Meals with Similar Fat Content from Different Dairy Products Induce Different Postprandial Triglyceride Responses in Healthy Adults: A Randomized Controlled Cross-Over Trial.

BACKGROUND: Postprandial lipemia is a risk factor for cardiovascular disease. Dairy products differ in nutrient content and food matrix, and little is known about how different dairy products affect postprandial triglyceride (TG) concentrations. OBJECTIVE: We investigated the effect of meals with similar amounts of fat from different dairy products on postprandial TG concentrations over 6 h in healthy adults. METHODS: A randomized controlled cross-over study was performed on 47 subjects (30% men), with median (25th-75th percentile) age of 32 (25-46) y and body mass index of 23.6 (21.0-25.8) kg/m2. Meals included 1 of butter, cheese, whipped cream, or sour cream, corresponding to 45 g of fat (approximately 60 energy%). Serum concentrations of TGs (primary outcome), and total cholesterol (TC), low density lipoprotein cholesterol (LDL cholesterol), high density lipoprotein cholesterol (HDL cholesterol), insulin, glucose, non-esterified fatty acids, and plasma glucose-dependent insulinotropic polypeptide (secondary outcomes) were measured before the meal and 2, 4, and 6 h postprandially. Incremental AUC (iAUC) was calculated for the responses, and data were analyzed using a linear mixed model. RESULTS: Sour cream induced a 61% larger TG-iAUC0-6 h compared to whipped cream (P < 0.001), a 53% larger TG-iAUC0-6 h compared to butter (P < 0.001), and a 23% larger TG-iAUC0-6 h compared to cheese (P = 0.05). No differences in TG-iAUC0-6 h between the other meals were observed. Intake of sour cream induced a larger HDL cholesterol-iAUC0-6 h compared to cheese (P = 0.01). Intake of cheese induced a 124% larger insulin iAUC0-6 h compared to butter (P = 0.006). No other meal effects were observed. CONCLUSIONS: High-fat meals containing similar amount of fat from different dairy products induce different postprandial effects on serum TGs, HDL cholesterol, and insulin in healthy adults. The potential mechanisms and clinical impact of our findings remain to be further elucidated. The study was registered at www.clinicaltrials.gov as NCT02836106.

Cholesterol concentrations in lipoprotein fractions separated by anion-exchange-high-performance liquid chromatography in healthy dogs and dogs with hypercholesterolemia.

Anion-exchange (AEX)-high-performance liquid chromatography (HPLC) for measurement of cholesterol can be used to separate serum lipoproteins (high-density lipoprotein (HDL); low-density lipoprotein (LDL); intermediate-density lipoprotein (IDL); very-low-density lipoprotein (VLDL)) in humans. However, AEX-HPLC has not been applied in veterinary practice. We had three objectives: (i) the validation of AEX-HPLC methods including the correlation of serum cholesterol concentration in lipoprotein fraction measured by AEX-HPLC and gel permeation-HPLC (GP-HPLC) in healthy dogs and those with hypercholesterolemia was investigated; (ii) the reference intervals of lipoprotein fractions measured by AEX-HPLC from healthy dogs (n=40) was established; (iii) lipoprotein fractions from the serum of healthy dogs (n=12) and dogs with hypercholesterolemia (n=23) were compared. Analytic reproducibility and precision of AEX-HPLC were acceptable. Positive correlation between serum concentrations of total cholesterol (Total-Chol), HDL cholesterol (HDL-Chol), LDL cholesterol (LDL-Chol)+IDL cholesterol (IDL-Chol), and VLDL cholesterol (VLDL-Chol) was noted for AEX-HPLC and GP-HPLC in healthy dogs and dogs with hypercholesterolemia. Reference intervals measured by AEX-HPLC for serum concentrations of Total-Chol, HDL-Chol, and LDL-Chol were determined to be 2.97-9.32, 2.79-6.57, 0.16-3.28mmol/L (2.5-97.5% interval), respectively. Furthermore, there was significant difference in lipoprotein profiles between healthy and dogs with hypercholesterolemia. These results suggest that AEX-HPLC can be used to evaluate lipoprotein profiles in dogs and could be a new useful indicator of hyperlipidemia in dogs.

Assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction ­ ALPS-AMI study.

