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1.
Int J Mol Sci ; 22(6)2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33805714

RESUMO

Trifluoperazine (TFP), an antipsychotic drug approved by the Food and Drug Administration, has been show to exhibit anti-cancer effects. Pulmonary arterial hypertension (PAH) is a devastating disease characterized by a progressive obliteration of small pulmonary arteries (PAs) due to exaggerated proliferation and resistance to apoptosis of PA smooth muscle cells (PASMCs). However, the therapeutic potential of TFP for correcting the cancer-like phenotype of PAH-PASMCs and improving PAH in animal models remains unknown. PASMCs isolated from PAH patients were exposed to different concentrations of TFP before assessments of cell proliferation and apoptosis. The in vivo therapeutic potential of TFP was tested in two preclinical models with established PAH, namely the monocrotaline and sugen/hypoxia-induced rat models. Assessments of hemodynamics by right heart catheterization and histopathology were conducted. TFP showed strong anti-survival and anti-proliferative effects on cultured PAH-PASMCs. Exposure to TFP was associated with downregulation of AKT activity and nuclear translocation of forkhead box protein O3 (FOXO3). In both preclinical models, TFP significantly lowered the right ventricular systolic pressure and total pulmonary resistance and improved cardiac function. Consistently, TFP reduced the medial wall thickness of distal PAs. Overall, our data indicate that TFP could have beneficial effects in PAH and support the view that seeking new uses for old drugs may represent a fruitful approach.


Assuntos
Fármacos Cardiovasculares/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Hipóxia/prevenção & controle , Miócitos de Músculo Liso/efeitos dos fármacos , Trifluoperazina/farmacologia , Animais , Antipsicóticos/farmacologia , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Reposicionamento de Medicamentos , Feminino , Proteína Forkhead Box O3/genética , Proteína Forkhead Box O3/metabolismo , Hemodinâmica/efeitos dos fármacos , Humanos , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/fisiopatologia , Hipóxia/induzido quimicamente , Hipóxia/genética , Hipóxia/fisiopatologia , Indóis/administração & dosagem , Monocrotalina/administração & dosagem , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Artéria Pulmonar/citologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Pirróis/administração & dosagem , Ratos , Ratos Sprague-Dawley , Survivina/genética , Survivina/metabolismo
2.
J Trauma Acute Care Surg ; 90(2): 369-375, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33502148

RESUMO

BACKGROUND: Uncontrolled hemorrhage is the leading cause of potentially survivable combat casualty mortality, with 86.5% of cases resulting from noncompressible torso hemorrhage. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive technique used to stabilize patients with noncompressible torso hemorrhage; however, its application can take an average of 8 minutes to place. One therapeutic capable of bridging this gap is adenosine-lidocaine-magnesium (ALM), which at high doses induces a reversible cardioplegia. We hypothesize by using ALM as an adjunct to REBOA, the ALM-induced cardiac arrest will temporarily halt exsanguination and reduce blood loss, allowing for REBOA placement and control of bleeding. METHODS: Male Yorkshire swine (60-80 kg) were randomly assigned to REBOA only or ALM-REBOA (n = 8/group). At baseline, uncontrolled hemorrhage was induced via a 1.5-cm right femoral arteriotomy, and hemorrhaged blood was quantified. One minute after injury (S1), ALM was administered, and 7 minutes later (T0), zone 1 REBOA inflation occurred. If cardiac arrest ensued, cardiac function either recovered spontaneously or advanced life support was initiated. At T30, surgical hemostasis was obtained, and REBOA was deflated. Animals were resuscitated until they were humanely euthanized at T90. RESULTS: During field care phase, heart rate and end-tidal CO2 of the ALM-REBOA group were significantly lower than the REBOA only group. While mean arterial pressure significantly decreased from baseline, no significant differences between groups were observed throughout the field care phase. There was no significant difference in survival between the two groups (ALM-REBOA = 89% vs. REBOA only = 100%). Total blood loss was significantly decreased in the ALM-REBOA group (REBOA only = 24.32 ± 1.89 mL/kg vs. ALM-REBOA = 17.75 ± 2.04 mL/kg, p = 0.0499). CONCLUSION: Adenosine-lidocaine-magnesium is a novel therapeutic, which, when used with REBOA, can significantly decrease the amount of blood loss at initial presentation, without compromising survival. This study provides proof of concept for ALM and its ability to bridge the gap between patient presentation and REBOA placement.


