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1.
N Engl J Med ; 382(3): 244-255, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31893580

RESUMO

BACKGROUND: Lipoprotein(a) levels are genetically determined and, when elevated, are a risk factor for cardiovascular disease and aortic stenosis. There are no approved pharmacologic therapies to lower lipoprotein(a) levels. METHODS: We conducted a randomized, double-blind, placebo-controlled, dose-ranging trial involving 286 patients with established cardiovascular disease and screening lipoprotein(a) levels of at least 60 mg per deciliter (150 nmol per liter). Patients received the hepatocyte-directed antisense oligonucleotide AKCEA-APO(a)-LRx, referred to here as APO(a)-LRx (20, 40, or 60 mg every 4 weeks; 20 mg every 2 weeks; or 20 mg every week), or saline placebo subcutaneously for 6 to 12 months. The lipoprotein(a) level was measured with an isoform-independent assay. The primary end point was the percent change in lipoprotein(a) level from baseline to month 6 of exposure (week 25 in the groups that received monthly doses and week 27 in the groups that received more frequent doses). RESULTS: The median baseline lipoprotein(a) levels in the six groups ranged from 204.5 to 246.6 nmol per liter. Administration of APO(a)-LRx resulted in dose-dependent decreases in lipoprotein(a) levels, with mean percent decreases of 35% at a dose of 20 mg every 4 weeks, 56% at 40 mg every 4 weeks, 58% at 20 mg every 2 weeks, 72% at 60 mg every 4 weeks, and 80% at 20 mg every week, as compared with 6% with placebo (P values for the comparison with placebo ranged from 0.003 to <0.001). There were no significant differences between any APO(a)-LRx dose and placebo with respect to platelet counts, liver and renal measures, or influenza-like symptoms. The most common adverse events were injection-site reactions. CONCLUSIONS: APO(a)-LRx reduced lipoprotein(a) levels in a dose-dependent manner in patients who had elevated lipoprotein(a) levels and established cardiovascular disease. (Funded by Akcea Therapeutics; ClinicalTrials.gov number, NCT03070782.).


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Lipoproteína(a)/sangue , Oligonucleotídeos/administração & dosagem , Adulto , Idoso , Doenças Cardiovasculares/sangue , Colesterol/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipolipemiantes/efeitos adversos , Hipolipemiantes/uso terapêutico , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Oligonucleotídeos/efeitos adversos , Fatores de Risco
2.
Expert Opin Pharmacother ; 21(1): 107-120, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31738617

RESUMO

Introduction: Hypertriglyceridemia is associated with both the development of cardiovascular disease (CVD) when mild-to-moderate and high risk of pancreatitis when more severe. The residual CVD risk after low-density lipoprotein cholesterol (LDL-C) lowering is, in part, attributed to high triglyceride (TG) levels. Therefore, there appears to be a need for effective TG-lowering agents.Areas covered: This review presents the most recent advances in hypertriglyceridemia treatment; specifically, it discusses the results of clinical trials and critically comments on apolipoprotein C-III inhibitors, angiopoietin-like 3 inhibitors, alipogene tiparvovec, pradigastat, pemafibrate and novel formulations of omega-3 fatty acids.Expert opinion: In the era of extreme lowering of LDL-C levels with several agents, there seems to be space for novel therapeutic options to combat parameters responsible for residual CVD risk, among which are elevated TGs. Furthermore, a significant number of individuals have very high TG levels and encounter the risk of acute pancreatitis. The most recently developed TG-lowering drugs appear to have a role in both conditions; the choice is mainly based on baseline TG levels. Dyslipidemia guidelines are likely to change in the near future to include some of these agents. Of course, long-term data regarding their safety and efficacy in terms of CVD outcomes and pancreatitis are warranted.


Assuntos
Hipertrigliceridemia/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Doença Aguda , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Ácidos Graxos Ômega-3/uso terapêutico , Humanos , Pancreatite/prevenção & controle , Triglicerídeos/sangue
3.
J Agric Food Chem ; 68(1): 147-159, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31826616

RESUMO

This study was aimed at investigating the hypoglycemic and hypolipidemic effects of a polysaccharide (RTFP) isolated from Rosa roxburghii Tratt fruit on type-2 diabetic db/db mice. The results indicated that the oral administration of RTFP could significantly decrease the body weight, fat, and liver hypertrophy and the levels of fasting blood glucose, serum insulin, and serum lipids of the db/db mice. Histopathological observation showed that RTFP could effectively protect the pancreas, liver, and epididymal fat against damage and dysfunction. Real-time quantitative polymerase chain reaction analysis confirmed that the gene expression levels of peroxisome proliferator-activated receptors-γ (PPAR-γ), sterol regulatory element-binding protein-1 (SREBP-1c), acetyl-CoA carboxylase-1 (ACC-1), fatty acid synthase (FAS), and glucose-6-phosphatase (G6 Pase) were significantly down-regulated in the liver of db/db mice after treatment with RTFP. Moreover, RTFP treatment reversed gut dysbiosis by lowering the Firmicutes-to-Bacteroidetes ratio and enhancing the relative abundances of beneficial bacteria including Bacteroidaceae, Bacteroidaceae S24-7 group, and Lactobacillaceae. These findings suggest that RTFP can be used as a promising functional supplement for the prevention and treatment of type-2 diabetes mellitus.