BACKGROUND: Statins reduce the incidence of cardiovascular events, but no randomized trial has investigated the best statins for secondary prevention. We compared the efficacy of hydrophilic pravastatin with that of lipophilic atorvastatin in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: A prospective, multicenter study enrolled 508 patients (410 men; mean age, 66.0 ± 11.6 years) with AMI who were randomly assigned to atorvastatin (n=255) or pravastatin (n=253). The target control level of low-density lipoprotein cholesterol (LDL-C) was <100 mg/dl, and patients were followed for 2 years. The primary endpoint was the composite of death due to any cause, non-fatal myocardial infarction, non-fatal stroke, unstable angina or congestive heart failure requiring hospital admission, or any type of coronary revascularization. The primary endpoint occurred in 77 patients (30.4%) and in 80 patients (31.4%) in the pravastatin and atorvastatin groups, respectively (hazard ratio, 1.181; 95% confidence interval: 0.862-1.619; P=0.299), whereas greater reductions in serum total cholesterol and LDL-C were achieved in the atorvastatin group (P<0.001 for each). Changes in hemoglobin A1c, brain natriuretic peptide, and creatinine were not significant between the 2 regimens, and safety and treatment adherence were similar. CONCLUSIONS: On 2-year comparison of hydrophilic and lipophilic statins there was no significant difference in prevention of secondary cardiovascular outcome.

Serum non-high-density lipoprotein cholesterol levels and the incidence of ischemic stroke in a Japanese population: the Jichi Medical School cohort study.

The predictive value of serum non-high-density lipoprotein cholesterol (non-HDL-C) levels for the incidence of ischemic stroke and its subtypes has not yet been established. The present cohort study investigated their relationships in a Japanese population. The first incidence of ischemic stroke and its subtypes was documented as the primary outcome. A total of 249 ischemic stroke patients (men/women = 145/104) were identified during a follow-up period of 10.7 years among 10 760 community-dwelling subjects (men/women = 4212/6548). Cox proportional hazard model analyses revealed that when compared with the lowest tertile of non-HDL-C, multivariate-adjusted hazard ratios for the highest tertile were 0.55 (95% confidence interval = 0.32-0.95, P = .03) on ischemic stroke and 0.29 (95% confidence interval = 0.08-1.05, P = .06) on cardioembolic infarction in women. Men did not show such significant relationships. Low serum non-HDL-C levels may be a predictive marker associated with an increase in the incidence of ischemic stroke and possibly of cardioembolic infarction in Japanese women.

Efeito do simbiótico no funcionamento gastrointestinal e perfil lipídico de idosos institucionalizados: um estudo randomizado, duplo cego controlado por placebo / Effect of symbiotic preparations on the gastrointestinal behavior and lipid profile of institutionalized elderly people: a randomized double-blind placebo-controlled study

The use of symbiotic preparations has been studied as an alternative to improve the physiologic functions on the elderly, because this group of people is more susceptible to nutritional diseases. The present study aimed to investigate the effect of using symbiotic preparations on the gastrointes¬tinal behavior and lipid profile of elderly people admitted in a long-stay institution on the coast of Santa Catarina state, Brazil. A randomized double-blind placebo-controlled study was carried out with elderly people who presented intestinal constipation. The elderly were distributed in two groups: the first group received two packages of Lactofos® symbiotic diluted in 100 ml of water twice a day for five weeks; the second group followed the same protocol but received maltodrexina as placebo. The protocol based on Roma III symptoms for intestinal constipation diagnosis was applied before and after the experiment. Two fecal samples were collected for functional coprologic exam: one before starting the administration of the product and the other at to the end study. Blood samples were used to determine the serum concentration of total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides before and after to the intervention. Improvement was observed regarding intestinal constipation symptoms and parameters associated with digestion and fat absorption, with reduction of fatty acids in the feces. No significant alterations were observed in the lipid profile. It is possible to conclude that the use of symbiotic preparation can improve the gastrointestinal function of the elderly.

