Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.667
Filtrar
1.
Brasília; s.n; 14 maio 2020.
Não convencional em Português | LILACS, Coleciona SUS, PIE | ID: biblio-1097392

RESUMO

Essa é uma produção do Departamento de Ciência e Tecnologia (Decit) da Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde (SCTIE) do Ministério da Saúde (Decit/SCTIE/MS), que tem como missão promover a ciência e tecnologia e o uso de evidências científicas para a tomada de decisão do SUS, tendo como principal atribuição o incentivo ao desenvolvimento de pesquisas em saúde no Brasil, de modo a direcionar os investimentos realizados em pesquisa pelo Governo Federal às necessidades de saúde pública. Informar sobre as principais evidências científicas descritas na literatura internacional sobre tratamento farmacológico para a COVID-19. Além de resumir cada estudo identificado, o informe apresenta também uma avaliação da qualidade metodológica e a quantidade de artigos publicados, de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, entre outros). Foram encontrados 15 artigos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Progressão da Doença , Betacoronavirus/efeitos dos fármacos , Primaquina/uso terapêutico , Ivermectina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Vacina BCG/administração & dosagem , Oxigenação por Membrana Extracorpórea/instrumentação , Cloroquina/uso terapêutico , Azitromicina/uso terapêutico , Ritonavir/uso terapêutico , Losartan/uso terapêutico , Terapia Antirretroviral de Alta Atividade/instrumentação , Combinação de Medicamentos , Oseltamivir/uso terapêutico , Lopinavir/uso terapêutico , Darunavir/uso terapêutico , Telmisartan/uso terapêutico , Hidroxicloroquina/uso terapêutico , Anticoagulantes/uso terapêutico
2.
Wiad Lek ; 73(2): 321-324, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32248168

RESUMO

OBJECTIVE: The aim: To evaluate the hemodynamic and echocardiographic parameters, the level of adiponectin and IL-6 in such patients under the influence of therapy with sartans (telmisartan or olmesartan) and atorvastatin 12 weeks later. PATIENTS AND METHODS: Materials and methods: Fifty patients with arterial hypertension of II stage and 2 level, who underwent elective in-patient treatment were examined. During the next 12 weeks, they took olmesartan (1st group) or telmisartan (2nd group) in combination with atorvastatin. RESULTS: Results: The combined use of olmesartan or telmisartan in with atorvastatin for 12 weeks had a resulted in a significant decrease in systolic and diastolic blood pressure, heart rate and myocardial mass. After treatment with olmesartan in combination with atorvastatin, the adiponectin content in the blood increased by 41.6% (p <0.05). In the group of patients who receiving telmisartan, an increase adiponectin level was noted in 80.0% of patients and a had shown a significantly higher increase in adiponectin levels, namely for 59.4% after treatment (p <0.01). The level of IL-6 has significantly decreased, both with the administration of olmesartan (2.7 times) and telmisartan (2.6 times) (p<0.01). CONCLUSION: Conclusions: Telmisartan, in comparison with olmesartan, significantly reduces the size of the left ventricular and left atrium myocardium, and decreased left ventricular mass index. Telmisartan improves the cardio-metabolic profile of obese and hypertensive patients by increase of adiponectin concentrations and decrease of IL-6 levels.


Assuntos
Hipertensão , Pressão Sanguínea , Humanos , Imidazóis , Obesidade , Telmisartan , Tetrazóis
3.
Life Sci ; 245: 117388, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32007576

RESUMO

AIMS: The higher incidence rate of Alzheimer's disease (AD) among women has led to explorations on the association between estrogen deficiency and AD. Also, usage of antihypertensive drugs has been suggested to reduce the incidence of AD in elderly hypertensive patients. Thus, this study aimed to investigate the effects of telmisartan and/or 17ß-estradiol on a cognitively impaired ovariectomized rat model of AD. MAIN METHODS: 75 female Wistar rats were randomly allocated into five groups. One group was sham operated and the other four groups were subjected to ovariectomy, received D-galactose and either untreated or treated with telmisartan and/or 17ß-estradiol for 6 weeks. KEY FINDINGS: Ovariectomized rats showed cognitive impairment in Morris water maze and novel object recognition tests, increasing inflammatory biomarkers (tumor necrosis factor-α, and interleukin-1ß), increasing AD biomarkers (amyloid beta1-42, and acetylcholine esterase), and over activation of classical arm of renin angiotensin system (RAS) (ACE1/Ang2/AT1) in hippocampi. Also, hippocampi histopathological examination revealed amyloid beta deposition. Whereas, administration of telmisartan and/or 17ß-estradiol improved animals' behavior, alleviated histopathological alterations and reduced the level of inflammatory and AD biomarkers, modulated RAS activity favoring the novel neuroprotective arm (ACE2/Ang(1-7)/MasR). SIGNIFICANCE: Our findings suggest that combined administration of both drugs has synergetic neuroprotective effects; supporting their potential application in AD treatment.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Estradiol/uso terapêutico , Nootrópicos/uso terapêutico , Telmisartan/uso terapêutico , Doença de Alzheimer/patologia , Animais , Western Blotting , Disfunção Cognitiva/tratamento farmacológico , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Aprendizagem em Labirinto , Ovariectomia , Ratos , Ratos Wistar , Sistema Renina-Angiotensina/efeitos dos fármacos
4.
Am J Clin Nutr ; 111(4): 795-803, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31965140