Assuntos
Colo/microbiologia , Hiperglicemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipolipemiantes/administração & dosagem , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Rosa/química , Animais , Colo/metabolismo , Modelos Animais de Doenças , Frutas/química , Microbioma Gastrointestinal , Humanos , Hiperglicemia/metabolismo , Hiperglicemia/microbiologia , Hiperlipidemias/metabolismo , Hiperlipidemias/microbiologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Triglicerídeos/metabolismo
4.
J Sci Food Agric ; 100(5): 2007-2017, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31849068

RESUMO

BACKGROUND: Previous studies have shown that Lactobacillus plantarum LIP-1 (hereafter LIP-1) has an obvious hypolipidemic effect, and microencapsulated probiotics can ensure the strains live through the gastrointestinal tract. Although there has been much research on both preparation and assessment methods for probiotics microcapsules, most assessments were made in vitro and few were validated in vivo. In this study, the protective effect of microencapsulation and the possible hypolipidemic mechanisms of probiotic LIP-1 were evaluated in rats. Treatments included rats fed on a normal diet, a high-fat diet, and a high-fat diet with an intragastric supplement of either non-microencapsulated LIP-1 cells (NME LIP-1) or microencapsulated LIP-1 (ME LIP-1). Lipid metabolism indicators were measured during the experiment and following euthanasia. RESULTS: Microencapsulation increased survival and colonization of LIP-1 in the colon. ME LIP-1 was superior to NME LIP-1 in reducing cholesterol. The mechanisms behind the hypolipidemic effect exerted by LIP-1 are possibly due to promoting the excretion of cholesterol, improving antioxygenic potentials, enhancing recovery from the injury in the liver, cardiovascular intima and intestinal mucosa, promoting the generation of short-chain fatty acids, and improving lipid metabolism. CONCLUSIONS: This study confirms that microencapsulation provides effective protection of LIP-1 in the digestive system and the role of LIP-1 in the prevention and cure of hyperlipidaemia, providing theoretical support for probiotics to enter clinical applications. © 2019 Society of Chemical Industry.


Assuntos
Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Lactobacillus plantarum/metabolismo , Probióticos/administração & dosagem , Animais , Cápsulas/administração & dosagem , Dieta Hiperlipídica/efeitos adversos , Humanos , Hiperlipidemias/metabolismo , Lactobacillus plantarum/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar
5.
Expert Opin Investig Drugs ; 28(12): 1059-1079, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31752565

RESUMO

Introduction: Elevated triglyceride (TG) level is a prevalent condition in the general population and in patients with cardiovascular (CV) risk even under statin therapy. Severe hypertriglyceridemia (HTG) puts patients at risk for acute pancreatitis. Several TG-lowering drugs failed in clinical trials, but subgroup analyses suggest that high-risk patients, such as those with atherogenic dyslipidemia or diabetes, benefit from TG lowering.Areas covered: We review advances for TG-lowering drugs in clinical development. These include selective PPARα modulators, omega-3 fatty acid formulations that have been approved for severe HTG, and inhibitors of apolipoprotein C-III, angiopoietin-like-3 or microsomal transfer protein. Lessons learned from the success of the phase 3 trial REDUCE-IT with high-dose icosapent ethyl are also reviewed.Expert opinion: We believe that TG-lowering therapies are coming of age as they will allow to treat patients with high CV risk and moderate HTG, including T2D subjects, as well as patients with severe HTG or even homozygous familial hypercholesterolemia, all of which being 'optimally' treated with a statin. More studies on the impact of therapy on quality of life in patients with severe HTG should be conducted with the help of patient registries.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Hipertrigliceridemia/tratamento farmacológico , Hipolipemiantes/farmacologia , Animais , Doenças Cardiovasculares/etiologia , Desenvolvimento de Medicamentos , Drogas em Investigação/administração & dosagem , Drogas em Investigação/farmacologia , Humanos , Hipertrigliceridemia/complicações , Hipolipemiantes/administração & dosagem , Índice de Gravidade de Doença , Triglicerídeos/sangue
6.
BMC Complement Altern Med ; 19(1): 278, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640743

RESUMO

BACKGROUND: Recent epidemiological and experimental studies suggest that cadmium and diabetes-related hyperglycemia may act synergistically to worsen metabolic regulation. The present study aims to evaluate the potential effects of Enhydra fluctuans extract in diabetes and dyslipidemia in cadmium (CdCl2) induced- normal and type 2 diabetic model rats. METHOD: Forty-eight Long-Evans rats were divided equally into the following six groups: Normal Control (N-C), Normal treated with CdCl2 (N-Cd), Normal treated with plant extract (N-P), Normal treated with both plant extract and CdCl2 (N-PCd), Diabetic treated with plant extract (DM-P) and Diabetic treated with both plant extract and CdCl2 (DM-PCd). Blood glucose and other biochemical parameters were estimated by the enzymatic colorimetric method. Histological analysis of liver and heart was done by the hematoxylin-eosin (H & E) method. RESULTS: Twenty-one days treatment of E. fluctuans extracts at a dose of 200 mg/kg significantly reduced blood glucose level in N-PCd and DM-PCd (p < 0.05), and DM-P (p < 0.01) group. The plant extract had no direct effects on total blood lipids but, it had beneficial effects on TG/HDL-C ratio in N-P and DM-PCd groups (p < 0.05). Cd induction significantly reduced body weight [(N-Cd, N-PCd, DM-PCd) (p < 0.01)], and induced liver [N-Cd (p < 0.05), N-PCd, p < 0.001] and renal impairment [N-Cd (p < 0.05)]. In bi-variate association, a significant positive correlation between serum glucose and SGPT (p < 0.05) as well as SGPT and TG/HDL ratio (p = 0.019) was found in DM-P and in the merged group. The histology of liver and heart showed severe damages including inflammation, nuclear pyknosis, loss of myocardial fibers, necrosis and fibrosis in the Cd treated groups compared to plant treated groups. CONCLUSION: E. fluctuans seems to have potent antihyperglycemic effects in diabetes and Cd toxicity along with partial antidyslipidemic properties in euglycemic and diabetic rats. Our study suggests a novel oral antihyperglycemic agent in the present environmental context.


