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1.
Chem Pharm Bull (Tokyo) ; 67(5): 419-425, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061366

RESUMO

Patients with type 2 diabetes (T2DM) and hyperlipidemia are with high risk of myocardial infarction (MI) or coronary death events. The combined use of ezetimibe and atorvastatin could improve treatment efficacy and safety. To explore the efficacy and safety of ezetimibe in combination with atorvastatin for the treatment of patients with T2DM and acute coronary syndrome (ACS). This was a non-randomized cohort study of 95 consecutive, treatment-naïve patients with T2DM and ACS treated at the Quanzhou First Hospital of Fujian Province between February 2014 and March 2016. According to the treatment strategy they selected, the patients were categorized into the atorvastatin (n = 46) and atorvastatin + ezetimibe (n = 49) groups. The patients were followed up at 2 weeks and 12 months. The primary endpoints included the incidence of adverse cardiovascular events and changed in blood lipids and high-sensitivity C-reactive protein (hs-CRP). At 12 months, serum total cholesterol (TC), triglycerides, and low-density lipoprotein cholesterol (LDL-C) levels were significantly lower, and high-density lipoprotein cholesterol (HDL-C) levels were significantly higher in the atorvastatin + ezetimibe (EZ) group than in the atorvastatin group (all p < 0.05). The LDL-C control rate at 12 months was significantly higher in the atorvastatin + EZ group compared with the atorvastatin group (p = 0.006). Seven patients in the atorvastatin group were re-hospitalized for angina pectoris, while only one patient in the atorvastatin + EZ group was re-hospitalized for angina pectoris (p = 0.02). The efficacy of atorvastatin + EZ in treating T2DM patients accompanied with ACS was significantly higher than using atorvastatin alone. This combined strategy has good safety profile, and could be recommended for clinical application.


Assuntos
Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/tratamento farmacológico , Anticolesterolemiantes/uso terapêutico , Atorvastatina/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Ezetimiba/uso terapêutico , Síndrome Coronariana Aguda/sangue , Anticolesterolemiantes/efeitos adversos , Atorvastatina/efeitos adversos , Proteína C-Reativa/análise , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Quimioterapia Combinada , Ezetimiba/efeitos adversos , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Miocárdio/enzimologia
2.
Biomolecules ; 9(4)2019 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-30934759

RESUMO

OBJECTIVE: The aim of this study was to investigate the effect of combined intake of a high dose of aspirin, atorvastatin, captopril and metformin on oxidative stress in the brain cortex and hippocampus of streptozotocin (STZ)-induced diabetic rats. MATERIAL AND METHODS: Rats were randomly divided into the following 11 groups: control and diabetic (D), as well as 9 groups that were treated with metformin (M, 300 mg/kg) or aspirin (ASA, 120 mg/kg) alone or in different combinations with captopril (C, 50 mg/kg) and/or atorvastatin (AT, 40 mg/kg) as follows: (D + M), (D + ASA), (D + M + ASA), (D + M + C), (D + M + AT), (D + M + C + ASA), (D + M + C + AT), (D + M + AT + ASA) and (D + M + C + AT + ASA). The rats in treatment groups received drugs by gavage daily for six weeks. Serum lipid profile and levels of oxidative markers in the brain cortex and hippocampus tissues were evaluated. RESULTS: The levels of malondialdehyde in the brain cortex and hippocampus in all the treated groups decreased significantly (p < 0.05). There was a significant increase in the total thiol concentration as well as catalase activity in treated rats in (M + AT), (M + C + ASA), (M + C + AT), (M + AT + ASA) and (M + C + AT + ASA) groups in cortex and hippocampus in comparison with the diabetic rats (p < 0.05). Also, the superoxide dismutase activity in all treated rats with medications was significantly increased compared to the diabetic rats (p < 0.05⁻0.01). CONCLUSION: Our findings showed that the combined use of high-dose aspirin, metformin, captopril and atorvastatin potentiated their antioxidant effects on the brain, and hence could potentially improve cognitive function with their neuroprotective effects on hippocampus.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Animais , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Atorvastatina/administração & dosagem , Atorvastatina/uso terapêutico , Captopril/administração & dosagem , Captopril/uso terapêutico , Diabetes Mellitus Experimental/induzido quimicamente , Hipoglicemiantes/administração & dosagem , Masculino , Metformina/administração & dosagem , Metformina/uso terapêutico , Fármacos Neuroprotetores/administração & dosagem , Ratos , Ratos Wistar , Estreptozocina
3.
Drug Des Devel Ther ; 13: 633-645, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30858694

