -38.35±0.65 mV and Q6h of 59.60±0.24%. PB15 showed higher deformability index (28.39±5.71 g) compared to traditional bilosomes (5.88±0.90 g) and transethosomes (14.94±0.63 g). Further, PB15 showed superior skin permeation from rat's skin relative to the drug suspension. Moreover, confocal laser scanning microscopy examination revealed efficient penetration of the fluoro-labeled PB15 through skin. Histopathological study ensured the safety of PB15. In addition, in-vivo skin deposition studies showed higher OLM deposition in rat's skin from PB15 compared to transethosomes and OLM suspension. Furthermore, pharmacodynamic and pharmacokinetic studies performed using male Wistar rats and male Albino rabbits, respectively, showed the superiority of PB15 over oral tablets. PB15 was found to have significantly higher AUC0-48 and AUC0-∞ relative to the oral tablets. As well, the relative bioavailability of PB15 was found to be 235.04%. Conclusion: Overall, the obtained results confirmed the creditable effect of PB15 for transdermal delivery.


Assuntos
Ácidos e Sais Biliares/química , Sistemas de Liberação de Medicamentos , Olmesartana Medoxomila/administração & dosagem , Polietilenoglicóis/química , Administração Cutânea , Administração Oral , Animais , Anti-Hipertensivos/administração & dosagem , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Masculino , Olmesartana Medoxomila/farmacocinética , Olmesartana Medoxomila/farmacologia , Tamanho da Partícula , Permeabilidade , Coelhos , Ratos Wistar , Pele/efeitos dos fármacos , Absorção Cutânea , Comprimidos
13.
Rev Med Suisse ; 15(668): 1946-1949, 2019 Sep 23.
Artigo em Francês | MEDLINE | ID: mdl-31643156

RESUMO

High blood pressure is a major risk factor for cardiovascular disease, leading to a high and increasing rate of morbidity and mortality with our current lifestyle. This is therefore a real public health problem. About 20 % of refractory hypertension is caused by a poor drug intake. The new 2018 European recommendations for high blood pressure emphasize the importance of improving patients' therapeutic adherence. To achieve that, the general practitioner must promote a bio-psycho-social approach, targeted to patient empowerment and to develop multidisciplinarity with the other care providers. Concerning the medication, physicians are encouraged to use combination therapies in a single pill.


Assuntos
Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/psicologia , Adesão à Medicação , Atenção Primária à Saúde , Combinação de Medicamentos , Humanos , Adesão à Medicação/psicologia
15.
AAPS PharmSciTech ; 20(8): 321, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31650430

RESUMO

Combined dissolution and permeation systems are designed to simultaneously assess the dissolution of a pharmaceutical dosage form and the permeation of dissolved drugs therefrom. However, there were still some limitations on predicting the possible absorption rate-limiting steps and improving the in vitro-in vivo correlation (IVIVC) of a complete dosage form. In this study, the modified biorelevant media with some solubilizers and pH modifiers were integrated into the drug dissolution/absorption simulating system (DDASS). Indapamide, a poorly soluble compound (pKa = 8.8), was selected to validate the applicability of the modified biorelevant media. The elution and permeation dynamics of indapamide were investigated by using appropriate solubilizing agents in the DDASS. The absorption behaviors were analyzed after oral administration of indapamide in beagle dogs. The absorption rate-limiting steps and IVIVCs were predicted from the dissolution-permeation-absorption dynamic parameters. As a result, the absorption fraction of indapamide in the FaSSIFmod of DDASS was estimated to be approximately 100%, in accordance with its high permeability. The ratios of permeation rate to elution rate were 2.55 and 3.34 for the immediate- and sustained-release tablets of indapamide, respectively, suggesting a dissolution rate-limiting absorption for indapamine. In addition, point-to-point correlations were established between in vitro elution and in vivo absorption by the nonlinear and linear regression analysis ways (r > 0.85). The findings indicate that DDASS is a promising technique to develop improved IVIVCs of a complete dosage form, and the FaSSIFmod is suitable to predict the possible absorption rate-limiting steps of poorly soluble drugs in DDASS.