RESUMO

BACKGROUND: Eggs are a rich source of essential nutrients, but they are also a source of dietary cholesterol. Therefore, some guidelines recommend limiting egg consumption. However, there is contradictory evidence on the impact of eggs on diseases, largely based on studies conducted in high-income countries. OBJECTIVES: Our aim was to assess the association of egg consumption with blood lipids, cardiovascular disease (CVD), and mortality in large global studies involving populations from low-, middle-, and high-income countries. METHODS: We studied 146,011 individuals from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study. Egg consumption was recorded using country-specific validated FFQs. We also studied 31,544 patients with vascular disease in 2 multinational prospective studies: ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global End Point Trial) and TRANSCEND (Telmisartan Randomized Assessment Study in ACEI Intolerant Subjects with Cardiovascular Disease). We calculated HRs using multivariable Cox frailty models with random intercepts to account for clustering by study center separately within each study. RESULTS: In the PURE study, we recorded 14,700 composite events (8932 deaths and 8477 CVD events). In the PURE study, after excluding those with history of CVD, higher intake of egg (≥7 egg/wk compared with <1 egg/wk intake) was not significantly associated with blood lipids, composite outcome (HR: 0.96; 95% CI: 0.89, 1.04; P-trend = 0.74), total mortality (HR: 1.04; 95% CI: 0.94, 1.15; P-trend = 0.38), or major CVD (HR: 0.92; 95% CI: 0.83, 1.01; P-trend = 0.20). Similar results were observed in ONTARGET/TRANSCEND studies for composite outcome (HR 0.97; 95% CI: 0.76, 1.25; P-trend = 0.09), total mortality (HR: 0.88; 95% CI: 0.62, 1.24; P-trend = 0.55), and major CVD (HR: 0.97; 95% CI: 0.73, 1.29; P-trend = 0.12). CONCLUSIONS: In 3 large international prospective studies including ∼177,000 individuals, 12,701 deaths, and 13,658 CVD events from 50 countries in 6 continents, we did not find significant associations between egg intake and blood lipids, mortality, or major CVD events. The ONTARGET and TRANSCEND trials were registered at clinicaltrials.gov as NCT00153101. The PURE trial was registered at clinicaltrials.gov as NCT03225586.


Assuntos
Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/mortalidade , Ovos/análise , Lipídeos/sangue , Adulto , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Ramipril/administração & dosagem , Telmisartan/administração & dosagem
5.
Life Sci ; 241: 117108, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31786192

RESUMO

AIMS: Telmisartan (TLM), a highly selective angiotensin II type 1 receptor blocker (ARB) and partial PPAR-γ agonist, has versatile beneficial effects against oxidative stress, apoptosis, inflammatory responses and epithelial-mesenchymal transition (EMT). However, its underlying mechanism of inhibiting oxalate and calcium oxalate (CaOx) crystal-induced EMT by activating the PPAR-γ pathway remains unclear. MAIN METHODS: CCK-8 assays were used to evaluate the effects of TLM on cell viability. In addition, intracellular reactive oxygen species (ROS) levels were measured by the cell-permeable fluorogenic probe 2,7-dichlorofluorescein diacetate (DCFH-DA). Wound-healing and Transwell assays were used to evaluate the migration ability of HK2 cells exposed to oxalate. Moreover, immunofluorescence, immunohistochemistry and western blotting were used to examine the expression of E-cadherin, N-cadherin, vimentin and α-SMA and explore the underlying molecular mechanisms in HK2 cells and a stone-forming rat model. KEY FINDINGS: Our results showed that TLM treatment could protect HK2 cells from oxalate-induced cytotoxicity and oxidative stress injury. Additionally, TLM prevented EMT induction by oxalate and CaOx crystals via the PPAR-γ-AKT/STAT3/p38 MAPK-Snail pathway in vitro and in vivo. However, knockdown of PPAR-γ with small interfering RNA or the PPAR-γ-specific antagonist GW9662 abrogated these protective effects of TLM. SIGNIFICANCE: As a PPAR-γ agonist, TLM can ameliorate oxalate and CaOx crystal-induced EMT by exerting an antioxidant effect through the PPAR-γ-AKT/STAT3/p38 MAPK-Snail signaling pathway. Therefore, TLM can block EMT progression and could be a potential therapeutic agent for preventing and treating calcium oxalate urolithiasis formation and recurrence.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Oxalatos/toxicidade , PPAR gama/metabolismo , Telmisartan/farmacologia , Animais , Oxalato de Cálcio/toxicidade , Linhagem Celular , Transição Epitelial-Mesenquimal/fisiologia , Humanos , Túbulos Renais/citologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Fator de Transcrição STAT3/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Fator de Crescimento Transformador beta1/toxicidade , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
6.
Biomed Chromatogr ; 34(2): e4755, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31755118

