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1.
Isr Med Assoc J ; 24(11): 719-726, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36436038

RESUMO

BACKGROUND: Statin-induced myalgia is defined as muscle pain without elevation of serum creatine phosphokinase levels and is a well-known complaint among statin users. Chronic pain syndromes affect a high percentage of the population. These pain syndromes may confound the reports of statin-induced myalgia. OBJECTIVES: To compare the occurrence of chronic pain among patients on statin therapy who developed myalgia with those who did not. METHODS: This study included 112 statin-treated patients, who were followed at the lipid center at Sheba Medical Center. Fifty-six patients had a diagnosis of statin-associated muscle symptoms (SAMS) and 56 did not. Verified questionnaires were used to assess the diagnoses of fibromyalgia, pain intensity, functional impairment, anxiety, and depression in the study population. RESULTS: Patients with statin myalgia were more likely to fulfil the diagnostic criteria for fibromyalgia than patients without statin myalgia (11 [19.6%] vs. 0, respectively). Patients in the SAMS group exhibited higher levels of anxiety and depression compared with the control group. Female sex, higher scores on the Brief Pain Inventory pain intensity scale, and a Hamilton rating scale level indicative of an anxiety disorder were found to be significant predictors for fibromyalgia in patients presenting with statin myalgia. CONCLUSIONS: A significant percentage of patients diagnosed with statin myalgia fulfilled the diagnostic criteria for fibromyalgia depression or anxiety disorder. Detection of these patients and treatment of their primary pain disorders or psychiatric illnesses has the potential to prevent unnecessary cessation of effective statin therapy.


Assuntos
Dor Crônica , Fibromialgia , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Feminino , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Mialgia/induzido quimicamente , Mialgia/epidemiologia , Mialgia/diagnóstico , Dor Crônica/tratamento farmacológico , Fibromialgia/induzido quimicamente , Fibromialgia/diagnóstico , Fibromialgia/tratamento farmacológico , Síndrome , Músculos
2.
Curr Atheroscler Rep ; 23(6): 30, 2021 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-33963467

RESUMO

PURPOSE OF REVIEW: To elucidate the current approach of care in pediatric patients with familial hypercholesterolemia (FH). We sought an answer to the question whether the advances and major changes in lipid management are relevant and apply to children and adolescents. RECENT FINDINGS: Latest research findings clearly demonstrate that lowering cholesterol levels at a young age prevents vascular atherosclerotic changes and decreases cardiovascular events in adulthood and emphasizes the importance of early detection and intervention in the pediatric FH patients group. FH is a common genetic disease caused by mutations in genes associated with the metabolism of low-density lipoproteins (LDL). The hallmark of FH is elevated LDL cholesterol (LDL-C) levels from birth and premature atherosclerotic cardiovascular disease (ASCVD). Often FH is either undiagnosed or diagnosed with a considerable delay, leading to vascular atherosclerotic changes and cardiovascular disease. Prompt identification of FH subjects is essential, to initiate early preventive measures. Safe and efficient pharmacological agents are approved for use in children and adolescents. Statins are the first line of therapy, in combination of ezetimibe. Unfortunately, these drugs do not warrant the achievement of therapeutic target, especially in HoFH patient. In the latter, lipoprotein apheresis (LA), which has been shown to be safe and effective, is strongly recommended. Finally, the new drugs still under study will allow a multimodal customized treatment. Lowering cholesterol levels at a young age hinders vascular atherosclerotic changes decreasing cardiovascular events in adulthood. Therefore, early detection, diagnosis, and intervention in FH patients are priority objectives.


Assuntos
Anticolesterolemiantes , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipoproteinemia Tipo II , Adolescente , Adulto , Anticolesterolemiantes/uso terapêutico , Criança , Ezetimiba , Heterozigoto , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/epidemiologia
3.
Harefuah ; 160(3): 170-174, 2021 Mar.
Artigo em Hebraico | MEDLINE | ID: mdl-33749180

