Lipoprotein a Research Papers - Academia.edu (original) (raw)
The aim of this study was to determine the extent of accumulation of lipoprotein(a) [Lp(a)] in human arterial wall and to define its potential role in atherogenesis. Biopsies routinely taken from the ascending aorta of 107 patients... more
The aim of this study was to determine the extent of accumulation of lipoprotein(a) [Lp(a)] in human arterial wall and to define its potential role in atherogenesis. Biopsies routinely taken from the ascending aorta of 107 patients undergoing aortocoronary bypass surgery were analyzed for lipid and lipoprotein parameters, which were then correlated to serum values. A significant positive correlation was established between serum Lp(a) and arterial wall apolipoprotein (apo)(a) by enzyme-linked immunosorbent assay. High serum Lp(a) also led to a significant increase of apo B in the arterial wall. No significant correlation was found between apo B in serum and aortic tissue. Apo B was found to be partially linked to apo(a) in the aortic extract. Furthermore, apo(a) was found to be intact, as determined by its molecular weight in sodium dodecyl sulfate electrophoresis. This technique also revealed that the apo(a) isoform pattern of aortic homogenate was comparable to the individual seru...
Positive effect of thyroid hormone replacement (THR) on lipid profile is well defined. Effectiveness of THR on lipid profile and function among elderly patients with subclinical hypothyroidism (SCH) has not yet been concluded. This is a... more
Positive effect of thyroid hormone replacement (THR) on lipid profile is well defined. Effectiveness of THR on lipid profile and function among elderly patients with subclinical hypothyroidism (SCH) has not yet been concluded. This is a population-based cross-sectional study. Twenty-six elderly patients with SCH were compared with 31 patients with clinical hypothyroidism (CH). Before the study neither group had received THR therapy. Data on lipid profile, demographic, functional, and cognitive status were obtained at baseline. SCH was defined as an elevated thyroid-stimulating hormone (TSH) level (>4.67 mU/l) and normal serum free thyroxine (FT 4) level. Total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and triglycerides (TG) were measured after overnight fast. The level of lower density lipoprotein (LDL) cholesterol was calculated. Both studied groups received levothyroxyne replacement and re-evaluated after 3 months of euthyroidism. Functional and cognitive status were evaluated by the activity of daily living (ADL) and mini mental state evaluation (MMSE), respectively. Participants with SCH did not differ from patients with CH regarding age, gender, cognitive, and functional status, and prevalence of cardiovascular disease (CD) was similar in both groups. Most patients (24/26) with SCH had TSH levels lower than 10 mU/l. Response to THR therapy regarding the improvement of blood levels of TC, LDL, and TG had a non-significant trend, which seemed to be better in patients with SCH than in those with CH. Decreases, TC/HDL and LDL/HDL ratios were greater in patients SCH (p < 0.0001 and p = 0.0004, respectively) than in patients with CH.
Human lecithin:cholesterol acyltransferase (LCAT) is a key enzyme in the metabolism of cholesterol and is postulated to participate in the physiological process called reverse cholesterol transport. We have used transgenic mice (Tgm)... more
Human lecithin:cholesterol acyltransferase (LCAT) is a key enzyme in the metabolism of cholesterol and is postulated to participate in the physiological process called reverse cholesterol transport. We have used transgenic mice (Tgm) expressing either both human apolipoprotein AI (apo AI) and human LCAT genes or only the human apo AI gene (HuAILCAT or HuAI Tgm, respectively) to assess the consequences of LCAT overexpression on serum lipid and lipoprotein profiles and on the ability of each serum to promote bidirectional flux of cholesterol between serum and Fu5AH hepatoma cells. Mean serum LCAT activity of HuAILCAT Tgm was 2-fold increased compared to the HuAI group (48 9 9 vs. 24 9 5 nmol/ml per h, PB 0.01 for HuAILCAT and HuAI Tgm, respectively) and the cholesterol esterification rates were not significantly different between the two groups of animals (66911 vs. 74918 nmol/ml per h for HuAILCAT and HuAI Tgm, respectively). HuAILCAT Tgm exhibited higher total cholesterol serum values (2.3-fold) due to an increase in both HDL-cholesterol (1.9-fold) and non-HDL-cholesterol (3-fold). The HDL particles from HuAILCAT Tgm were relatively phospholipid depleted and cholesterol enriched compared to HuAI mice. When cells were incubated for six hours with the mouse serum, the fractional efflux of radiolabeled cholesterol was slightly increased with the HuAILCAT Tgm (1.2-fold) but the increase in intracellular cholesterol content was also 2-fold higher than with the HuAI Tgm. Fu5AH can be viewed as a model for the evaluation of bidirectional flux of cholesterol in SR-BI-rich cells. In this model LCAT overexpression in mice, by increasing both HDL and non-HDL-cholesterol, mostly enhances the uptake of cholesterol by the cells, which would be of benefit for the last step of reverse cholesterol transport in hepatocytes.
The demonstration in animals that recombinant tissue-type plasminogen activator produces prolonged thrombolysis after its clearance from the circulation has prompted a few pilot studies of bolus administration in patients. Alteplase... more
The demonstration in animals that recombinant tissue-type plasminogen activator produces prolonged thrombolysis after its clearance from the circulation has prompted a few pilot studies of bolus administration in patients. Alteplase (bolus dose of 70 mg) resulted in the highest recanalixation rate in our previous pilot study comparing bolus doses of 50,60 and 70 mg of alteplase in patients with acute myocardial infarction. The aim of the present trial was to assess the efficacy and safety of the same bolus dose in a larger number of patients. A further objective was to study the anglographic reocclusion rate at 12 to 24 hours in patients who had a recanaliied infarct-related coronary artery at 90 minutes and were randomized at that time to a bolus dose or an infusion for 3 hours of 30 mg of alteplase.