RESUMO

The main objective of this study was to establish an efficient extraction procedure for the estimation of telmisartan, amlodipine and chlorthalidone from their combination in sample matrix using an analytical quality by design approach. Initial screening studies were performed for optimization of a suitable diluent to extract active components from sample matrix. Further, the same study was extended for the identification of critical method attributes and the factors affecting the analytical target profile. This study also explains the rugged and robust quantitative determination of combinations drugs with a shorter run time. The design of experimental studies confirms that the current center point parameters are well suited to recoveries. The chromatographic separation was achieved with an X-Terra RP8, 150 × 4.6 mm, 3.5 µm column with an isocratic mobile phase (mixture of 20 mm aqueous ammonium acetate and acetonitrile). To demonstrate the stability-indicating nature of the optimized method, forced degradation studies were conducted and proved. The optimized method was validated according to International Conference on Harmonization guidelines.


Assuntos
Anlodipino/análise , Clortalidona/análise , Telmisartan/análise , Anlodipino/química , Anlodipino/isolamento & purificação , Clortalidona/química , Clortalidona/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodos , Combinação de Medicamentos , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Projetos de Pesquisa , Comprimidos , Telmisartan/química , Telmisartan/isolamento & purificação
7.
Eur J Med Chem ; 185: 111748, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31648125

RESUMO

Recent studies examined the possibility to overcome imatinib resistance in chronic myeloid leukemia (CML) patients by combination therapy with peroxisome proliferator-activated receptor gamma (PPARγ) ligands. Pioglitazone, a full PPARγ agonist, improved the survival of patients by the gradual elimination of the residual CML stem cell pool. To evaluate the importance of the pharmacological profile of PPARγ agonists on the ability to circumvent resistance, the partial PPARγ agonist 4'-((2-propyl-1H-benzo[d]imidazol-1-yl)methyl)-[1,1'-biphenyl]-2-carboxylic acid, derived from telmisartan, and other related derivatives were investigated. The 4-substituted benzimidazole derivatives bearing a [1,1'-biphenyl]-2-carboxamide moiety sensitized K562-resistant cells to imatinib treatment. Especially the derivatives 18a-f, which did not activate PPARγ to more than 40% at 10 µM, retrieved the cytotoxicity of imatinib in these cells. The cell death modulating properties were higher than that of pioglitazone. It is of interest to note that all novel compounds were not cytotoxic neither on non-resistant nor on resistant cells. They exerted antitumor potency only in combination with imatinib.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Mesilato de Imatinib/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Telmisartan/farmacologia , Animais , Antineoplásicos/química , Células COS , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Humanos , Mesilato de Imatinib/química , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Estrutura Molecular , PPAR gama/agonistas , Relação Estrutura-Atividade , Telmisartan/análogos & derivados , Telmisartan/química
8.
J Ethnopharmacol ; 248: 112306, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31626909

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine Leonurus japonicus Houtt. has a long history in the treatment of cardiovascular diseases. Stachydrine hydrochloride, the main bioactive ingredient extracted from Leonurus japonicus Houtt., has been shown to have cardioprotective effects. However, the underlying mechanisms of stachydrine hydrochloride haven't been comprehensively studied so far. AIM OF THE STUDY: The aim of this study was to investigate the protective role of stachydrine hydrochloride in heart failure and elucidate its possible mechanisms of action. MATERIALS AND METHODS: In vivo, transverse aorta constriction was carried out in C57BL/6J mice, and thereafter, 7.2 mg/kg telmisartan (a selective AT1R antagonist as positive control) and 12 mg/kg stachydrine hydrochloride was administered daily intragastrically for 4 weeks. Cardiac function was evaluated by assessing morphological changes as well as echocardiographic and haemodynamic parameters. In vitro, neonatal rat cardiomyocytes or adult mice cardiomyocytes were treated with stachydrine hydrochloride and challenged with phenylephrine (α-AR agonist). Ventricular myocytes were isolated from the hearts of C57BL/6J mice by Langendorff crossflow perfusion system. Intracellular calcium was measured by an ion imaging system. The length and movement of sarcomere were traced to evaluate the systolic and diastolic function of single myocardial cells. RESULTS: Stachydrine hydrochloride improved the cardiac function and calcium transient amplitudes, and inhibited the SR leakage and the amount of sparks in cardiac myocytes isolated from TAC mice. We also demonstrated that stachydrine hydrochloride could ameliorated phenylephrine-induced enhance in sarcomere contraction, calcium transients and calcium sparks. Moreover, our data shown that stachydrine hydrochloride blocked the hyper-phosphorylation of CaMKII, RyR2, PLN, and prevented the disassociation of FKBP12.6 from RyR2. CONCLUSION: Our results suggest that stachydrine hydrochloride exerts beneficial therapeutic effects against heart failure. These cardioprotective effects may be associated with the regulation of calcium handling by stachydrine hydrochloride through inhibiting the hyper-phosphorylation of CaMKII.


