LDL-Ch Levels Research Articles

Functional state of skin microvascular bed according to laser doppler flowmetry in patients with arterial hypertension combined with hypercholesterolemia

Introduction. The great importance of risk factors, such as arterial hypertension (AH) and low-density lipoprotein cholesterol (LDL-H), for development of cardiovascular diseases, makes highly relevant to obtain the data of the nature of microcirculation (MC) changes that are a key link of maintaining homeostasis under their concomitant influence. Aim – to evaluate functional state of skin microvascular bed using laser Doppler flowmetry in patients with arterial hypertension (AH) and combined with hypercholesterolemia. Materials and Methods. The study involved 37 practically healthy volunteers and 94 patients with 2–3 stage of AH, which were divided into 2 groups: Gr.1 with LDL-CH level ≤3.5 mmol/l (n = 35) and Gr.2 with LDL-H level >3.5 mmol/l (n = 59). MC of the forearm skin was assessed by laser Doppler flowmetry. Parameters of basal blood flow, the amplitude-frequency spectrum of its fluctuations, nutritional MC, and parameters of occlusion test were evaluated. Results. Analyzing rhythm structure of blood flow fluctuations, statistically significant decrease in standardized parameters of their amplitude in endothelial and myogenic frequency ranges was revealed in patients with elevated LDL-CH levels compared to patients of Gr.1 by 19.7 % and 9.7 % (р = 0.045), respectively, which indicated weakening of endothelial function and constriction of precapillary segment of MC. These changes were accompanied by decrease in reserve of microvascular blood flow by 9.1 % in Gr.2 of patients (p = 0.044) with pronounced trend towards reduction of capillary perfusion and activation of blood flow through arteriolovenular shunts. Conclusion. More pronounced functional disorders of MC, characterized by endothelial dysfunction, constriction of precapillary segment, and decrease in reserve potential of tissue hemoperfusion were revealed in AH patients with atherogenic hyperlipidemia vs AH patients.

The effects of 3-year statin therapy and the achievement of LDL cholesterol target values in familial hypercholesterolemia patients: An experience from Serbia

Background and aimsDespite the use of statins, familial hypercholesterolemia (FH) patients often have increased LDL-cholesterol (Ch) and high risk for atherosclerotic cardiovascular disease (ASCVD). This study aimed to analyze the effect of statin therapy on attainment of LDL-Ch treatment targets and appearance of new ASCVD and diabetes in FH patients. MethodsThis study is a retrospective analysis of data from medical records of 302 FH patients treated continuously with statins during 3 years. At baseline and once yearly, anthropometric measurements, lipids (total Ch, LDL-Ch, HDL-Ch, triglycerides, apoliporotein A1 and B), fasting plasma glucose, and insulin were determined. ResultsIn FH patients, high intensity statin was prescribed only in 17.9% of cases. LDL-Ch levels were significantly lower after 3 years of statin treatment (3.61 ± 1.19 mmol/l) vs. baseline (4.51 ± 1.69 mmol/l; p < 0.01), but only 6.9% of FH patients reached the recommended ≥50% LDL-Ch reduction and 16.2% attained the LDL-Ch <2.6 mmol/l target. Simultaneously, 9.6% of FH patients developed new ASCVD, with lower HDL-Ch after 3 years of statin treatment than in those who remained free of ASCVD. In addition, we observed new onset diabetes in 6.4% of FH patients who were more obese, older and with higher fasting glucose at baseline than FH patients free of diabetes, regardless of the type of statin. ConclusionsThese results imply that only a small proportion of FH patients achieved the recommended LDL-Ch treatment targets, mostly due to the use of low statin dose and infrequent implementation of high-intensity statin treatment, which altogether could not prevent the increase in residual cardiovascular risk.

Potential immunomodulatory and antioxidant effects of walnut Juglans regia vegetable oil against lead-mediated hepatic damage and their interaction with lipase activity in rats.