in life when bone catabolism supersedes anabolism, the significant loss of bone mass (osteoporosis) becomes a common medical problem ). tures (NIH Consensus Development Panel on Osteopo-Shauna Heeger, George Sabatakos, Suneel Apte, rosis... more
in life when bone catabolism supersedes anabolism, the significant loss of bone mass (osteoporosis) becomes a common medical problem ). tures (NIH Consensus Development Panel on Osteopo-Shauna Heeger, George Sabatakos, Suneel Apte, rosis Prevention, 2001). The worldwide annual incidence William N. Adkins, Jeremy Allgrove, of osteoporotic hip fracture exceeds 1.7 million cases Mine Arslan-Kirchner, Jennifer A. Batch, (http://www.who.int/inf-pr-1 999/en/pr99-58.html). Peter Beighton, Graeme C. M. Black, Numerous factors have been implicated in the develop-Richard G. Boles, Laurence M. Boon, ment of osteoporosis. Family and epidemiological stud-Carla Borrone, Han G. Brunner, Georges F. Carle, ies indicate that the peak bone mass attained during Bruno Dallapiccola, Anne De Paepe, Barbara Floege, growth is an important risk factor (NIH Consensus Devel-Melissa Lees Halfhide, Bryan Hall, opment Panel on Osteoporosis Prevention, 2001; See-Raoul C. Hennekam, Tatsuo Hirose, Ab Jans, man et al., 1994). Harald Jü ppner, Chong Ae Kim, Kim Keppler-Noreuil, Two principal cell types are responsible for the depo-Alfried Kohlschuetter, Didier LaCombe, sition and degradation of bone matrix. The bone-forming Marie Lambert, Emmanuelle Lemyre, cells, osteoblasts, differentiate from mesenchymal stem Tom Letteboer, Leena Peltonen, cells at sites of membranous bone formation, in perios-Rajkumar S. Ramesar, Marta Romanengo, teum of endochondral bones, and in bone marrow Hannu Somer, Elisabeth Steichen-Gersdorf, stroma (Aubin, 1998). The bone-degrading cells, osteo-Beat Steinmann, Beth Sullivan, clasts, differentiate from hematopoietic mononuclear Andrea Superti-Furga, Walter Swoboda, cells present in peripheral blood and bone marrow Marie-José van den Boogaard, Wim Van Hul, (Roodman, 1996). In order for bone mass to accrue dur-Miikka Vikkula, Marcela Votruba, Bernhard Zabel, ing the growth and maturation of the skeleton, bone Teresa Garcia, Roland Baron, Bjorn R. Olsen, formation by osteoblasts must exceed bone degradaand Matthew L. Warman 1 tion by osteoclasts. The Osteoporosis-Pseudoglioma Syndrome Children with the autosomal recessive disorder osteo-Collaborative Group 3 porosis-pseudoglioma syndrome (OPPG) (Gong et al., 1996) have very low bone mass and are prone to developing fractures and deformation ( .
Approximately 20% of the population has elevated circulating levels of lipoprotein(a) (Lp[a]), one of the most robust predictors of cardiovascular disease risk. This is particularly true for women. Many female patients with... more
Approximately 20% of the population has elevated circulating levels of lipoprotein(a) (Lp[a]), one of the most robust predictors of cardiovascular disease risk. This is particularly true for women. Many female patients with "normal" traditional risk factors or low atherosclerotic cardiovascular disease (ASCVD) risk scores may harbor high risk related to elevated levels of Lp(a). A retrospective, cross-sectional study of consecutive female patients presenting to Heart Centers for Women was performed. Discordance between low-density lipoprotein cholesterol (LDL-C) and Lp(a) was determined. The ASCVD risk and Reynolds Risk Score models A (RRS-A) and B (RRS-B) were calculated, and level of agreement in patients meeting treatment threshold (≥7.5% for ASCVD, ≥10% for RRS-A and RRS-B) were compared. Among 713 women, 290 (41%) had elevated Lp(a); however, LDL-C and Lp(a) were weakly correlated (r = 0.08). Significant discordance was observed between abnormal LDL-C and Lp(a) levels...
In this work we describe the ability of living Trypanosoma rangeli to hydrolyze extracellular ATP. In these intact parasites whose viability was assessed before and after the reactions by motility and by Trypan blue dye exclusion, there... more
In this work we describe the ability of living Trypanosoma rangeli to hydrolyze extracellular ATP. In these intact parasites whose viability was assessed before and after the reactions by motility and by Trypan blue dye exclusion, there was a low level of ATP hydrolysis in the absence of any divalent metal (1.53 § 0.12 nmol Pi/h £ 10 7 cells). The ATP hydrolysis was stimulated by MgCl 2 and the Mg-dependent ecto-ATPase activity was 5.24 § 0.64 nmol Pi/h £ 10 7 cells. The Mg-dependent ecto-ATPase activity was linear with cell density and with time for at least 60 min. This stimulatory eVect on the ATP hydrolysis was also observed when MgCl 2 was replaced by MnCl 2 , but not by CaCl 2 , SrCl 2 , and ZnCl 2 . The apparent K m for Mg-ATP2-was 0.53 § 0.11 mM. The optimum pH for the T. rangeli Mg-dependent ecto-ATPase activity lies in the alkaline range. This ecto-ATPase activity was insensitive to inhibitors of other ATPase and phosphatase activities, such as oligomycin, sodium azide, baWlomycin A1, ouabain, furosemide, vanadate, molybdate, sodium Xuoride, tartrate, and levamizole. To conWrm that this Mg-dependent ATPase was an ecto-ATPase, we used an impermeant inhibitor, DIDS (4, 4Ј-diisothiocyanostylbene 2Ј-2Ј-disulfonic acid) as well as suramin, an antagonist of P2 purinoreceptors and inhibitor of some ecto-ATPases. These two reagents inhibited the Mg 2+ -dependent ATPase activity in a dose-dependent manner. This ecto-ATPase activity was stimulated by carbohydrates involved in the attachment/invasion of salivary glands of Rhodnius prolixus and by lipophorin, an insect lipoprotein circulating in the hemolymph.
Recentemente, indicadores associados à aptidão física relacionada à saúde vêm sendo interpretados mediante informações referenciadas por critério. Informações referenciadas por critério direcionadas à saúde representam níveis desejáveis... more
Recentemente, indicadores associados à aptidão física relacionada à saúde vêm sendo interpretados mediante informações referenciadas por critério. Informações referenciadas por critério direcionadas à saúde representam níveis desejáveis consistentes com reduzido risco de aparecimento e desenvolvimento de disfunções orgânicas que deverão ser alcançados pelos adolescentes. Objetivo do estudo foi analisar a validade de pontos de corte associados às informações referenciadas por critério preconizados pela proposta Physical Best na identificação de adolescentes portadores e não-portadores de fatores de risco predisponentes às doenças cardiovasculares. A amostra foi constituída por 281 adolescentes (157 moças e 124 rapazes) com idades entre 15 e 18 anos. Informações acerca da aptidão física relacionada à saúde foram obtidas mediante indicadores morfológicos (índice de massa corporal e somatório de espessuras das dobras cutâneas tricipital e subescapular) e resultados de testes motores (sentar-e-alcançar, abdominal modificado e caminhada/corrida de 1600 metros). Quanto aos fatores de risco predisponentes às doenças cardiovasculares, recorreu-se ao conteúdo de gordura corporal, ao consumo máximo de oxigênio, aos níveis de pressão arterial e às concentrações de lipídios-lipoproteínas plasmáticas. Estimativas quanto aos índices de sensibilidade, especificidade, valor preditivo positivo e eficiência foram utilizados para descrever a validade relativa. Os resultados mostraram que os índices de sensibilidade se apresentaram entre 20% e 70% e os de especificidade entre 30% e 85%. Os indicadores morfológicos demonstraram que podem identificar corretamente três em cada quatro adolescentes com fatores de risco predisponentes às doenças cardiovasculares. Os pontos de corte associados aos resultados dos testes motores demonstraram baixos níveis de sensibilidade e elevada proporção de casos falso-positivos. Como conclusão, os achados sugerem que, independentemente dos pontos de corte utilizados, o índice de massa corporal e o somatório das espessuras das dobras cutâneas caracterizam-se como razoável alternativa para identificar a presença de fatores de risco predisponentes às doenças cardiovasculares em adolescentes.