Assuntos
Aorta/fisiopatologia , Pressão Arterial , Sinalização do Cálcio/efeitos dos fármacos , Fármacos Cardiovasculares/farmacologia , Insuficiência Cardíaca/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Prolina/análogos & derivados , Função Ventricular Esquerda/efeitos dos fármacos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Aorta/cirurgia , Proteínas de Ligação ao Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Fosforilação , Prolina/farmacologia , Ratos , Ratos Sprague-Dawley , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Sarcômeros/efeitos dos fármacos , Sarcômeros/metabolismo , Retículo Sarcoplasmático/efeitos dos fármacos , Retículo Sarcoplasmático/metabolismo , Telmisartan/farmacologia
9.
AAPS PharmSciTech ; 21(1): 10, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31802267

RESUMO

Crystal engineering approach was utilized for the development of different multicomponent solid forms of telmisartan (TEL) to improve its oral bioavailability. In this context, two cocrystals, gentisic acid (GA) and maleic acid (MA), while two eutectic mixtures, para-aminobenzoic acid (PABA) and adipic acid (AA), were successfully prepared and characterized by different analytical tools. Both the cocrystals exhibited characteristic heterosynthons, viz. OHacid⋯Narom and OHacid⋯O, to propagate new network. Structural features of coformers has been correlated with the outcomes of cocrystallization approach. Coformers having auxiliary functionality in addition to complementary functional groups have high propensity to generate cocrystals. However, multicomponent where auxiliary functionality is lacking, such combinations, is shown to form eutectic mixtures owing to strong homomeric interaction. Besides, the developed cocrystals and eutectic mixtures showed higher aqueous solubility (3-5.5-fold) and intrinsic dissolution rate (1-2.6-fold) over pure TEL. In vivo studies also revealed significant improvement in relative bioavailability (2-2.6-fold). The study also shed light on the implications of eutectic mixtures in mitigating the solubility issues of drugs which are often considered negative results of cocrystallization strategy.


Assuntos
Produtos Biológicos/síntese química , Produtos Biológicos/farmacocinética , Telmisartan/síntese química , Telmisartan/farmacocinética , Animais , Anti-Hipertensivos/síntese química , Anti-Hipertensivos/farmacocinética , Disponibilidade Biológica , Cristalização/métodos , Masculino , Ratos , Ratos Wistar , Solubilidade , Relação Estrutura-Atividade
10.
J Korean Med Sci ; 34(42): e266, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31674157

RESUMO

BACKGROUND: Apart from its blood pressure-lowering effect by blocking the renin-angiotensin-aldosterone system, telmisartan, an angiotensin II type 1 receptor blocker (ARB), exhibits various ancillary effects including cardiovascular protective effects in vitro. Nonetheless, the protective effects of telmisartan in cerebrocardiovascular diseases are somewhat variable in large-scale clinical trials. Dysregulation of endothelial nitric oxide (NO) synthase (eNOS)-derived NO contributes to the developments of various vascular diseases. Nevertheless, the direct effects of telmisartan on endothelial functions including NO production and vessel relaxation, and its action mechanism have not been fully elucidated. Here, we investigated the mechanism by which telmisartan regulates NO production and vessel relaxation in vitro and in vivo. METHODS: We measured nitrite levels in culture medium and mouse serum, and performed inhibitor studies and western blot analyses using bovine aortic endothelial cells (BAECs) and a hyperglycemic mouse model. To assess vessel reactivity, we performed acetylcholine (ACh)-induced vessel relaxation assay on isolated rat aortas. RESULTS: Telmisartan decreased NO production in normoglycemic and hyperglycemic BAECs, which was accompanied by reduced phosphorylation of eNOS at Ser1179 (p-eNOS-Ser1179). Telmisartan increased the expression of protein phosphatase 2A catalytic subunit (PP2Ac) and co-treatment with okadaic acid completely restored telmisartan-inhibited NO production and p-eNOS-Ser1179 levels. Of the ARBs tested (including losartan and fimasartan), only telmisartan decreased NO production and p-eNOS-Ser1179 levels, and enhanced PP2Ac expression. Co-treatment with GW9662 had no effect on telmisartan-induced changes. In line with in vitro observations, telmisartan reduced serum nitrite and p-eNOS-Ser1179 levels, and increased PP2Ac expression in high fat diet-fed mice. Furthermore, telmisartan attenuated ACh-induced rat aorta relaxation. CONCLUSION: We demonstrated that telmisartan inhibited NO production and vessel relaxation at least in part by PP2A-mediated eNOS-Ser1179 dephosphorylation in a peroxisome proliferator-activated receptor γ-independent manner. These results may provide a mechanism that explains the inconsistent cerebrocardiovascular protective effects of telmisartan.