RESUMO

INTRODUCTION: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder caused by mutations affecting the function of the LDL receptor. In the Israeli population, the carrier heterozygote state is quite common, with the prevalence of 1:250, and the estimated prevalence of homozygote (hoFH) patients is 1:500,000. The life span of untreated hoFH patients is significantly shortened due to premature atherosclerosis and cardiovascular mortality. The basis of the appropriate treatment for hoFH is aggressive lipid lowering therapy from an early age and therefore, our approach is intensive LDL-C lowering as soon as the diagnosis is made. We recommend referring patients with hoFH to lipid-specialist clinics .We recommend genetic evaluation to confirm the diagnosis and cascade screening of family members for heterozygosity. Lipid goals are as recommended by the European Atherosclerosis Society. Aggressive and low as possible LDL-C targets (at least 50% reduction) are recommended. The initial treatment is high-dose potent statin and additional ezetimibe10 mg daily. PCSK9 inhibitor - Evolocumab is a novel additional option for hoFH with residual LDL receptor activity. The most effective method of reduction of plasma LDL levels is LDL-C apheresis. Lomitapide is a microsomal triglyceride transfer protein (MTP) inhibitor that should be added to reduce the frequency of the apheresis procedures.


Assuntos
Anticolesterolemiantes , Aterosclerose , Hiperlipoproteinemia Tipo II , Aterosclerose/genética , Aterosclerose/terapia , LDL-Colesterol , Homozigoto , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/terapia , Pró-Proteína Convertase 9
4.
Harefuah ; 160(1): 38-44, 2021 01.
Artigo em Hebraico | MEDLINE | ID: mdl-33474877

RESUMO

INTRODUCTION: Despite the impressive decline in mortality from atherosclerotic cardiovascular diseases (ASCVD), these diseases still account for a large proportion of the overall morbidity and mortality worldwide. A vast amount of research has demonstrated the key role played by circulating lipoproteins, and especially low-density lipoprotein (LDL), in the etiology of atherosclerosis, and numerous studies have proven the efficacy of interventions that lower the atherogenic lipoproteins in reducing morbidity and mortality from ASCVD. While previous guidelines placed an emphasis on the use HMG-CoA reductase inhibitors (statins) for the treatment of dyslipidemia, recent studies have shown that other LDL cholesterol lowering drugs, including ezetimibe and the PCSK9 inhibitors, can provide additional benefit when used in combination with (and in certain cases instead of) statins. These studies have also shown that blood LDL cholesterol levels lower than previously recommended targets provide additional benefit, without evidence of a threshold beyond which the benefit ceases and without excess adverse effects. The updated guidelines were formulated by a committee that consisted of representatives from the Israeli Society for the Research, Prevention and Treatment of Atherosclerosis, the Israel Society of Internal Medicine, the Israeli Heart Association, the Israeli Neurology Association and the Israel Association of Family Medicine. They provide recommendations for revised risk stratification of patients, novel target goals, and the use of evidence-based treatment and follow-up strategies with reference to specific patient sub-groups.


Assuntos
Anticolesterolemiantes , Doenças Cardiovasculares , Dislipidemias , Inibidores de Hidroximetilglutaril-CoA Redutases , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Dislipidemias/tratamento farmacológico , Humanos , Israel , Pró-Proteína Convertase 9
5.
Nutr Metab Cardiovasc Dis ; 30(4): 709-716, 2020 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-32007335

RESUMO

BACKGROUND AND AIMS: Mediterranean diet has been associated with decreased cardiovascular morbidity and mortality. Both fish and olive oil are key components of this diet. Therefore, we compared their effects on nonalcoholic fatty liver disease (NAFLD) and atherogenesis in a mouse model, fed a high fat diet. METHODS AND RESULTS: Forty nine, female LDL receptor knockout (LDLR KO) mice were allocated into 3 groups and fed an atherogenic high fat (HF) diet for 9 weeks. The HF group was fed a high fat diet alone. A HF + OO group was fed a HF diet with added olive oil (60 ml/kg feed), and the third group (HF + FO) was fed a HF diet with added fish oil (60 ml/kg feed). Both additions of fish and olive oil, significantly decreased plasma cholesterol elevation compared to HF diet. Nevertheless, only fish oil addition reduced significantly atherosclerotic lesion area by 51% compared to HF group. Liver levels of eicosapentenoic (EPA) and docosahexaenoic (DHA) acids were several folds higher in HF + FO group than in HF and HF + OO groups. Liver levels of oleic acid were higher in HF + OO compared to the other groups. Moreover, Fish oil addition significantly decreased NAFLD scores related to steatosis and inflammation and lowered the expression of the inflammatory genes interleukin 6 (IL6) and monocyte chemoattractant protein 1 (MCP1). CONCLUSION: These results suggest that fish oil addition on top of an atherogenic, HF diet, is beneficial, while olive oil is not, in its effect on plaque formation and NAFLD in LDLR KO mice.