Assuntos
Adenosina/farmacologia , Oclusão com Balão/métodos , Soluções Cardioplégicas/farmacologia , Fármacos Cardiovasculares/farmacologia , Exsanguinação/terapia , Parada Cardíaca Induzida/métodos , Lidocaína/farmacologia , Magnésio/farmacologia , Animais , Aorta , Modelos Animais de Doenças , Procedimentos Endovasculares/métodos , Hemostasia Cirúrgica/métodos , Soluções Farmacêuticas , Cuidados Pré-Operatórios/métodos , Ressuscitação/métodos , Suínos
3.
J Ethnopharmacol ; 269: 113688, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33338592

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Scrophularia ningpoensis Hemsl. (known as Xuanshen) has been used in China for centuries as a traditional medicinal plant to treat numerous diseases including inflammation, hypertension, cancer, and diabetes. AIM OF REVIEW: In this review, we provide an update on the botany, pharmacology, phytochemistry, pharmacokinetics, traditional uses, and safety of S. ningpoensis to highlight future research needs and potential uses of this plant. MATERIALS AND METHODS: All information on S. ningpoensis was obtained from scientific databases including ScienceDirect, Springer, PubMed, Sci Finder, China Knowledge Resource Integrated Database from the China National Knowledge Infrastructure (CNKI), Google Scholar, and Baidu Scholar. Additional information was collected from Chinese herbal medicine books, Ph.D. dissertations, and M.Sc. Theses. Plant taxonomy was verified by "The Plant List" database (http://www.theplantlist.org). RESULTS: S. ningpoensis displays fever reducing, detoxifying, and nourishing 'Yin' effects in traditional Chinese medicine (TCM). More than 162 compounds have been identified and isolated from S. ningpoensis, including iridoids and iridoid glycosides, phenylpropanoid glycosides, organic acids, volatile oils, terpenoids, saccharides, flavonoids, sterols, and saponins. These compounds possess a diverse variety of pharmacological properties that affect the cardiovascular, hepatic, and nervous systems, and protect the body against inflammation, oxidation, and carcinogenesis. CONCLUSIONS: Modern pharmacological studies have confirmed that S. ningpoensis is a valuable Chinese medicinal herb with many pharmacological uses in the treatment of cardiovascular, diabetic, and liver diseases. Most of the S. ningpoensis activity may be attributed to iridoid glycosides and phenylpropanoid glycosides; however, detailed information on the molecular mechanisms, metabolic activity, toxicology, and structure-function relationships of active components is limited. Further comprehensive research to evaluate the medicinal properties of S. ningpoensis is needed.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Etnofarmacologia/métodos , Medicina Tradicional Chinesa/métodos , Compostos Fitoquímicos/uso terapêutico , Scrophularia , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Fármacos Cardiovasculares/isolamento & purificação , Fármacos Cardiovasculares/farmacologia , Fármacos Cardiovasculares/uso terapêutico , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
4.
J Ethnopharmacol ; 269: 113690, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33309917

