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1.
Medicine (Baltimore) ; 99(36): e21991, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899044

RESUMO

OBJECTIVE: To assess the clinical efficacy and safety of Zhibitai, as a kind of natural lipid-lowering Chinese medicine, in treating coronary heart disease patients with hyperlipemia METHODS: : A systematic literature search for articles up to July 2020 will be performed in following electronic databases: PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journals Database Database, Chinese Biomedical Database, Chinese Biomedical Literature Service System, and Wanfang Database. Inclusion criteria are randomized controlled trials of Zhibitai applied on coronary heart disease patients with hyperlipemia. The primary outcome measures will be serum lipid levels (including total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) and acute cardiovascular events. The secondary outcome measures will be inflammatory factors (high sensitive C-reactive protein, interleukin-6, etc), safety index (liver function, renal function, etc), and adverse events. RevMan 5.3 software will be used for data synthesis, sensitivity analysis, meta-regression, subgroup analysis, and risk of bias assessment. A funnel plot will be developed to evaluate reporting bias and Egger tests will be used to assess funnel plot symmetries. We will use the grading of recommendations assessment, development, and evaluation system to assess the quality of evidence.Trial registration number PROSPERO CRD42018103341.


Assuntos
Doença das Coronárias/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Doença das Coronárias/complicações , Humanos , Hiperlipidemias/complicações , Metanálise como Assunto , Fitoterapia , Revisões Sistemáticas como Assunto
2.
Yonsei Med J ; 61(9): 780-788, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32882762

RESUMO

PURPOSE: This research was designed to investigate how miR-542-5p regulates the progression of hyperglycemia and hyperlipoidemia. MATERIALS AND METHODS: An in vivo model with diabetic db/db mice and an in vitro model with forskolin/dexamethasone (FSK/DEX)-induced primary hepatocytes and HepG2 cells were employed in the study. Bioinformatics analysis was conducted to identify the expression of candidate miRNAs in the liver tissues of diabetic and control mice. H&E staining revealed liver morphology in diabetic and control mice. Pyruvate tolerance tests, insulin tolerance tests, and intraperitoneal glucose tolerance test were utilized to assess insulin resistance. ELISA was conducted to evaluate blood glucose and insulin levels. Red oil O staining showed lipid deposition in liver tissues. Luciferase reporter assay was used to depict binding between miR-542-5p and forkhead box O1 (FOXO1). RESULTS: MiR-542-5p expression was under-expressed in the livers of db/db mice. Further in vitro experiments revealed that FSK/DEX, which mimics the effects of glucagon and glucocorticoids, induced cellular glucose production in HepG2 cells and in primary hepatocytes cells. Notably, these changes were reversed by miR-542-5p. We found that transcription factor FOXO1 is a target of miR-542-5p. Further in vivo study indicated that miR-542-5p overexpression decreases FOXO1 expression, thereby reversing increases in blood glucose, blood lipids, and glucose-related enzymes in diabetic db/db mice. In contrast, anti-miR-542-5p exerted an adverse influence on blood glucose and blood lipid metabolism, and its stimulatory effects were significantly inhibited by sh-FOXO1 in normal control mice. CONCLUSION: Collectively, our results indicated that miR-542-5p inhibits hyperglycemia and hyperlipoidemia by targeting FOXO1.


Assuntos
Diabetes Mellitus Tipo 2/genética , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Hiperglicemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , MicroRNAs/genética , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Regulação da Expressão Gênica , Glucose/metabolismo , Teste de Tolerância a Glucose , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Hiperglicemia/metabolismo , Hiperlipidemias/metabolismo , Resistência à Insulina , Metabolismo dos Lipídeos , Fígado/metabolismo , Camundongos , MicroRNAs/metabolismo , MicroRNAs/farmacologia
3.
J Mol Cell Cardiol ; 146: 41-42, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32687852
4.
Clín. investig. arterioscler. (Ed. impr.) ; 32(3): 111-116, mayo-jun. 2020. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-193355

RESUMO

BACKGROUND: Hyperlipidemia is a prevalent disorder and a main component of the metabolic syndrome resulting from various factors. The aerial parts and flowers of Lavandula officinalis possesses antioxidant activity, therefore, in this study; the effects of L. officinalis extract were investigated on serum lipid levels of mice. METHODS: Experimental mature female BALB/c mice were treated with 100, 300 or 500 mg/kg/day of lavender aqueous extract or distilled water for 15 days via intraperitoneally injections. At the end of 15th day, the serum biochemical parameters include cholesterol, triglyceride, HDL and LDL levels as well as the liver cell function test were determined. RESULTS: The aqueous extract of lavender significantly decreased serum cholesterol and LDL levels. Serum cholesterol level was lower in the 300 and 500 mg/kg/day experimental groups when compared with the control group. In liver histology evaluation, fat accumulation was not observed in the experimental group, which treated with high-fat foods and receiving high doses of extract. CONCLUSION: L. officinalis extract exerts a hypolipidemic effect in studied groups, however, further phytochemical and biological tests are suggested to determine the active chemical constituent responsible for these activities