Assuntos
Aterosclerose/prevenção & controle , Dieta Hiperlipídica , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Azeite de Oliva/administração & dosagem , Animais , Aterosclerose/sangue , Aterosclerose/genética , Aterosclerose/patologia , Biomarcadores/sangue , Quimiocina CCL2/metabolismo , Colesterol/sangue , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Feminino , Interleucina-6/metabolismo , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Ácido Oleico/administração & dosagem , Ácido Oleico/metabolismo , Placa Aterosclerótica , Receptores de LDL/deficiência , Receptores de LDL/genética , Fatores de Tempo
6.
Harefuah ; 152(12): 729-31, 751, 2013 Dec.
Artigo em Hebraico | MEDLINE | ID: mdl-24482998

RESUMO

Phytosterols are sterols found naturally in various oils from plants. Phytosterols compete with cholesterol for a place in the mixed micelles, needed for cholesterol absorption by the small intestine. As a result, cholesterol absorption, either from food or from bile salts is lowered by about 50%, leading to a towering of about 10% of blood cholesterol level, despite an increase in hepatic cholesterol synthesis. This reduction is achieved when phytosterols are given both as monotherapy, and in addition to statin therapy. The average Western diet contains about 400-800 mg of phytosterols per day, while the dose needed for lowering the blood cholesterol level is about 2-3 grams per day. Therefore, for the purpose of reducing blood cholesterol, they should be given either as phytosterol-enriched food or as supplements. The reduction in the level of LDL-choLesterol achieved with phytosterols may reduce the risk of coronary disease by about 25%. Hence, the American Heart Association recommended the consumption of phytosterols, as part of a balanced diet, for towering blood cholesterol levels.


Assuntos
Anticolesterolemiantes/administração & dosagem , LDL-Colesterol/sangue , Fitosteróis/administração & dosagem , American Heart Association , Anticolesterolemiantes/farmacologia , Doença das Coronárias/prevenção & controle , Suplementos Nutricionais , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Fitosteróis/farmacologia , Estados Unidos
7.
Nutrients ; 15(19)2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37836583

RESUMO

BACKGROUND: Low serum magnesium (sMg) is associated with cardiovascular risk factors and atherosclerotic disease. OBJECTIVE: To evaluate the association between sMg levels on admission and clinical outcomes in hospitalized non-ST-elevation myocardial infarction (NSTEMI) patients. METHODS: A retrospective analysis of all patients admitted to a single tertiary center with a primary diagnosis of NSTEMI. Patients with advanced chronic kidney disease were excluded. Clinical data were collected and compared between lower sMg quartile patients (Q1; sMg < 1.9 mg/dL) and all other patients (Q2-Q4; sMg ≥ 1.9 mg/dL). RESULTS: The study cohort included 4552 patients (70% male, median age 69 [IQR 59-79]) who were followed for a median of 4.4 (IQR 2.4-6.6) years. The median sMg level in the low sMg group was 1.7 (1.6-1.8) and 2.0 (2.0-2.2) mg/dL in the normal/high sMg group. The low sMg group was older (mean of 72 vs. 67 years), less likely to be male (64% vs. 72%), and had higher rates of comorbidities, including diabetes, hypertension, and atrial fibrillation (59% vs. 29%, 92% vs. 85%, and 6% vs. 5%; p < 0.05 for all). Kaplan-Meier survival analysis demonstrated significantly higher cumulative death probability at 4 years in the low sMg group (34% vs. 22%; p log rank <0.001). In a multivariable analysis model adjusted for sex, significant comorbidities, coronary interventions during the hospitalization, and renal function, the low sMg group exhibited an independent 24% increased risk of death during follow up (95% CI 1.11-1.39; p < 0.001). CONCLUSIONS: Low sMg is independently associated with higher risk of long-term mortality among patients recovering from an NSTEMI event.