Assuntos
Óxido Nítrico Sintase Tipo III/química , Óxido Nítrico/metabolismo , Proteína Fosfatase 2/metabolismo , Telmisartan/farmacologia , Acetilcolina/química , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Aorta/metabolismo , Bovinos , Modelos Animais de Doenças , Endotélio Vascular/patologia , Hiperglicemia/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nitritos/química , Fosforilação , Proteína Fosfatase 2C/metabolismo , Ratos , Serina/química
11.
Kardiologiia ; 59(9S): 42-50, 2019 Jul 23.
Artigo em Russo | MEDLINE | ID: mdl-31644416

RESUMO

AIM: The study assesses the effects of therapy based on the use of telmisartan in patients with arterial hypertension and stable angina on the clinical and functional indicators of the cardiovascularvascular system. MATERIAL AND METHODS: 52 patients with a combination of arterial hypertension (AH) I and II stages and coronary artery disease II with the mean age 63.5 ± 5.4 years (79% males and 21% of females) were enrolled in the trial. The duration of AH and CAD were 17.5±3.8 and 12.5±3.1 accordingly. All patients took a daily 80 mg dose of telmisartan. The efficacy of treatment was estimated in 3,6 and 12 months. RESULTS: The use of telmisartan in complex treatment of high-risk patients with AH has led to decreasing blood pressure to the target level, increasing exercise tolerance (walking the distance from 315.5 m to 410.2 m in 6 minutes). 12 months of therapy based on telmisartan showed significant decrease in left hy­ pertrophy ventricle (LV myocardial mass index on average by 10.4%), a decrease in the total duration of depression ST segment from 9.6±2.9 to 2.7±1.5 mm and a decrease in the depth of depression from 1.5±0.3 mm to 0.3±0.09 mm, with a trend towards decrease in the number of episodes of ST-segment depression, as well as the absence of a significant change in heart rate. After 12 months of en­ dothelium-dependent vasodilation therapy, the condition of 31 (60%) patients improved, and 18 (35%) patients showed the tendency to improvement. The tests with reactive hyperemia conducted after 12 months of treatment revealed decreased linear velocity of blood flow in the brachial artery on average by 17%. CONCLUSION: The use of telmisartan in complex therapy improves the quality of life according to the EQ-VAS questionnaire by 25 points after 12 months of therapy, contributes to lowering blood pressure in 96% of patients, reduc­ ing myocardial hypertrophy, endothelial dysfunction and severity of ischemic manifestations (reducing the need for nitroglycerin intake to an average of 0,5 inhalations, as well as a decrease in the ST segment depression of 40% after 12 months of therapy).


Assuntos
Hipertensão/tratamento farmacológico , Telmisartan/uso terapêutico , Idoso , Pressão Sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Vasodilatação
12.
Life Sci ; 237: 116890, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31606379

RESUMO

AIMS: Telmisartan (TEL), an angiotensin II type I receptor blocker and PPARγ partial agonist, has been used for to treat hypertension. It is known that PPARγ activation induces bone loss. Therefore, we evaluate the effects of telmisartan on PPARγ protein expression, biomechanics, density and bone microarchitecture of femurs and lumbar vertebrae in SHR ovariectomized animals, a model of hypertension in which preexisting bone impairment has been demonstrated. MAIN METHODS: SHR females (3 months old) were distributed into four groups: sham (S), sham + TEL (ST), OVX (C) and OVX + TEL (CT). TEL (5 mg/kg/day) or vehicle were administered according to the groups. After the protocol, blood pressure was measured and density, microarchitecture and biomechanics of bone were analyzed. Western blotting analysis was performed to evaluate PPARγ protein expression in the bones. KEY FINDINGS: Castration induced a deleterious effect on mineral density and trabecular parameters, with telmisartan enhancing such effects. Telmisartan increased PPARγ levels, which were at their highest when the treatment was combined with castration. As to biomechanical properties, telmisartan reduced the stiffness in the castration group (CT vs. S or C group), as well as resilience and failure load in ST group (vs. all others groups). SIGNIFICANCE: These results demonstrated that telmisartan compromised bone density and microarchitecture in animals that shows preexisting osteoporotic bone disorders, probably via mechanisms associated with increased PPARγ. If this translates to humans, a need for greater caution in the use of telmisartan by patients that have preexisting bone problems, as in the postmenopausal period, may be in order.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Doenças Ósseas/tratamento farmacológico , Osso Esponjoso/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Osteoporose/tratamento farmacológico , PPAR gama/metabolismo , Telmisartan/farmacologia , Animais , Densidade Óssea/efeitos dos fármacos , Doenças Ósseas/metabolismo , Doenças Ósseas/fisiopatologia , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/patologia , Feminino , Osteoporose/metabolismo , Osteoporose/fisiopatologia , PPAR gama/genética , Ratos , Ratos Endogâmicos SHR , Tomografia Computadorizada por Raios X
13.
Molecules ; 24(19)2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31581427