Assuntos
Asteraceae/química , Cádmio/toxicidade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipolipemiantes/administração & dosagem , Extratos Vegetais/administração & dosagem , Animais , Glicemia/metabolismo , Cádmio/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Masculino , Ratos , Ratos Long-Evans
7.
Medicina (Kaunas) ; 55(9)2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31505863

RESUMO

Background and Objectives: Dyslipidemia is gaining much attention among healthcare professionals because of its high association with the malfunctioning of a number of normal physiological and metabolic processes in the body. Obesity is directly interconnected with dyslipidemia and is said to be a denouement of hyperlipidemia and, if left untreated, may lead to intense damage to organs that are directly involved in fat metabolism. The objective of this study was to investigate the synergistic antiobesity and anti-hyperlipidemic activities along with hepato- and renoprotective potential of nanoemulsomes (NES) of lovastatin (LTN)-loaded ginger (GR) and garlic (GL) oils. Materials and Methods: LTN nanoemulsomes co-encapsulated with GR oil and GL oil were prepared by a thin hydration technique. Eight-week-old male Wistar rats weighing 200-250 g were induced with hyperlipidemia via a high-fat diet (HFD) comprising 40% beef tallow. Body weight, serum biochemical lipid parameters, and those for liver and kidney functions, serum TC, LDL-C, vLDL-C, HDL-C, TG, atherogenic index (AI), ALT, AFT, ALP, γ-GT, total protein (TP), serum albumin and globulin ratio (A/G), serum creatinine, blood urea nitrogen (BUN) and blood urea, and histopathology of hematoxylin and eosin (H&E) stained liver and kidney sections of all aforementioned groups were examined in the treated animals. Results: Nanoemulsomes of LTN-loaded GR and GL oils provided synergistic effects with LTN, exerted better ameliorative actions in reducing serum TC, LDL-C, vLDL-C, triglycerides, and AI, and improved serum HDL-C levels. Serum ALT, AST, ALP, and γ-GT levels were in the normal range for nanoemulsome groups. H&E stained liver and kidney sections of these animals confirmed better hepatoprotective and renoprotective effects than LTN alone. Serum biochemical parameters for renal functions also claimed to be in the moderate range for nanoemulsome-treated groups. Conclusion: This study demonstrated that nanoemulsomes of LTN-loaded GR and GL oils synergistically provided better antihyperlipidemic, hepatoprotective, and renoprotective effects as compared to LTN alone.


Assuntos
Fármacos Antiobesidade/farmacologia , Alho , Gengibre , Hipolipemiantes/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Lovastatina/farmacologia , Óleos Vegetais , Administração Oral , Animais , Fármacos Antiobesidade/administração & dosagem , Emulsões , Hiperlipidemias/complicações , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Nefropatias/etiologia , Nefropatias/prevenção & controle , Hepatopatias/etiologia , Hepatopatias/prevenção & controle , Lovastatina/administração & dosagem , Masculino , Nanoestruturas , Ratos , Ratos Wistar
8.
J Agric Food Chem ; 67(38): 10614-10623, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31483658

RESUMO

Type 2 diabetes (T2D) is a pandemic disease chiefly characterized by hyperglycemia. In this study, the combination of serum lipidomic and metabolomic approach was employed to investigate the effect of arabinoxylan on type 2 diabetic rats and identify the critical biomarkers of T2D. Metabolomics analysis revealed that branched-chain amino acids, 12α-hydroxylated bile acids, ketone bodies, and several short- and long-chain acylcarnitines were significantly increased in T2D, whereas lysophosphatidylcholines (LPCs) were significantly decreased. Lipidomics analysis indicated T2D-related dyslipidemia was mainly associated with the increased levels of acetylcarnitine, free fatty acids (FFA), diacylglycerols, triacylglycerols, and cholesteryl esters and the decreased levels of some unsaturated phosphatidylcholines (less than 22 carbons). These variations indicated the disturbed amino acid and lipid metabolism in T2D, and the accumulation of incompletely oxidized lipid species might eventually contribute to impaired insulin action and glucose homeostasis. Arabinoxylan treatment decreased the concentrations of 12α-hydroxylated bile acids, carnitines, and FFAs and increased the levels of LPCs. The improved bile acid and lipid metabolism by arabinoxylan might be involved in the alleviation of hypercholesterolemia and hyperlipidemia in T2D.