ANTECEDENTES: La hiperlipidemia es un trastorno prevalente y un componente principal del síndrome metabólico originada por diversos factores. Las partes aéreas y flores de la Lavandula officinalis tienen una actividad antioxidante y, por tanto, investigamos en este estudio los efectos de su extracto en los niveles lipídicos séricos en ratones. MÉTODOS: Se trataron ratones BALB/c hembra maduras experimentales con 100, 300 o 500 mg/kg/día de extracto acuoso de lavanda o agua destilada durante 15 días, mediante inyecciones intraperitoneales. Al finalizar el 15.° día se investigaron los parámetros bioquímicos séricos incluyendo colesterol, triglicéridos, niveles de HDL y LDL, así como la prueba de la función hepática. RESULTADOS: El extracto acuoso de lavanda disminuyó significativamente los niveles séricos de colesterol y LDL. El nivel de colesterol sérico fue inferior en los grupos experimentales de 300 y 500 mg/kg/día, en comparación con el grupo control. En la evaluación de la histología hepática no se observó acumulación de grasa en el grupo experimental, que fue tratado con alimentos de alto contenido en grasa y recibió altas dosis de extracto. CONCLUSIÓN: El extracto de Lavandula officinalis ejerce un efecto hipolipidémico en el grupo estudiado, aunque son precisas más pruebas fitoquímicas y biológicas para determinar el constituyente químico activo responsable de estas actividades


Assuntos
Animais , Feminino , Camundongos , Lavandula , Extratos Vegetais/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/veterinária , LDL-Colesterol/administração & dosagem , Camundongos Endogâmicos BALB C , LDL-Colesterol/efeitos dos fármacos , Modelos Animais
5.
Life Sci ; 254: 117756, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32389832

RESUMO

Polydatin (PD) is a monocrystalline metabolite from the underground parts of Polygonum cuspidatum Sieb. et Zucc., a member of the Polygonaceae family, which has been traditionally used in Asian countries as both foodstuffs and medicine. PD, also reckoned as pieceid, 3,4',5-trihydroxystilbene-3-ß-D-glucoside, (E)-piceid, (E)-polydatin, and trans-polydatin. It possesses potent biological activities i.e. analgesic, anti-inflammatory, antidiabetic, anticancer, and anti-atherosclerotic properties. The initial part of this report specifically explains distinct sequential mechanisms underlying the initiation and development of atherosclerotic plaques and later part deals with the pharmacological efficacy of PD in the management of major cardiac event i.e. atherosclerotic cardiovascular diseases (ASCVD) via modulation of a set of molecular mechanisms i.e. antioxidant potential, lipid and lipoprotein metabolism including total cholesterol (TC) and low density lipoprotein (LDL) levels, ß-hydroxy-ß-methyl-glutaryl-CoA reductase (HMG-R) expression and functionality, SIRT signalling, LDL-receptor (LDL-R), LDL oxidation status (Ox-LDL), effects on endothelial cells (ECs), smooth muscle cells (SMCs), macrophage, foam cell formation and plaque stabilization, inflammatory signalling pathways and hypertension. In contrast, one of the major insight into the potential cardioprotective molecular mechanism is the PD-mediated targeting of proprotein convertase subtilisin/kexin type-9 (PCSK-9) and LDL-R pathway, both at transcriptional and protein functional level, which makes it a better alternative therapeutic medicinal candidate to treat hypercholesterolemia, especially for the patients facing inadequate lipid lowering with classical HMG-R inhibitors (statins) and statin intolerance. Finally, to sum up the whole, we concluded that PD may be promoted from alternative to mainstream medicine in targeting risk factors mediated ASCVD.


Assuntos
Aterosclerose/tratamento farmacológico , Glucosídeos/farmacologia , Estilbenos/farmacologia , Anticolesterolemiantes/uso terapêutico , LDL-Colesterol/metabolismo , Células Endoteliais/metabolismo , Fallopia japonica/metabolismo , Glucosídeos/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Lipoproteínas LDL , Placa Aterosclerótica/tratamento farmacológico , Receptores de LDL/metabolismo , Fatores de Risco , Estilbenos/uso terapêutico
6.
Am J Trop Med Hyg ; 102(6): 1205-1207, 2020 06.
Artigo em Inglês | MEDLINE | ID: covidwho-602003