RESUMO

Purpose: Coexistence of hypertension (HTN) and hypercholesterolemia is a major synergistic and modifiable risk factor for cardiovascular disease (CVD). Thus, a fixed-dose combination (FDC) of anti-HTN drugs and statins may be useful for treating CVD. This study evaluated the efficacy of an FDC of irbesartan and atorvastatin (Rovelito®) in Korean patients. Patients and methods: Patients with HTN and hypercholesterolemia were screened for this prospective, observational, descriptive, multi-center, phase IV study. Eligible patients were administered with Rovelito for 3 months. Dose adjustment was allowed based on the physician's discretion. Blood pressure (BP) goal was <140/90 mmHg, and blood lipid goal was based on Adult Treatment Panel III. Compliance with therapeutic lifestyle modification and safety of the study drugs were evaluated. Results: Of the 2,777 patients enrolled in this study, 931 were analyzed for clinical efficacy. BP and low-density lipoprotein cholesterol (LDL-C) goals were achieved in 801 (86.04%) and 797 (85.61%) patients, respectively. For the BP goal, higher baseline BP and higher body mass index were risk factors for treatment failure. For LDL-C goal, baseline LDL-C level, number of concomitant drugs, smoking status, and alcohol consumption were risk factors for treatment failure. Of the 931 participants, 694 (74.54%) achieved the treatment goals for both BP and LDL-C. Smoking status, alcohol consumption, number of concomitant drugs, and higher baseline LDL-C and BP levels were risk factors for treatment failure in both BP and LDL-C goals. Adherence with Rovelito was 97.90%±5.79%, and incidence of adverse events was 4.19% (116). Conclusion: FDC of irbesartan and atorvastatin (Rovelito) could be extremely helpful in treating patients with both HTN and hypercholesterolemia. Poor metabolic profiles were risk factors for poor treatment response and the reason for choosing Rovelito. Therapeutic lifestyle modification should still be underscored despite the 75% treatment success rate with Rovelito for both conditions.


Assuntos
Atorvastatina/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipertensão/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Atorvastatina/administração & dosagem , Atorvastatina/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários
4.
J Med Case Rep ; 13(1): 35, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30764883

RESUMO

BACKGROUND: In the list of named numerical neuro-ophthalmological syndromes, such as one-and-a-half syndrome and others, we report for the first time twenty-and-a-half syndrome, which is characterized by one-and-a-half syndrome with bilateral seventh and right fifth nerve palsy (1.5 + 7 + 7 + 5 = 20.5) in a patient with ischemic stroke. CASE PRESENTATION: A 45-year-old Asian Hindu woman presented with vomiting and imbalance of 1 day's duration. She had left-sided ataxic hemiparesis with one-and-a-half syndrome with bilateral seventh and right fifth nerve palsy. Magnetic resonance imaging of her brain revealed acute non-hemorrhagic infarct in the right posterolateral aspect of pons and medulla, with normal brain vessels angiography. We described her disorder as twenty-and-a-half syndrome. She was put on antiplatelet therapy. CONCLUSIONS: Twenty-and-a-half syndrome is reported for the first time. It is due to posterior circulation stroke; in our case, it was due to lacunar infarcts in the pons and medulla, manifesting as one-and-a-half syndrome with bilateral seventh and right fifth nerve palsy.


Assuntos
Isquemia Encefálica/complicações , Doenças dos Nervos Cranianos/complicações , Paresia/complicações , Acidente Vascular Cerebral/complicações , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Atorvastatina/uso terapêutico , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Doenças dos Nervos Cranianos/diagnóstico por imagem , Doenças dos Nervos Cranianos/terapia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Paresia/patologia , Paresia/terapia , Modalidades de Fisioterapia , Inibidores da Agregação de Plaquetas/uso terapêutico , Ramipril/uso terapêutico , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Síndrome
5.
Int J Nanomedicine ; 14: 649-665, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30697048

RESUMO

Background: Atherosclerosis is a major cardiovascular disease that causes ischemia of the heart, brain, or extremities, and can lead to infarction. The hypolipidemic agent atorvastatin calcium (Ato) alleviates atherosclerosis by reducing plasma lipid and inflammatory factors. However, the low bioavailability of Ato limits its widespread use and clinical effectiveness. Curcumin (Cur), a natural polyphenol with antioxidation and anti-inflammation bioactivities, has potential anti-atherosclerosis activity and may reduce Ato-induced cytotoxicity. Materials and methods: Liposomes modified using a targeting ligand (E-selectin-binding peptide) were prepared to co-deliver Ato and Cur to dysfunctional endothelial cells (ECs) overexpressing E-selectin. Molecules involved in the inhibition of adhesion (E-selectin and intercellular cell adhesion molecule-1 [ICAM-1]) and inflammation (IL-6 and monocyte chemotactic protein 1 [MCP-1]) in human aortic endothelial cells were evaluated using real-time quantitative PCR, flow cytometry, and immunofluorescence staining. The antiatherosclerosis effects of liposomes co-loaded with Ato and Cur in vivo were evaluated using ApoE knockout (ApoE-/-) mice. Results: Targeted liposomes delivered Ato and Cur to dysfunctional ECs, resulting in synergistic suppression of adhesion molecules (E-selectin and ICAM-1) and plasma lipid levels. Moreover, this treatment reduced foam cell formation and the secretion of inflammatory factors (IL-6 and MCP-1) by blocking monocyte migration into the intima. In addition, Cur successfully reduced Ato-inducible cytotoxicity. Conclusion: Both in vitro and in vivo experiments demonstrated that cell-targeted co-delivery of Ato and Cur to dysfunctional ECs drastically reduces atherosclerotic lesions with fewer side effects than either Ato or Cur alone.