There is increasing evidence from epidemiological studies that exogenous estrogen (hormone replacement therapy) protects against the elevated risk of cardiovascular disease in women after the menopause. However, it is still uncertain... more
There is increasing evidence from epidemiological studies that exogenous estrogen (hormone replacement therapy) protects against the elevated risk of cardiovascular disease in women after the menopause. However, it is still uncertain whether the postmenopausal decrease in endogenous estrogen in itself contributes significantly to this increase in risk. Most of the studies that have provided evidence linking cardiovascular disease with menopause have involved North American women, who may differ significantly from Europeans in terms of lifestyle and diet. ICARUS (Italian Climacteric Research Group Study) is an observational study that involves Italian Menopause Clinics, with the objective of collecting observational data on menopause and its management. The results of a cross-sectional analysis of 9309 women, free from any hormonal treatment and enrolled up to March 1997, are reported here. Data show that the menopause has a marked effect on the circulating levels of lipids and lipoproteins. From pre-to post-menopause there are significant increases in total cholesterol (6.9% before and 4.4% after adjustment for covariates including chronological age, educational level, center, BMI, smoking habits, hypertension and diabetes, previous contraceptive use, and time since menopause), LDL (7.5% before, 4.0% after), and triglycerides (9.0% before, 3.2% (ns) after). However, there is no significant change in HDL. Among postmenopausal women, no effect on lipid profile of time since menopause was observed.
The purpose of this study was to investigate the effects of resistance training (RT) on novel cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM). We enrolled 52 overweight/obese, type 2 diabetic patients, with... more
The purpose of this study was to investigate the effects of resistance training (RT) on novel cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM). We enrolled 52 overweight/obese, type 2 diabetic patients, with inadequate glycemic control (HbA1c [ 6.5 %), but without overt diabetic vascular complications. Participants were randomly assigned into two equivalent groups (n = 26): (1) Resistance exercise group: subjects underwent a supervised RT program (3-times/week, 60 min/session, 2-3 sets of 8 machine-weight exercises, 60-80 % of onerepetition maximum). (2) Control group (CG): at study entrance, they received a structured exercise counseling to increase daily physical activity. Clinical parameters, cardiorespiratory capacity, glycemic and lipid profile, apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB), Lipoprotein(a) [Lp(a)], insulin resistance (HOMA-IR), highsensitivity CRP (hsCRP), fibrinogen were measured before and after 3 months. RT significantly reduced glycemic indexes, insulin resistance and systolic blood pressure, compared to CG (p \ 0.05). Moreover, exercise-treated patients conferred a remarkable downregulation in ApoB levels (from 135.92 ± 30.97 mg/dL to 85.9 ± 26.46 mg/dL, p \ 0.001) as compared to CG (from 126.33 ± 36.59 mg/dL to 116.23 ± 27.52 mg/dL, p = 0.872) (p \ 0.001). Similarly, ApoB/ApoA-I ratio was considerably decreased in REG rather than CG (-0.32 ± 0.09 vs 0.02 ± 0.01, p \ 0.001). Notably, ApoA-I, Lp(a), hsCRP, fibrinogen, the rest of lipid parameters, body weight and exercise capacity remained unaltered in both groups (p [ 0.05). Among variables, HOMA-IR reduction was found to be an independent predictor of changes in ApoB/ApoA-I ratio (R 2 = 0.406, p = 0.041) in REG. Long-term RT ameliorated glycemic control, insulin sensitivity and ApoB/ApoA-I ratio in individuals with T2DM. Although we did not observe significant benefits in the rest of cardiovascular risk factors, our results indicate a merely beneficial impact of RT.
Background: n-3 Polyunsaturated fatty acids (n-3 PUFA) convey several health benefits, including a reduction of serum concentration of triglycerides (TG). Aim: To examine the effect on blood lipids, particularly TG, of a diet with n-3... more
Background: n-3 Polyunsaturated fatty acids (n-3 PUFA) convey several health benefits, including a reduction of serum concentration of triglycerides (TG). Aim: To examine the effect on blood lipids, particularly TG, of a diet with n-3 PUFA enriched eggs in healthy volunteers in the Seychelles (Indian Ocean). Methods: Double-blind crossover trial with one group of volunteers fed with 5 normal eggs per week during 3 weeks followed by 5 enriched eggs per week during the next 3 weeks while the other group received eggs in the inverse sequence. Hen feed was supplemented at 5% with tuna oil. Enriched eggs contained nine times more n-3 PUFA than usual eggs (mainly docosahexaenoic acid). Results: Twenty-five healthy volunteers participated in the study. Based on pooled results observed during the two 3-week periods, consumption of enriched eggs was associated with a significant 16e18% decrease in serum triglycerides (P < 0.01) but with no significant difference in serum LDL-cholesterol and HDL-cholesterol. Serum LDL-cholesterol increased during the first 3-week period and decreased during the second 3-week period with both normal and enriched eggs. Participants did not report a systematic preference for either type of eggs.
Aronia melanocrpa fruit juice (AMFJ) used in our experiment was very rich in phenolic substances (709.3 mg gallic acid equivalents/100 ml juice). Anthocyanins (106.8 mg cyanidin-3-glucoside equivalents/100 ml juice) were the main... more
Aronia melanocrpa fruit juice (AMFJ) used in our experiment was very rich in phenolic substances (709.3 mg gallic acid equivalents/100 ml juice). Anthocyanins (106.8 mg cyanidin-3-glucoside equivalents/100 ml juice) were the main flavonoid group. The aim of this study was to assess the influence of AMFJ on plasma lipids and lipoprotein profile, and histopathology of liver and aorta in rats with dietary-induced hyperlipidemia. AMFJ was administered by gavage for 30 days at doses of 5, 10 and 20 ml/kg body weight to rats fed a standard diet (SD) or a 4% cholesterol-containing diet (4% ChD). The 4% ChD caused a significant elevation of plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). AMFJ did not significantly influence plasma lipids in rats fed the SD and significantly hindered the elevation of plasma TC, LDL-C and TG in rats fed the 4% ChD. High-density lipoprotein cholesterol (HDL-C) levels were not significantly influenced either by...