RESUMO

The initial cases of novel coronavirus disease-19 (COVID-19) in a country are of utmost importance given their impact on healthcare providers, the country's preparedness response, and the initial molding of the public perception toward this pandemic. In Bhutan, the index case was a 76-year-old immunocompromised man who had traveled from the United States and entered Bhutan as a tourist. He presented initially with vague gastrointerestinal symptoms and later a cough. His atypical presentation led to a delay in diagnosis, but ultimately he was isolated and tested. On confirming the diagnosis of COVID-19, the patient was isolated in a separate hospital with a dedicated medical care team. All contacts were traced and quarantined. The patient's respiratory status deteriorated despite broad-spectrum antivirals, antibiotics, and intensive supportive care. He required intubation and was given a trial of intravenous immunoglobulin to modulate his likely aberrant immune response. Subsequently, the patient's clinical status improved, and after 8 days of hospitalization, he was transferred out of the country, where he recovered. This was a learning experience for the treating medical staff, the government, and the people of Bhutan.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico por imagem , Hiperlipidemias/diagnóstico por imagem , Hipertensão/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Idoso , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Butão , Busca de Comunicante , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Humanos , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/imunologia , Hiperlipidemias/patologia , Hipertensão/tratamento farmacológico , Hipertensão/imunologia , Hipertensão/patologia , Hospedeiro Imunocomprometido , Imunoglobulinas Intravenosas/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Masculino , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Tomografia Computadorizada por Raios X , Viagem , Resultado do Tratamento , Ultrassonografia , Estados Unidos
7.
Am J Trop Med Hyg ; 102(6): 1205-1207, 2020 06.
Artigo em Inglês | MEDLINE | ID: covidwho-101333

RESUMO

The initial cases of novel coronavirus disease-19 (COVID-19) in a country are of utmost importance given their impact on healthcare providers, the country's preparedness response, and the initial molding of the public perception toward this pandemic. In Bhutan, the index case was a 76-year-old immunocompromised man who had traveled from the United States and entered Bhutan as a tourist. He presented initially with vague gastrointerestinal symptoms and later a cough. His atypical presentation led to a delay in diagnosis, but ultimately he was isolated and tested. On confirming the diagnosis of COVID-19, the patient was isolated in a separate hospital with a dedicated medical care team. All contacts were traced and quarantined. The patient's respiratory status deteriorated despite broad-spectrum antivirals, antibiotics, and intensive supportive care. He required intubation and was given a trial of intravenous immunoglobulin to modulate his likely aberrant immune response. Subsequently, the patient's clinical status improved, and after 8 days of hospitalization, he was transferred out of the country, where he recovered. This was a learning experience for the treating medical staff, the government, and the people of Bhutan.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico por imagem , Hiperlipidemias/diagnóstico por imagem , Hipertensão/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Idoso , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Butão , Busca de Comunicante , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Humanos , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/imunologia , Hiperlipidemias/patologia , Hipertensão/tratamento farmacológico , Hipertensão/imunologia , Hipertensão/patologia , Hospedeiro Imunocomprometido , Imunoglobulinas Intravenosas/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Masculino , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Tomografia Computadorizada por Raios X , Viagem , Resultado do Tratamento , Ultrassonografia , Estados Unidos
8.
Am J Trop Med Hyg ; 102(6): 1205-1207, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32314685

RESUMO

The initial cases of novel coronavirus disease-19 (COVID-19) in a country are of utmost importance given their impact on healthcare providers, the country's preparedness response, and the initial molding of the public perception toward this pandemic. In Bhutan, the index case was a 76-year-old immunocompromised man who had traveled from the United States and entered Bhutan as a tourist. He presented initially with vague gastrointerestinal symptoms and later a cough. His atypical presentation led to a delay in diagnosis, but ultimately he was isolated and tested. On confirming the diagnosis of COVID-19, the patient was isolated in a separate hospital with a dedicated medical care team. All contacts were traced and quarantined. The patient's respiratory status deteriorated despite broad-spectrum antivirals, antibiotics, and intensive supportive care. He required intubation and was given a trial of intravenous immunoglobulin to modulate his likely aberrant immune response. Subsequently, the patient's clinical status improved, and after 8 days of hospitalization, he was transferred out of the country, where he recovered. This was a learning experience for the treating medical staff, the government, and the people of Bhutan.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico por imagem , Hiperlipidemias/diagnóstico por imagem , Hipertensão/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Idoso , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Butão , Busca de Comunicante , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Humanos , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/imunologia , Hiperlipidemias/patologia , Hipertensão/tratamento farmacológico , Hipertensão/imunologia , Hipertensão/patologia , Hospedeiro Imunocomprometido , Imunoglobulinas Intravenosas/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Masculino , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Tomografia Computadorizada por Raios X , Viagem , Resultado do Tratamento , Ultrassonografia , Estados Unidos
9.
Life Sci ; 252: 117648, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32275937