Assuntos
Anticolesterolemiantes/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipercolesterolemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipolipemiantes/administração & dosagem , Xilanos/administração & dosagem , Aminoácidos de Cadeia Ramificada/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , Carnitina/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Glucose/metabolismo , Humanos , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Metabolismo dos Lipídeos , Lipídeos/química , Metabolômica , Ratos
9.
J Oleo Sci ; 68(8): 781-792, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366855

RESUMO

The possibility of improving brain function coupled with its preferential uptake in the brain has garnered attention for docosahexaenoic acid-bound lysophosphatidylcholine (DHA-LPC). However, studies focusing on the health benefits of dietary DHA-LPC are lacking. We prepared a dietary oil rich in DHA-LPC (DHA-LPC rich oil) via enzymatic modification of phospholipids (PL) extracted from squid (Todarodes pacificus) meal and purification of active carbon, ion exchange resin, and silica gel. We then examined the effects of dietary DHA-LPC rich oil on male Wistar rats by evaluating serum and liver lipid profiles, fatty acid (FA) metabolizing enzyme activity, and the FA composition of serum and brain. The rats were fed a basal diet containing either soybean oil alone (7%) or soybean oil (4.5%) with DHA-LPC rich oil (2.5%) for 28 days, and then evaluated. The rats fed the diet containing DHA-LPC rich oil showed reduced triacylglycerol concentration due, in part, to the enhancement of carnitine palmitoyltransferase 2 and acyl-CoA oxidase activities and suppression of acetyl-CoA carboxylase and glucose-6-phosphate dehydrogenase activities in the liver. Moreover, the dietary DHA-LPC rich oil moderately increased DHA in the FA composition of the rat hippocampus, which may be due to elevated DHA composition in serum LPC. These results suggest that DHA-LPC rich oil has hypolipidemic effect and moderate increase in hippocampal DHA amount in normal rats.


Assuntos
Encéfalo/metabolismo , Gorduras Insaturadas na Dieta/farmacologia , Ácidos Docosa-Hexaenoicos/farmacologia , Hipolipemiantes/farmacologia , Fígado/metabolismo , Lisofosfatidilcolinas/farmacologia , Administração Oral , Animais , Química Encefálica , Hidrolases de Éster Carboxílico/química , Decapodiformes/química , Gorduras Insaturadas na Dieta/administração & dosagem , Ácidos Docosa-Hexaenoicos/administração & dosagem , Hipocampo/química , Hipocampo/metabolismo , Hipolipemiantes/administração & dosagem , Fígado/química , Lisofosfatidilcolinas/administração & dosagem , Masculino , Fosfolipídeos/química , Fosfolipídeos/isolamento & purificação , Ratos Wistar , Rhizopus/enzimologia
10.
Nutrients ; 11(9)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443489

RESUMO

Blood lipids are an important biomarker of cardiovascular health and disease. Among the lipid biomarkers that have been widely used to monitor and predict cardiovascular diseases (CVD), elevated LDL and low HDL cholesterol (C), as well as elevated triglyceride-rich lipoproteins, deserve special attention in their predictive abilities, and thus have been the targets of several therapeutic and dietary approaches to improving lipid profiles. Among natural foods and nutraceuticals, dietary berries are a rich source of nutrients, fiber, and various types of phytochemicals. Berries as whole fruits, juices, and purified extracts have been shown to lower total and LDL-C, and increase HDL-C in clinical studies in participants with elevated blood lipids, type 2 diabetes or metabolic syndrome. This short review aimed to further discuss the mechanisms and magnitude of the lipid-lowering effects of dietary berries, with emphasis on reported clinical studies. Based on the emerging evidence, colorful berry fruits may thus be included in a healthy diet for the prevention and management of CVD.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/dietoterapia , Suplementos Nutricionais , Sucos de Frutas e Vegetais , Frutas/química , Hiperlipidemias/dietoterapia , Hipolipemiantes/administração & dosagem , Lipídeos/sangue , Lipoproteínas/sangue , Síndrome Metabólica/dietoterapia , Compostos Fitoquímicos/administração & dosagem , Animais , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/diagnóstico , Hiperlipidemias/epidemiologia , Hipolipemiantes/isolamento & purificação , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Compostos Fitoquímicos/isolamento & purificação
11.
J Complement Integr Med ; 16(3)2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31318693