Assuntos
Diabetes Mellitus , Infarto do Miocárdio sem Supradesnível do Segmento ST , Humanos , Masculino , Idoso , Feminino , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio sem Supradesnível do Segmento ST/epidemiologia , Magnésio , Estudos Retrospectivos , Comorbidade , Fatores de Risco
8.
J Clin Med ; 10(21)2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34768450

RESUMO

Heterozygous familial hypercholesterolaemia (FH) is among the most common genetic metabolic lipid disorders characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels from birth and a significantly higher risk of developing premature atherosclerotic cardiovascular disease. The majority of the current pediatric guidelines for clinical management of children and adolescents with FH does not consider the impact of genetic variations as well as characteristics of vascular phenotype as assessed by recently developed non-invasive imaging techniques. We propose a combined integrated approach of cardiovascular (CV) risk assessment and clinical management of children with FH incorporating current risk assessment profile (LDL-C levels, traditional CV risk factors and familial history) with genetic and non-invasive vascular phenotyping. Based on the existing data on vascular phenotype status, this panel recommends that all children with FH and cIMT ≥0.5 mm should receive lipid lowering therapy irrespective of the presence of CV risk factors, family history and/or LDL-C levels Those children with FH and cIMT ≥0.4 mm should be carefully monitored to initiate lipid lowering management in the most suitable time. Likewise, all genetically confirmed children with FH and LDL-C levels ≥4.1 mmol/L (160 mg/dL), should be treated with lifestyle changes and LLT irrespective of the cIMT, presence of additional RF or family history of CHD.

9.
J Nutr Biochem ; 91: 108597, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33545323

RESUMO

Docosahexaenoic acid (DHA) is critical for normal brain development and function. DHA is in danger of being significantly reduced in the human food supply, and the question of whether its metabolic precursor, the essential n-3 alpha linolenic acid (ALA) during pregnancy, can support fetal brain DHA levels for optimal neurodevelopment, is fundamental. Female mice were fed either ALA-enriched or Control diet during pregnancy and lactation. The direct effect of maternal dietary ALA on lipids was analyzed in liver, red blood cells, brain and brain vasculature, together with genes of fatty acid metabolism and transport in three-week-old offspring. The long-term effect of maternal dietary ALA on brain fatty acids and memory was studied in 19-week-old offspring. Three-week-old ALA offspring showed higher levels of n-3 fatty acids in liver, red blood cell, blood-brain barrier (BBB) vasculature and brain parenchyma, DHA enrichment in brain phospholipids and higher gene and protein expression of the DHA transporter, major facilitator superfamily domain containing 2a, compared to Controls. 19-week-old ALA offspring showed higher brain DHA levels and better memory performance than Controls. The increased brain DHA levels induced by maternal dietary ALA during pregnancy-lactation, together with the up-regulated levels of major facilitator superfamily domain containing 2a, may indicate a mode for greater DHA uptake with long-term impact on better memory in ALA offspring.


Assuntos
Encéfalo/metabolismo , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido alfa-Linolênico/farmacologia , Animais , Animais Recém-Nascidos , Encéfalo/efeitos dos fármacos , Feminino , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Desmame
10.
Artigo em Inglês | MEDLINE | ID: mdl-34487973

RESUMO

Maternal docosahexaenoic acid (DHA) is required during pregnancy to supply for normal fetal growth and development. This pilot study aimed to assess the unknown fatty acid (FA) composition in a cohort of non-pregnant and pregnant Israeli women at term and their offspring on a normal diet without n-3 FA supplementation. The fatty acid profile, analyzed using gas chromatography, showed significantly higher plasma monounsaturated (MUFA) and lower n-6 FA percent distribution with similar n-3 index, in pregnant compared to non-pregnant women. RBC exhibited significantly higher MUFA with similar n-3 index, in pregnant compared to non-pregnant women. N-3 FA significantly correlated between neonates' plasma, with higher n-3 index, and pregnant women's DHA. Conclusion: DHA levels in non-pregnant and pregnant Israeli women at term were comparable and the DHA in pregnant women's plasma positively correlated with their neonate's level, suggesting an efficient mother-fetus FA transfer and/or fetal fatty acid metabolism to longer FA products.


Assuntos
Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Troca Materno-Fetal , Adulto , Proteínas de Arabidopsis/sangue , Carbono-Oxigênio Ligases/sangue , Estudos de Casos e Controles , Ácidos Docosa-Hexaenoicos/sangue , Ácidos Graxos Essenciais/sangue , Ácidos Graxos Insaturados/sangue , Feminino , Humanos , Recém-Nascido , Israel , Fenômenos Fisiológicos da Nutrição Materna , Projetos Piloto , Gravidez , Triglicerídeos/sangue , Ácido alfa-Linolênico/sangue , Ácido gama-Linolênico/sangue
11.
Pediatr Blood Cancer ; 54(5): 703-6, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20063421