El uso de simbióticos ha sido estudiado como una alternativa para mejorar las funciones fisiológicas de los ancianos, una vez que este grupo es más susceptible a las enfermedades nutricionales. El presente estudio tuvo por objetivo investigar el efecto del uso de simbióticos en el funcionamiento gastrointestinal y el perfil lipídico de ancianos internados en instituciones de permanencia prolongada en la costa de Santa Catarina. Se realizó un estudio doble ciego, randomizado, controlado por placebo, con ancianos que presentan síntomas de estreñimiento distribuidos en dos grupos. El primer grupo recibió dos sachets del simbiótico Lactofos® diluido en un vaso con 100 ml. de agua, administrado dos veces al día, durante un periodo de cinco semanas. El segundo grupo siguió el mismo protocolo recibiendo maltodextrina como placebo. El protocolo con base en los síntomas de Roma III, para diagnóstico de estreñimiento, se aplicó antes y después del experimento. Se recogieron dos muestras de materiales fecales para realización del examen cropológico funcional, una antes de empezar la administración del producto y otra después al terminar el estudio. Las muestras de sangre se utilizaron para determinaciones de las concentraciones séricas de colesterol total, HDL-colesterol, LDL-colesterol y triglicéridos, antes y después de la intervención. A pesar de que el estudio no ha evidenciado alteración significativa en el perfil lipídico, se observó mejora en los síntomas de estreñimiento y en los parámetros relacionados a la digestión y absorción de grasas, con reducción de la presencia de ácidos grasos en los materiales fecales. Se concluye que el uso del simbiótico puede ser un coadyuvante en la mejora de la función gastrointestinal de los ancianos.

O uso de simbióticos tem sido estudado como uma alternativa para melhorar as funções fisiológicas dos idosos, uma vez que este grupo é mais suscetível às doenças nutricionais. O presente estudo teve por objetivo investigar o efeito do uso de simbiótico no funcionamento gastrointestinal e perfil lipídico de idosos internados em instituição de longa permanência do litoral de Santa Catarina. Foi realizado um estudo duplo cego, randomizado, controlado por placebo, com idosos apresentando constipação intestinal distribuídos em dois grupos. O primeiro grupo recebeu dois sachês do simbiótico Lactofos® diluído em um copo com 100 mL de água, administrado duas vezes ao dia, durante um período de cinco semanas. O segundo grupo seguiu o mesmo protocolo, recebendo maltodextrina como placebo. O protocolo com base nos sintomas de Roma III, para diagnóstico de constipação intestinal, foi aplicado antes e após o experimento. Foram coletadas duas amostras de fezes para realização do exame coprológico funcional, sendo uma antes de iniciar a administração do produto e outra após o término do estudo. Amostras de sangue foram utilizadas para determinações das concentrações séricas de colesterol total, HDL-coles¬terol, LDL-colesterol e triglicerídeos, antes e após a intervenção. Observou-se melhora nos sintomas de constipação intestinal e nos parâmetros relacionados à digestão e absorção de gorduras, com redução da presença de ácidos graxos nas fezes. Não se evidenciou alteração significativa no perfil lipídico. Conclui-se que o uso do sim¬biótico pode ser um coadjuvante na melhora da função gastrointestinal de idosos.

Anti-atherogenic effect of chromium picolinate in streptozotocin-induced experimental diabetes.

BACKGROUND: Several studies have implicated changes in the levels of trace elements in diabetes. Chromium is one such element that seems to potentiate insulin action, thereby regulating carbohydrate and lipid metabolism. The aim of the present study was to evaluate the effect of chromium supplementation as chromium picolinate on the lipid profile of streptozotocin (STZ)-induced diabetic rats. METHODS: Rats were rendered diabetic by a single injection of STZ (50 mg/kg, i.p.). Chromium picolinate (1 mg/kg per day, p.o.) was administered to rats for a period of 4 weeks. At the end of the treatment period, plasma total lipids, triglycerides, total cholesterol and lipoprotein levels were determined, as was hepatic glucose-6-phosphate dehydrogenase activity. RESULTS: Total plasma lipids increased significantly in diabetic rats and this increase was ameliorated by chromium treatment for 4 weeks. Elevated total lipids in diabetic rats were due to increased plasma triglyceride and cholesterol levels. Chromium supplementation lowered plasma triglyceride and cholesterol levels to near normal. Chromium treatment also normalized low-density lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein-cholesterol levels and improved the total cholesterol:high-density lipoprotein-cholesterol (HDL-C) and HDL-C:LDL-C ratios, suggesting an anti-atherogenic effect. In addition to improving the plasma lipid profile, chromium supplementation normalized liver glucose-6-phosphate dehydrogenase activity in diabetic rats. CONCLUSIONS: These results provide evidence that chromium picolinate effectively attenuates the dyslipidemia associated with diabetes and thus can be used as an adjuvant therapy in the treatment of diabetes and its associated complications.