RESUMO

Background Antidiabetic activity of aqueous root extract of Strophanthus hispidus (SHP) was evaluated based on its folklore used in traditional medicine for the treatment of diabetes. Objectives: This study aimed to investigate the in-vitro and in-vivo antidiabetic potential of the aqueous root extract of SHP. Methods SHP (50, 100 and 200 mg/kg p.o.), glibenclamide (5 mg/kg p.o.), normal saline (10 mL/kg; diabetic control) and distilled water (10 mL/kg; normal control) were administered once daily for 28 days, with the measurement of fasting blood glucose level at 7 days interval. Blood samples were collected on day 28 for serum biochemical (albumin, total protein [TP], creatinine, alanine transaminase [ALT], aspartate transaminase [AST], alkaline phosphatase [ALP], triglycerides [TG], total cholesterol [TC], high-density lipoprotein [HDL], low-density lipoprotein [LDL], bilirubin and urea) and hematological assays. The in-vitro antidiabetic activity was investigated using α-amylase and α-glucosidase enzymes inhibitory assays. Results SHP produced a day-dependent reduction in glucose level. Peak reduction (82.94 %; p < 0.05) was produced at the dose of 100 mg/kg. SHP significantly (p < 0.05) increased the level of HDL and TP but significantly (p < 0.05) reduced the levels of TG, LDL, TC, AST, ALT, ALP, bilirubin, creatinine and urea compared with diabetic control rats. Furthermore, SHP significantly (p < 0.05) increased the level of catalase, superoxide dismutase and reduced glutathione compared to diabetic control rats. SHP significantly (p < 0.05) inhibited α-amylase and α-glucosidase enzymes compared with acarbose. Conclusion The findings in this study showed that SHP possesses beneficial antidiabetic activity.


Assuntos
Antioxidantes/administração & dosagem , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipolipemiantes/administração & dosagem , Extratos Vegetais/administração & dosagem , Strophanthus/química , Alanina Transaminase/genética , Alanina Transaminase/metabolismo , Animais , Antioxidantes/química , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Glicemia/metabolismo , Catalase/genética , Catalase/metabolismo , Diabetes Mellitus/metabolismo , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Hipoglicemiantes/química , Hipolipemiantes/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Extratos Vegetais/química , Raízes de Plantas/química , Ratos , Ratos Wistar , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , alfa-Amilases/genética , alfa-Amilases/metabolismo , alfa-Glucosidases/genética , alfa-Glucosidases/metabolismo
12.
Clin Investig Arterioscler ; 31(5): 203-209, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31320121

RESUMO

AIM: To describe the management of atherogenic dyslipidemia (AD) in routine clinical practice in the Primary Care (PC) setting in Spain. METHODS: Observational, descriptive, cross-sectional study based on a structured questionnaire designed for this study and addressed to PC physicians. The questionnaire content was based on a literature review and was validated by 3 experts in AD. RESULTS: A total of 1029 PC physicians participated in the study. 96.99% indicated that AD is determinant for cardiovascular risk, even if LDL-C levels are appropriate. 88.43% evaluated residual cardiovascular risk in their clinical practice, however, only 27.89% of them evaluated it in secondary prevention. Regarding diagnosis, 82.22% reported that TC, TG, HDL-C and non-HDL-C are essential measures when evaluating AD. Almost all physicians reported that they can request fractionated cholesterol to assess HDL-C and LDL-C, however 3.69% could not. Physicians (95.63%) considered that the first step in AD treatment should be diet, regular exercise, smoking cessation and pharmaceutical treatment, if necessary. 19.1% agreed partially or completely that gemfibrozil is the most suitable fibrate to associate with statins. 74.83% completely agreed that fenofibrate is the most suitable fibrate to combine with statins. CONCLUSIONS: Physicians have access to general Spanish guidelines and recommendations associated with AD management, however, it is necessary to continue rising awareness about the importance of early detection and optimal control of AD to reduce patients' cardiovascular risk.


Assuntos
Aterosclerose/terapia , Dislipidemias/terapia , Médicos de Atenção Primária/estatística & dados numéricos , Atenção Primária à Saúde/métodos , Aterosclerose/diagnóstico , Estudos Transversais , Dislipidemias/diagnóstico , Feminino , Fenofibrato/administração & dosagem , Genfibrozila/administração & dosagem , Pesquisas sobre Serviços de Saúde , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipolipemiantes/administração & dosagem , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde/estatística & dados numéricos , Espanha
13.
Food Funct ; 10(8): 4868-4876, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31334540

RESUMO

In this study, a polysaccharide was extracted from Physalis pubescens L. (named PP). Its antihyperglycemic and antihyperlipidemic activities were evaluated in STZ-induced diabetic mice. Results showed that PP was determined to be composed of rhamnose (Rha), arabinose (Ara), fucose (Fuc), xylose (Xyl), mannose (Man), glucose (Glc) and galactose (Gal) with molar percentages of 4.65%, 17.34%, 1.43%, 6.24%, 5.52%, 45.5%, and 19.31%, respectively. The average molecular weight (Mw) was found to be 20.0 kDa. It had a strong α-glucosidase inhibitory activity in vitro. PP treatment could enhance the oral glucose tolerance, and increase the levels of SOD, GSH, CAT, vitamin C, vitamin E, HDL-c, C-peptide, GCK and hepatic glycogen in diabetic mice. Besides, PP treatment could also decrease the levels of MDA, TG, TC, LDL-c, BUN and G-6-Pase. The regulating effects were stronger in high dose PP treatment than those in the low and medium dose treatments. In short, PP played an important role in protecting STZ-induced diabetic mice, and the effect was closely related to its activities in antioxidation and regulating glucose and lipid metabolism.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipolipemiantes/administração & dosagem , Physalis/química , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Animais , Glicemia/metabolismo , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/metabolismo , Teste de Tolerância a Glucose , Humanos , Hipoglicemiantes/química , Hipolipemiantes/química , Insulina/metabolismo , Metabolismo dos Lipídeos , Masculino , Camundongos , Extratos Vegetais/química , Polissacarídeos/química , Estreptozocina
14.
Nutrients ; 11(8)2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31349559