Serum lipoprotein(a) (Lp(a)) was serially determined after acute attacks of myocardial infarction and after surgical operations. Acute phase proteins, such as C-reactive protein, cw,-acid glycoprotein, cy,-antitrypsin and haptoglobin,... more
Serum lipoprotein(a) (Lp(a)) was serially determined after acute attacks of myocardial infarction and after surgical operations. Acute phase proteins, such as C-reactive protein, cw,-acid glycoprotein, cy,-antitrypsin and haptoglobin, increased rapidly and markedly after the episodes. Initial values of serum Lp(a) concentrations were almost the same in both groups. Increases in serum Lp(a) levels were also observed during the first few days, with a return to the initial levels after more than 1 month. The periods for reaching maximal levels of acute phase proteins were similar in both groups of patients. On the contrary, the period required for Lp(a) to reach the maximal level in the myocardial infarction group was significantly longer than in the post-operative group. The present study suggests that Lp(a) has the characteristics of an acute phase reactant and may play an important role in recovery from tissue damage.
Background: Coronary artery disease (CAD) is one of the major causes of morbidity and mortality in the world. The disease is determined by many risk factors such as age, gender, diabetes, dyslipidemia, smoking, as well as elevated serum... more
Background: Coronary artery disease (CAD) is one of the major causes of morbidity and mortality in the world. The disease is determined by many risk factors such as age, gender, diabetes, dyslipidemia, smoking, as well as elevated serum levels of lipoprotein (a) (Lp(a)), homocysteine, C-reactive protein (CRP) and uric acid. In this study, we evaluated the association of biologic and metabolic parameters with CAD in a group of Lebanese patients. Methods: Three hundred patients were recruited for the study. Biologic and blood metabolic parameters were measured. Patients were then divided into 3 groups according to their catheterization result: 0% stenosis (controls), b 50% stenosis and z 50% stenosis. Results: Hyperlipidemias, CRP, homocysteine and uric acid levels in CAD patients were not different from those of the controls. However, age, elevated fasting blood glucose (FBG) and elevated serum Lp(a) levels were found to be strong independent predictors of CAD in our study population. Association with CAD was also shown for gender, hypertension, diabetes and family history of CAD. Conclusion: We report the importance of serum Lp(a) levels and FBG in the prediction and prevention of CAD in our population. D
- by Sami Azar
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- Lebanon, Blood Glucose, Fasting, Risk factors
mediated lipid transfer. Of note, MAb C167 also potently blocked Huh-7.5 infection by an HCV strain recovered from HCVcc-infected chimpanzees. These results demonstrate that SR-B1 is essential for infection with HCV produced in vitro and... more
mediated lipid transfer. Of note, MAb C167 also potently blocked Huh-7.5 infection by an HCV strain recovered from HCVcc-infected chimpanzees. These results demonstrate that SR-B1 is essential for infection with HCV produced in vitro and in vivo and suggest the possible use of anti-SR-B1 antibodies as therapeutic agents.
Atherothrombosis is a complex disease in which cholesterol deposition, inflammation, and thrombus formation play a major role. Rupture of high-risk, vulnerable plaques is responsible for coronary thrombosis, the main cause of unstable... more
Atherothrombosis is a complex disease in which cholesterol deposition, inflammation, and thrombus formation play a major role. Rupture of high-risk, vulnerable plaques is responsible for coronary thrombosis, the main cause of unstable angina, acute myocardial infarction, and sudden cardiac death. In addition to rupture, plaque erosion may also lead to occlusive thrombosis and acute coronary events. Atherothrombosis can be evaluated according to histologic criteria, most commonly categorized by the American Heart Association (AHA) classification. However, this classification does not include the thin cap fibroatheroma, the most common form of high-risk, vulnerable plaque. Furthermore, the AHA classification does not include plaque erosion. As a result, new classifications have emerged and are reviewed in this article. The disease is asymptomatic during a long period and dramatically changes its course when complicated by thrombosis. This is summarized in five phases, from early lesions to plaque rupture, followed by plaque healing and fibrocalcification. For the early phases, the role of endothelial dysfunction, cholesterol transport, high-density lipoprotein, and proteoglycans are discussed. Furthermore, the innate and adaptive immune response to autoantigens, the Toll-like receptors, and the mechanisms of calcification are carefully analyzed. For the advanced phases, the role of eccentric remodeling, vasa vasorum neovascularization, and mechanisms of plaque rupture are systematically evaluated. In the final thrombosis section, focal and circulating tissue factor associated with apoptotic macrophages and circulatory monocytes is examined, closing the link between inflammation, plaque rupture, and blood thrombogenicity.
The National Cholesterol Education Program Adult Treatment Panel guidelines have established low-density lipoprotein cholesterol (LDL-C) treatment goals, and secondary non-high-density lipoprotein (HDL)-C treatment goals for persons with... more
The National Cholesterol Education Program Adult Treatment Panel guidelines have established low-density lipoprotein cholesterol (LDL-C) treatment goals, and secondary non-high-density lipoprotein (HDL)-C treatment goals for persons with hypertriglyceridemia. The use of lipid-lowering therapies, particularly statins, to achieve these goals has reduced cardiovascular disease (CVD) morbidity and mortality; however, significant residual risk for events remains. This, combined with the rising prevalence of obesity, which has shifted the risk profile of the population toward patients in whom LDL-C is less predictive of CVD events (metabolic syndrome, low HDL-C, elevated triglycerides), has increased interest in the clinical use of inflammatory and lipid biomarker assessments.