RESUMO

OBJECTIVE: To determine the incidence and clinical consequences of asparaginase-associated lipid abnormalities in children with acute lymphoblastic leukemia (ALL). METHODS: Sixty-five newly diagnosed children and adolescents aged 0.4-21 years with ALL or lymphoblastic lymphoma were retrospectively evaluated for lipid abnormalities. They were treated according to the ALLIC-BFM 2002 protocol between 2002 and 2005. Fasting cholesterol levels were measured in all patients and triglycerides (TG) in 42/65 patients. RESULTS: Prior to treatment, mean cholesterol level was 149 +/- 50 mg/dl, and increased to maximal level 274 +/- 124 mg/dl during treatment. Mean TG level during treatment was 459 +/- 526 mg/dl (range 54-3,009). Twelve patients (28%) had TG levels <200 mg/dl, 18 (43%) had 200-400 mg/dl, 3 (7%) had 400-600 mg/dl, 4 (10%) between 600 and 1,000 mg/dl, and 5 (12%) patients had >1,000 mg/dl. No association was found between TG levels and age or gender. One of the 12 patients with TG >400 mg/dl developed left saggital sinus thrombosis and left frontal lobe infarct. TG level at the time of the event was 2,640 mg/dl. None of the five patients with TG levels >1,000 mg/dl developed pancreatitis. Children with TG levels between 400 and 600 mg/dl were treated by fasting. Fibrates and heparin were added to those with levels >600 mg/dl. Lipid abnormalities normalized in all children upon completion of asparaginase treatment. CONCLUSIONS: Abnormalities of lipid profile in children with ALL during asparaginase therapy are relatively common. We recommend measuring TG before and during asparaginase treatment. Initiation of conservative treatment could prevent further increase of TG and decrease the risk of potential complications.


Assuntos
Antineoplásicos/efeitos adversos , Asparaginase/efeitos adversos , Monitoramento de Medicamentos , Hipercolesterolemia/prevenção & controle , Hipertrigliceridemia/prevenção & controle , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Asparaginase/administração & dosagem , Criança , Pré-Escolar , Ácido Clofíbrico/administração & dosagem , Dieta com Restrição de Carboidratos , Dieta com Restrição de Gorduras , Jejum , Feminino , Humanos , Hipercolesterolemia/induzido quimicamente , Hipercolesterolemia/etnologia , Hipertrigliceridemia/induzido quimicamente , Hipertrigliceridemia/etnologia , Hipolipemiantes/administração & dosagem , Lactente , Israel/epidemiologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/etnologia , Indução de Remissão , Estudos Retrospectivos , Adulto Jovem
12.
Cardiovasc Drugs Ther ; 24(5-6): 429-37, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20617456

RESUMO

PURPOSE: The aim of the current study was to evaluate the therapeutic effects of omega-3 plant sterol esters (n-3-PSE) on lipid profile and other coronary heart disease risk factors in subjects with mixed hyperlipidemia. METHODS: Ninety-one patients with mixed hyperlipidemia were randomized in a double blind fashion to receive either placebo (corn oil) or n-3-PSE. Twenty four patients dropped out or were excluded from the efficacy analysis due to protocol violation. The primary efficacy endpoint was mean change in plasma low-density lipoprotein cholesterol (LDL-C) levels after 12 weeks of treatment. Other efficacy measures included plasma lipids, lipoproteins, and high-sensitivity C-reactive protein (hsCRP) levels. Participants who completed the double-blind study were given the option to continue into an open-label, 12-weeks follow up phase. RESULTS: n-3-PSE treatment did not result in a significant change in LDL-C levels. Triglyceride levels were reduced significantly by 19% (51 mg/dL, p < 0.0001) in the n-3-PSE group in comparison with the placebo group (p = 0.025). Diastolic blood pressure and hsCRP were reduced by 7% (5.9 mmHg) and 7.8% (0.6 mg/L), respectively, and were significantly different from the placebo group (p = 0.036 and p = 0.018, respectively). CONCLUSIONS: In patients with mixed hyperlipidemia, n-3-PSE treatment may offer a safe and effective therapy for triglyceride level reduction while avoiding the typical increase in LDL-C levels associated with n-3 fatty acid treatment. The observed reduction in blood pressure and inflammation markers warrants further evaluation. The positive effect of n-3-PSE treatment was preserved at the end of the follow up phase.


Assuntos
Ácidos Graxos Ômega-3/uso terapêutico , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Fitosteróis/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Proteína C-Reativa/metabolismo , LDL-Colesterol/sangue , Método Duplo-Cego , Ésteres/efeitos adversos , Ésteres/uso terapêutico , Ácidos Graxos Ômega-3/efeitos adversos , Feminino , Humanos , Hipercolesterolemia/fisiopatologia , Lipídeos/sangue , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Fitosteróis/efeitos adversos , Placebos , Triglicerídeos/sangue
14.
Nutrients ; 12(6)2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32492795

RESUMO

Vitamin A deficiency (VAD) is a major health problem, especially in developing countries. In this study, we investigated the effect of VAD from weaning to adulthood in apoE-/- mice. Three-week-old male mice were allocated into four diet groups: I. VAD II. VAD+vitamin A (VA), 1500 IU retinyl-palmitate; III. VAD+ß-carotene (BC), 6 g/kg feed, containing 50% all-trans and 50% 9-cis BC. IV. VAD with BC and VA (BC+VA). After 13 weeks, we assessed the size of atherosclerotic plaques and measured VA in tissues and BC in plasma and tissues. VAD resulted in diminished hepatic VA levels and undetectable brain VA levels compared to the other groups. BC completely replenished VA levels in the liver, and BC+VA led to a two-fold elevation of hepatic VA accumulation. In adipose tissue, mice fed BC+VA accumulated only 13% BC compared to mice fed BC alone. Atherosclerotic lesion area of BC group was 73% lower compared to VAD group (p < 0.05). These results suggest that BC can be a sole source for VA and inhibits atherogenesis.


Assuntos
Apolipoproteínas E/deficiência , Aterosclerose/etiologia , Aterosclerose/prevenção & controle , Suplementos Nutricionais , Fitoterapia , Deficiência de Vitamina A/tratamento farmacológico , beta Caroteno/administração & dosagem , Animais , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
15.
J Nutr ; 138(10): 1923-30, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18806102

RESUMO

Our aim was to study the effect of 9-cis beta-carotene-rich powder of the alga Dunaliella bardawil on lipid profile, atherogenesis, and liver steatosis in high-fat diet-fed LDL receptor knockout mice. In 4 sets of experiments, mice were distributed into the following groups: control, fed an unfortified diet; Dunaliella 50, fed a diet composed of 50% 9-cis and 50% all-trans beta-carotene; Dunaliella 25, fed a diet containing 25% 9-cis and 75% all-trans beta-carotene; beta-carotene-deficient Dunaliella, fed beta-carotene-deficient Dunaliella powder; and all-trans beta-carotene, fed a synthetic all-trans beta-carotene. All fortified diets contained 0.6% total beta-carotene. Algal 9-cis beta-carotene was absorbed by the mice and accumulated in the liver. Synthetic all-trans beta-carotene was not converted to 9-cis beta-carotene. Dunaliella 50 inhibited high-fat diet-induced plasma cholesterol elevation by 40-63% and reduced cholesterol concentrations in the atherogenic VLDL and LDL. Atherosclerotic lesion area in mice treated with Dunaliella 50 was 60-83% lower compared with mice fed the high-fat diet alone. beta-Carotene-deficient Dunaliella did not influence plasma cholesterol and atherogenesis, suggesting that beta-carotene is essential for a Dunaliella protective effect. Moreover, by administrating Dunaliella powder containing different levels of 9-cis and all-trans beta-carotene isomers, we found that the effect on plasma cholesterol concentration and atherogenesis is 9-cis-dependent. Dunaliella 50 also inhibited fat accumulation and inflammation in the livers of mice fed a high-fat diet, which was accompanied by reduced mRNA levels of inflammatory genes. These results in mice suggest that 9-cis beta-carotene may have the potential to inhibit atherogenesis in humans.


Assuntos
Aterosclerose/prevenção & controle , Dieta , Fígado Gorduroso/prevenção & controle , Receptores de LDL/deficiência , beta Caroteno/uso terapêutico , Animais , Colesterol/sangue , Eucariotos , Hipercolesterolemia/prevenção & controle , Absorção Intestinal , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Retinoides/metabolismo , beta Caroteno/administração & dosagem , beta Caroteno/farmacocinética
16.
Diab Vasc Dis Res ; 5(1): 44-7, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18398812