RESUMO

Poly(vinyl chloride) (PVC), a polymer widely used in common household and industrial materials, undergoes photodegradation upon ultraviolet irradiation, leading to undesirable physicochemical properties and a reduced lifetime. In this study, four telmisartan organotin(IV) compounds were tested as photostabilizers against photodegradation. PVC films (40-µm thickness) containing these compounds (0.5 wt%) were irradiated with ultraviolet light at room temperature for up to 300 h. Changes in various polymeric parameters, including the growth of hydroxyl, carbonyl, and alkene functional groups, weight loss, reduction in molecular weight, and appearance of surface irregularities, were investigated to test the efficiency of the photostabilizers. The changes were more noticeable in the blank PVC film than in the films containing the telmisartan organotin(IV) compounds. These results reflect that these compounds effectively inhibit the photodegradation of PVC, possibly by acting as hydrogen chloride and radical scavengers, peroxide decomposers, and primary photostabilizers. The synthesized organotin(IV) complexes could be used as PVC additives to enhance photostability.


Assuntos
Compostos Orgânicos de Estanho/síntese química , Cloreto de Polivinila/química , Telmisartan/química , Ácido Clorídrico/química , Estrutura Molecular , Peso Molecular , Compostos Orgânicos de Estanho/química , Fotólise , Espectroscopia de Infravermelho com Transformada de Fourier
14.
Drug Metab Pharmacokinet ; 34(5): 293-299, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31564410

RESUMO

The pharmacokinetics of telmisartan are nonlinear within the clinical dose range. To identify the underlying mechanism of this nonlinearity, we conducted a PET study in healthy subjects using [11C]telmisartan. Eight healthy male subjects were enrolled in a 2-way crossover study. PET imaging was performed after intravenous administration of [11C]telmisartan with or without a 1-h oral predose of two 40 mg Micardis® tablets. About 60% of the injected [11C]telmisartan accumulated in the liver within 10 min after injection. With predosing of 80 mg telmisartan, the systemic elimination of [11C]telmisartan was slightly delayed, but the liver exposure started to decrease earlier and biliary excretion was greatly enhanced. Hepatic uptake clearance of the radioactivity was not changed by telmisartan predosing, whereas the biliary clearance of radioactivity from the liver was significantly increased. Thus, the alteration in the pharmacokinetics of the radioactivity could not be explained simply by the saturation of hepatic uptake. Therefore, other mechanisms, such as the saturation of intracellular binding of telmisartan and/or its glucuronide, and the glucuronidation of telmisartan by uridine 5'-diphospho-glucuronosyltransferases, should be considered. This is the first reported human PET study using [11C]telmisartan, the results of which can assist understanding of the hepatobiliary transport of telmisartan in humans.


Assuntos
Bile/metabolismo , Fígado/metabolismo , Tomografia por Emissão de Pósitrons , Telmisartan/análise , Adulto , Transporte Biológico , Radioisótopos de Carbono , Estudos Cross-Over , Voluntários Saudáveis , Humanos , Injeções Intravenosas , Fígado/química , Masculino , Estrutura Molecular , Telmisartan/administração & dosagem , Telmisartan/metabolismo , Adulto Jovem
15.
Brain Nerve ; 71(9): 961-970, 2019 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-31506398

RESUMO

To date, all clinical trials of disease-modifying drugs for Alzheimer's disease (AD) have been unsuccessful, making investments into AD drug development very risky despite the high unmet need. Drug repositioning or repurposing approaches are relatively less expensive and more promising compared to novel drug development in AD. About 40% of clinical trials for AD currently in progress across the world use the drug repositioning method. They are expected to be a trigger for AD drug discovery that breaks the current deadlock situation. By using drugs approved for other indications, these clinical trials target dysregulated pathways of AD with different or a combination of modes of action, including anti-amyloid, anti-tau, anti-inflammatory, metabolic, neuroprotective, and neurotransmission-based approaches. In these clinical trials, cardiovascular drugs such as insulin, cilostazol, probucol, telmisartan, and dabigatran are tested for their effect on different mechanisms of AD pathology. This is in line with the recent emphasis that AD should be studied as a complex multifactorial disorder, not dominated by one dominant biological factor such as beta-amyloid, and without disregarding any relevant pathologic factor, such as vascular dysregulation. It is strongly expected that drug repositioning approaches will create a paradigm shift in treatment approaches for AD patients.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Reposicionamento de Medicamentos , Cilostazol , Dabigatrana , Humanos , Insulina , Probucol , Telmisartan
16.
Int J Mol Sci ; 20(17)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480330