RESUMO

(1) Background: the composition of high-density lipoproteins (HDL) becomes altered during the postprandial state, probably affecting their functionality vis-à-vis the endothelium. Since acute coronary syndrome (ACS) in women is frequently associated with endothelial dysfunction, it is likely that HDL are unable to improve artery vasodilation in these patients. Therefore, we characterized HDL from women with ACS in fasting and postprandial conditions. We also determined whether microencapsulated pomegranate (MiPo) reverts the HDL abnormalities, since previous studies have suggested that this fruit improves HDL functionality. (2) Methods: Eleven women with a history of ACS were supplemented daily with 20 g of MiPo, for 30 days. Plasma samples were obtained during fasting and at different times, after a lipid load test to determine the lipid profile and paraoxonase-1 (PON1) activity. HDL were isolated by sequential ultracentrifugation to determine their size distribution and to assess their effect on endothelial function, by using an in vitro model of rat aorta rings. (3) Results: MiPo improved the lipid profile and increased PON1 activity, as previously reported, with fresh pomegranate juice. After supplementation with MiPo, the incremental area under the curve of triglycerides decreased to half of the initial values. The HDL distribution shifted from large HDL to intermediate and small-size particles during the postprandial period in the basal conditions, whereas such a shift was no longer observed after MiPo supplementation. Consistently, HDL isolated from postprandial plasma samples hindered the vasodilation of aorta rings, and this endothelial dysfunction was reverted after MiPo consumption. (4) Conclusions: MiPo exhibited the same beneficial effects on the lipid profile and PON1 activity as the previously reported fresh pomegranate. In addition, MiPo supplementation reverted the negative effects of HDL on endothelial function generated during the postprandial period in women with ACS.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Hipertrigliceridemia/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Lipoproteínas HDL/sangue , Extratos Vegetais/administração & dosagem , Período Pós-Prandial , Triglicerídeos/sangue , Vasodilatação/efeitos dos fármacos , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Administração Oral , Adulto , Animais , Arildialquilfosfatase/sangue , Biomarcadores/sangue , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Frutas , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/diagnóstico , Hipolipemiantes/efeitos adversos , Pessoa de Meia-Idade , Extratos Vegetais/efeitos adversos , Ratos Wistar , Fatores de Tempo , Resultado do Tratamento
15.
Lipids Health Dis ; 18(1): 157, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31351498

RESUMO

BACKGROUND: The hypolipidemic effect of phytosterols has been wildely recognized, but its application is limited due to its insolubility in water and low solubility in oil. In this study, ß-sitosterol ester with linoleic acids and ß-sitosterol self-microemulsions were prepared and their hypolipidemic effects on hyperlipidemia mice were studied. METHODS: Firstly, the mice were randomly divided into normal group and model group,they were fed with basic diet and high-fat diet for 70 days respectively. After high-fat model mice was successfully established, the model group was further divided into eight groups: HFD (high-fat diet feeding), SELA-TSO(8 ml/kg, SELA:700 mg/kg), TSO (8 ml/kg), SSSM (8 ml/kg,SS:700 mg/kg), NLSM (8 ml/kg), SSHT-TSO (8 ml/kg, SS: 700 mg/kg) and SS-TSO (8 ml/kg, SS: 700 mg/kg) groups, and treated with ß-sitosterol ester with linoleic acid, ß-sitosterol self-microemulsion, commercial ß-sitosterol health tablets and ß-sitosterol powder for 35 days, respectively, and blank control groups were established. At the end of the treatment period, the blood lipid level, tissues, cholesterol and lipids in feces of mice in each group were investigated. Statistical and analytical data with SPSS 17.0 Software,statistical significance was set at p* < 0.05 and p** < 0.01 levels . RESULTS: The order of lowering blood lipid effect is listed as: SSSM> SELA-TSO > SSHT-TSO > SS-TSO, which shows that ß-sitosterolself-microemulsion have the highest treatment effect among the experimental groups. CONCLUSIONS: In this study, a new formulation of ß-sitosterol was developed, and its hypolipidemic effect was investigated. The results showed that ß-sitosterol self-microemulsion has a good blood lipid lowering effect.


Assuntos
Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Ácido Linoleico/farmacologia , Sitosteroides/farmacologia , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Emulsões/administração & dosagem , Emulsões/química , Emulsões/farmacologia , Fezes/química , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Hipolipemiantes/administração & dosagem , Hipolipemiantes/química , Ácido Linoleico/administração & dosagem , Ácido Linoleico/química , Lipídeos/sangue , Masculino , Camundongos , Microscopia Eletrônica de Transmissão , Tamanho do Órgão/efeitos dos fármacos , Sitosteroides/administração & dosagem , Sitosteroides/química , Comprimidos/administração & dosagem , Comprimidos/farmacologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-31233943

RESUMO

In the present study, a simple and efficient method based on orthogonal experimental design and macroporous resin chromatography was established for the first time for enrichment of polymethoxyflavones (PMFs) from the peels of Citrus reticulata 'Chachi' (CRC). The optimum conditions of extraction and enrichment process were as follows: use of a liquid to solid ratio of 1 to 14, two-hour extraction time repeated twice with 70% ethanol; use of HPD-450 macroporous resin, wash solvent of purified water and 25% aqueous ethanol, and 70% aqueous ethanol as desorption solvent. The purity of PMFs in the resulting extract reached 62.26%. Our data indicate that the PMFs purified could potently alleviate high-fat diet-induced hyperlipidaemia. The PMFs were nontoxic as determined by acute toxicity test. The method established was suitable for large-scale separation of PMFs from CRC peels and the PMFs might be developed as an anti-hyperlipidaemia agent or dietary supplement.