Background and aim: Most but not all studies in children, adolescents and young adults with a family history of coronary artery disease have reported an increase in lipoprotein(a) (Lp(a)) concentrations. The aim of this study was to... more
Background and aim: Most but not all studies in children, adolescents and young adults with a family history of coronary artery disease have reported an increase in lipoprotein(a) (Lp(a)) concentrations. The aim of this study was to assess if healthy children, adolescents and young adults with a parental history of premature myocardial infarction (PHPMI) have increased Lp(a) levels and are at higher risk of elevated (>30 mg/dl) Lp(a) concentrations. Methods and results: One hundred fifty healthy children, adolescents and young adults with PHPMI (55% males; age 18 AE 6.7 years) and 150 age-(AE1 year) and gender-matched control subjects participated in the study. Concentrations of total plasma cholesterol, low-density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol, apolipoprotein (Apo) A-I and B, triglycerides and Lp(a) were determined after fasting for 14 h. Participants with PHPMI had higher concentrations of LDL-cholesterol (107.9 AE 31.1 vs. 99.2 AE 28.7 mg/dl, p Z 0.01), Apo B (89.6 AE 26.4 vs. 82.8 AE 20.2 mg/dl, p Z 0.011) and Lp(a) (26.7 AE 34.0 vs. 19.2 AE 23.2 mg/dl, p Z 0.012) and lower HDL-cholesterol concentrations (47.9 AE 11.3 vs. 50.7 AE 13.9 mg/dl, p Z 0.038) than participants without PHPMI. Thirty percent of PHPMI positive subjects had elevated Lp(a) concentrations vs. 16.7% of PHPMI negative subjects (p Z 0.009; relative risk 2.14; 95% CI 1.23e3.73). In a conditional logistic regression analysis, Lp(a) concentration was significantly and independently associated with PHPMI. a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / n m c d Nutrition, Metabolism & Cardiovascular Diseases (2008) 18, 492e496
Plasma and serum biochemical markers proposed for cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin and predementia syndromes (mild cognitive impairment and other related entities) are based on... more
Plasma and serum biochemical markers proposed for cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin and predementia syndromes (mild cognitive impairment and other related entities) are based on pathophysiologic processes such as lipoprotein metabolism (total cholesterol, apolipoprotein E, 24S-hydroxy-cholesterol), and vascular disease (homocysteine, lipoprotein(a)); SP formation (amyloid h(Ah)-protein, Ah autoantibodies, platelet APP isoforms), oxidative stress (isoprostanes, vitamin E), and inflammation (cytokines). This review will focus on the current knowledge on circulating serum and plasma biomarkers of cognitive decline and dementia that are linked to cholesterol homeostasis and lipoprotein abnormalities, senile plaque formation and amyloid precursor protein (APP) metabolism, oxidative stress, and inflammatory reactions. Special emphasis will, however, be placed on biomarkers related to lipoprotein metabolism and vascular disease. Analytically, most plasma and serum proteins or metabolites lack reproducibility, sensitivity, or specificity for the diagnosis, risk and progression assessment, or therapeutic monitoring of AD and other dementing disorders. Measures linked to lipoprotein metabolism and vascular disease, APP metabolism, oxidative stress, or inflammation appear altered in AD relative to controls, but lack sufficient discriminatory power. Measures combining several biomarkers or incorporating a range of proteins in plasma and small molecule metabolites are promising approaches for the development of plasma or serum-based diagnostic tests for AD and other dementing disorders, as well as for predementia syndromes. D
- by Antonio Capurso and +1
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- Dementia, Mild Cognitive Impairment, Cholesterol, Apolipoprotein E
Hypercholesterolemia confers susceptibility to cardiovascular disease (CVD). Both serum total cholesterol (TC) and LDL-cholesterol (LDL-C) exhibit a strong genetic component (heritability estimates 0.41-0.50). However, a large part of... more
Hypercholesterolemia confers susceptibility to cardiovascular disease (CVD). Both serum total cholesterol (TC) and LDL-cholesterol (LDL-C) exhibit a strong genetic component (heritability estimates 0.41-0.50). However, a large part of this heritability cannot be explained by the variants identified in recent extensive genome-wide association studies (GWAS) on lipids. Our aim was to find genetic causes leading to high LDL-C levels and ultimately CVD in a large Austrian family presenting with what appears to be autosomal dominant inheritance for familial hypercholesterolemia (FH). We utilized linkage analysis followed by whole-exome sequencing and genetic risk score analysis using an Austrian multi-generational family with various dyslipidemias, including elevated TC and LDL-C, and one family branch with elevated lipoprotein (a) (Lp(a)). We did not find evidence for genome-wide significant linkage for LDL-C or apparent causative variants in the known FH genes rather, we discovered a p...
- by Stephanie Fuller and +1
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- Metabolism, Polymorphism, Attention, Neurochemistry
The Venereal Disease Research Laboratory (VDRL) test is a microflocculation test for syphilis that uses an antigen containing cardiolipin, lecithin, and cholesterol. For more than 50 years, the preparation of natural cardiolipin and... more
The Venereal Disease Research Laboratory (VDRL) test is a microflocculation test for syphilis that uses an antigen containing cardiolipin, lecithin, and cholesterol. For more than 50 years, the preparation of natural cardiolipin and lecithin for this test has been based on the Pangborn method which involves isolating and purifying these components from beef hearts. This process is tedious and time-consuming and results in a variable purity range. In our studies, we found that a VDRL antigen using synthetic tetramyristoyl cardiolipin and synthetic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (lecithin) was as specific in detecting syphilis as a VDRL antigen made with natural components. In 85% of the cases, we obtained an endpoint titer of 1/2 or 1 dilution more than a titer obtained with a VDRL antigen made with natural components. The use of these pure synthetic compounds, with a purity of 99%, would offer advantages in the standardization and stability of the VDRL antigen. Because this antigen is the basic ingredient in the preparation of nontreponemal reagents such as the rapid plasma reagin, toluidine red unheated serum test, and the unheated serum reagin, the use of this synthetic VDRL antigen should also increase the reactivity of these reagents.
- by Luiz Alberto P. Ferreira and +1
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- Immunology, Syphilis, Intact polar lipids, Lipoprotein(a)
Objective: Oxidative damage has been suggested to be a contributory factor in the development and complications of atherosclerosis, and of recent the beneficial effects of antioxidants against some pathologies have gained considerable... more
Objective: Oxidative damage has been suggested to be a contributory factor in the development and complications of atherosclerosis, and of recent the beneficial effects of antioxidants against some pathologies have gained considerable interest. We evaluated the protective effects of flavonoids from Garcinia kola seeds on the oxidation of human low-density lipoprotein (LDL) and their ability to scavenge reactive oxygen species (ROS) in vitro. Setting: Methods: Human low-density lipoprotein (LDL) was prepared from fresh blood donated by volunteers with informed consent. The inhibitory effect of varying concentrations of flavonoids from Garcinia kola seeds, namely; Kolaviron (KV), Garcinia biflavanone (GB) 1, GB 2 and kolaflavanone (KF) on Fe/ ascorbate-induced peroxidation in LDL was investigated. Likewise the scavenging effect of these flavonoids on superoxide radicals and hydrogen peroxide in vitro was examined. Results: In the present study, KV, GB1, GB2 and KF exhibited marked scavenging effect (41-93 %) on H 2 O 2 , in vitro and the scavenging activities of these flavonoids were concentration dependent. Furthermore, KV, GB1, GB2 and KF showed marked activity as superoxide radicals (O 2 . ) scavenger. At 1 mg/ ml, KV, GB1, GB2 and KF scavenged O 2 . by 71%, 52 %, 66 % and 48 %, respectively. In addition, KV, GB1, GB2 and KF showed marked reducing property on potassium ferricyanide in vitro. KV, GB1 and GB2 were effective at preventing LDL lipid peroxidation (LPO) induced by Fe/ ascorbate system. Specifically at 0.01 mM, 0.1 mM and 1.0 mM, KV inhibited LPO by 29 %, 61 % and 79 %, while GB1 inhibited LPO by 29 %, 56 % and 86 %, respectively. At these concentrations, GB2 reduced LPO by 41 %, 72 % and 91 %, respectively. However, the inhibition of LDL peroxidation by KV, GB1 and GB2 were concentrations dependent. KF showed significant (p<0.05) inhibition of LDL peroxidation at 1.0 mM only. The inhibition of LDL peroxidation by these flavonoids follow the trend GB2 > GB1 > KV > KF at 1.0 mM. Conclusion: These flavonoids are active scavengers of H 2 O 2 and O 2 . radicals in vitro and their antilipoperoxidative effect might be linked to free radical scavenging ability, and this could be a pointer to their possible anti-atherogenic property.