Metformin-based treatment for obesity-related hypertension: a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Obesity and hypertension are associated with an adverse metabolic profile and systemic low-grade inflammation. Metformin reduces weight and inflammation in patients with diabetes, but it is unclear whether it has beneficial effects in patients without diabetes. The objective was to explore whether metformin-based treatment could benefit obesity-related hypertension without diabetes. METHODS: A randomized, double-blind, placebo-controlled factorial trial was conducted in 360 obese hypertensive patients without diabetes in Chongqing, China. After a 1-2-week run-in period, patients were randomly assigned to metformin (500 mg once per day) or placebo, as well as to an antihypertensive medication. Change in blood pressure, obesity measurements and metabolic profile were assessed at 24 weeks. RESULTS: The 180 participants randomized to metformin and 180 randomized to placebo were similar at baseline. At 24 weeks, metformin compared with placebo did not have significant effects on blood pressure, blood glucose, high-density or low-density lipoprotein cholesterol, but it did reduce total serum cholesterol (0.2 mmol/l, P = 0.038). Metformin also significantly reduced weight (-0.7 kg, P = 0.006), BMI (-0.2 kg/m, P = 0.024), waist circumference (-0.9 cm, P = 0.008), and both subcutaneous (-6.1 cm, P = 0.043) and visceral adiposity (-5.4 cm, P = 0.028) as measured by computed tomography, and lowered serum high-sensitivity C-reactive protein levels (-0.6 mg/dl, P < 0.001). There was no significant difference in adverse events (P = 0.785). CONCLUSIONS: Metformin has no effect on blood pressure and blood glucose levels, but it does reduce total cholesterol, abdominal obesity and C-reactive protein levels in obese hypertensive patients without diabetes.

Results of a randomized,open-label,clinical trial investigating the effects of supplementation with Heracleumpersicum extract as an adjunctive therapy for dyslipidemia.

The present study evaluated the potential benefit of supplementation with Heracleumpersicum as an adjunctive therapy to atorvastatin in dyslipidemic subjects. In a randomized, open-label, clinical trial, 100 dyslipidemic subjects were randomly assigned to: (1) H. persicum group (n=50, completers=18), receiving H. persicum extract (500 mg/day) + atorvastatin (10 mg/day) for 8 weeks, or (2) atorvastatin group (n=50, completers=34), receiving only atorvastatin (20 mg/day) for 8 weeks. Weight, body mass index (BMI), lipid profile, and biomarkers of hepatic and renal injury were determined at baseline and at the end of the trial. There were significant reductions in serum total cholesterol and LDL-C in both the H. persicum (p=0.001) and atorvastatin (p< 0.001) groups. Serum HDL-C was elevated in the atorvastatin group (p< 0.05), while no significant change was observed in the H. persicum group (p> 0.05). Serum triglyceride levels remained statistically unchanged by the end of the trial in both groups (p> 0.05). Serum alanine (p=0.049) and aspartate aminotransferase (p=0.013) levels rose in the atorvastatin, but not the H. persicum(p> 0.05) group. In comparison with baseline values, no significant change was observed in weight and BMI, as well as serum levels of creatinine, blood urea nitrogen, and fasting blood sugar in either of the groups (p> 0.05). Apart from HDL-C, the effects of atorvastatin (20 mg/day) on other lipid profile parameters do not appear to be significantly superior to those achieved by combination therapy with H. persicum+ atorvastatin (10 mg/day).

[Research on the blood components detecting by multi-optical path length spectroscopy technique].

To discuss the feasibility of using the serum's multi-optical path length spectroscopy information for measuring the concentration of the human blood components, the automatic micro-displacement measuring device was designed, which can obtain the near-infrared multi-optical path length from 0 to 4.0 mm (interval is 0.2 mm) spectra of 200 serum samples with multioptical path length spectrum of serum participated in building the quantitative analysis model of four components of the human blood: glucose (GLU), total cholesterol (TC), total protein (TP) and albumin (ALB), by mean of the significant non-linear spectral characteristic of blood. Partial least square (PLS) was used to set up the calibration models of the multi-optical path length near-infrared absorption spectrum of 160 experimental samples against the biochemical analysis results of them. The blood components of another 40 samples were predicted according to the model. The prediction effect of four blood components was favorable, and the correlation coefficient (r) of predictive value and biochemical analysis value were 0.9320, 0.9712, 0.9462 and 0.9483, respectively. All of the results proved the feasibility of the multi-optical path length spectroscopy technique for blood components analysis. And this technique established the foundation of detecting the components of blood and other liquid conveniently and rapidly.