RESUMO

AIMS: This study was conducted to determine the relationship between mesencephalic astrocyte-derived neurotrophic factor (MANF), autophagy and endoplasmic reticulum (ER) stress, and whether liraglutide (LRG) can protect ß cells, promote autophagy and alleviate ER stress by regulating MANF expression. MAIN METHODS: Human serum samples were collected from healthy controls (NC), simple hyperlipidemia (HLD), and newly diagnosed type 2 diabetes (T2D). The MANF levels were detected using ELISA. In vitro, after the mouse islet MIN6 cells were treated with glucose (GLU), palmitate (PA), thapsigargin (TG), LRG, and chloroquine (CQ), cell proliferation was detected using cell counting kit-8 (CCK-8), apoptosis-related protein cleaved caspase 3 (C-cas-3), ER stress, and autophagy-related proteins were detected by Western blotting, MANF, insulin, and C-cas-3 proteins were detected via immunofluorescence. Subcellular structures and autophagosomes were examined using electron microscopy. KEY FINDINGS: Compared with the NC group, the MANF levels in the HLD and T2D groups increased significantly. After ER stress induced by GLU, PA, and TG, cell viability decreased, while MANF, c-cas3, ERS, and autophagy-related proteins increased, which was related to the concentration of GLU, PA, and TG. Compared with the BSA group, the number of mitochondria and autophagosomes in the PA group increased and the mitochondria were damaged. In the PA and TG plus CQ groups, the effect was further exaggerated. But after co-treatment with LRG, the effects of GLU, PA, and TG were attenuated. SIGNIFICANCE: LRG protects islet ß cells from ER stress by upregulating MANF to promote autophagy turnover.


Assuntos
Autofagia/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Liraglutida/farmacologia , Fatores de Crescimento Neural/genética , Animais , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/farmacologia , Células Secretoras de Insulina/metabolismo , Camundongos , Regulação para Cima/efeitos dos fármacos
10.
Chin J Nat Med ; 18(3): 161-168, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32245585

RESUMO

The liver is an important metabolic organ and controls lipid, glucose and energy metabolism. Dysruption of hepatic lipid metabolism is often associated with fatty liver diseases, including nonalcoholic fatty liver disease (NAFLD), alcoholic fatty liver diseases (AFLD) and hyperlipidemia. Recent studies have uncovered the contribution of hormones, transcription factors, and inflammatory cytokines to the pathogenesis of dyslipidemia and fatty liver diseases. Moreover, a significant amount of effort has been put to examine the mechanisms underlying the potential therapeutic effects of many natural plant products on fatty liver diseases and metabolic diseases. We review the current understanding of insulin, thyroid hormone and inflammatory cytokines in regulating hepatic lipid metabolism, focusing on several essential transcription regulators, such as Sirtuins (SIRTs), Forkhead box O (FoxO), Sterol-regulatory element-binding proteins (SREBPs). We also discuss a few representative natural products with promising thereapeutic effects on fatty liver disease and dyslipidemia.


Assuntos
Fígado Gorduroso Alcoólico/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Fitoterapia , Alcaloides/farmacologia , Animais , Citocinas/metabolismo , Dislipidemias , Flavonoides/farmacologia , Fatores de Transcrição Forkhead/metabolismo , Humanos , Insulina/metabolismo , Metabolismo dos Lipídeos , Fígado/efeitos dos fármacos , Saponinas/farmacologia , Sirtuínas/metabolismo , Proteínas de Ligação a Elemento Regulador de Esterol/metabolismo , Hormônios Tireóideos/metabolismo
11.
Metabolism ; 107: 154221, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32240727

RESUMO

BACKGROUND: Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL) particle containing apolipoprotein(a) (apo(a)) covalently linked to apolipoprotein B-100 (apoB). Statin-treated patients with elevated Lp(a) have an increased risk of atherosclerotic cardiovascular disease (ASCVD). Recent trials show that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition decreases Lp(a) and cardiovascular events, particularly in high risk patients with elevated Lp(a). We investigated the kinetic mechanism whereby alirocumab, a PCSK9 inhibitor, lowers Lp(a) in statin-treated patients with high Lp(a) and ASCVD. METHODS: The effects of 12-week alirocumab treatment (150 mg every 2 weeks) on apo(a) kinetics were studied in 21 patients with elevated Lp(a) concentration (>0.5 g/L). Apo(a) fractional catabolic rate (FCR) and production rate (PR) were determined using intravenous D3-leucine administration, mass spectrometry and compartmental modelling. All patients were on long-term statin treatment. RESULTS: Alirocumab significantly decreased plasma concentrations of total cholesterol (-39%), LDL-cholesterol (-67%), apoB (-56%), apo(a) (-25%) and Lp(a) (-22%) (P< 0.001 for all). Alirocumab also significantly lowered plasma apo(a) pool size (-26%, P <0.001) and increased the FCR of apo(a) (+28%, P< 0.001), but did not alter apo(a) PR, which remained significantly higher relative to a reference group of patients on statins with normal Lp(a) (P< 0.001). CONCLUSIONS: In statin-treated patients, alirocumab lowers elevated plasma Lp(a) concentrations by accelerating the catabolism of Lp(a) particles. This may be consequent on marked upregulation of hepatic receptors (principally for LDL) and/or reduced competition between Lp(a) and LDL particles for these receptors; the mechanism could contribute to the benefit of PCSK9 inhibition with alirocumab on cardiovascular outcomes.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/sangue , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Lipoproteína(a)/metabolismo , Pró-Proteína Convertase 9/antagonistas & inibidores , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Apoproteína(a)/sangue , Colesterol/sangue , Doença da Artéria Coronariana/tratamento farmacológico , Feminino , Humanos , Hipolipemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
Am J Chin Med ; 48(3): 579-595, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32329643