Assuntos
Liberação Controlada de Fármacos , Indapamida/administração & dosagem , Indapamida/metabolismo , Absorção Intestinal/efeitos dos fármacos , Administração Oral , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/metabolismo , Cães , Composição de Medicamentos , Avaliação Pré-Clínica de Medicamentos/métodos , Previsões , Absorção Intestinal/fisiologia , Jejuno/efeitos dos fármacos , Jejuno/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Solubilidade , Comprimidos/administração & dosagem , Comprimidos/química , Comprimidos/farmacocinética
16.
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
17.
N Engl J Med ; 381(12): 1114-1123, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31532959

RESUMO

BACKGROUND: Persons with low socioeconomic status and nonwhite persons in the United States have high rates of cardiovascular disease. The use of combination pills (also called "polypills") containing low doses of medications with proven benefits for the prevention of cardiovascular disease may be beneficial in such persons. However, few data are available regarding the use of polypill therapy in underserved communities in the United States, in which adherence to guideline-based care is generally low. METHODS: We conducted a randomized, controlled trial involving adults without cardiovascular disease. Participants were assigned to the polypill group or the usual-care group at a federally qualified community health center in Alabama. Components of the polypill were atorvastatin (at a dose of 10 mg), amlodipine (2.5 mg), losartan (25 mg), and hydrochlorothiazide (12.5 mg). The two primary outcomes were the changes from baseline in systolic blood pressure and low-density lipoprotein (LDL) cholesterol level at 12 months. RESULTS: The trial enrolled 303 adults, of whom 96% were black. Three quarters of the participants had an annual income below $15,000. The mean estimated 10-year cardiovascular risk was 12.7%, the baseline blood pressure was 140/83 mm Hg, and the baseline LDL cholesterol level was 113 mg per deciliter. The monthly cost of the polypill was $26. At 12 months, adherence to the polypill regimen, as assessed on the basis of pill counts, was 86%. The mean systolic blood pressure decreased by 9 mm Hg in the polypill group, as compared with 2 mm Hg in the usual-care group (difference, -7 mm Hg; 95% confidence interval [CI], -12 to -2; P = 0.003). The mean LDL cholesterol level decreased by 15 mg per deciliter in the polypill group, as compared with 4 mg per deciliter in the usual-care group (difference, -11 mg per deciliter; 95% CI, -18 to -5; P<0.001). CONCLUSIONS: A polypill-based strategy led to greater reductions in systolic blood pressure and LDL cholesterol level than were observed with usual care in a socioeconomically vulnerable minority population. (Funded by the American Heart Association Strategically Focused Prevention Research Network and the National Institutes of Health; ClinicalTrials.gov number, NCT02278471.).


Assuntos
Anti-Hipertensivos/administração & dosagem , Combinação de Medicamentos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipercolesterolemia/tratamento farmacológico , Hipertensão/tratamento farmacológico , Área Carente de Assistência Médica , Adesão à Medicação/estatística & dados numéricos , Adulto , Alabama , Anlodipino/administração & dosagem , Atorvastatina/administração & dosagem , LDL-Colesterol/sangue , Centros Comunitários de Saúde , Feminino , Humanos , Hidroclorotiazida/administração & dosagem , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Hipertensão/complicações , Losartan/administração & dosagem , Masculino , Pessoa de Meia-Idade
18.
Pan Afr Med J ; 33: 91, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489069

RESUMO

Introduction: Haemodialysis (HD) which is a form of renal replacement therapy commonly prescribed for patients with chronic kidney disease (CKD). However, it is not without deleterious haemodynamic responses which may occur either during or immediately after the termination of the procedure. These may include hypotension or hypertension. Methods: This was a retrospective study that reviewed chronic kidney disease (CKD) patients on maintenance haemodialysis at the renal unit of University of Calabar Teaching Hospital, Calabar, Nigeria. In all, 71 patients were reviewed but only 64 patients had complete data for analysis. Socio-demographic, clinical and biochemical data were obtained from the records in the dialysis unit. Results: There were more males 38 (59.4%) than females 26 (40.6%) in the study. The mean age was 51.71±15.43 years and 43.04±14.03years for males and females respectively. The prevalence of intradialysis hypertension 29 (45.3%) was higher than that of intradialysis hypotension 20 (31.3%) and the commonest cause of CKD requiring haemodialysis was diabetic nephropathy. The factors associated with intradialysis hypotension were lower post-dialysis systolic blood pressure (PDSBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and less number of antihypertensive medications; while the factors associated with intradialysis hypertension were higher post-dialysis systolic blood pressure (SBP), MAP, greater number of antihypertensive medications and longer duration of haemodialysis. Conclusion: Our study shows that there are several modifiable factors associated with blood pressure fluctuations among CKD patients on maintenance haemodialysis in the renal unit of the University of Calabar Teaching Hospital, Calabar.


Assuntos
Hipertensão/epidemiologia , Hipotensão/epidemiologia , Diálise Renal/métodos , Insuficiência Renal Crônica/terapia , Adolescente , Adulto , Idoso , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea , Feminino , Hospitais de Ensino , Humanos , Hipertensão/etiologia , Hipotensão/etiologia , Masculino , Pessoa de Meia-Idade , Nigéria , Prevalência , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária , Fatores de Tempo , Adulto Jovem
20.
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
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