ApoE-/- PGC-1α-/- mice display reduced IL-18 levels and do not develop enhanced atherosclerosis.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease that evolves from the interaction of activated endothelial cells, macrophages, lymphocytes and modified lipoproteins (LDLs). In the last years many molecules with crucial metabolic functions have been shown to prevent important steps in the progression of atherogenesis, including peroxisome proliferator activated receptors (PPARs) and the class III histone deacetylase (HDAC) SIRT1. The PPARγ coactivator 1 alpha (Ppargc1a or PGC-1α) was identified as an important transcriptional cofactor of PPARγ and is activated by SIRT1. The aim of this study was to analyze total PGC-1α deficiency in an atherosclerotic mouse model. METHODOLOGY/PRINCIPAL FINDINGS: To investigate if total PGC-1α deficiency affects atherosclerosis, we compared ApoE(-/-) PGC-1α(-/-) and ApoE(-/-) PGC-1α(+/+) mice kept on a high cholesterol diet. Despite having more macrophages and a higher ICAM-1 expression in plaques, ApoE(-/-) PGC-1α(-/-) did not display more or larger atherosclerotic plaques than their ApoE(-/-) PGC-1α(+/+) littermates. In line with the previously published phenotype of PGC-1α(-/-) mice, ApoE(-/-) PGC-1α(-/-) mice had marked reduced body, liver and epididymal white adipose tissue (WAT) weight. VLDL/LDL-cholesterol and triglyceride contents were also reduced. Aortic expression of PPARα and PPARγ, two crucial regulators for adipocyte differentiation and glucose and lipid metabolism, as well as the expression of some PPAR target genes was significantly reduced in ApoE(-/-) PGC-1α(-/-) mice. Importantly, the epididymal WAT and aortic expression of IL-18 and IL-18 plasma levels, a pro-atherosclerotic cytokine, was markedly reduced in ApoE(-/-) PGC-1α(-/-) mice. CONCLUSIONS/SIGNIFICANCE: ApoE(-/-) PGC-1α(-/-) mice, similar as PGC-1α(-/-) mice exhibit markedly reduced total body and visceral fat weight. Since inflammation of visceral fat is a crucial trigger of atherogenesis, decreased visceral fat in PGC-1α-deficient mice may explain why these mice do not develop enhanced atherosclerosis.

Efecto del consumo de dietas con avena y caraotas negras sobre el perfil lipídico en un modelo experimental en rata / Effect of consumption of diets with oats and black beans on the lipid profile of an experimental model in rat

El consumo de alimentos ricos en fibra dietética (FD) soluble e insoluble, afecta favorablemente el perfil de lípidos séricos al reducir las concentraciones de colesterol total, colesterol- LDL y triglicéridos (TG). El objetivo de este trabajo, fue comparar el efecto del consumo de dietas con avena (Avena sa tiva) y con caraotas negras (Phaseolus vulgaris ) sobre el perfil lipídico de ratas. Quince ratas machos, cepa Sprague Dawley, fueron alimentadas ad libitum por 18 días, con tres tipos de dietas: un con trol, una conteniendo caraotas negras (15% p/p) y otra con avena (15% p/p). La concentración del colesterol total sérico disminuyo 50,56% en el grupo alimentado con avena y 40,52% en el alimentado con caraotas. Así mismo, se observó una disminución de colesterol-LDL de 49,21% en el grupo alimentado con avena y un 42,93% en el grupo alimentado con caraotas. Hubo una reducción de 52,47% del colesterol-HDL en el grupo alimentado con avena y 31,29% para el grupo alimentado con caraotas; esta reducción no es beneficiosa. La concentración de TG séricos fue significativamente menor, un 50,20% para el grupo alimentado con avena y de 51,8% para el grupo alimentado con caraota. La disminución de los lípidos séricos debido a la dieta, con avena o con caraotas, mostró diferencias significativas respecto al control, pero, no entre ellas. La consideración de estos resultados en el caso de la salud humana es bien importante, particularmente en la disminución de la prevalencia de enfermedades cardiovasculares. El efecto de FD sobre los niveles de colesterol-HDL, son hasta los momentos, contradictorios.

The consumption of foods rich in soluble and insoluble dietary fiber (DF) favorably affects the serum lipid profile by lowering total cholesterol, LDL-cholesterol and triglycerides (TG). The objective of this work was to compare the effect of consumption of diets with oats (Avena sativa) and black beans (Pha seo lus vulgaris) on the lipid profile of rats. Fifteen male rats, Spra gue Dawley strain were fed ad libitum for 18 days, with three different diets: a control, one containing black beans (15% w / w) and another with oats (15% w / w). The serum total cholesterol concentration decreased 50.56% in the group fed with oats and 40.52% in the group fed with beans. Also a de crease of LDL-cholesterol 49.21% in the group fed with oats and 42.93% in the group fed with beans was observed. There was 52.47% reduction of HDLcho lesterol in the group fed with oats and 31.29% for the group fed with beans, this is not a be neficial reduction. The serum TG concentration was significantly lower, 50.20% for the group fed with oats and 51.8% for the group fed with beans. The decrease of these lipids due to diet containing oats or beans, was significantly different from control but not between them. Consideration of these results for human health is very important, particularly in reducing the prevalence of cardiovascular disease. The FD effect on HDL-cholesterol levels, are until now contradictory.