RESUMO

Corosolic acid (CA) is the main active component of Lagetstroemia speciosa and has been known to serve as several different pharmacological effects, such as antidiabetic, anti-oxidant, and anticancer effects. In this study, effects of CA on the hepatic lipid accumulation were examined using HepG2 cells and tyloxapol (TY)-induced hyperlipidemia ICR mice. CA significantly inhibited hepatic lipid accumulation via inhibition of SREBPs, and its target genes FAS, SCD1, and HMGCR transcription in HepG2 cells. These effects were mediated through activation of AMPK, and these effects were all abolished in the presence of compound C (CC, an AMPK inhibitor). In addition, CA clearly alleviated serum ALT, AST, TG, TC, low-density lipoprotein cholesterol (LDL-C), and increased high-density lipoprotein cholesterol (HDL-C) levels, and obviously attenuated TY-induced liver steatosis and inflammation. Moreover, CA significantly upregulated AMPK, ACC, LKB1 phosphorylation, and significantly inhibited lipin1, SREBPs, TNF-α, F4/80, caspase-1 expression, NF-κB translocation, and MAPK activation in TY-induced hyperlipidemia mice. Our results suggest that CA is a potent antihyperlipidemia and antihepatic steatosis agent and the mechanism involved both lipogenesis and cholesterol synthesis and inflammation response inhibition via AMPK/SREBPs and NF-κB/MAPK signaling pathways.


Assuntos
Hiperlipidemias/tratamento farmacológico , Hipolipemiantes , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Fitoterapia , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Animais , Células Hep G2 , Humanos , Inflamação , Lagerstroemia/química , Camundongos Endogâmicos ICR , Estearoil-CoA Dessaturase/metabolismo , Receptor fas/metabolismo
13.
Public Health Res Pract ; 30(1)2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32152615

RESUMO

OBJECTIVES: Previous Australian research has shown that following the 21% increase in patient copayments for medications on the Pharmaceutical Benefits Scheme (PBS) in 2005, the use of lipid-lowering therapy declined by 5%. This study aimed to determine the demographic and clinical characteristics of individuals who continued, reduced or ceased their use of statin medication in 2005. STUDY TYPE: Retrospective observational study using routinely collected administrative data. METHOD: We used pharmaceutical claims, hospital separations and mortality records from 2000 to 2005 for the Western Australian population. The cohort comprised stable users of statin medication in 2004. Based on changes in statin use between 2004 and 2005, we identified individuals who: 1) continued using statins; 2) reduced their use by ≥20%; or 3) ceased therapy for at least the first 6 months in 2005. Multivariate logistic regression models were used to determine whether the demographic and clinical characteristics of the three groups differed. RESULTS: There were 205 924 statin users identified in Western Australia as of December 2004. After the January 2005 Pharmaceutical Benefits Scheme (PBS) copayment increase, 3.2% of users ceased their regular statin therapy, 12.9% reduced statin use and 83.9% continued statin use. This represented a 2.1% increase in statin users reducing or ceasing therapy compared to 2004. Predictors of cessation and reduction of statin therapy included younger age, greater socio-economic disadvantage, residing in very remote areas, having general beneficiary status, being a new statin user, having no prior history of ischaemic heart disease, having no prior history of a coronary artery revascularisation procedure, taking no other cardiovascular medication or diabetic medication, taking an increased number of medications, and having a lower level of adherence to statin medication in 2004. CONCLUSION: Compared to 2004, an additional 2.1% of statin users reduced or discontinued medication use in 2005, which may be attributed to an increase in the medication copayment. Individuals with general beneficiary status, and younger and healthier people were at particular risk of cessation or reduction in statin use in 2005.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Duração da Terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Austrália Ocidental
14.
Open Heart ; 7(1): e001163, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32206316