Assuntos
Aterosclerose/tratamento farmacológico , Atorvastatina/uso terapêutico , Curcumina/uso terapêutico , Células Endoteliais/patologia , Animais , Apolipoproteínas E/deficiência , Apolipoproteínas E/metabolismo , Aterosclerose/sangue , Aterosclerose/patologia , Atorvastatina/farmacologia , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CCL2/metabolismo , Curcumina/química , Sinergismo Farmacológico , Selectina E/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/patologia , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/metabolismo , Ligantes , Lipídeos/sangue , Lipossomos/ultraestrutura , Camundongos Knockout , Tamanho da Partícula , Eletricidade Estática
6.
BMJ Case Rep ; 12(1)2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30696648

RESUMO

A 67-year-old man was admitted to our hospital after his relatives found him to have severe personality and behavioural changes. His behaviour was inappropriate and uninhibited. The patient reported no symptoms and he showed poor insight into his own behaviour. Neuroimaging showed an orbitofrontal lesion, due to an infarction of the anterior cerebral artery. The patient was diagnosed with frontal lobe syndrome.


Assuntos
Lobo Frontal/patologia , Comportamento Problema/psicologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/psicologia , Idoso , Atorvastatina/uso terapêutico , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Infarto Cerebral/complicações , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/psicologia , Lobo Frontal/diagnóstico por imagem , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Imagem por Ressonância Magnética , Masculino , Neuroimagem/métodos , Acidente Vascular Cerebral/patologia , Síndrome , Tomografia Computadorizada por Raios X
7.
J Vet Pharmacol Ther ; 42(3): 258-267, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30666669

RESUMO

Myxomatous mitral valve disease (MMVD) is the most common acquired cardiac disorder found in dogs. The disease process can lead to heart failure (HF) and has been found to be associated with oxidative stress and inflammation. Statins exert antioxidant and anti-inflammatory effects in human HF patients. However, the beneficial effects of statins in MMVD dogs are still unclear. Thirty MMVD dogs were enrolled in the study and were divided into two groups: MMVD without HF dogs (n = 15) and MMVD with HF dogs (n = 15). Atorvastatin (8 mg kg-1  day-1 ) was administered orally to all dogs for 4 weeks. All dogs underwent physical examination and cardiac examination at the beginning and end of the experiment, including baseline values for hematology, blood chemistry profile, lipid profile, N-terminal pro B-type natriuretic peptide, oxidative stress marker (8-isoprostane), and inflammatory marker (tumor necrosis factor alpha). The results showed that atorvastatin reduced plasma cholesterol levels in both groups. In addition, plasma concentrations of 8-isoprostane, tumor necrosis factor alpha, and N-terminal pro B-type natriuretic peptide were significantly lower after atorvastatin administration, but only in MMVD dogs in the HF group. Atorvastatin found to be associated with possible antioxidant and inflammatory effects in dogs with HF secondary to MMVD. The potential benefits of statins in dogs with HF merits further investigation in larger, placebo-controlled studies.


Assuntos
Atorvastatina/farmacologia , Doenças do Cão/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inflamação/veterinária , Prolapso da Valva Mitral/veterinária , Estresse Oxidativo/efeitos dos fármacos , Animais , Doenças Assintomáticas , Atorvastatina/uso terapêutico , Doenças do Cão/metabolismo , Cães , Ecocardiografia/veterinária , Feminino , Hemodinâmica/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Prolapso da Valva Mitral/diagnóstico por imagem , Prolapso da Valva Mitral/tratamento farmacológico , Prolapso da Valva Mitral/metabolismo , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Fator de Necrose Tumoral alfa/sangue
8.
J Med Case Rep ; 13(1): 22, 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-30678717

RESUMO

INTRODUCTION: Simultaneous occurrence of transient global amnesia and Takotsubo syndrome has been only rarely reported. Here we report another patient with a transient global amnesia and concomitant Takotsubo syndrome. CASE PRESENTATION: Our patient is a 64-year-old white man with a previous history of myocarditis from borreliosis who developed sudden-onset confusional state with perseverations and repetition of the same questions during a funeral for his brother-in-law. Upon neurological work-up and after spontaneous resolution of most of the neurological deficits, transient global amnesia was diagnosed. Blood tests revealed moderate renal insufficiency, elevated troponin-T, and elevated N-terminal prohormone of brain natriuretic peptide. Electrocardiography showed left anterior hemiblock and negative T-waves in V2-V6. Upon transthoracic echocardiography the apical type of a Takotsubo syndrome was suspected. Since coronary angiography was normal and electrocardiography and echocardiographic abnormalities resolved under candesartan, bisoprolol, acetyl-salicylic acid, and atorvastatin within a few days after onset, Takotsubo syndrome was diagnosed. CONCLUSIONS: Since Takotsubo syndrome may be associated with transient global amnesia a causal relation may exist. A possible trigger for both conditions could be severe emotional stress from the loss of a close relative. A possible common pathomechanism could be overstimulation of adrenergic receptors in the myocardium, the cerebrum, or the coronary or cerebral arteries. Whether pre-existing myocardial compromise promotes the development of Takotsubo syndrome requires further investigations.