Reduction in cardiovascular risk by sodium-bicarbonated mineral water in moderately hypercholesterolemic young adults.

The effects of drinking sodium-bicarbonated mineral water on cardiovascular risk in young men and women with moderate cardiovascular risk were studied. Eighteen young volunteers (total cholesterol levels >5.2 mmol/L) without any disease participated. The study consisted of two 8-week intervention periods. Subjects consumed, as supplement to their usual diet, 1 L/day control low mineral water, followed by 1 L/day bicarbonated mineral water (48 mmol/L sodium, 35 mmol/L bicarbonate and 17 mmol/L chloride). Determinations were performed at the end of the control water period and on Weeks 4 and 8 of the bicarbonated water period. Body weight, body mass index (BMI), blood pressure, dietary intake, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, apolipoprotein (Apo) A-I, Apo B, triacylgycerols, glucose, insulin, adiponectin, high-sensitivity C-reactive protein (hs-CRP), soluble adhesion molecules [soluble intercellular adhesion molecule (sICAM) and soluble vascular adhesion molecule (sVCAM)], sodium and chloride urinary excretion, and urine pH were measured. Dietary intake, body weight and BMI showed no significant variations. Systolic blood pressure decreased significantly after 4 weeks of bicarbonated water consumption, without significant differences between Weeks 4 and 8. After bicarbonated water consumption, significant reductions in total cholesterol (by 6.3%; P=.012), LDL cholesterol (by 10%; P=.001), total/HDL cholesterol (P=.004), LDL/HDL cholesterol (P=.001) and Apo B (P=.017) were observed. Serum triacylglycerol, Apo A-I, sICAM-1, sVCAM-1 and hs-CRP levels did not change. Serum glucose values tended to decrease during the bicarbonated water intervention (P=.056), but insulin levels did not vary. This sodium-bicarbonated mineral water improves lipid profile in moderately hypercholesterolemic young men and women and could therefore be applied in dietary interventions to reduce cardiovascular risk.

Lipid composition in rats with nonischemic chronic heart failure.

The initial stages of nonischemic chronic heart failure in rats (model of oleothorax) were accompanied by the development of dyslipidemia. This state was characterized by an increase in total cholesterol concentration (due to the fraction of low-density lipoproteins) and atherogenicity index. The concentrations of plasma total cholesterol and low-density lipoproteins were shown to decrease in animals with severe course of nonischemic chronic heart failure. These changes were accompanied by a decrease in the atherogenicity index. Intragastric administration of cholesterol had little effect on the lipid composition of blood plasma in rats, irrespective of the severity of heart failure.

Effect of ezetimibe/simvastatin compared with atorvastatin on lipoprotein subclasses in patients with type 2 diabetes and hypercholesterolaemia.