RESUMO

Objectives: The primary objective was to examine the association between hyperlipidaemia (HLP) and 5-year survival after incident acute myocardial infarction (AMI). The secondary objectives were to assess the effect of HLP on survival to discharge across patient subgroups, and the impact of statin prescription, intensity and long-term statin adherence on 5-year survival. Methods: Retrospective cohort study of 7071 patients hospitalised for AMI at Mayo Clinic from 2001 through 2011. Of these, 2091 patients with HLP (age (mean±SD) 69.7±13.5) were propensity score matched to 2091 patients without HLP (age 70.6±14.2). Results: In matched patients, HLP was associated with higher rate of survival to discharge than no HLP (95% vs 91%; log-rank <0.0001). At year 5, the adjusted HR for all-cause mortality in patients with HLP versus no HLP was 0.66 (95% CI 0.58-0.74), and patients with prescription statin versus no statin was 0.24 (95% CI 0.21 to 0.28). The mean survival was 0.35 year greater in patients with HLP than in those with no HLP (95% CI 0.25 to 0.46). Patients with HLP gained on an average 0.17 life year and those treated with statin 0.67 life year at 5 years after AMI. The benefit of concurrent HLP was consistent across study subgroups. Conclusions: In patients with AMI, concomitant HLP was associated with increased survival and a net gain in life years, independent of survival benefit from statin therapy. The results also reaffirm the role of statin prescription, intensity and adherence in reducing the mortality after incident AMI.


Assuntos
Hospitalização , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Lipídeos/sangue , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/diagnóstico , Hiperlipidemias/mortalidade , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio sem Supradesnível do Segmento ST/mortalidade , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Fatores de Tempo
15.
PLoS One ; 15(3): e0229541, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130251

RESUMO

BACKGROUND: Hyperlipidemia and hypertension are modifiable risk factors for Alzheimer's disease and related dementias (ADRD). Approximately 25% of adults over age 65 use both antihypertensives (AHTs) and statins for these conditions. While a growing body of evidence found statins and AHTs are independently associated with lower ADRD risk, no evidence exists on simultaneous use for different drug class combinations and ADRD risk. Our primary objective was to compare ADRD risk associated with concurrent use of different combinations of statins and antihypertensives. METHODS: In a retrospective cohort study (2007-2014), we analyzed 694,672 Medicare beneficiaries in the United States (2,017,786 person-years) who concurrently used both statins and AHTs. Using logistic regression adjusting for age, socioeconomic status and comorbidities, we quantified incident ADRD diagnosis associated with concurrent use of different statin molecules (atorvastatin, pravastatin, rosuvastatin, and simvastatin) and AHT drug classes (two renin-angiotensin system (RAS)-acting AHTs, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin-II receptor blockers (ARBs), vs non-RAS-acting AHTs). FINDINGS: Pravastatin or rosuvastatin combined with RAS-acting AHTs reduce risk of ADRD relative to any statin combined with non-RAS-acting AHTs: ACEI+pravastatin odds ratio (OR) = 0.942 (CI: 0.899-0.986, p = 0.011), ACEI+rosuvastatin OR = 0.841 (CI: 0.794-0.892, p<0.001), ARB+pravastatin OR = 0.794 (CI: 0.748-0.843, p<0.001), ARB+rosuvastatin OR = 0.818 (CI: 0.765-0.874, p<0.001). ARBs combined with atorvastatin and simvastatin are associated with smaller reductions in risk, and ACEI with no risk reduction, compared to when combined with pravastatin or rosuvastatin. Among Hispanics, no combination of statins and RAS-acting AHTs reduces risk relative to combinations of statins and non-RAS-acting AHTs. Among blacks using ACEI+rosuvastatin, ADRD odds were 33% lower compared to blacks using other statins combined with non-RAS-acting AHTs (OR = 0.672 (CI: 0.548-0.825, p<0.001)). CONCLUSION: Among older Americans, use of pravastatin and rosuvastatin to treat hyperlipidemia is less common than use of simvastatin and atorvastatin, however, in combination with RAS-acting AHTs, particularly ARBs, they may be more effective at reducing risk of ADRD. The number of Americans with ADRD may be reduced with drug treatments for vascular health that also confer effects on ADRD.


Assuntos
Doença de Alzheimer/prevenção & controle , Anti-Hipertensivos/administração & dosagem , Demência/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/etiologia , Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Estudos de Coortes , Demência/epidemiologia , Demência/etiologia , Quimioterapia Combinada , Feminino , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/tratamento farmacológico , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Incidência , Modelos Logísticos , Masculino , Medicare , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-32110901

RESUMO

Background: Previous research found that statins, in addition to its efficiency in treating hyperlipidemia, may also incur adverse drug reactions, which mainly include myopathies and abnormalities in liver function. Aim: This study aims to assess the risk for newly onset sarcopenia among patients with chronic kidney disease using statins. Material and Method: In a nationwide retrospective population-based cohort study, 75,637 clinically confirmed cases of chronic kidney disease between 1997 and 2011were selected from the National Health Insurance Research Database of Taiwan. The selection of the chronic kidney disease cohort included a discharge diagnosis with chronic kidney disease or more than 3 outpatient visits with the diagnosis of chronic kidney disease found within 1 year. After consideration of patient exclusions, we finally got a total number of 67,001 cases of chronic kidney disease in the study. The Cox proportional hazards model was used to perform preliminary analysis on the effect of statins usage on the occurrence of newly diagnosed sarcopenia; the Cox proportional hazards model with time-dependent covariates was conducted to take into consideration the individual temporal differences in medication usage, and calculated the hazard ratio (HR) and 95% confidence interval after controlling for gender, age, income, and urbanization. Results: Our main findings indicated that patients with chronic kidney disease who use statins seem to effectively prevent patients from occurrences of sarcopenia, high dosage of statins seem to show more significant protective effects, and the results are similar over long-term follow-up. In addition, the risk for newly diagnosed sarcopenia among patients with lipophilic statins treatment was lower than that among patients with hydrophilic statins treatment. Conclusion: It seems that patients with chronic kidney disease could receive statin treatment to reduce the occurrence of newly diagnosed sarcopenia. Additionally, a higher dosage of statins could reduce the incidence of newly diagnosed sarcopenia in patients with chronic kidney disease.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipidemias , Insuficiência Renal Crônica , Sarcopenia , Idoso , Estudos de Coortes , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/complicações , Hiperlipidemias/tratamento farmacológico , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/complicações , Estudos Retrospectivos , Sarcopenia/induzido quimicamente , Sarcopenia/complicações , Taiwan
17.
Vnitr Lek ; 65(12): 761-769, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32013518

RESUMO

AIM: A multicountry observational study was conducted to gain insight into the current management of elevated low density lipoprotein cholesterol (LDL-C) in high-risk (HR) and very high-risk (VHR) patients with hyperlipidaemia across central and eastern Europe and Israel. Here we present data from the Slovakian subpopulation. METHODS: We enrolled adult patients who were receiving lipid-lowering therapy (LLT) and attending a specialist (cardiologist/diabetologist/internist) for a routine visit at 9 sites (including academic/specialist centers) across Slovakia. Data were collected retrospectively from patients records for the 12 months preceding enrolment. RESULTS: 150 patients, mean (range) age 62.8 (26-84) years were enrolled, including 24 with familial hypercholesterolemia and 109 secon-dary prevention patients. Almost all patients (147; 98.0 %) were receiving statins, as monotherapy (114; 76.0 %) or in combination with other LLT (33; 22.0 %): 11 (7.3 %) were classified as having statin intolerance symptoms. Mean LDL-C levels were 3.0 (1.1-7.1) mmol/l at the first, and 2.6 (0.7-7.7) mmol/l at the last, visit of the observation period. Only 2/16 (12.5 %; 95 % CI 1.6-38.4 %) HR patients and 40/134 (29.9 %; 22.3-38.4 %) VHR patients achieved their recom-mended LDL-C targets of < 2.5 and < 1.8 mmol/l, respectively, during observation. In the FH subset 2/15 (13.3 %; 1.7-40.5 %) HR and 2/9 (22.2 %; 2.8-60.0 %) VHR patients achieved these targets. In patients with definite/probable FH (Dutch Lipid Clinic Network score 6), these targets were attained by 2/15 (13.3 %; 1.7-40.5) HR patients and 0/6 VHR patients. A total of 41 patients (27.3 %) experienced CV events ( 3) during the 12-month observation period. CONCLUSION: Our findings provide a picture of patients treated for hyperlipidemia across Slovakia. We found that, despite widespread statin use, a substantial proportion of patients, particularly those with FH, are undertreated and fail to achieve the LDL-C targets recommended in European guidelines. They consequently remain at excess risk of cardiovascular events.


Assuntos
Anticolesterolemiantes , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipidemias , Adulto , Anticolesterolemiantes/uso terapêutico , Europa Oriental , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Estudos Retrospectivos , Eslováquia , Resultado do Tratamento
18.
Am J Physiol Gastrointest Liver Physiol ; 318(4): G682-G693, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32003602

RESUMO

Postprandial dyslipidemia is a common feature of insulin-resistant states and contributes to increased cardiovascular disease risk. Recently, bile acids have been recognized beyond their emulsification properties as important signaling molecules that promote energy expenditure, improve insulin sensitivity, and lower fasting lipemia. Although bile acid receptors have become novel pharmaceutical targets, their effects on postprandial lipid metabolism remain unclear. Here, we investigated the potential role of bile acids in regulation of postprandial chylomicron production and triglyceride excursion. Healthy C57BL/6 mice were given an intraduodenal infusion of taurocholic acid (TA) under fat-loaded conditions, and circulating lipids were measured. Targeting of bile acid receptors was achieved with GW4064, a synthetic agonist to the farnesoid X receptor (FXR), and deoxycholic acid (DCA), an activator of the Takeda G-protein-coupled receptor 5. TA, GW4064, and DCA treatments all lowered postprandial lipemia. FXR agonism also reduced intestinal triglyceride content and activity of microsomal triglyceride transfer protein, involved in chylomicron assembly. Importantly, TA (but not DCA) effects were largely lost in FXR knockout mice. These bile acid effects are reminiscent of the antidiabetic hormone glucagon-like peptide-1 (GLP-1). Although the GLP-1 receptor agonist exendin-4 retained its ability to acutely lower postprandial lipemia during bile acid sequestration and FXR deficiency, it did raise hepatic expression of the rate-limiting enzyme for bile acid synthesis. Bile acid signaling may be an important mechanism of controlling dietary lipid absorption, and bile acid receptors may constitute novel targets for the treatment of postprandial dyslipidemia.NEW & NOTEWORTHY We present new data suggesting potentially important roles for bile acids in regulation of postprandial lipid metabolism. Specific bile acid species, particularly secondary bile acids, were found to markedly inhibit absorption of dietary lipid and reduce postprandial triglyceride excursion. These effects appear to be mediated via bile acid receptors, farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). Importantly, bile acid signaling may trigger glucagon-like peptide-1 (GLP-1) secretion, which may in turn mediate the marked inhibitory effects on dietary fat absorption.