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Coreopsis tinctoria Nutt. (family Asteraceae) is an important traditional medicine in North America, Europe, and Asia for quite a long historical period, which has received great attention due to its health-benefiting activities, including disinfection, treatment sexual infection, diarrhoea, acute and chronic dysentery, red-eye swelling as well as pain, heat, thirst, hypertension, palpitation, gastrointestinal discomfort, and loss of appetite. AIM OF THE REVIEW: The purpose of this review is to give an overview of the current phytochemistry and pharmacological activities of C. tinctoria, and reveals the correlation among its traditional uses, phytochemistry, pharmacological profile, and potential toxicity. MATERIALS AND METHODS: This review is based on published studies and books from electronic sources and library, including the online ethnobotanical database, ethnobotanical monographs, Scopus, SciFinder, Baidu Scholar, CNKI, and PubMed. These reports are related to the traditional uses, phytochemistry, pharmacology, and toxicology of C. tinctoria. RESULTS: Coreopsis tinctoria is traditionally used in diarrhoea, infection, and chronic metabolic diseases. From 1954 to now, more than 120 chemical constituents have been identified from C. tinctoria, such as flavonoids, polyacetylenes, polysaccharides, phenylpropanoids, and volatile oils. Flavonoids are the major bioactive components in C. tinctoria. Current research has shown that its extracts and compounds possess diverse biological and pharmacological activities such as antidiabetes, anti-cardiovascular diseases, antioxidant, anti-inflammatory, protective effects on organs, neuroprotective effects, antimicrobial, and antineoplastic. Studies in animal models, including acute toxicity, long-term toxicity, and genotoxicity have demonstrated that Snow Chrysanthemum is a non-toxic herb, especially for its water-soluble parts. CONCLUSIONS: Recent findings regarding the main phytochemical and pharmacological properties of C. tinctorial have confirmed its traditional uses in anti-infection and treatment of chronic metabolic disease and, more importantly, have revealed the plant as a valuable medicinal plant resource for the treatment of a wide range of diseases. The available reports indicated that most of the bioactivities in C. tinctorial could be attributed to flavonoids. However, higher quality studies on animals and humans studies are required to explore the efficacy and mechanism of action of C. tinctoria in future.


Assuntos
Coreopsis , Etnofarmacologia/métodos , Medicina Tradicional/métodos , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Fármacos Cardiovasculares/isolamento & purificação , Fármacos Cardiovasculares/farmacologia , Fármacos Cardiovasculares/uso terapêutico , Humanos , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia
5.
Medicine (Baltimore) ; 99(52): e23901, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33350788

RESUMO

BACKGROUND: Qishen granules (QSG) is a famous traditional Chinese Medicine (TCM) formula used to treat chronic heart failure (CHF). The objective of this protocol is to clarify the efficacy and safety of QSG for treating CHF. METHODS: Six databases will be electronically searched up to November 1, 2020 for randomized controlled trials (RCTs) in English and Chinese languages. Two independent reviewers will complete tasks of literature retrieval and data extraction. After that, the Cochrane Collaboration risk of bias tool will be utilized to assess methodological quality. The primary outcomes are left ventricular ejection fraction, left ventricular fractional shortening, and N-terminal B-type natriuretic peptide. The secondary outcomes consist of composite cardiac events, adverse effects, and quality of life. Meta-analysis will be performed using the Revman version 5.3. RESULTS: This study will provide a high-quality synthesis of current evidence of QSG for CHF from primary and secondary outcomes. CONCLUSION: This study will provide evidence for the effectiveness and safety of QSG in the treatment of CHF. PROSPERO REGISTRATION NUMBER: CRD42020150442.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Fármacos Cardiovasculares/farmacologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/psicologia , Humanos , Medicina Tradicional Chinesa/métodos , Metanálise como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento
6.
Medicine (Baltimore) ; 99(52): e23911, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33350791

RESUMO

BACKGROUND: More than 11 million people suffer from coronary heart disease (CHD) angina in China, showing high morbidity and mortality rates. Yufengingxin (YFNX) is a commonly used Chinese patent medicine in CHD angina treatment. The purpose of this protocol is to evaluate the effectiveness and safety of YFNX for the treatment of CHD angina. METHODS: A systematic search of randomized controlled trials related to the effectiveness and safety of YFNX in the treatment of CHD angina will be performed from relevant databases, including PubMed, Cochrane Library, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Scientific Journal Database (VIP) and Chinese Biomedical Literature Database (CBM). We will screen all the literatures from the database inception to November 1, 2020. The data including study ID, study characteristics, methodological information, patients information, interventions, comparisons and outcomes will be extracted. The frequency and duration of angina attacks will be served as the primary outcome. Review Manager 5.3 and STATA 14.0 software will be used for data analysis. CONCLUSION: This systematic review will provide strong evidence for the effectiveness and safety of YFNX in the treatment of CHD angina. TRIAL REGISTRATION NUMBER: INPLASY2020110040.