RESUMO

Atherosclerotic cardiovascular disease (CVD) is the universal leading cause of mortality and a major cause of morbidity. Additionally, the global epidemic of diabetes is associated with considerable cardiovascular mortality risk due to accelerated premature atherosclerosis. Development of effective therapies for atherosclerosis is dependent upon improved tools to assess atherosclerotic lesion progression in animal models. We present a novel technique that utilises scanning electron microscopy (SEM) for imaging wet biological specimens, thus enabling rapid and high-resolution imaging of atherosclerotic lesions. This wet SEM technique was used in an apoE-deficient mice model for morphological characterisation of early and advanced atherosclerotic lesions. Further demonstration of lipid-rich atherosclerotic lesions was carried out with osmium tetroxide staining for cholesterol. Gold immunolabelling of specific epitopes was applied in identification of the cellular and molecular components within the atherosclerotic lesions, namely foam cells, smooth muscle cells and collagen. The wet SEM technique demonstrates an accurate and detailed structural evaluation of the pathological process of atherosclerosis. Understanding the mechanisms that precipitate the atherosclerotic process, utilising this novel technique, may assist in the development of innovative therapeutic interventions for CVD management and prevention in the general population and in those with diabetes.


Assuntos
Aterosclerose/metabolismo , Aterosclerose/patologia , Colesterol/metabolismo , Microscopia Eletrônica de Varredura/métodos , Animais , Aorta/metabolismo , Aorta/patologia , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Colágeno/metabolismo , Modelos Animais de Doenças , Epitopos , Feminino , Células Espumosas/citologia , Células Espumosas/metabolismo , Imuno-Histoquímica , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo
17.
Atherosclerosis ; 189(1): 215-21, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16413556

RESUMO

The effect of fibrates on high density lipoprotein (HDL)-cholesterol levels is suggested to be mediated by its binding to peroxisome proliferator-activated receptor-alpha (PPARalpha). Upon ligand binding, PPARalpha heterodimerizes with the 9-cis retinoic acid receptor (RXR) and it is this heterodimer which regulates gene expression. We assessed the hypothesis that a combined treatment with fibrate plus 9-cis beta-carotene-rich powder of the alga Dunaliella bardawil, as a source of 9-cis retinoic acid, would improve the drug's effect on HDL-cholesterol levels. In an open-labeled first trial, 20 fibrate-treated men with plasma HDL-cholesterol levels below 40 mg/dl were given Dunaliella capsules, providing 60 mg beta-carotene/day, containing all-trans and 9-cis beta-carotene (1:1 ratio, w/w). Twenty-two fibrate-treated patients participated in a double-blind placebo-controlled second trial. Eleven patients were treated with Dunaliella capsules, and 11 patients were treated with beta-carotene-deficient Dunaliella capsules. Following 6 weeks of the dual treatment plasma HDL-cholesterol increased by 24.5 and 12.7% in the first and second trials, respectively (P=0.002 and 0.012). The dual treatment also increased HDL-cholesterol levels in human apolipoprotein A-I transgenic mice by 87.5% (P=0.021). The results show that a combination treatment of fibrate plus 9-cis beta-carotene-rich Dunaliella powder amplifies the effect of the drug on HDL-cholesterol levels.


Assuntos
Aterosclerose/tratamento farmacológico , Clorófitas , HDL-Colesterol/sangue , Antagonistas Colinérgicos/uso terapêutico , Ácido Clofíbrico/uso terapêutico , Vitaminas/uso terapêutico , beta Caroteno/uso terapêutico , Adulto , Idoso , Animais , Apolipoproteína A-I/sangue , Apolipoproteína A-I/efeitos dos fármacos , Aterosclerose/sangue , HDL-Colesterol/efeitos dos fármacos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Pós , Resultado do Tratamento
18.
Harefuah ; 145(11): 831-5, 861, 860, 2006 Nov.
Artigo em Hebraico | MEDLINE | ID: mdl-17183957

RESUMO

Hypercholesterolemia is a major risk factor for atherosclerosis. HMG-CoA Reductase inhibitors (statins), which block hepatic synthesis of cholesterol, are the mainstay of therapy of hypercholesterolemia. Recent trials have demonstrated the importance of maintaining very low LDL-cholesterol levels in high-risk patients. Such low levels are sometimes hard to reach with statin monotherapy. Another source of cholesterol is intestinal absorption of dietary cholesterol and bile salts. Recent studies have elucidated the mechanism of intestinal cholesterol absorption. Ezetimibe, a specific inhibitor of cholesterol absorption can be used as an add-on therapy to statins in order to achieve treatment goals.


Assuntos
Colesterol na Dieta/farmacocinética , Hipercolesterolemia/terapia , Absorção Intestinal , Anticolesterolemiantes/uso terapêutico , Azetidinas/uso terapêutico , LDL-Colesterol/sangue , Ezetimiba , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico
19.
Cancer Lett ; 229(1): 127-34, 2005 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-16157225

RESUMO

Oxygenases are a family of enzymes that dioxygenate unsaturated fatty acids, thus initiating membrane oxidation and signaling molecule synthesis. The lipoxygenases (LOs), a family of lipid-peroxidizing enzymes that induce structural and metabolic changes in the cell in a number of pathophysiological conditions, belong to the oxygenases family. This class of enzymes has several subgroups, named 5-, 8-, 12- and 15-LOs, and these LO-isoforms are capable of oxygenating arachidonic and linoleic acid. 15-LOs were reported to play an inhibitory role in tumor angiogenesis and, consequently, they slow down carcinogenesis. It has been suggested that its anti-carcinogenic effect is conferred by promoting cell differentiation and apoptosis. Using transgenic mice that over-express 15-LO-1 in endothelial cells under the regulation of the murine preproendothelin-1 promoter, we studied its effect on tumor and metastasis growth. We found that 15-LO-1 inhibited tumor and metastasis growth in the transgenic mice in two different models of cancer (mammary gland and Lewis lung carcinoma). This inhibition was concomitant with a higher number of apoptotic cells in the metastases of the transgenic mice and with a complicated network of multiple small blood vessels. This finding targets 15-LO as a new candidate in the treatment of carcinogenesis.


Assuntos
Araquidonato 15-Lipoxigenase/fisiologia , Transformação Celular Neoplásica/genética , Endotelina-1/fisiologia , Neovascularização Patológica/genética , Animais , Apoptose/genética , Apoptose/fisiologia , Araquidonato 15-Lipoxigenase/biossíntese , Araquidonato 15-Lipoxigenase/genética , Vasos Sanguíneos , Carcinoma Pulmonar de Lewis/irrigação sanguínea , Carcinoma Pulmonar de Lewis/genética , Carcinoma Pulmonar de Lewis/fisiopatologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Metástase Neoplásica/genética , Metástase Neoplásica/fisiopatologia , Regiões Promotoras Genéticas , Regulação para Cima
20.
Biol Trace Elem Res ; 90(1-3): 251-9, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12666839

RESUMO

Magnesium (Mg) modulates blood lipid levels, atherogenesis, and atherosclerosis in rabbits, when supplemented to diet. We have recently reported that a high concentration (50 g/L) of Mg sulfate fortification of drinking water attenuates atherogenesis in male and female LDL-receptor-deficient mice fed a high-cholesterol diet. The aims of the current study were to examine whether lower concentrations and another Mg salt could also have such an antiatherogenic effect. Thirty male LDL-receptor-deficient mice were divided into three groups (n=10 in each group). The mice received either distilled water or water fortified with 0.83 g or with 8.3 g Mg-chloride per liter. In the first (27 wk) and second (5 wk) stages of the experiment, the mice received normal chow and Western-type diet, respectively. Blood was drawn for determination of plasma Mg, calcium, and lipid levels. The extent of atherosclerotic lesions was determined at the aortic sinus. Magnesium-chloride fortification of drinking water did not result in higher plasma Mg concentrations, whereas a trend toward lower plasma calcium concentrations did not reach statistical significance. Even though plasma lipid levels were similar at the beginning and the end of the study, there were decreased plasma cholesterol and triglyceride levels in the Mg groups after stage I. The atherosclerosis extent at the aortic sinus was significantly decreased in the 8.3-g Mg-chloride/L group (23,437 +/- 10,083 micron2) compared with the control group (65,937 +/- 31,761 microm2). There was also a trend toward lower atherosclerosis extent at the aortic sinus in the 0.83-g Mg-chloride/L group. An additional Mg salt (Mg-chloride) fortification of drinking water is capable of inhibiting atherogenesis in male LDL-receptor-deficient mice. That is done in a lower concentration of Mg than previously reported.


Assuntos
Arteriosclerose/prevenção & controle , Cloreto de Magnésio/farmacologia , Abastecimento de Água/normas , Animais , Arteriosclerose/sangue , Arteriosclerose/tratamento farmacológico , Peso Corporal/efeitos dos fármacos , Cálcio/sangue , Alimentos Fortificados , Lipídeos/sangue , Magnésio/sangue , Cloreto de Magnésio/sangue , Cloreto de Magnésio/uso terapêutico , Masculino , Camundongos , Fatores de Tempo
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