Assuntos
Ácido Desoxicólico/farmacologia , Hiperlipidemias/tratamento farmacológico , Isoxazóis/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Período Pós-Prandial , Receptores Citoplasmáticos e Nucleares/agonistas , Animais , Ácidos e Sais Biliares/metabolismo , Ácidos e Sais Biliares/farmacologia , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , Exenatida/farmacologia , Esvaziamento Gástrico/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Insulina/sangue , Mucosa Intestinal , Intestinos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores Acoplados a Proteínas-G/agonistas , Ácido Taurocólico/farmacologia
19.
Acta Diabetol ; 57(7): 809-818, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32030508

RESUMO

AIMS: Lowering postprandial lipemia may mitigate cardiovascular risk in patients with diabetic dyslipidemia. This study was aimed to investigate whether saroglitazar suppresses postprandial lipemia in patients with diabetes and dyslipidemia. METHODS: This was a 12-week, prospective, multicenter, randomized, double-blinded, placebo-controlled study of saroglitazar in patients with diabetes and dyslipidemia. Thirty patients were randomized (1:1) to receive saroglitazar 4 mg or placebo orally once daily with metformin for 12 weeks. The primary endpoint was change in plasma triglyceride (TG) area under the curve (AUC) on a standardized 8-h fat tolerance test. RESULTS: Thirty participants were randomized for interventions and eventually data of 19 participants qualified for per protocol analyses. Mean (SD) age in saroglitazar was 53.1 (8.8) years and 54.9 (7.7) years in placebo group. After 12 weeks, saroglitazar significantly lowered postprandial TG-AUC by - 458.3 (144.0) (- 25.7%, 95% CI - 765.1 to - 151.4) versus an increase of + 10.9 (157.9) (+ 0.5%, 95% CI - 325.6 to 347.3) mg/dL h in placebo group (P < 0.05). Saroglitazar lowered postprandial TG incremental AUC versus placebo: - 329.4 (89.9) (- 59%) versus + 80.4 (99.4) (+ 10%) mg/dL h (P < 0.05). HbA1c (%) decreased by - 0.36 (0.42) in the saroglitazar group as compared to an increase of + 1.26 (0.46) (P < 0.05) with placebo. CONCLUSIONS: The saroglitazar treatment significantly improved postprandial TGs in people with diabetic dyslipidemia. TRIAL REGISTRATION: Clinical Trial Registry of India; trial Registration No.: CTRI/2015/06/005845 and Date of registration: June 02, 2015.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fenilpropionatos/uso terapêutico , Pirróis/uso terapêutico , Triglicerídeos/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Feminino , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/complicações , Índia , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , PPAR alfa/agonistas , PPAR gama/agonistas , Placebos , Período Pós-Prandial/efeitos dos fármacos
20.
Phytother Res ; 34(7): 1609-1618, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32026537

RESUMO

Diabetes mellitus is associated with increased levels of inflammation and oxidative stress in patients. The aim of the present study was to test the hypothesis that aqueous extract of Cichorium intybus seeds (AECIS) would have add-on beneficial effect in type 2 diabetes mellitus (T2DM). In this double-blind randomized clinical study, 150 subjects were enrolled to assess the add-on efficacy and safety of AECIS in T2DM patients. The subjects were randomized (1:1) to the AECIS (n = 51) and placebo (n = 49) groups. The subjects in both groups continued to take prescribed doses of metformin. The standardization of AECIS was carried out by liquid chromatography-mass spectrometry and phytochemical analysis. The mean hemoglobin A1c (HbA1c) level in the AECIS and placebo groups at baseline was 8.6% and 8.5%, respectively. Mean values of HbA1c at the end of 12 weeks of intervention were 7.42% in the AECIS group (a reduction of 1.18% from baseline) and 8.4% in the placebo group (mean reduction of 0.1% from baseline). Besides, significant reduction in inflammation, oxidative stress, and hypertriglyceridemia was seen in the AECIS group (p < .05). The study shows for the first time that AECIS supplementation ameliorates the disease progression and it is beneficial as a potential adjunct dietary supplement for the management of T2DM.


Assuntos
Chicória/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Sementes/química , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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