Assuntos
Cromatografia/métodos , Citrus/química , Flavonas/isolamento & purificação , Hipolipemiantes/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Animais , Feminino , Flavonas/administração & dosagem , Flavonas/química , Frutas/química , Humanos , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Hipolipemiantes/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química
17.
AAPS PharmSciTech ; 20(6): 234, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31236817

RESUMO

The objective of this study is to explore the surface wettability modulated by a surfactant and its effects on the drug release and absorption of fenofibrate solid dispersions (FF SDs). Both the polyvinylpyrrolidone/sodium lauryl sulfate (PVP/SLS) coprecipitate and FF SDs were prepared by solvent evaporation method. The contact angle of PVP/SLS coprecipitate with various PVP/SLS weight ratios was determined to screen out the suitable content of SLS incorporated in FF SDs. Scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) was used to analyze the surface composition of the PVP/SLS coprecipitate, suggesting that SLS molecules were prone to concentrate on the carrier surface. The physicochemical characteristics of FF, PVP, SLS, FF SDs, and FF physical mixtures (PMs) were evaluated by thermal analysis, XRD, FTIR, and SEM, which revealed that FF was molecularly dispersed in SDs. The interaction between SLS and PVP or FF confirmed by FTIR would affect the surface morphology of SDs. Finally, the contact angle of FF SDs was measured to explore the effects of surface wettability on the dissolution behavior and drug absorption of FF SDs. The interesting thing is that the wettability of the PVP/SLS coprecipitate was positively related to that of FF SDs. The improved wettability of FF SDs or the PVP/SLS coprecipitate by adding SLS contributed to the slight enhancement of initial drug release and absorption, which implied that wettability would be a promising tool in the formulation studies.


Assuntos
Fenofibrato/administração & dosagem , Hipolipemiantes/administração & dosagem , Tensoativos/química , Molhabilidade , Animais , Liberação Controlada de Fármacos , Masculino , Microscopia Eletrônica de Varredura , Povidona/química , Ratos , Ratos Sprague-Dawley , Dodecilsulfato de Sódio/química , Espectrometria por Raios X , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície
18.
J Med Food ; 22(9): 919-927, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31233372

RESUMO

Echinodorus grandiflorus is an important medicinal plant species that is native to South America. Despite extensive popular usage as a hypolipidemic drug, its effects as an atheroprotective agent remain unknown. The aim of this study was to evaluate the effects of an ethanol-soluble fraction that was obtained from E. grandiflorus (ESEG) leaves against the development of atherosclerosis in rabbits. Male rabbits received a diet that was supplemented with 1% cholesterol (cholesterol-rich diet [CRD]) for 60 days. After 30 days of the CRD, the animals were divided into five groups (n = 6) and treated with ESEG (10, 30, and 100 mg/kg), simvastatin (2.5 mg/kg), or vehicle once daily for 30 days. The negative control group was fed a cholesterol-free diet and treated orally with vehicle. At the end of 60 days, serum lipids, oxidized low-density lipoprotein, thiobarbituric acid reactive substances, nitrotyrosine, and serum interleukin 1 beta (IL-1ß), IL-6, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were determined. Samples from the aortic arch and thoracic segment were also collected to investigate the tissue antioxidant defense system and perform histopathological analysis. Oral ESEG administration significantly reduced serum lipid levels in CRD-fed rabbits. This treatment also modulated the arterial antioxidant defense system by reducing lipid and protein oxidation. Similarly, serum IL-1ß, IL-6, sICAM-1, and sVCAM-1 levels significantly decreased, accompanied by a reduction of atherosclerotic lesions in all arterial branches. These findings suggest that ESEG may be a new herbal medicine that can be directly applied for the treatment and prevention of atherosclerotic disease.


Assuntos
Alismataceae/química , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Aterosclerose/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Aterosclerose/sangue , Aterosclerose/genética , Colesterol/sangue , Humanos , Hipolipemiantes/administração & dosagem , Interleucina-1beta/sangue , Interleucina-1beta/genética , Lipoproteínas LDL/sangue , Masculino , Folhas de Planta/química , Coelhos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Molécula 1 de Adesão de Célula Vascular/sangue , Molécula 1 de Adesão de Célula Vascular/genética
19.
Clín. investig. arterioscler. (Ed. impr.) ; 31(3): 93-100, mayo-jun. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-182702