RESUMO

BACKGROUND: Psoriasis is hallmarked by vascular dysfunction, arterial hypertension, and an increased risk for cardiovascular diseases. We have shown recently that skin-driven interleukin (IL)-17A expression promotes psoriasis-like disease in mice, and this is associated with vascular inflammation, vascular dysfunction, and hypertension. As an intensive risk-factor reduction is recommended for psoriasis patients, we aimed to elucidate the impact of the angiotensin II receptor type 1 (AT1) antagonist telmisartan in a mouse model of severe psoriasis-like skin disease. METHODS AND RESULTS: Elevated blood pressure measured by tail-cuff plethysmography in mice with keratinocyte-specific IL-17A overexpression (K14-IL-17Aind/+ mice) was significantly reduced in response to telmisartan. Importantly, vascular dysfunction, as assessed by isometric tension studies of isolated aortic rings, vascular inflammation measured by flow cytometry analysis of CD45+CD11b+ immune cells, as well as the increased peripheral oxidative stress levels assessed by L-012-enhanced chemiluminescence were not attenuated by telmisartan treatment of K14-IL-17Aind/+ mice, nor was the persisting skin inflammation. CONCLUSION: We provide first evidence for an effective antihypertensive treatment in experimental psoriasis by AT1 blockade, but without any impact on vascular inflammation and dysfunction in our mouse model of severe psoriasis-like skin disease. This suggests that vascular function and inflammation in psoriasis might not be attenuated as long as skin inflammation persists.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Inflamação/patologia , Psoríase/tratamento farmacológico , Psoríase/fisiopatologia , Telmisartan/uso terapêutico , Animais , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/patologia , Telmisartan/farmacologia
17.
Neurourol Urodyn ; 38(8): 2112-2120, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31436351

RESUMO

AIMS: The goal of this study was to test whether central corticotropin-releasing factor (CRF) was involved in angiotensin II (Ang II) and Ang II type 1 (AT1) receptor-mediated facilitation of micturition reflex and to investigate whether peripherally administered telmisartan, AT1 receptor antagonist, suppresses the central Ang II-induced facilitation of micturition reflex in rats. METHODS: Urethane anesthetized male Wistar rats were placed under continuous cystometry before and after intracerebroventricular administration of each drug. Rats were intracerebroventricularly administered telmisartan (AT1 receptor antagonist), CP154526 (CRF1 receptor antagonist), or K41498 (CRF2 receptor antagonist) 30 minutes before intracerebroventricular administration of Ang II. Some male Wistar rats were perorally pretreated with either vehicle, AT1 receptor antagonist telmisartan or valsartan, once daily for 8 days, then measured blood pressure. Thereafter, Ang II was intracerebroventricularly administered for continuous cystometry. RESULTS: Intracerebroventricularly administered telmisartan or CP154526 dose-dependently suppressed the central Ang II-induced intercontraction interval (ICI) reduction. In contrast, intracerebroventricularly administered K41498 did not affect the central Ang II-induced response compared to vehicle pretreatment. Peripherally administered telmisartan but not valsartan suppressed the central Ang II-induced ICI reduction in rats compared to vehicle administration without altering blood pressure. CONCLUSIONS: Central Ang II induced facilitation of the micturition reflex through AT1 and CRF1 receptors. Peripherally administered telmisartan suppressed central Ang II-induced facilitation of micturition reflex.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Telmisartan/farmacologia , Micção/efeitos dos fármacos , Proteínas de Anfíbios/farmacologia , Angiotensina II/administração & dosagem , Animais , Masculino , Hormônios Peptídicos/farmacologia , Pirimidinas/farmacologia , Pirróis/farmacologia , Ratos , Ratos Wistar , Receptores de Hormônio Liberador da Corticotropina/antagonistas & inibidores
18.
Drug Des Devel Ther ; 13: 2533-2542, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440035

RESUMO

Purpose: Hypertension and dyslipidemia are major risk factors for cardiovascular diseases, and reduction of cardiovascular risks can be achieved by combining antihypertensive therapy with statins. The objective of this study was to evaluate the pharmacokinetic interaction between telmisartan/amlodipine fixed dose combination and rosuvastatin in healthy Korean male volunteers. Patients and methods: An open-label, two-cohort, multiple-dose, single-sequence crossover study was conducted in healthy male subjects. In Cohort 1, the subjects were administered one tablet of telmisartan/amlodipine 80 mg/5 mg once daily for 14 days with or without one tablet of rosuvastatin 20 mg once daily. In Cohort 2, the subjects were administered one tablet of rosuvastatin 20 mg once daily for 14 days with or without one tablet of telmisartan/amlodipine 80 mg/5 mg once daily. Serial blood samples were collected up to 24 hrs post-dose on the 9th and 14th days in Cohort 1 and on the 5th and 14th days in Cohort 2. Plasma drug concentrations were measured by liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters, including maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration versus time curve over dosing interval (AUCτ,ss), were determined by non-compartmental analysis. The geometric least-square mean (GLSM) ratios and associated 90% confidence intervals (CIs) of log-transformed Cmax,ss and AUCτ,ss for separate or concurrent therapy were calculated to evaluate pharmacokinetic interactions. Results: Thirty-eight subjects from Cohort 1 and nineteen subjects from Cohort 2 completed the study. The GLSM ratios and 90% CIs of Cmax,ss and AUCτ,ss, were 0.9829 (0.8334-1.1590) and 1.0003 (0.9342-1.0710) for telmisartan; 0.9908 (0.9602-1.0223) and 1.0081 (0.9758-1.0413) for amlodipine; and 2.2762 (2.0113-2.5758) and 1.3261 (1.2385-1.4198) for rosuvastatin, respectively. Conclusion: The pharmacokinetic parameters of telmisartan/amlodipine, but not rosuvastatin, met the pharmacokinetic equivalent criteria. The increase in systemic exposure to rosuvastatin caused by telmisartan/amlodipine co-administration would not be clinically significant in practice. Nevertheless, an appropriately designed two-sequence crossover study is needed to confirm the results of this study.