Assuntos
Amnésia Global Transitória/fisiopatologia , Hipertensão/fisiopatologia , Miocardite/fisiopatologia , Estresse Psicológico/fisiopatologia , Cardiomiopatia de Takotsubo/fisiopatologia , Amnésia Global Transitória/tratamento farmacológico , Amnésia Global Transitória/etiologia , Amnésia Global Transitória/psicologia , Anti-Hipertensivos/uso terapêutico , Aspirina/uso terapêutico , Atorvastatina/uso terapêutico , Benzimidazóis/uso terapêutico , Bisoprolol/uso terapêutico , Angiografia Coronária , Eletrocardiografia , Fibrinolíticos/uso terapêutico , Pesar , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estresse Psicológico/psicologia , Cardiomiopatia de Takotsubo/complicações , Cardiomiopatia de Takotsubo/tratamento farmacológico , Cardiomiopatia de Takotsubo/psicologia , Tetrazóis/uso terapêutico , Resultado do Tratamento
9.
Mult Scler Relat Disord ; 28: 193-196, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30623857

RESUMO

BACKGROUND: Current treatments for relapsing remitting multiple sclerosis (RRMS) reduce inflammation, but have a partial or modest effect on disability. This effect may require a much longer follow-up than standard trial design, in particular in RRMS with relatively-preserved functional reserve. We aimed to assess the long-term clinical evolution of RRMS patients exposed to atorvastatin in two trials (ACTIVE and ARIANNA). METHODS: We retrospectively looked at 69 participants randomized with atorvastatin or placebo as add-on therapy to interferon-beta for 24 months at a single MS centre. We recorded relapses, 1-point EDSS progression and progression to EDSS 4.0. Cox regression was performed for these three questions. A Poisson regression model was used to evaluate the association between atorvastatin treatment and annualized relapse rate (ARR). RESULTS: After 8.4 ±â€¯2.3 (3.7-11.9) years from trial, the use of atorvastatin was associated with reduced risk of 1-point EDSS progression (HR = 0.440; 95%CI = 0.225-0.861; p = 0.017), and of EDSS 4.0 (HR = 0.310; 95%CI = 0.123-0.784; p = 0.013). We found no significant association between atorvastatin and relapses. DISCUSSION: These data suggest that a delayed treatment effect may be seen with atorvastatin added to interferon-beta, eight years after entering the clinical trials. Long-term follow-up of trial cohorts should be mandated.


Assuntos
Atorvastatina/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Interferon beta/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/terapia , Adulto , Avaliação da Deficiência , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Fatores de Tempo
10.
Medicine (Baltimore) ; 98(1): e13986, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30608441

RESUMO

RATIONALE: Congenital internal carotid artery hypoplasia (CICAH) is rarely reported. This study aimed to discuss the epidemiological characteristics, clinical manifestation, imaging and treatment of CICAH. PATIENT CONCERNS: The case was male who showed barylalia and limited abilities of the left limbs as their main clinical manifestation. This patient was diagnosed CICAH by digital subtraction angiography (DSA) and computed tomography (CT). DIAGNOSIS: CICAH. INTERVENTIONS: The patient underwent anti platelet aggregation, lipid-lowering, improving cerebral circulation. OUTCOMES: The patient was in a stable condition after management of cerebrovascular risk. LESSONS: Given the asymptomatic and congenital nature of carotid agenesis, no treatment is necessary or possible to re-establish the internal carotid artery (ICA). However, with the high risk of aneurysm and cerebrovascular insufficiency, management of cerebrovascular risk is important. Urgent radiological assessment is necessary for patients with suspicious neurological symptoms.


Assuntos
Artéria Carótida Interna/anormalidades , Artéria Carótida Interna/patologia , Transtornos Cerebrovasculares/tratamento farmacológico , Angiografia Digital/métodos , Anticolesterolemiantes/uso terapêutico , Atorvastatina/uso terapêutico , Artéria Carótida Interna/diagnóstico por imagem , Transtornos Cerebrovasculares/prevenção & controle , Clopidogrel/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Distúrbios da Fala/diagnóstico , Distúrbios da Fala/etiologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
11.
Med Sci Monit ; 25: 590-597, 2019 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-30698163

RESUMO

BACKGROUND Currently, statins are used to treat polycystic ovary syndrome (PCOS). This systematic review and meta-analysis aimed to investigate the effect of statins on serum or plasma levels of dehydroepiandrosterone (DHEA) in women with PCOS. MATERIAL AND METHODS Databases that were searched included PubMed, Embase, and the Cochrane Library from their inception to August of 2018. Published randomized controlled trials (RCTs) were identified that evaluated the impact of statins on plasma DHEA levels in women with PCOS. The Cochrane risk of bias tool was used to assess the quality of the included RCTs. A random-effects model was used to analyze the pooled results. RESULTS Meta-analysis was performed on data from ten published studies that included 735 patients and showed that statin treatment could significantly reduce plasma DHEA levels when compared with controls (SMD, -0.43; 95% CI, -0.81-0.06; p=0.02; I²=82%). Statins were significantly more effective than placebo in reducing the levels of DHEAs. Subgroup analysis based on statin type showed that atorvastatin significantly reduced DHEA levels (SMD, -0.63; 95% CI, -1.20 - -0.05; p=0.03; I²=38%) but simvastatin did not significantly reduce DHEA levels (SMD: -0.14; 95% CI, -0.49-0.28; p=0.43; I²=77%). Subgroup analysis based on duration of treatment showed no significant difference between 12 weeks of statin treatment (SMD, -0.61; 95% CI, -1.23-0.02; p=0.06; I²=85%) and 24 weeks (SMD, -0.34; 95% CI -0.95-0.28; p=0.29; I²=83%). CONCLUSIONS Meta-analysis showed that statins significantly reduced the levels of DHEA when compared with placebo in patients with PCOS.