RESUMO

Introducción y objetivos: El adecuado control lipídico tras un síndrome coronario agudo (SCA) es una estrategia de prevención secundaria crucial para disminuir el riesgo de reinfarto y muerte cardiovascular. Existen tablas que predicen la dosificación necesaria del tratamiento hipolipidemiante según el colesterol LDL (cLDL) inicial pero no han sido probadas en el SCA. Analizamos los factores asociados al control del cLDL tras un SCA y la utilidad de las tablas de Masana y Plana en este contexto. Métodos: Entre enero de 2015 y mayo de 2016 se incluyeron 326 pacientes con SCA. Se registraron las concentraciones basales de cLDL y el tratamiento hipolipidemiante al alta. Se analizaron las variables asociadas a un adecuado control del cLDL (< 70 mg/dL) en el seguimiento. Resultados: La edad media fue 66 ± 13 años, el 72% varones. El tratamiento hipolipidemiante al alta se ajustó a las recomendaciones de Masana en 196 (60%) pacientes. Tras 122 [66-184] días, en 148 (45%) se alcanzó el objetivo de cLDL, siendo este porcentaje mayor (109/196 -56%- vs. 39/130 -30%- pacientes) cuando el tratamiento fue planificado según las tablas de Masana y Plana (p < 0,001). En el análisis multivariante, el género masculino (p < 0,001), la ausencia de dislipidemia previa (p < 0,001) y la aplicación de las tablas de Masana y Plana (p = 0,007) fueron predictores independientes para alcanzar el cLDL objetivo. Conclusiones: El control lipídico adecuado tras un SCA se alcanza en menos de la mitad de casos. La dosificación de la terapia hipolipidemiante según las tablas de Masanay Plana mejora la consecución de este crucial objetivo terapéutico


Introduction and objectives: Adequate LDL cholesterol (LDLc) control after an acute coronary syndrome (ACS) is a crucial secondary prevention strategy to minimize the incidence of recurrent myocardial infarction and cardiovascular death. There are tables that predict the necessary dosage of lipid-lowering treatment from the initial LDLc but have not been tested in ACS. Variables associated with optimal LDLc after an ACS were analyzed and the therapeutic yield of the use of Masana's recommendations in this setting. Methods: A total number of 326 ACS-patients were included between January-2015 and May-2016. Baseline LDLc concentration and prescribed hypolipemiant treatment at hospital discharge were registered. We analyzed the variables associated with optimal LDLc levels (< 70 mg/dL) control during follow-up. Results: Among our patient population (72% male, age 66 ± 13 years), the hypolipemiant treatment at hospital discharge fulfilled the Masana's recommendations in 196 (60%) patients. After a follow-up period of 122 [66-184] days the targeted LDLc levels were achieved in 148 (45%) patients, being this percentage greater among those in whom the Masana's recommendations were fulfilled (109/196, 56%), as compared with the remaining (39/130, 30%; P < .001). The male gender (P < .001), the absence of prior history of dyslipemia (P < .001) and the adherence to Masana's recommendations (P = .007) were independent predictors for the achievement of targeted LDLc levels during follow-up. Conclusions: In less than half of ACS-patients adequate mid-term LDLc control is obtained. The dosage of the lipid-lowering therapy according to Masana's recommendations helps to achieve this important therapeutic goal


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , LDL-Colesterol/efeitos dos fármacos , Síndrome Coronariana Aguda/complicações , Prevenção Secundária , Fatores de Risco , Metabolismo dos Lipídeos/efeitos dos fármacos , LDL-Colesterol/metabolismo , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/prevenção & controle , Hipolipemiantes/administração & dosagem , Dislipidemias , Análise Multivariada , Lipídeos/sangue
20.
Breast Cancer Res Treat ; 176(3): 669-677, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31087198

RESUMO

INTRODUCTION: The use of statins has been associated with improved survival in patients with breast cancer in several studies but results have been mixed. This study evaluates the impact of duration of statin use on breast cancer patient outcomes. METHODS: This is a single-institution, retrospective cohort, examining the impact of statin use on the outcomes of 1523 women diagnosed with operable breast cancer between1995 and 2015. Clinical variables were compared using Student's t test, Fisher's exact and Chi square tests. Overall (OS) and disease-free (DFS) survival were performed using Kaplan-Meier and Cox-Proportional Hazard (Cox-PH) analysis in the statistical software R. RESULTS: Patients were grouped by duration of statin use: never-statin user [N] (n = 1092), short (< 3 years) [S] (n = 115), moderate [M] (3-5 years) (n = 109) and long [L] (> 5 years) (n = 207) term. Over a median follow-up of 70.2 months, 138 women died (84 died of breast cancer) and 125 had disease recurrence. On multivariable Cox-PH analysis adjusting for clinical variables including metabolic comorbidities using the Charlson comorbidity index, OS in the [S] and [M] subgroups did not differ [N], while OS was improved in [L] (adjusted hazard ratio (AHR) 0.38, confidence interval (CI) 0.17-0.85, p < 0.018). DFS was also significantly improved in the [L] subgroup (adjusted HR 0.15, CI 0.05-0.48, p < 0.001). Subanalysis stratified by receptor status showed a trend towards improved DFS in all tumor subtypes including triple-negative breast cancer. CONCLUSIONS: Our retrospective analyses suggest that long-term statin use (> 5 years) was associated with improved OS and DFS in women with breast cancer regardless of receptor subtype, even after adjusting for metabolic comorbidities.


Assuntos
Neoplasias da Mama/epidemiologia , Hipolipemiantes/administração & dosagem , Idoso , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Comorbidade , Feminino , Seguimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Avaliação de Resultados da Assistência ao Paciente , Vigilância em Saúde Pública , Fatores de Tempo
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