Assuntos
Angina Pectoris/tratamento farmacológico , Isoflavonas/farmacologia , Fármacos Cardiovasculares/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Medicina Tradicional Chinesa/métodos , Metanálise como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento
7.
Chirurgia (Bucur) ; 115(6): 707-714, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33378629

RESUMO

Background-Objectives: It has been reported, that high posthepatectomy portal vein pressure (PVP) has deleterious effect on the liver parenchyma and causes posthepatectomy liver failure (PHLF) and increased 90-day mortality. Terlipressin, is widely used to mitigate the effects of portal hyper-tension. Randomised clinical trials (RCTs) demonstrated encouraging results of use of terlipressin for modulation of increased posthepatectomy PVP. The aim of the present study was to evaluate the effectiveness of the pharmacological modulation of the increased posthepatectomy PVP after major hepatectomy. Methods: Systematic literature searches of electronic databases in accordance with PRISMA was conducted. Meta-analysis was conducted using both fixed- and random-effects models. Results: Three randomised controlled trials (RCTs) comparing terlipressin versus placebo including 284 patients of pooled 60 studies were selected. Placebo cohort patients were significantly younger by 5 years compared to terlipressin cohort. However, the terlipressin cohort demonstrated significantly shorter intensive care unit (ICU) stay compared to placebo cohort. Conclusions: The first meta-analysis demonstrated that terlipressin cohort patients although significantly older by 5 years had significantly shorter ICU stay compared to placebo cohort. Furthermore, though statistically nonsignificant only 6% of terlipressin patients needed inotropic support compared to 16.4% of placebo cohort.


Assuntos
Fármacos Cardiovasculares/farmacologia , Hepatectomia , Hepatopatias/cirurgia , Pressão na Veia Porta/efeitos dos fármacos , Veia Porta , Terlipressina/farmacologia , Hepatectomia/efeitos adversos , Humanos , Cirrose Hepática/cirurgia , Veia Porta/efeitos dos fármacos , Veia Porta/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
8.
Curr Atheroscler Rep ; 22(12): 72, 2020 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-33009957

RESUMO

PURPOSE OF REVIEW: The review highlights selected studies related to cardiovascular disease (CVD) prevention that were presented at the 2020 European Society of Cardiology (ESC) Congress-The Digital Experience. RECENT FINDINGS: The studies reviewed include clinical trials on novel RNA interference-based lipid-lowering therapies AKCEA-APOCIII-LRx and vupanorsen (AKCEA-ANGPTL3-LRx); the EVAPORATE trial assessing the effects of icosapent ethyl on coronary plaque volume progression; the LoDoCo2 trial evaluating the efficacy of low-dose colchicine in cardiovascular disease risk reduction among patients with chronic coronary artery disease; as well as the EMPEROR-Reduced trial evaluating cardiovascular and renal outcomes with empagliflozin in patients with heart failure and reduced ejection fraction. In addition, we review the BPLTTC analysis on blood pressure treatment across blood pressure levels and CVD status and discuss findings from the BRACE CORONA study that examined continuing versus suspending angiotensin-converting enzyme inhibitor or angiotensin receptor blockers in patients on these antihypertensive medications who were hospitalized with COVID-19 infection. The studies presented at the 2020 digital ESC Congress highlight the continuing advancements in the field of CVD prevention.


Assuntos
Betacoronavirus/fisiologia , Cardiologia , Fármacos Cardiovasculares/farmacologia , Doenças Cardiovasculares , Infecções por Coronavirus , Reguladores do Metabolismo de Lipídeos/farmacologia , Pandemias , Pneumonia Viral , Compostos Benzidrílicos/farmacologia , Cardiologia/métodos , Cardiologia/tendências , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Ensaios Clínicos como Assunto , Congressos como Assunto , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/farmacologia , Europa (Continente) , Glucosídeos/farmacologia , Humanos , Oligonucleotídeos/farmacologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Sociedades Médicas , Telecomunicações
10.
Life Sci ; 261: 118306, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32828943