AIM: To evaluate the effects of the usual starting and next higher doses of ezetimibe/simvastatin and atorvastatin on the cholesterol content of lipoprotein subclasses in patients with type 2 diabetes and hypercholesterolaemia. METHODS: This post hoc analysis compared the effects of treatment with ezetimibe/simvastatin 10/20 mg vs. atorvastatin 10 and 20 mg/day and ezetimibe/simvastatin 10/40 mg/day vs. atorvastatin 40 mg/day on the cholesterol content of lipoprotein subclasses in the modified intent-to-treat (mITT) population (n = 1013) and in subgroups of patients with triglyceride (TG) levels <200 mg/dl (n = 600) and >or=200 mg/dl (2.6 mmol/l) (n = 413). RESULTS: Ezetimibe/simvastatin significantly reduced low-density lipoprotein cholesterol (LDL-C) subclasses LDL(1)-C, LDL(2)-C and LDL(3)-C; real LDL-C (LDL-C(r)); intermediate-density lipoprotein cholesterol (IDL-C), IDL(1)-C, IDL(2)-C; very low-density lipoprotein cholesterol (VLDL-C), VLDL(3)-C; and remnant-like lipoprotein cholesterol (RLP-C) from baseline more than atorvastatin at all dose comparisons (p < 0.01) in the mITT population. Significant improvements were also observed in high-density lipoprotein cholesterol (HDL-C) subclass HDL(3)-C at the ezetimibe/simvastatin 10/20 mg vs. atorvastatin 20 mg and highest dose comparisons (p < 0.001) and in VLDL(1 + 2)-C at the lowest and highest dose comparisons (p < 0.001). Changes in LDL(4)-C and LDL-C subclass patterns (A, B and I) were comparable for both treatments. Generally, similar results were observed for patients with TG levels <200 and >or=200 mg/dl (2.3 mmol). For both treatments, notable differences between TG subgroups were that patients with elevated TGs had smaller reductions in LDL(2)-C, slightly smaller decreases in all IDL subclasses and greater decreases in all VLDL-C subclasses than those with lower TG levels. Frequency of pattern B was also reduced more in patients with higher TGs for both treatments. CONCLUSIONS: Ezetimibe/simvastatin reduced the cholesterol content of most lipoprotein subclasses from baseline with generally similar efficacy in patients with low and high TGs. Despite the different mechanism of action of ezetimibe, the response to ezetimibe/simvastatin and atorvastatin treatment related to these lipoprotein subclasses was generally consistent with the overall effects of these therapies on the major lipid/lipoprotein classes. The clinical significance of these results awaits further study.

Plasma cholesterol and related lipid levels of seemingly healthy public service employees in Kampala, Uganda.

BACKGROUND: As Uganda's economy improves, many people tend to adopt western diets and sedentary life styles that predispose to cardiovascular diseases including hypertension. These may be in silent danger without any typical symptoms to send early warning signals. In Uganda, cardiovascular diseases (CVD) and diabetes mellitus are rapidly emerging as major causes of morbidity and mortality. OBJECTIVE: This study was conducted to determine spot levels of plasma lipid indicators of CVD in seemingly healthy public service employees in Kampala, Uganda. The purpose of this study was achieved through analysis of fasting plasma samples for the following: Total cholesterol (TC), Triacylglycerols (TG), High density lipoprotein cholesterol (HDL), Low density lipoprotein cholesterol (LDL), and molar ratios of LDL/HDL, TC/ HDL, and TC/TG. METHODS: One hundred and seventy four fasting executives 85 males and 89 females employed in public service in Kampala, Uganda, were investigated to determine enzymatically spot levels of TC, TG, HDL, and LDL from which their mutual ratios were calculated. RESULTS: In each of the 7 parameters studied, the samples showed risk factors for CVD at the following rates: HDL 10%, LDL/HDL 12%, TG 47%, LDL 48%, TC/HDL 53% TC 66%, TG/HDL 68%,. CONCLUSIONS: In all the cut off points used, each analyte had a significant percentage of public service employees at risk of CVD. It is therefore concluded that hypercholesterolaemia and other dyslipidemias exist among seemingly healthy public service employees in Kampala, Uganda, and this needs urgent intervention at both individual and national levels.

Regulation of hippocampal cholesterol metabolism by apoE and environmental stimulation.

Alzheimer's disease is associated with genetic risk factors, of which the allele E4 of apolipoprotein E (apoE4) is the most prevalent, and it is also affected by environmental factors such as early life education. We have recently shown, utilizing apoE-deficient and apoE transgenic mice, that synaptogenesis in the hippocampus following environmental stimulation is affected by apoE. In view of the pivotal role of cholesterol in synaptic plasticity, and of its suggested role in synaptogenesis, we presently examined the effects of apoE and environmental stimulation on brain cholesterol homeostasis. The hippocampal levels of cholesterol and its precursors and metabolites in control mice were not affected by exposure to environmental stimulation. In contrast, the hippocampal levels of cholesterol and its precursors lathosterol and desmosterol and metabolite 24S-hydroxycholesterol were lower in apoE-deficient mice that were maintained in a regular environmental than those of corresponding control mice, whereas they were markedly elevated following environmental stimulation. Histological and immunohistochemical experiments revealed that the combined stimulatory effects of apoE deficiency and environmental stimulation on cholesterol metabolism were associated with marked activation of hippocampal astrocytes and with the abnormal accumulation of cholesterol in neurons and astrocytes. These effects were rescued similarly in apoE3 and apoE4 transgenic mice. These findings suggest that apoE plays an important role in the translocation of cholesterol from astrocytes to neurons in vivo and in the regulation and homeostasis of this process.