Introduction The aim was to monitor the changes in haemocoagulation parameters in healthy volunteers after a thrombotripsy with 1-hour transcranial Doppler monitoring using a 2-4 MHz probe. Materials and methods About 10 healthy... more
Introduction The aim was to monitor the changes in haemocoagulation parameters in healthy volunteers after a thrombotripsy with 1-hour transcranial Doppler monitoring using a 2-4 MHz probe. Materials and methods About 10 healthy volunteers underwent a 1-hour thrombotripsy of the middle cerebral artery (MCA), thrombotripsy of the radial artery and a standard 20-min neurosonologic examination (NSE) in 2week intervals. Platelet count, aPTT, prothrombin time, fibrinogen, D-dimers, tPA, FDP, a-2-antiplasmin (AP), plasminogen, PAI-1 antigen, time of euglobulin clot lysis (ECL), homocysteine, and lipoprotein (a) were examined before, at the end and 24 h after a thrombotripsy. All adverse events were monitored.
- by David Skoloudík and +1
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- Ultrasound, Blood Coagulation, Homocysteine, Lipoprotein(a)
Whether metabolic control in type 2 diabetes mellitus (DM) is best achieved with the traditional high-carbohydrate (CHO), low-fat diet or a low-CHO, high-fat diet is still controversial. In a randomized crossover study, we compared the... more
Whether metabolic control in type 2 diabetes mellitus (DM) is best achieved with the traditional high-carbohydrate (CHO), low-fat diet or a low-CHO, high-fat diet is still controversial. In a randomized crossover study, we compared the effects of a low-fat (30% of daily energy) diet and a high-fat (40% of daily energy), high-monounsaturated-fat diet for 6 weeks each on fasting and postprandial glucose, insulin, and lipoprotein concentrations in 12 patients with well-controlled type 2 DM (fasting blood glucose, 176 ؎ 54 mg/dL; hemoglobin A 1c , 6.4% ؎ 0.7%) and no overt dyslipidemia (serum total cholesterol, 235 ؎ 43 mg/dL; triglycerides, 180 ؎ 63 mg/dL). Home-prepared foods were used and olive oil was the main edible fat, accounting for 8% and 25% of daily energy requirements in the low-fat and high-fat diets, respectively. For postprandial studies, the same mixed meal containing 36% fat was used in both dietary periods. Body weight and fasting and 6-hour postprandial blood glucose, insulin, and lipoprotein levels were similar after the two diets. The mean incremental area under the curve of serum triglycerides 0 to 6 hours after the challenge meal, adjusted for baseline levels, did not change significantly after the high-fat diet compared with the low-fat diet (1,484 ؎ 546 v 1,714 ؎ 709 mg · 6 h/dL, respectively, P ؍ .099). Mean postprandial triglyceride levels at 6 hours were increased about 2 times over fasting levels and were still greater than 300 mg/dL after either diet. A diet high in total and monounsaturated fat at the expense of olive oil is a good alternative diet to the traditional low-fat diet for patients with type 2 DM. However, ongoing postprandial hypertriglyceridemia with either diet points to the need for other therapies to decrease triglyceride-rich lipoproteins (TRL) and the inherent atherogenic risk in type 2 diabetics.
ଝ Disclaimer: The ESC Guidelines represent the views of the ESC and the EAS, and were arrived at after careful consideration of the available evidence at the time they were written. Health professionals are encouraged to take them fully... more
ଝ Disclaimer: The ESC Guidelines represent the views of the ESC and the EAS, and were arrived at after careful consideration of the available evidence at the time they were written. Health professionals are encouraged to take them fully into account when exercising their clinical judgement. The guidelines do not, however, override the individual responsibility of health professionals to make appropriate decisions in the circumstances of the individual patients, in consultation with that patient, and where appropriate and necessary the patient's guardian or carer. It is also the health professional's responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription.
Plasma and Lp(a)-associated PAF-acetylhydrolase activity in uremic patients undergoing different dialysis procedures.BackgroundPlatelet-activating factor (PAF) is a potent inflammatory mediator associated with several physiopathological... more
Plasma and Lp(a)-associated PAF-acetylhydrolase activity in uremic patients undergoing different dialysis procedures.BackgroundPlatelet-activating factor (PAF) is a potent inflammatory mediator associated with several physiopathological conditions, including renal diseases. PAF is degraded to the inactive metabolite lyso-PAF by PAF-acetylhydrolase (PAF-AH), which is considered as a potent anti-inflammatory and anti-atherogenic enzyme associated with lipoproteins. In this study, we evaluated the plasma- and lipoprotein(a)
Objective: Triglyceride-rich lipoproteins (TGRLs) are a cardiovascular risk factor and induce endothelial dysfunction. In the present study, we investigated the effects of post-prandial TGRLs from type IV hyperlipidemic subjects on... more
Objective: Triglyceride-rich lipoproteins (TGRLs) are a cardiovascular risk factor and induce endothelial dysfunction. In the present study, we investigated the effects of post-prandial TGRLs from type IV hyperlipidemic subjects on endothelial activation addressing the effects of the lipoproteins on intracellular pathways and gene expression. Methods: Thirty fasted hypertriglyceridemic patients were given an oral fat load (OFL) and blood samples were collected before the OFL (T0) and 2, 4, 6 and 8 h thereafter. Endothelial function, determined as flow-mediated dilatation of the brachial artery, was assessed at the same time points. TGRLs were isolated at T0 and T4 (PP-TGRL) for in vitro studies. Results: Compared with TGRLs, PP-TGRLs induced to a larger extent phosphorylation of p38 MAPK, CREB and IKB-␣ in human endothelial cells and increased the DNA binding activity of CREB, NFAT and NF-B. Furthermore, PP-TRGLs upregulated the expression of several pro-inflammatory genes including vascular cell adhesion molecule-1 (VCAM-1), PECAM-1, ELAM-1, intercellular adhesion molecule-1 (ICAM-1), P-selectin, MCP-1, interleukin-6 (IL-6), TLR-4, CD40, ADAMTS1 and PAI-1. Conclusion: These effects may relate to the severe impairment of endothelial function seen during the post-prandial phase in hypertriglyceridemic patients.