RESUMO

AIMS: Diabetic cardiomyopathy (DCM) is a common diabetes complication that can cause arrhythmia, heart failure, and even sudden death. Ranolazine is an antianginal agent used to treat chronic stable angina and has been demonstrated as an effective treatment for many cardiovascular diseases. However, the mechanism by which ranolazine alleviates DCM is unclear, motivating this study investigating the effects of ranolazine in DCM. MATERIALS AND METHODS: DCM rats were treated with one of three doses of ranolazine (10, 30, and 90 mg/kg/day) for 12 weeks. B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), cysteinyl aspartate specific proteinase-3 (Caspase-3), Notch homolog 1 (NOTCH1), and Neuregulin 1 (NRG1) expression was assayed using western blot and qRT-PCR. Cardiac changes were assayed using echocardiography, CT, HE staining, and Masson's trichrome staining. TUNEL staining and flow cytometry were used to detect cell apoptosis. NOTCH1 inhibitor (DAPT) was used to explore the mechanism of ranolazine. KEY FINDINGS: Compared with the DCM group, the ranolazine groups had no obvious weight loss and significantly decreased blood glucose levels. Ranolazine prevented diabetes-caused cardiac injury. Ranolazine also decreased the number of apoptotic cells and altered the expression of apoptosis-related mRNAs and proteins. Ranolazine-induced NOTCH1 activated NRG1 and inhibited the downstream apoptosis-related pathway, while DAPT partially inhibited ranolazine-induced NOTCH1 and NRG1 expression. SIGNIFICANCE: To our knowledge, this study is the first to demonstrate that ranolazine protects against DCM-induced apoptosis by activating the NOTCH1/NRG1 signaling pathway. Moreover, our study identified new mechanisms involved in DCM.


Assuntos
Fármacos Cardiovasculares/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Ranolazina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Fármacos Cardiovasculares/administração & dosagem , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/fisiopatologia , Cardiomiopatias Diabéticas/fisiopatologia , Relação Dose-Resposta a Droga , Masculino , Neuregulina-1/metabolismo , Ranolazina/administração & dosagem , Ratos , Ratos Sprague-Dawley , Receptor Notch1/metabolismo , Transdução de Sinais/efeitos dos fármacos
11.
Fundam Clin Pharmacol ; 34(5): 530-547, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32603486

RESUMO

Patients with COVID-19 are sometimes already being treated for one or more other chronic conditions, especially if they are elderly. Introducing a treatment against COVID-19, either on an outpatient basis or during hospitalization for more severe cases, raises the question of potential drug-drug interactions. Here, we analyzed the potential or proven risk of the co-administration of drugs used for the most common chronic diseases and those currently offered as treatment or undergoing therapeutic trials for COVID-19. Practical recommendations are offered, where possible.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Medicamentos sob Prescrição/farmacologia , Analgésicos/farmacologia , Antiasmáticos/farmacologia , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Anticoagulantes/farmacologia , Antineoplásicos/farmacologia , Antituberculosos/farmacologia , Antivirais/farmacologia , Betacoronavirus , Fármacos Cardiovasculares/farmacologia , Interações Medicamentosas , Humanos , Hidroxicloroquina/farmacologia , Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Interferon beta-1b/farmacologia , Pandemias , Medicamentos sob Prescrição/farmacocinética , Psicotrópicos/farmacologia , Receptores de Interleucina/antagonistas & inibidores , Medição de Risco , Hormônios Tireóideos/farmacologia
12.
Future Med Chem ; 12(19): 1743-1757, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32698626

RESUMO

At the end of 2019, a novel virus causing severe acute respiratory syndrome to spread globally. There are currently no effective drugs targeting SARS-CoV-2. In this study, based on the analysis of numerous references and selected methods of computational chemistry, the strategy of integrative structural modification of small molecules with antiviral activity into potential active complex molecules has been presented. Proposed molecules have been designed based on the structure of triterpene oleanolic acid and complemented by structures characteristic of selected anti-COVID therapy assisted drugs. Their pharmaceutical molecular parameters and the preliminary bioactivity were calculated and predicted. The results of the above analyses show that among the designed complex substances there are potential antiviral agents directed mainly on SARS-CoV-2.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos , Pneumonia Viral/tratamento farmacológico , Antivirais/química , Fármacos Cardiovasculares/química , Fármacos Cardiovasculares/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Pandemias
13.
Phytomedicine ; 71: 153240, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32450461