Assuntos
Desidroepiandrosterona/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Atorvastatina/uso terapêutico , China , Desidroepiandrosterona/análise , Desidroepiandrosterona/fisiologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Pessoa de Meia-Idade , Síndrome do Ovário Policístico/sangue , Sinvastatina/uso terapêutico
12.
Int J Mol Med ; 43(2): 821-829, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30535427

RESUMO

One of the pathological functions of heat shock protein 22 (HSP22) is the association with inflammatory diseases and atherosclerosis. However, the effects of a high­fat diet (HFD) or oxidized low­density lipoprotein (ox­LDL) combined with atorvastatin (ATV) on HSP22 expression are entirely unknown. The present study investigated the effects of ATV on HSP22 expression in HFD­induced atherosclerotic apolipoprotein E­deficient (ApoE­/­) mice and in ox­LDL­induced human umbilical vein endothelial cells (HUVECs). Furthermore, the influence of HSP22­knockdown on the HFD- or ox­LDL­induced atherosclerotic model was also examined. It was found that HFD or ox­LDL treatment significantly increased HSP22 expression in the serum and aorta, accompanied by decreased phosphorylated (p)­endothelial nitric oxide synthase (p-eNOS) activity and activated p38 mitogen­activated protein kinase (MAPK). However, these effects were suppressed by treatment with ATV. Furthermore, HSP22-knockdown showed reduced ox­LDL­induced lesions, evidenced by increased p­eNOS activity and inactivated p38 MAPK, while suppression of cell proliferation inhibition and cell cycle arrest were also observed. Taken together, the results of this study suggest that HFD or ox­LDL increased the expression of HSP22 and p­p38 MAPK, and decreased the p­eNOS activity in vitro and in vivo, and ATV could reduce the effects by downregulating HSP22 expression.


Assuntos
Anticolesterolemiantes/farmacologia , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Atorvastatina/farmacologia , Proteínas de Choque Térmico HSP20/biossíntese , Proteínas de Choque Térmico/biossíntese , Proteínas Musculares/biossíntese , Proteínas Serina-Treonina Quinases/biossíntese , Animais , Anticolesterolemiantes/uso terapêutico , Atorvastatina/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Dieta Hiperlipídica , Regulação para Baixo , Células Endoteliais da Veia Umbilical Humana , Humanos , Lipoproteínas LDL/metabolismo , Masculino , Camundongos , Óxido Nítrico Sintase Tipo III/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
Artigo em Inglês | MEDLINE | ID: mdl-30580183

RESUMO

A combination of antiplatelet drugs with high-intensity statin therapy is a standard in patients with coronary events. Concomitant treatment with ticagrelor, a moderate CYP3A4 inhibitor, and CYP3A4-metabolized statins such as atorvastatin, might lead to an increased risk of muscle-related adverse events. Therefore, investigation of concentrations of these compounds in clinical samples is necessary. For this purpose, an LC-MS/MS method was developed for simultaneous determination of ticagrelor and its active metabolite (AR-C124910XX), as well as 2-hydroxyatorvastatin, which is the main metabolite of atorvastatin. Protein precipitation was used for sample preparation and afterwards the analytes were separated on a Kinetex XB-C18 column with an isocratic elution (water and acetonitrile with 0.1% formic acid, 57:43, v/v). Detection was performed on a triple-quadrupole MS with multiple-reaction-monitoring via electrospray ionization. The method was fully validated according to the EMA's recommendations. Determination was possible within ranges: 1.25-2000 ng/mL for ticagrelor, 1.25-1000 ng/mL for its AR-C124910XX, 1.25-50 ng/mL for atorvastatin and 1.14-45.73 for 2-hydroxyatorvastatin. Within and between-run accuracy, expressed as a relative error, was within 0.05-10.56% for all analytes, while within and between-run precision, expressed as coefficient of variation, was within 0.61-9.91%. Ticagrelor, atorvastatin and their main metabolites were found to be stable in acetonitrile stock solutions, and in plasma samples stored for 24 h at room temperature, 1 month at -25 °C, after 3 cycles of freezing and thawing, and in processed samples stored as a dry residue for 24 h at 4 °C and for 24 h in autosampler at room temperature. This simple and rapid method allowed simultaneous determination of the analytes for the first time. The procedure was applied for the pharmacokinetic study of ticagrelor, its active metabolite AR-C124910XX, and 2-hydroxyatorvastatin in patients simultaneously treated with ticagrelor and atorvastatin.