Results of recent clinical studies have lead to the hypothesis that isoflavones are cardioprotective. The aims of this trial were to determine the effect of supplementation with isoflavonoid phytoestrogens on plasma cholesterol... more
Results of recent clinical studies have lead to the hypothesis that isoflavones are cardioprotective. The aims of this trial were to determine the effect of supplementation with isoflavonoid phytoestrogens on plasma cholesterol concentrations and its distribution among lipoproteins and whether supplementation with isoflavones influences oxidisability of low density lipoprotein (LDL) ex vivo. Fourteen healthy premenopausal women participated in a randomised cross-over trial lasting four menstrual cycles (approximately 4 months). The subjects were asked to consume 86 mg of isoflavones daily for the duration of two menstrual cycles followed by placebo for an equivalent period, or vice versa. Venous blood samples were collected initially and at the end of the second and fourth menstrual cycles for the determination of plasma lipid concentrations and the resistance of LDL to copper-induced oxidation ex vivo. Accustomed dietary intake of isoflavones and lignans during the placebo period were 6.87 93.0 and 1.80 90.22 mg/day (mean 9 S.E.M.), respectively, and these did not change during the supplementation period. The intake of other dietary components remained constant during the trial. Supplementation resulted in a 5-fold increase in urinary isoflavone excretion (12.2 914.2 versus 70.19 10.3 mmol/24 h, placebo and isoflavone periods, respectively, P = 0.0001). No changes in the oxidisability of LDL (lag time of 32.99 3.1 versus 30.49 2.9 min) or the plasma concentrations of total cholesterol (4.03 90.21 versus 4.11 90.18 mmol/l) or triacylglycerol (0.67 9 0.04 versus 0.73 9 0.06 mmol/l) were observed following supplementation. However a significant period effect (P =0.024) was observed and a trend towards a carryover effect (P = 0.086) was noted for the concentration of HDL 3 cholesterol. Further studies are required to clarify the potential effect of isoflavones on HDL metabolism and the interaction with plasma steroid hormones during the menstrual cycle.
sured, based on standard protocols, and LDL-cholesterol was calculated. Associations between nutritional knowledge, attitude, practice, sex, age and educational level, and between knowledge, attitude and practice and BMI, waist to hip... more
sured, based on standard protocols, and LDL-cholesterol was calculated. Associations between nutritional knowledge, attitude, practice, sex, age and educational level, and between knowledge, attitude and practice and BMI, waist to hip ratio and levels of lipid and lipoproteins, were determined. Results: For knowledge 26.5, 52.7 and 20.8%, for attitude, 27.6, 48.9 and 23.5% and for practice, 27.4, 51.7 and 20.9% of individuals had desirable, moderate and weak knowledge scores, respectively. With increases in educational levels, knowledge scores increased (p ! 0.001). Attitudes of illiterate and poorly literate groups were weaker than those of other groups (p ! 0.001). However, illiterate and poorly literate groups had higher practice scores as compared to middle school and high school graduates (p ! 0.001). Mean practice scores of university graduates were higher than high school graduates (p ! 0.05). Those aged 30-50 years had higher knowledge scores than older individuals (p ! 0.001). LDLand total cholesterol were correlated to practice scores (p ! 0.001, r = 0.23). Subjects with borderline triglyceride levels had better practice scores than normal individuals (p ! 0.001). Conclusions: The findings revealed that age, educational level and gender are factors that can influence knowledge, attitude and practices, regarding nutrition. It is vital to develop approaches and implement programs to improve the nutritional practices of the population.
In this paper we propose a calculation of LDL-cholesterol (LDL-C) not affected by hypertriglyceridemia by using lipid quantities directly measured in total serum. We also propose an algorithm for the classification of nonchylomicronemic... more
In this paper we propose a calculation of LDL-cholesterol (LDL-C) not affected by hypertriglyceridemia by using lipid quantities directly measured in total serum. We also propose an algorithm for the classification of nonchylomicronemic dyslipemias. Plasma apolipoproteins (apo) A-I, B, total cholesterol (TC), triglycerides (TG), and cholesterol of lipoproteins were measured in a group of 38 normolipemic and 120 dyslipemic patients (42 phenotype IIa, 38 IIb, and 40 IV) classified according to TG and LDL-C values. Discriminant analysis was applied to obtain the best classification with the lowest number of quantities directly measured from total serum (TC, TG, and apo B), and multiple regression analysis was performed to find an equation to calculate LDL-C from these quantities. Apo B seems to be a useful discriminator between normolipemic and phenotype IIa patients, by using a cutoff value of 1.35 g/L obtained by ROC curve analysis. The proposed algorithm, based on lipid quantities measured by easily automated methods, is shown to be a good alternative for the classification of nonhyperchylomicronemic dyslipemia. LDL-C calculated from TC, TG, and apo B proved a better estimate of true LDL-C than the estimate obtained with Friedewald's formula.
The effect of additional dietary tmm fatty acids (7% energy) on plasma lipids was assessed in a double-blind comparison of four separate diets: 1, enriched with butter fat (lauricmyristic-palmitic); 2, oleic acid-rich; 3, elaidic... more
The effect of additional dietary tmm fatty acids (7% energy) on plasma lipids was assessed in a double-blind comparison of four separate diets: 1, enriched with butter fat (lauricmyristic-palmitic); 2, oleic acid-rich; 3, elaidic acid-rich; 4, palmitic acid-rich. The total dietary period was 11 weeks and comprised normal foods plus specific fat supplements. In 27 mildly hypercholesterolemic men, total and LDL cholesterol were significantly lower during the 3-week oleic acid-rich diet, and were similar during the other three diets. For the four diets LDL cholesterol levels were in mg/dl: 1, 163; 2, 151; 3, 165; 4, 161. HDL cholesterol was significantly higher with the palmitic acid-rich diet, 42 mg/dl, compared with elaidic acid, 38 mg/dl, which in turn was not lower than with oleic acid, 38 mg/dl. Plasma elaidic acid concentration rose seven-fold with the tram fatty acid diet but did not increase the vulnerability of LDL to oxidative change. The elaidic acid-rich diet led to significant elevations in the level of Lp[a] compared to all the other test diets. The Lp[a] level increased to 296 f 220 U/1 in the elaidic acidrich period from 235 + 182 (mean + SD) in the first ("butter") period ( P < 0.001) compared with 249 * 204 in the palmitic acid period (E' < 0.001) and 236 + 201 in the oleic acid period (NS). I We conclude that 3 weeks consumption of tram fatty acid (mainly elaidic) at about 7% energy (probably twice the Australian average) results in LDL cholesterol levels that do not differ from those seen with diets enriched with palmitic acid or butter fat and are higher than when oleic acid is substituted for elaidic acid.-Nestel, P., M. Noakes, B. Belling, R. McArthur, P. Clifton, E. Janus, and M. Abbey. Plasma lipoprotein lipid and Lp[a] changes with substitution of elaidic acid for oleic acid in the diet.