RESUMO

BACKGROUND: Bioflavonoids, secondary metabolites of plants, are beneficial in regulating human physiological mechanisms. Bioflavonoids majorly exist in the dietary intake of fruits, vegetables, legumes, pulses, etc. In addition to their cardio-protective and neuroprotective activities, they also possess prominent pharmacological effects including anti-oxidant, anti-inflammatory, anti-proliferative and anti-thrombogenic actions. However, therapeutic efficacy of the bioflavonoids is hampered by their lipophilic nature, low solubility and variable bioavailability which catch the eyes of formulation scientists. PURPOSE: Nanocrystal formulations were studied for many bioflavonoids, although enough attention has not been given to their commercial exploitation, unlike drug nanocrystals. Nanocrystals of bioflavonoid can be prepared by top-down technique, bottom-up technique or combination of both. This review primarily focuses on nanocrystal technology for bioflavonoids, methods of production, critical process parameters, in vitro and in vivo studies conducted to evaluate the efficiency. METHOD: The detailed literature survey was systematically carried out using different electronic databases. It includes Scopus, Web of Science, Medline via PubMed, EMBASE, and Google Scholar. Also up-to-date patent search was conducted to understand the prior art and available intellectual properties. RESULT AND CONCLUSION: It was observed that several formulation and process parameters have an impact on flavonoids nanocrystals and their therapeutic efficacy. Also, clinical studies of flavonoid nanocrystals are barely done so far and thus, substantial safety and efficacy data is necessary for its commercial applications. Nevertheless, nanocrystals can be explored as a promising technology platform for improving overall therapeutic performance of flavonoids in future.


Assuntos
Flavonoides/química , Flavonoides/farmacologia , Nanopartículas/química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Disponibilidade Biológica , Fármacos Cardiovasculares/química , Fármacos Cardiovasculares/farmacologia , Flavonoides/uso terapêutico , Humanos , Nanopartículas/uso terapêutico , Solubilidade
14.
Eur J Prev Cardiol ; 27(10): 1017-1025, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32391719

RESUMO

Patients with cardiovascular risk factors or established cardiovascular disease have an increased risk of developing coronavirus disease 19 and have a worse outcome when infected, but translating this notion into effective action is challenging. At present it is unclear whether cardiovascular therapies may reduce the likelihood of infection, or improve the survival of infected patients. Given the crucial importance of this issue for clinical cardiologists and all specialists dealing with coronavirus disease 19, we tried to recapitulate the current evidence and provide some practical recommendations.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Causas de Morte , Infecções por Coronavirus/epidemiologia , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Fármacos Cardiovasculares/farmacologia , Doenças Cardiovasculares/diagnóstico , Comorbidade , Infecções por Coronavirus/prevenção & controle , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Prevalência , Medição de Risco , Análise de Sobrevida
15.
Rev. esp. cardiol. (Ed. impr.) ; 73(5): 368-375, mayo 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-194544

RESUMO

INTRODUCCIÓN Y OBJETIVOS: La ivabradina es un inhibidor de la corriente If, principal determinante de la función marcapasos del nódulo sinusal, aprobado como antianginoso y para tratar la insuficiencia cardiaca. Existen indicios sobre su capacidad para inhibir la conducción a través del nódulo auriculoventricular (NAV). Sobre esta base, el proyecto BRAKE-AF plantea el uso de ivabradina como agente cronotrópico negativo en fibrilación auricular (FA). MÉTODOS: Se realizará un ensayo clínico multicéntrico de fase III, aleatorizado, abierto, en paralelo, con diseño de no inferioridad, para comparar la ivabradina frente a la digoxina en 232 pacientes con FA permanente no controlada con bloqueadores beta o antagonistas del calcio; el objetivo primario es la reducción de la frecuencia cardiaca media diurna en un Holter de 24 h a los 3 meses. El ensayo se apoyará en un estudio electrofisiológico que analizará el efecto de la ivabradina en el potencial de acción del NAV humano, utilizando un modelo experimental en células de ovario de hámster chino transfectadas con el ADN que codifica la expresión de los distintos canales que componen dicho potencial de acción, registrando las corrientes iónicas mediante la técnica del parche de membrana. RESULTADOS: Se obtendrá información tanto del efecto de la ivabradina en las corrientes iónicas y el potencial de acción del NAV como de su eficacia y su seguridad en pacientes con FA permanente. CONCLUSIONES: Los resultados del proyecto BRAKE-AF podrían permitir que la ivabradina se incluyera en el limitado arsenal de fármacos disponibles actualmente para el control de frecuencia en la FA


INTRODUCTION AND OBJECTIVES: Ivabradine is an inhibitor of the If channel, the main determinant of the pacemaker function of the sinus node. The drug has been approved for the treatment of angina and heart failure. There is some evidence of its role as an inhibitor of atrial-ventricular node (AVN) conduction. The aim of the BRAKE-AF project is to assess ivabradine use for rate control in atrial fibrillation (AF). METHODS: A multicenter, randomized, parallel, open-label, noninferiority phase III clinical trial will be conducted to compare ivabradine vs digoxin in 232 patients with uncontrolled permanent AF despite beta-blockers or calcium channel blockers. The primary efficacy endpoint is the reduction in daytime heart rate measured by 24-hour Holter monitoring at 3 months. This clinical trial will be supported by an electrophysiological study of the effect of ivabradine on the action potential of the human AVN. To do this, an experimental model will be used with Chinese hamster ovarium cells transfected with the DNA encoding the expression of the t channels involved in this action potential and recording of the ionic currents with patch clamp techniques. RESULTS: New data will be obtained on the effect of ivabradine on the human AVN and its safety and efficacy in patients with permanent AF. CONCLUSIONS: The results of the BRAKE-AF project might allow inclusion of ivabradine within the limited arsenal of drugs currently available for rate control in AF


Assuntos
Humanos , Animais , Feminino , Adulto Jovem , Idoso , Idoso de 80 Anos ou mais , Ivabradina/farmacologia , Fibrilação Atrial/tratamento farmacológico , Fármacos Cardiovasculares/farmacologia , Digoxina/farmacologia , Antiarrítmicos/farmacologia , Técnicas de Patch-Clamp , Potenciais de Ação , Fibrilação Atrial/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos
16.
Cardiovasc Drugs Ther ; 34(3): 303-310, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32236860

RESUMO

PURPOSE: The melatonin receptor (MT) agonist ramelteon has a higher affinity to MT1 than for MT2 receptors and induces cardioprotection by involvement of mitochondrial potassium channels. Activation of mitochondrial potassium channels leads to release of free radicals. We investigated whether (1) ramelteon-induced cardioprotection is MT2 receptor specific and (2) if free radicals are involved in ramelteon-induced cardioprotection. METHODS: Hearts of male Wistar rats were randomized, placed on a Langendorff system, and perfused with Krebs-Henseleit buffer at a constant pressure of 80 mmHg. All hearts were subjected to 33 min of global ischemia and 60 min of reperfusion. Before ischemia hearts were perfused with ramelteon (Ram) with or without the MT2 receptor inhibitor 4-phenyl-2-propionamidotetralin (4P-PDOT+Ram, 4P-PDOT). In subsequent experiments, ramelteon was administered together with the radical oxygen species (ROS) scavenger N-2-mercaptopropionylglycine (MPG+Ram). To determine whether the blockade of ramelteon-induced cardioprotection can be restored, we combined ramelteon and MPG with mitochondrial permeability transition pore (mPTP) inhibitor cyclosporine A (CsA) at different time points. Infarct size was determined by triphenyltetrazolium chloride (TTC) staining. RESULTS: Ramelteon-induced infarct size reduction was completely blocked by 4P-PDOT and MPG. Ramelteon and MPG combined with CsA before ischemia were not cardioprotective but CsA at the onset of reperfusion could restore infarct size reduction. CONCLUSIONS: This study shows for the first time that despite the higher affinity to MT1 receptors, (1) ramelteon-induced cardioprotection involves MT2 receptors, (2) cardioprotection requires ROS release, and (3) inhibition of the mPTP can restore infarct size reduction.


Assuntos
Fármacos Cardiovasculares/farmacologia , Indenos/farmacologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Receptor MT2 de Melatonina/agonistas , Animais , Modelos Animais de Doenças , Preparação de Coração Isolado , Masculino , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos Wistar , Receptor MT2 de Melatonina/metabolismo , Transdução de Sinais , Função Ventricular Esquerda/efeitos dos fármacos
17.
Front Biosci (Schol Ed) ; 12: 161-172, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32114453

RESUMO

Coronary artery disease (CAD) and heart failure (HF) are major worldwide threat to health and well-being. Important progress in the treatment of CAD and HF have contributed to a decline in mortality around the world. A considerable number of epidemiological studies reported a strong independent association between elevated heart rate and major cardiovascular risk factors including atherosclerosis, ventricular arrhythmias, and left ventricular dysfunction. Ivabradine (IVA) is a pure heart rate-lowering agent with well-documented anti-anginal and anti-ischemic properties comparable to well-established anti-anginal agents, such as beta-blockers and calcium channel blockers. The heart rate reduction with IVA is beneficial in patients with CAD, chronic stable angina pectoris, and chronic HF, with an acceptable tolerance and safety profile. The pharmacodynamic and pharmacokinetic properties of this drug make it an important agent in the management of patients with CAD and HF. The aim of this short review is to explore recent results with IVA, a new medication that lowers heart rate by selectively inhibiting the If current, and to describe others future potential applications.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Ivabradina/uso terapêutico , Animais , Fármacos Cardiovasculares/efeitos adversos , Fármacos Cardiovasculares/farmacologia , Fármacos Cardiovasculares/uso terapêutico , Frequência Cardíaca/efeitos dos fármacos , Humanos , Ivabradina/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Heart Fail Clin ; 16(2): 187-200, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32143763

RESUMO

Acute decompensated heart failure (ADHF) requires immediate treatments because it impairs perfusion to systemic organs and their function. Half of all patients with ADHF are diagnosed with heart failure with reduced left ventricular ejection fraction (HFrEF). The initial goal of management for ADHF is to stabilize hemodynamic status. Pulmonary edema is treated with vasodilators or diuretics. Inhibitors of the renin-angiotensin-aldosterone system and ß-blockers should be started and/or increased to meet the maximum dose, ideally the target dose, that the patient can tolerate as a treatment of HFrEF. Patients with severe circulatory failure need inotropic drugs or mechanical circulatory support.


Assuntos
Circulação Assistida/métodos , Fármacos Cardiovasculares/farmacologia , Tratamento de Emergência/métodos , Insuficiência Cardíaca , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Volume Sistólico/efeitos dos fármacos
20.
Environ Toxicol ; 35(6): 707-713, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32023008

RESUMO

Excessive intake of high fat diet (HFD) and associated obese conditions are critical contributors of cardiac diseases. In this study, an active metabolite andrographolide from Andrographis paniculata was found to ameliorate HFD-induced cardiac apoptosis. C57/BL6 mouse were grouped as control (n = 9), obese (n = 8), low dose (25 mg/kg/d) andrographolide treatment (n = 9), and high dose (50 mg/kg/d) andrographolide treatment (n = 9). The control group was provided with standard laboratory chow and the other groups were fed with HFD. Andrographolide was administered through oral gavage for 1 week. Histopathological analysis showed increase in apoptotic nuclei and considerable cardiac-damages in the obese group signifying cardiac remodeling effects. Further, Western blot results showed increase in pro-apoptotic proteins and decrease in the proteins of IGF-1R-survival signaling. However, feeding of andrographolide significantly reduced the cardiac effects of HFD. The results strongly suggest that andrographolide supplementation can be used for prevention and treatment of cardiovascular disease in obese patients.


Assuntos
Apoptose/efeitos dos fármacos , Fármacos Cardiovasculares/farmacologia , Dieta Hiperlipídica/efeitos adversos , Diterpenos/farmacologia , Coração/efeitos dos fármacos , Obesidade/patologia , Andrographis/química , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Fármacos Cardiovasculares/isolamento & purificação , Diterpenos/isolamento & purificação , Masculino , Camundongos , Camundongos Obesos , Miocárdio/metabolismo , Miocárdio/patologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Transdução de Sinais
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