Assuntos
Cromatografia Líquida/métodos , Inibidores da Agregação de Plaquetas/sangue , Espectrometria de Massas em Tandem/métodos , Ticagrelor/sangue , Atorvastatina/uso terapêutico , Humanos , Limite de Detecção , Modelos Lineares , Pessoa de Meia-Idade , Doença Arterial Periférica/terapia , Inibidores da Agregação de Plaquetas/química , Inibidores da Agregação de Plaquetas/farmacocinética , Inibidores da Agregação de Plaquetas/uso terapêutico , Reprodutibilidade dos Testes , Ticagrelor/química , Ticagrelor/farmacocinética , Ticagrelor/uso terapêutico
14.
J Stroke Cerebrovasc Dis ; 28(3): 830-837, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30563776

RESUMO

BACKGROUND: The present study aimed to explore the efficacy of atorvastatin on patients with carotid plaque, applying superb microvascular imaging (SMI), and contrast-enhanced ultrasound (CEUS) for evaluating carotid intraplaque neovascularization. METHODS: A total of 82 patients (82 carotid plaques) who were randomized into treatment group and control group underwent conventional ultrasound, CEUS, and SMI examinations. Patients in treatment group received a dose of 20 mg atorvastatin per day for 6 months while those in control group received placebo instead. Lipid parameters were assessed and intraplaque neovascularization were evaluated by CEUS and SMI before and 6 months after atorvastatin treatment. RESULTS: No significant differences were found between the 2 groups at the study entry. Patients with atorvastatin treatment received marked improvement in total cholesterol, triglyceride, and LDL-cholesterol compared with those in control group (P < .001). In treatment group, SMI-detected intraplaque neovascularization reduced from 69.23% to 48.72% while CEUS-detected ones reduced from 76.92% to 69.23%. By contrast, the percentage of intraplaque neovascularization in control group did not change too much either by SMI (65.12%, 67.44%) or CEUS (74.41%, 74.41%). The consistency between CEUS and SMI was above .75 at all assessments (P < .001). CONCLUSIONS: Atorvastatin treatment works for patients with carotid plaque by reducing LDL-cholesterol and improving plaque regression. Second, the consistency between SMI and CEUS in visualizing intraplaque neovascularization is good. That indicates a high possibility to identify carotid plaque instability by a safer and cheaper ultrasonography without contrast agent.


Assuntos
Atorvastatina/uso terapêutico , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Ultrassonografia Doppler em Cores/métodos , Idoso , Idoso de 80 Anos ou mais , Atorvastatina/efeitos adversos , Biomarcadores/sangue , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/patologia , China , LDL-Colesterol/sangue , Meios de Contraste/administração & dosagem , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica , Fosfolipídeos/administração & dosagem , Placa Aterosclerótica , Valor Preditivo dos Testes , Estudos Prospectivos , Hexafluoreto de Enxofre/administração & dosagem , Fatores de Tempo , Resultado do Tratamento
15.
Int J Cardiol ; 274: 326-330, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30454723

RESUMO

BACKGROUND: Epicardial adipose tissue (EAT) thickness and pro-inflammatory status has been shown to be associated with several cardiac diseases, including aortic stenosis (AS). Thus, cardiac visceral fat could represent a potential new target for drugs. In the present study we evaluate the effect of statin therapy on EAT accumulation and inflammation. METHODS: Echocardiographic EAT thickness was assessed in 193 AS patients taking (n.87) and not taking (n.106) statins, undergoing cardiac surgery. To explore the association between statin therapy and EAT inflammation, EAT biopsies were obtained for cytokines immunoassay determination in EAT secretomes. An in vitro study was also conducted and the modulation of EAT and subcutaneous adipose tissue (SCAT) secretomes by atorvastatin was assessed in paired biopsies. RESULTS: Statin therapy was significantly associated with lower EAT thickness (p < 0.0001) and with lower levels of EAT-secreted inflammatory mediators (p < 0.0001). Of note, there was a significant correlation between EAT thickness and its pro-inflammatory status. In vitro, atorvastatin showed a direct anti-inflammatory effect on EAT which was significantly higher compared to the SCAT response to statin incubation (p < 0.0001). CONCLUSIONS: The present study indicates a robust association between statin therapy and reduced EAT accumulation in patients with AS. The present data also suggest a direct relationship between EAT thickness and its inflammatory status, both modulated by statin therapy. The in vitro results support the hypothesis of a direct action of statins on EAT secretory profile. Overall our data suggest EAT as a potential new therapeutic target for statin therapy.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Atorvastatina/uso terapêutico , Doença da Artéria Coronariana/prevenção & controle , Inflamação/tratamento farmacológico , Pericárdio/diagnóstico por imagem , Idoso , Valva Aórtica/patologia , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/terapia , Biópsia , Calcinose/complicações , Calcinose/diagnóstico , Calcinose/terapia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etiologia , Citocinas/metabolismo , Ecocardiografia , Feminino , Seguimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inflamação/diagnóstico , Inflamação/metabolismo , Masculino , Estudos Retrospectivos
16.
BMJ Case Rep ; 11(1)2018 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-30567259

RESUMO

We present a case of reverse takotsubo syndrome (rTS) in a 68-year-old woman who presented with acute chest pain and flu-like symptoms. She was found to have elevated troponin and abnormal ECG. Urgent coronary angiogram revealed non-obstructive mild coronary artery disease of the left anterior descending artery. Left ventriculography demonstrated hypokinesis of the left ventricular base with sparing of the mid-ventricle and apex. Nasal viral PCR was positive for Influenza A. The diagnosis was confirmed with repeat echocardiogram 2 weeks later revealing resolution of regional wall motion abnormalities. rTS is a type of TS, mimicking acute coronary syndrome. It is seen in younger patients and often occurs with intense emotional and physical stress. Though many triggers have been reported, rTS associated with influenza A has not been previously documented.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Dor no Peito/etiologia , Vírus da Influenza A/patogenicidade , Influenza Humana/complicações , Cardiomiopatia de Takotsubo/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/fisiopatologia , Idoso , Antivirais/uso terapêutico , Aspirina/uso terapêutico , Atorvastatina/uso terapêutico , Dor no Peito/fisiopatologia , Angiografia Coronária , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Vírus da Influenza A/imunologia , Influenza Humana/tratamento farmacológico , Influenza Humana/fisiopatologia , Oseltamivir/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Cardiomiopatia de Takotsubo/tratamento farmacológico , Cardiomiopatia de Takotsubo/fisiopatologia , Resultado do Tratamento
17.
Cell Physiol Biochem ; 49(4): 1277-1288, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30205393

RESUMO

BACKGROUND/AIMS: Previous studies in rat models of myocardial ischemia showed that Panax quinquefolium saponins (PQS) could attenuate ischemic/reperfusion injury, increase vessel density and improve cardiac function. In the current study, we examined whether PQS could attenuate myocardial dysfunction in a swine model of chronic myocardial ischemia (CMI). METHODS: CMI was established in Bama mini-pigs by placing amroid constrictor on the left anterior descending artery (LAD). Starting from 2 months after the surgery, pigs randomly received PQS (30 mg/kg/day), atorvastatin (1.5 mg/kg/day), or no drug for one month (n=6). A group of pigs receiving sham surgery was included as an additional control. Glucose utilization was assessed with positron emission tomography-computer tomography (PET-CT). Cardiac function was assessed with echocardiography. Myocyte size, nuclear density, and arteriolar density were examined in tissue section obtained from the ischemia area. Potential molecular targets of PQS were identified using proteomic analysis with isobaric tags for relative and absolute quantitation (iTARQ) and network pharmacology. RESULTS: In comparison to the sham controls, pigs implanted with ameroid constrictor had decreased ventricular wall motion, left ventricular ejection fraction (LVEF), and glucose utilization. PQS significantly increased cardiac function and glucose utilization. Arteriole density and myocyte nuclear density were increased. Myocyte diameter was decreased. PQS also attenuated the CMI-induced change of protein expression profile. The effects of atorvastatin were generally similar to that of PQS. However, PQS attenuated the reduction of left ventricular systolic WT induced by CMI more robustly than atorvastatin. CONCLUSION: The results from the current study supports the use of PQS in patients with coronary artery disease.


Assuntos
Infarto do Miocárdio/prevenção & controle , Saponinas/uso terapêutico , Função Ventricular/fisiologia , Animais , Arteríolas/fisiologia , Atorvastatina/farmacologia , Atorvastatina/uso terapêutico , Cromatografia Líquida de Alta Pressão , Doença Crônica , Estenose Coronária/complicações , Regulação para Baixo/efeitos dos fármacos , Ecocardiografia , Glucose/metabolismo , Coração/diagnóstico por imagem , Coração/efeitos dos fármacos , Espectrometria de Massas , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Tomografia por Emissão de Pósitrons , Proteoma/análise , Proteômica , Saponinas/análise , Saponinas/farmacologia , Suínos , Regulação para Cima/efeitos dos fármacos , Função Ventricular/efeitos dos fármacos
18.
Turk Neurosurg ; 28(4): 571-581, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30192361

RESUMO

AIM: To assess the efficacy of Neural progenitor cell (NPC) transplantation in ischemic stroke, and to investigate whether atorvastatin enhances therapeutic potency of NPC after stroke. MATERIAL AND METHODS: The focal cerebral ischemia-reperfusion model was performed by transient occlusion of middle cerebral artery. Rats were assigned randomly to receive intracerebral transplantation of mouse NPC alone (mNPC), human NPC alone (hNPC), mouse NPC plus oral atorvastatin (mNPC+A), human NPC plus oral atorvastatin (hNPC+A), oral atorvastatin alone, or intracerebral Dulbecco"s Modified Eagle"s medium injection (control group). Adhesive removal, rotarod, cylinder tests, and magnetic resonance imaging (MRI) were used for assessment of rats during 4 weeks. After sacrification on 28th day, rats were investigated by immunofluorescent staining. RESULTS: The hNPC and mNPC groups showed significantly improved functional outcome and reduced infarct area ratio compared with the control group. The hNPC group had significantly better performance and lower infarct area ratio than the mNPC group. Addition of atorvastatin to stem cell therapy significantly improved functional outcome, although it did not affect the infarct area ratio on MRI. Anti-inflammatory response in the infarct area was higher in the mNPC group. NPC transplantation significantly reduced the amount of microglia and a significant increase in the amount of astrocytes. CD8a+ T lymphocyte and granzyme B activities were not detected in any of the subjects. CONCLUSION: Both hNPC and mNPC treatments significantly improved functional outcome, and reduced infarct area ratio after stroke. Atorvastatin enhanced the therapeutic potency of NPCs, including neurological improvement.