Substituting abacavir for hyperlipidemia-associated protease inhibitors in HAART regimens improves fasting lipid profiles, maintains virologic suppression, and simplifies treatment.

BACKGROUND: Hyperlipidemia secondary to protease inhibitors (PI) may abate by switching to anti-HIV medications without lipid effects. METHOD: An open-label, randomized pilot study compared changes in fasting lipids and HIV-1 RNA in 104 HIV-infected adults with PI-associated hyperlipidemia (fasting serum total cholesterol >200 mg/dL) who were randomized either to a regimen in which their PI was replaced by abacavir 300 mg twice daily (n = 52) or a regimen in which their PI was continued (n = 52) for 28 weeks. All patients had undetectable viral loads (HIV-1 RNA <50 copies/mL) at baseline and were naive to abacavir and non-nucleoside reverse transcriptase inhibitors. RESULTS: At baseline, the mean total cholesterol was 243 mg/dL, low density lipoprotein (LDL)-cholesterol 149 mg/dL, high density lipoprotein (HDL)-cholesterol 41 mg/dL, and triglycerides 310 mg/dL. Mean CD4+ cell counts were 551 and 531 cells/mm3 in the abacavir-switch and PI-continuation arms, respectively. At week 28, the abacavir-switch arm had significantly greater least square mean reduction from baseline in total cholesterol (-42 vs -10 mg/dL, P < 0.001), LDL-cholesterol (-14 vs +5 mg/dL, P = 0.016), and triglycerides (-134 vs -36 mg/dL, P = 0.019) than the PI-continuation arm, with no differences in HDL-cholesterol (+0.2 vs +1.3 mg/dL, P = 0.583). A higher proportion of patients in the abacavir-switch arm had decreases in protocol-defined total cholesterol and triglyceride toxicity grades, whereas a smaller proportion had increases in these toxicity grades. At week 28, an intent-to treat: missing = failure analysis showed that the abacavir-switch and PI-continuation arms did not differ significantly with respect to proportion of patients maintaining HIV-1 RNA <400 or <50 copies/mL or adjusted mean change from baseline in CD4+ cell count. Two possible abacavir-related hypersensitivity reactions were reported. No significant changes in glucose, insulin, insulin resistance, C-peptide, or waist-to-hip ratios were observed in either treatment arm, nor were differences in these parameters noted between treatments. CONCLUSION: In hyperlipidemic, antiretroviral-experienced patients with HIV-1 RNA levels <50 copies/mL and CD4+ cell counts >500 cells/mm3, substituting abacavir for hyperlipidemia-associated PIs in combination antiretroviral regimens improves lipid profiles and maintains virologic suppression over a 28-week period, and it simplifies treatment.

Effect of the statin atorvastatin on intracellular signalling by the prostacyclin receptor in vitro and in vivo.

Prostacyclin plays a central role within the vasculature. We have previously established that the prostacyclin receptor (IP) undergoes isoprenylation, a lipid modification obligate for its function. The aim of the current study was to investigate the effect of the hydroxy methyl glutaryl co-enzyme A reductase inhibitor atorvastatin on signalling and function of the IP expressed in mammalian whole cells and in platelets isolated from patients undergoing therapeutic intervention with atorvastatin. Initially, the effect of atorvastatin on signalling by the human (h) and mouse (m) IP overexpressed in human embryonic kidney 293 cells and the hIP endogenously expressed in human erythroleukaemic 92.1.7 cells was investigated. Atorvastatin significantly reduced IP-mediated cAMP generation (IC(50) 6.6-11.1 microm) and [Ca(2+)](i) mobilization (IC(50) 7.2-16.4 microm) in a concentration-dependent manner, but had no effect on signalling by the nonisoprenylated beta(2) adrenergic receptor or the alpha or beta isoforms of the human thromboxane A(2) receptor (TP). Moreover, atorvastatin significantly reduced IP-mediated crossdesensitization of signalling by TP alpha (IC(50) 10.4 microm), but not by TP beta. In contrast to the whole-cell data, atorvastatin therapy did not interfere with IP-mediated cAMP generation or IP-induced inhibition of TP-mediated aggregation of platelets isolated from human volunteers undergoing therapeutic intervention with atorvastatin (10-80 mg per daily dose). In conclusion, while data generated in whole cells indicated that atorvastatin significantly impairs signalling by both the hIP and mP, the in vivo clinical data indicated that, at the administered therapeutic dose, atorvastatin does not significantly compromise IP signalling and function in humans.