Assuntos
Anlodipino/administração & dosagem , Anlodipino/farmacocinética , Rosuvastatina Cálcica/administração & dosagem , Rosuvastatina Cálcica/farmacocinética , Telmisartan/administração & dosagem , Telmisartan/farmacocinética , Administração Oral , Adulto , Anlodipino/sangue , Estudos de Coortes , Estudos Cross-Over , Relação Dose-Resposta a Droga , Tolerância a Medicamentos , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Rosuvastatina Cálcica/sangue , Telmisartan/sangue , Adulto Jovem
19.
J Renin Angiotensin Aldosterone Syst ; 20(3): 1470320319862741, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31328615

RESUMO

INTRODUCTION: Telmisartan is an angiotensin-II receptor type-1 blocker and a partial agonist for peroxisome proliferator-activated receptor-γ. The aim of this study was to determine the potential effects of telmisartan on bone metabolism and turnover markers. METHODS: Forty-two patients with newly diagnosed stage I hypertension who were prescribed telmisartan 80 mg/day or losartan 100 mg/day were included. Serum levels of calcium, phosphorus, 25-hydroxy vitamin D, bone-specific alkaline phosphatase, osteocalcin, interleukin 6 and 24-hour urinary N-terminal telopeptide were measured at the beginning and after 12 weeks of treatment. RESULTS: When treatment arms were evaluated together, significantly increased 25-hydroxy vitamin D levels (p=0.01), and decreased parathormone (PTH) (p<0.001), bone-specific alkaline phosphatase (p=0.01), osteocalcin (p=0.045), urinary N-terminal telopeptide (p<0.001) and interleukin 6 levels (p=0.006) were observed. After eliminating the 25-hydroxy vitamin D effect, significant changes were not observed at any of the parameters. None of the levels of parameters were different between groups. CONCLUSIONS: Neither telmisartan, despite its partial peroxisome proliferator-activated receptor-γ agonistic effect, nor losartan treatment had significant effects on bone turnover markers in newly diagnosed stage I hypertensive patients.


Assuntos
Biomarcadores/sangue , Remodelação Óssea , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Losartan/uso terapêutico , Telmisartan/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Feminino , Seguimentos , Humanos , Hipertensão/sangue , Losartan/farmacologia , Masculino , Pessoa de Meia-Idade , Telmisartan/farmacologia
20.
Int Immunopharmacol ; 75: 105750, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31330445

RESUMO

Telmisartan, widely prescribed for the treatment of hypertension, has an anti-inflammatory property in addition to being an angiotensin II type 1 receptor antagonist. This study was carried out to explore the influence of telmisartan upon the elaboration of inflammatory mediators in murine macrophages stimulated with lipopolysaccharide (LPS) prepared from Prevotella intermedia, a periodontal pathogen, as well as its molecular mechanisms. Telmisartan significantly inhibited LPS-induced generation of inducible nitric oxide (NO) synthase-derived NO and interleukin-1ß (IL-1ß) as well as their gene expressions in RAW264.7 cells. Telmisartan treatment of LPS-activated cells significantly up-regulated arginase 1 (Arg-1) and chitinase-like 3 (Ym-1), which are specific markers of M2 macrophages. Telmisartan caused a significant increase in heme oxygenase-1 (HO-1) expression in cells stimulated with LPS, and its inhibitory action against NO production was reversed by treatment with SnPP, an HO-1 inhibitor. Phosphorylation of STAT1 and STAT3 induced by LPS was attenuated by telmisartan. Telmisartan inhibited LPS-induced generation of NO and IL-1ß independently of PPAR-γ activation. In addition, activation of NF-κB as well as JNK and p38 signaling induced by LPS was not modulated by telmisartan. In summary, telmisartan is a potent inhibitor of P. intermedia LPS-induced generation of NO and IL-1ß in RAW264.7 cells and promotes macrophage phenotype switching toward the M2 phenotype. Telmisartan may have potential to be developed into host modulatory agent for inflammatory periodontal disease, although additional studies are needed to confirm the therapeutic effect.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Anti-Inflamatórios/farmacologia , Interleucina-1beta/imunologia , Óxido Nítrico/imunologia , Prevotella intermedia , Telmisartan/farmacologia , Animais , Heme Oxigenase-1/genética , Heme Oxigenase-1/imunologia , Interleucina-1beta/genética , Lipopolissacarídeos , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Camundongos , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/imunologia , Células RAW 264.7
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA