RESUMO
Lactobacilli probiotics have been suggested to reduce cholesterol with low side effects to host. Bacteriocins and exopolysaccharides (EPSs) production are two meaningful examples of functional applications of lactobacilli in the food industry. Eight Lactobacillus strains were isolated from some Egyptian fermented food and tested for their probiotic properties. Analysis of the monosaccharide composition by thin layer chromatography showed the presence of glucose, galactose and unknown sugar. The main functional groups of EPSs were elucidated by Fourier-Transform Infrared Spectroscopy. Their fermentation cultures displayed powerful antioxidant activities extending from 97.5 to 99%, 40-75% for their EPSs and free cells, respectively, and exhibited in vitro cholesterol downgrading from 48 to 82% and 72 to 91% after 48 and 120 h, respectively. Their EPSs showed good anticancer activities against carcinoma cells with low IC50 values for HCT-116, PC-3 and HepG-2 cells. To the best of our knowledge, there have been no previous reports on the potential of Lactobacillus EPSs activity against PC-3. The selected strains, L. plantarum KU985433 and L. rhamnosus KU985436 produced two different bacteriocins as detected by gel permeation chromatography with good antimicrobial activities. In vivo study demonstrated that feeding Westar rats with fermented milk exhibited greater cholesterol, LDL and blood triglyceride reduction for both strains. Whereas, HDL was increased by about 43 and 38%, respectively, and the atherogenic indices decreased.
Assuntos
Anticolesterolemiantes/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Hipercolesterolemia/terapia , Polissacarídeos Bacterianos/farmacologia , Probióticos/farmacologia , Animais , Anticolesterolemiantes/isolamento & purificação , Antineoplásicos/isolamento & purificação , Antioxidantes/isolamento & purificação , Bacteriocinas , Sobrevivência Celular/efeitos dos fármacos , HDL-Colesterol/agonistas , HDL-Colesterol/metabolismo , LDL-Colesterol/antagonistas & inibidores , LDL-Colesterol/metabolismo , Modelos Animais de Doenças , Egito , Alimentos Fermentados/microbiologia , Células HCT116 , Células Hep G2 , Humanos , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patologia , Lactobacillus plantarum/química , Lactobacillus plantarum/metabolismo , Lacticaseibacillus rhamnosus/química , Lacticaseibacillus rhamnosus/metabolismo , Masculino , Células PC-3 , Polissacarídeos Bacterianos/isolamento & purificação , Probióticos/isolamento & purificação , Ratos , Ratos Wistar , Triglicerídeos/antagonistas & inibidores , Triglicerídeos/metabolismoRESUMO
Acquisition costs and cost-effectiveness have limited access and recommendations to use proprotein convertase subtilisin/kexin type 9 (PCSK9)-inhibiting monoclonal antibodies (mAbs). Recently, prices were reduced by 60% for alirocumab and evolocumab. This statement systematically reviewed subgroup analyses from statin and PCSK9 mAb trials to identify higher risk groups for which PCSK9 mAbs at the new price could be considered a reasonable (Assuntos
Anticorpos Monoclonais/uso terapêutico
, Doenças Cardiovasculares/tratamento farmacológico
, Pró-Proteína Convertase 9/imunologia
, Anticorpos Monoclonais/economia
, Anticorpos Monoclonais Humanizados/uso terapêutico
, Doenças Cardiovasculares/complicações
, Doenças Cardiovasculares/patologia
, Doenças Cardiovasculares/prevenção & controle
, LDL-Colesterol/sangue
, Análise Custo-Benefício
, Humanos
, Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico
, Hipercolesterolemia/complicações
, Hipercolesterolemia/tratamento farmacológico
, Hipercolesterolemia/patologia
, Hiperlipoproteinemia Tipo II/complicações
, Hiperlipoproteinemia Tipo II/tratamento farmacológico
, Hiperlipoproteinemia Tipo II/patologia
, Pró-Proteína Convertase 9/genética
, Qualidade de Vida
, Fatores de Risco
, Índice de Gravidade de Doença
, Sociedades Científicas
RESUMO
BACKGROUND: High blood lipoprotein concentrations are one of the major risk factors for cardiovascular diseases. Drug therapy is the base of treatment; statins in particular. Both brand-name and generic presentations are available for statin therapy of high cholesterol levels. Factors that may influence their use in routine medical practice include, among others, patient persistence and adherence to treatment as prescribed by physicians. The aim of this retrospective analysis was to provide real-world evidence of treatment persistence and adherence and their consequences on economic and patient outcomes of generic versus brand-name statins routinely used to treat high cholesterol levels in Spain. METHODS: Existing real-world electronic medical records abstracted from a database of two regions in Spain were analyzed. The analysis compared generic versus brand-name statins data from subjects' who started treatment between July 1, 2010 and June 30, 2012. Treatment persistence, adherence expressed as medication possession ratio (MPR), healthcare resource utilization and their costs were analyzed together with patient's at-goal rates of low-density-lipoprotein-cholesterol (LDL-c), incidence of any major cardiovascular event (CVE) and all-cause mortality during a 5-year follow-up period. Multivariate analyses were applied. RESULTS: A total of 13,244 records were included. Persistence was lower with generics; adjusted hazard ratio -HR- [95% confidence interval]: 0.86 [0.82-0.91], p < 0.001) and MPR was also lower: 61.5% vs. 65.1% (p < 0.001). Less patients with generics reached their LDL-c goal: 39.2% [38.3-40.2%] vs. 42.0% [40.2-43.7%]; adjusted odds ratio; 0.87 [0.80-0.95], p = 0.003. Compared to brand-name statins, the observed probability of occurrence of a CVE; HR: 1.31 [1.15-1.50], p < 0.001, and also all-cause deaths; HR: 1.36 [1.15-1.62], was significantly higher with generics; p < 0.001 in both cases. Adjusted mean total healthcare cost per patient was also higher with generic than with brand-name statins: 9118 (9059-9176) vs. 7980 (7853-8808) [adjusted difference: 1137 (997-1277), p < 0.001]. CONCLUSION: This retrospective cost-consequences analysis found poorer treatment persistence and adherence in patients who first started therapy with generic instead of brand-name statins in routine medical practice in Spain. Also, patients receiving generics were more unlikely to reach LDL-c goals, showed increased probability of having CVE and all-cause mortality at a higher cost to payers.
Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Medicamentos Genéricos/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipercolesterolemia/tratamento farmacológico , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , LDL-Colesterol/sangue , Estudos de Coortes , Medicamentos Genéricos/uso terapêutico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/sangue , Hipercolesterolemia/epidemiologia , Hipercolesterolemia/patologia , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha/epidemiologiaRESUMO
OBJECTIVE: The fatty acid profile of dietary fats may contribute to its channelling toward oxidation versus storage, influencing energy and weight balance. Our objective was to compare the effects of diets enriched with high-oleic canola oil (HOCO), alone or blended with flaxseed oil (FXCO), on energy expenditure, substrate utilization, and body composition versus a typical Western diet (WD). MATERIALS/METHODS: Using a randomized crossover design, 34 hypercholesterolemic subjects (n=22 females) consumed 3 controlled diets for 28 days containing ~49% energy from carbohydrate, 14% energy from protein, and 37% energy from fat, of which 70% of fat was provided by HOCO rich in oleic acid, FXCO rich in alpha-linolenic acid, or WD rich in saturated fat. Indirect calorimetry measured energy expenditure and substrate oxidation. Body composition was analyzed by dual-energy x-ray absorptiometry. RESULT: After 28 days, resting and postprandial energy expenditure and substrate oxidation were not different after consumption of the HOCO or FXCO diets compared with a typical Western diet. No significant changes in body composition measures were observed between diets. However, the android-to-gynoid ratio tended to increase (P=.055) after the FXCO diet compared with the HOCO diet. CONCLUSIONS: The data suggest that substituting a typical Western dietary fatty acid profile with HOCO or FXCO does not significantly modulate energy expenditure, substrate oxidation or body composition in hypercholesterolemic males and females.
Assuntos
Composição Corporal , Gorduras na Dieta/administração & dosagem , Metabolismo Energético , Ácidos Graxos Monoinsaturados/administração & dosagem , Hipercolesterolemia/metabolismo , Óleo de Semente do Linho/administração & dosagem , Ácido Oleico/administração & dosagem , Absorciometria de Fóton , Calorimetria Indireta , Estudos Cross-Over , Gorduras na Dieta/análise , Ácidos Graxos Monoinsaturados/química , Feminino , Humanos , Hipercolesterolemia/patologia , Óleo de Semente do Linho/química , Masculino , Ácido Oleico/análise , Oxirredução , Óleo de Brassica napus , Método Simples-CegoRESUMO
AIM: The present study examined the association between the radial augmentation index (AI), a marker of arterial wave reflection, and the MEGA risk prediction score (MEGA score), an indicator of coronary heart disease (CHD) risk, in middle-aged men with mild to moderate hypercholesterolemia. METHODS: Radial AI was measured during a company health examination in 266 men (age: 47+/-5 years) with total cholesterol levels ranging 220-270 mg/dL who were not taking antihypertensive, lipid-lowering, or antidiabetic agents. The MEGA score was calculated based on sex, age, low- and high-density lipoprotein cholesterol, blood pressure, glucose level, and smoking status. The higher MEGA score indicates increased CHD risk. A MEGA score > or = 22 corresponds to a 5-year CHD risk > or = 2.5% and we defined a MEGA score > or = 22 as a high estimated CHD risk. RESULTS: The mean AI was 74.4+/-12.6%. A high estimated CHD risk was seen in 32 subjects (12.0%). After adjusting for height and heart rate, the AI was higher in subjects with a high estimated CHD risk (81.5+/-10.6%) than in those without (73.4+/-10.4%, p<0.001). The odds ratio for high estimated CHD risk in the highest tertile of AI was 8.14 (p=0.002) in comparison to the lowest tertile, after adjusting for multiple potential confounders which did not constitute the MEGA score. CONCLUSION: The radial AI was positively associated with the estimated risk of CHD. These results suggest the usefulness of radial AI as a risk marker for future onset of CHD in middle-aged men with mild to moderate hypercholesterolemia.
Assuntos
Doença das Coronárias/diagnóstico , Indicadores Básicos de Saúde , Hipercolesterolemia/complicações , Artéria Radial/patologia , Adulto , Fatores Etários , Pressão Sanguínea , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Doença das Coronárias/etiologia , Doença das Coronárias/patologia , Frequência Cardíaca , Humanos , Hipercolesterolemia/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Triglicerídeos/metabolismoRESUMO
Animal models facilitate our understanding of human disease by providing a controlled environment permitting testing of mechanisms of disease, diagnostic technologies and therapeutic interventions. The ideal animal model should display coronary lesions resembling those seen in human atherosclerosis. No suitable large animal model of high-risk (vulnerable) plaque exists. Lack of such a model has hampered studies designed to validate imaging technologies and to scrutinise the effects of therapeutic interventions in atherosclerotic arteries. Several porcine models of advanced human-like coronary atherosclerosis exist. In this review some of the most promising porcine models are discussed, focusing on their applicability in the development and validation of coronary imaging technologies and interventional devices. In the evolving era of technological development, the availability and use of such animal models of advanced human-like coronary atherosclerosis and vulnerable plaque will become critically important in the preclinical testing of emerging technologies in interventional cardiology.
Assuntos
Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/terapia , Diagnóstico por Imagem , Modelos Animais de Doenças , Revascularização Miocárdica , Suínos , Animais , Cateterismo/efeitos adversos , Doença da Artéria Coronariana/etiologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Diagnóstico por Imagem/métodos , Progressão da Doença , Humanos , Hipercolesterolemia/complicações , Hipercolesterolemia/genética , Hipercolesterolemia/patologia , Revascularização Miocárdica/métodos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Especificidade da Espécie , Porco Miniatura , Resultado do TratamentoRESUMO
Ezetimibe belongs to a group of selective and very effective 2-azetidione cholesterol absorption inhibitors that act on the level of cholesterol entry into enterocytes. A rapid, specific reversed-phase HPLC method has been developed for assaying ezetimibe in pharmaceutical dosage forms. The assay involved an isocratic elution of ezetimibe in a Kromasil 100 C18 column using a mobile phase composition of water (pH 6.8, 0.05%, w/v 1-heptane sulfonic acid) and acetonitrile (30:70, v/v). The flow rate was 0.5 ml/min and the analyte monitored at 232 nm. The assay method was found to be linear from 0.5 to 50 microg/ml. All the validation parameters were within the acceptance range. The developed method was successfully applied to estimate the amount of ezetimibe in tablets.
Assuntos
Anticolesterolemiantes/análise , Anticolesterolemiantes/química , Azetidinas/análise , Azetidinas/química , Química Farmacêutica/métodos , Cromatografia Líquida de Alta Pressão/métodos , Indústria Farmacêutica/métodos , Acetonitrilas/química , Calibragem , Relação Dose-Resposta a Droga , Estabilidade de Medicamentos , Enterócitos/metabolismo , Ezetimiba , Heptanos/química , Concentração de Íons de Hidrogênio , Hipercolesterolemia/patologia , Modelos Químicos , Preparações Farmacêuticas/análise , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrofotometria Ultravioleta , Ácidos Sulfônicos/química , Comprimidos , Temperatura , Fatores de Tempo , Raios UltravioletaRESUMO
A obesidade e a hipercolesterolemia sao problemas de saude publica no primeiro mundo e nos paises desenvolvidos. O ginecologista e o profissional que tem contato com esta adolescente e pode orienta-la...