Assuntos
Atorvastatina/uso terapêutico , Células-Tronco Neurais/transplante , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/terapia , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/terapia , Animais , Escala de Avaliação Comportamental , Modelos Animais de Doenças , Humanos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/terapia , Imagem por Ressonância Magnética , Masculino , Camundongos , Células-Tronco Neurais/citologia , Ratos , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismo por Reperfusão/diagnóstico por imagem , Traumatismo por Reperfusão/patologia , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia
19.
Medicine (Baltimore) ; 97(31): e11718, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30075578

RESUMO

The aim of this study was to evaluate optical coherence tomography (OCT) as an assessment of the efficacy of atorvastatin treatment.Twenty-four acute coronary syndrome (ACS) patients were allocated to conventional-dose (20 mg atorvastatin, n = 12) and intensive-dose (40-80 mg atorvastatin, n = 12) groups and correlations between changes in the OCT measurements and blood routine indexes were analyzed 9 months post-percutaneous coronary intervention (PCI).Treatment with atorvastatin resulted in a significant increase in the target thin cap fibroatheroma (TCFA) fibrous cap thicknesses in both groups. The increase was bigger in the intensive-dose group than in the conventional-dose group (184.1 ±â€Š57.4 µm vs. 125.1 ±â€Š28.6, P = .005). The TCFA lipid core arc in both groups was significantly decreased compared with baseline (72.9 ±â€Š29.3 vs. 127.6 ±â€Š50.8, P < .01 and 74.6 ±â€Š32.9 vs. 132.6 ±â€Š51.3, P < .01, respectively). Correlation analyses showed an inverse relationship between low-density lipoprotein cholesterol (LDL-c) levels and the TCFA cap thickness, and a direct relationship between C-reactive protein (CRP) level and lipid core arc.Statins significantly increased the TCFA fibrous cap thickness and reduced the lipid core arc, and OCT measurements accurately reflected the levels of blood LDL-c and CRP. TRIAL REGISTRATION: (Chinese Clinical Trial Registry) ChiCTR-IPR-17010874.


Assuntos
Anticolesterolemiantes/uso terapêutico , Atorvastatina/uso terapêutico , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/tratamento farmacológico , Tomografia de Coerência Óptica/métodos , Idoso , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/efeitos adversos , Anticolesterolemiantes/farmacologia , Atorvastatina/administração & dosagem , Atorvastatina/efeitos adversos , Atorvastatina/farmacologia , Proteína C-Reativa/análise , LDL-Colesterol/sangue , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Lancet ; 392(10153): 1127-1137, 2018 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-30158072

RESUMO

BACKGROUND: In patients with hypertension, the long-term cardiovascular and all-cause mortality effects of different blood pressure-lowering regimens and lipid-lowering treatment are not well documented, particularly in clinical trial settings. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Legacy Study reports mortality outcomes after 16 years of follow-up of the UK participants in the original ASCOT trial. METHODS: ASCOT was a multicentre randomised trial with a 2 × 2 factorial design. UK-based patients with hypertension were followed up for all-cause and cardiovascular mortality for a median of 15·7 years (IQR 9·7-16·4 years). At baseline, all patients enrolled into the blood pressure-lowering arm (BPLA) of ASCOT were randomly assigned to receive either amlodipine-based or atenolol-based blood pressure-lowering treatment. Of these patients, those who had total cholesterol of 6·5 mmol/L or lower and no previous lipid-lowering treatment underwent further randomisation to receive either atorvastatin or placebo as part of the lipid-lowering arm (LLA) of ASCOT. The remaining patients formed the non-LLA group. A team of two physicians independently adjudicated all causes of death. FINDINGS: Of 8580 UK-based patients in ASCOT, 3282 (38·3%) died, including 1640 (38·4%) of 4275 assigned to atenolol-based treatment and 1642 (38·1%) of 4305 assigned to amlodipine-based treatment. 1768 of the 4605 patients in the LLA died, including 903 (39·5%) of 2288 assigned placebo and 865 (37·3%) of 2317 assigned atorvastatin. Of all deaths, 1210 (36·9%) were from cardiovascular-related causes. Among patients in the BPLA, there was no overall difference in all-cause mortality between treatments (adjusted hazard ratio [HR] 0·90, 95% CI 0·81-1·01, p=0·0776]), although significantly fewer deaths from stroke (adjusted HR 0·71, 0·53-0·97, p=0·0305) occurred in the amlodipine-based treatment group than in the atenolol-based treatment group. There was no interaction between treatment allocation in the BPLA and in the LLA. However, in the 3975 patients in the non-LLA group, there were fewer cardiovascular deaths (adjusted HR 0·79, 0·67-0·93, p=0·0046) among those assigned to amlodipine-based treatment compared with atenolol-based treatment (p=0·022 for the test for interaction between the two blood pressure treatments and allocation to LLA or not). In the LLA, significantly fewer cardiovascular deaths (HR 0·85, 0·72-0·99, p=0·0395) occurred among patients assigned to statin than among those assigned placebo. INTERPRETATION: Our findings show the long-term beneficial effects on mortality of antihypertensive treatment with a calcium channel blocker-based treatment regimen and lipid-lowering with a statin: patients on amlodipine-based treatment had fewer stroke deaths and patients on atorvastatin had fewer cardiovascular deaths more than 10 years after trial closure. Overall, the ASCOT Legacy study supports the notion that interventions for blood pressure and cholesterol are associated with long-term benefits on cardiovascular outcomes. FUNDING: Pfizer.


Assuntos
Anticolesterolemiantes/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/mortalidade , Hipertensão/tratamento farmacológico , Hipertensão/mortalidade , Adulto , Idoso , Anlodipino/uso terapêutico , Atenolol/uso terapêutico , Atorvastatina/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Doenças Cardiovasculares/mortalidade , Causas de Morte , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Reino Unido
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