This review will focus on the current knowledge on circulating serum and plasma risk factors of cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD) linked to cholesterol homeostasis and... more
This review will focus on the current knowledge on circulating serum and plasma risk factors of cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD) linked to cholesterol homeostasis and lipoprotein disturbances, i.e. total cholesterol (TC), 24S-hydroxy-cholesterol, lipoprotein(a) (Lp(a)), or apolipoprotein E (APOE). These measures linked to lipoprotein metabolism appear to be altered in AD, VaD, or predementia syndrome relative to controls, but with contrasting results. At present, several studies have demonstrated the dependence of APOE serum levels upon the APOE genotype, nonetheless serum APOE levels seems not to be a credible risk factor or a biochemical marker for AD instead of APOE genotyping. In fact, there was no consistent association of serum or plasma apoE protein levels with the disease when controlled for APOE genotype. In addition, there are some evidence that higher Lp(a) levels could be linked with AD, although there are studies suggesting an increased presence of low molecular weight apo(a) in AD, VaD, and frontotemporal dementia, that are associated with elevated Lp(a) levels. In fact, the apo(a) gene is highly polymorphic in length due to variation in the numbers of a sequence encoding the apo(a) kringle 4 domain, and plasma levels of Lp(a) are inversely correlated with apo(a) size. Furthermore, although serum/plasma levels of TC and 24Shydroxycholesterol are not credible diagnostic markers for AD and cognitive decline, the current evidence suggests that they may be modifiable risk/protective factors. The prevailing wisdom is that high TC is a risk factor for dementia. However, the relationship between TC and dementia may vary considerably depending on when cholesterol is measured over the life course or, alternatively, in relation to the underlying course of the disease. Several observational studies have suggested that statins, which are effective in lowering cholesterol, may reduce the risk of dementia, but the results of these reports are inconclusive. Thus, more studies with long-term follow-up and serial assessments of TC are needed to further clarify the causal relationship between cholesterol and dementia. ava i l a b l e a t w w w. s c i e n c e d i r e c t . c o m w w w. e l s ev i e r. c o m / l o c a t e / b r a i n r e s r ev ARTICLE IN PRESS
To examine the effects of unopposed estrogen (E) and tibolone therapy on coagulation and natural anticoagulant systems in surgical menopause. A randomized, double-blind, placebo-controlled study. University hospital clinic in Turkey.... more
To examine the effects of unopposed estrogen (E) and tibolone therapy on coagulation and natural anticoagulant systems in surgical menopause. A randomized, double-blind, placebo-controlled study. University hospital clinic in Turkey. Ninety healthy surgically postmenopausal women. Ninety surgically postmenopausal women were randomized into three groups: unopposed conjugated ET (0.625 mg/d, group 1), tibolone (2.5 mg/d, group 2), and identical tablets of placebo (group 3). Effects on parameters in the clotting cascade at baseline and after 24 weeks of treatment. After 6 months, fibrinogen, lipoprotein (a), and factor VIIa were decreased, and activated partial thromboplastin time was increased significantly in the ET group compared with in the placebo group. However, tibolone significantly decreased only the serum levels of factor VIIa and factor IX and prolonged the activated partial thromboplastin time, compared with placebo group. In addition, conjugated ET caused a significantly greater decrease in serum fibrinogen level than did tibolone. Neither E nor tibolone therapy led to activation of coagulation in the surgically menopausal women. Both preparations changed the overall hemostatic balance to a more fibrinolytic state.
We have analyzed in vivo and in vitro the antiatherogenic properties and mechanisms of action of all pomegranate fruit parts: peels (POMxl, POMxp), arils (POMa), seeds (POMo), and flowers (POMf), in comparison to whole fruit juice (PJ).... more
We have analyzed in vivo and in vitro the antiatherogenic properties and mechanisms of action of all pomegranate fruit parts: peels (POMxl, POMxp), arils (POMa), seeds (POMo), and flowers (POMf), in comparison to whole fruit juice (PJ). Atherosclerotic E 0 mice consumed POM extracts [200 µg of gallic acid equivalents (GAE)/mouse/day] for 3 months. Blood samples, peritoneal macrophages (MPM), and aortas were then collected. All POM extracts possess antioxidative properties in vitro. After consumption of PJ, POMxl, POMxp, POMa, or POMf by E 0 mice, the atherosclerotic lesion area was significantly decreased by 44, 38, 39, 6, or 70%, respectively, as compared to placebotreated group, while POMo had no effect. POMf consumption reduced serum lipids, and glucose levels by 18-25%. PJ, POMxl, POMxp, POMf, or POMa consumption resulted in a significant decrement, by 53, 42, 35, 27, or 13%, respectively, in MPM total peroxides content, and increased cellular paraoxonase 2 (PON2) activity, as compared to placebo-treated mice. The uptake rates of oxidized-LDL by E 0 -MPM were significantly reduced by ∼15% after consumption of PJ, POMxl, or POMxp. Similar results were obtained on using J774A.1 macrophage cell line. Finally, pomegranate phenolics (punicalagin, punicalin, gallic acid, and ellagic acid), as well as pomegranate unique complexed sugars, could mimic the antiatherogenic effects of pomegranate extracts. We conclude that attenuation of atherosclerosis development by some of the POM extracts and, in particular, POMf, could be related to the combined beneficial effects on serum lipids levels and on macrophage atherogenic properties.
- by Mark L Dreher PhD and +1
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- Engineering, Atherosclerosis, Diet, Oxidative Stress
Heterophils isolated from distinct broilers (lines A and B) differ in function and cytokine gene expression profiles. Nothing is known about Toll-like receptor (TLR) expression nor functional activation and cytokine/chemokine gene... more
Heterophils isolated from distinct broilers (lines A and B) differ in function and cytokine gene expression profiles. Nothing is known about Toll-like receptor (TLR) expression nor functional activation and cytokine/chemokine gene expression of line A and B heterophils when ...