Environmental pollutants, particularly lead, pose a serious threat to human and animal health that causes disturbances of several functions, including hepatotoxicity. Therefore, the search for a new treatment that could safely and effectively block or reverse liver injuries remains a challenge. This study was carried out to investigate the protective efficacy of Juglans regia vegetable oil (JRVO) against the hepatotoxicity induced by lead. To achieve this aim, adults male rats were treated for 10 days with Pb (0.344 g/kg bw) associated or not with JRVO (0.9 g/kg bw). The rats intoxicated by lead exhibited oxidative stress determined by TBARS, protein carbonyls, liver tumor necrosis factor-α (TNF-α), caspase-3, and antioxidant status: SOD, CAT, GPx, and GSH. Administration of lead increased the levels of plasma hepatic markers (AST, ALT, LDH) and bilirubin, the lipid profiles (total cholesterol, triglycerides, VLDL-Ch, LDL-Ch levels, TBARS, NOx, and PCO), the plasmatic lipase activity and the inflammatory markers, while the plasmatic ALP decreased. Coadministration of JRVO restored all the hepatic markers, the lipid profiles and the antioxidants to near-normal values and lowered the plasmatic lipase activity as well as the elevated thiobarbituric acid reactive substances. Hepatic histological studies confirmed the beneficial role of JRVO through the amelioration of all biochemical parameters. Our results suggest that Juglans regia vegetable oil contains promising substances to counteract the lead intoxication and may be efficient in the prevention of hepatotoxicity complications.

Effect of rosuvastatin on C-reactive protein and vascular cell adhesion molecule 1 in patients with acute cerebral infarction

Objective To observe the effect of rosuvastatin on vascular cell adhesion molecule-1 (VCAM-1), C-reactive protein (CRP), TG, TC and LDC in patients with acute cerebral infarction at the early stage. Methods According to the random number expression method, 90 patients with acute cerebral infarction were divided into rosuvastatin treatment group and control group, with 45 cases in each group.The course of treatment was 21 days.The control group was given conventional western medicine(aspirin, mannitol etc.), the treatment group received rosuvastatin on the basis of the control group.Before and after treatment, the plasma VCAM-l, CRP, TG, TC, LDLch levels, clinical efficacy, efficacy of regulating dyslipidemia and drug safety were compared. Results After treatment, the CRP levels in the two groups were improved.After treatment for 7 days, 14 days, the CRP levels of the treatment group were (23.68±5.23)mg/L, (16.68±6.76)mg/L, respectively, which improved more significantly than those of the control group[(30.12±6.68)mg/L, (21.12±6.35)mg/L], the differences were statistically significant (t=5.092, 3.230, all P 0.05). The VCAM-1 levels of the two groups after treatment were improved.After treatment for 7 days, 14 days, the VCAM-1 levels of the treatment group were (1 205.1±61.8)mg/L, (852.1±60.2)mg/L, respectively, which were improved more significantly than those of the control group[(1 415.6±62.9)mg/L, (963.1±53.3)mg/L], there were statistically significant differences between the two groups (t=21.815, 9.261, all P 0.05). The levels of TG, TC, LDC in the two groups were all decreased after treatment for 7 days, 14 days and 21 days, and the improvement in the treatment group was more obvious, the differences between the two groups were statistically significant (t=5.219, 7.303, 4.044, 2.232, 4.336, 3.612, 2.689, 7.817, 11.057, all P<0.05). Conclusion Compared with the conventional western medicine treatment, rosuvastatin can decrease the plasma levels of CRP, VCAM-l, TG, TC, LDC, further improve the pathological basis of ischemic cerebrovascular disease, eliminate the risk factors, it is more conducive to the prognosis of acute cerebral infarction. Key words: Rosuvastatin; Cerebral infarction; Vascular cell adhesion molecule-1; C reactive protein

Hypolipidemic effect of dihydroisoquinoline oxaziridine in high-fat diet-fed rats

Obesity is a serious health problem that increases the risk of many complications, including diabetes and cardiovascular disease. This study aims to evaluate, for the first time, the effects of oxaziridine 3 on lipoprotein lipase activity in the serum of rats fed with a high-fat diet (HFD) on body weight, lipid profile and liver-kidney functions. The administration of oxaziridine 3 to HFD-rats lowered body weight and inhibited the lipase activity of obese rats leading to notable decrease of T-Ch, TGs and LDL-Ch levels accompanied with an increase in HDL-Ch concentration in serum. Moreover, the findings of this study revealed that oxaziridine 3 helped to protect liver tissue from the appearance of fatty cysts. Additionally, oxaziridine 3 administration to HFD-rats induces antioxidant activity proven by the increase of superoxide dismutase (SOD) and catalase (CAT) activities and the decrease in Thiobarbituric acid reactive substances (TBARS) levels. It also induces the protection of liver-kidney functions confirmed by a decrease in the levels of toxicity parameters in blood.

CENTRALISED SURVEY ON THE UNDERTREATMENT OF THE HYPERCHOLESTEROLEMIA IN RUSSIA (CEPHEUS)

Aim.To assess the percentage of the patients who receive lipid-lowering drug therapy and achieve target levels of low-density lipoprotein cholesterol (LDL–CH), in accordance with the recommendations by the Russian Cardiology Society (RCS) and the 4th Joint European Task Force (4JETF).Material and methods.The CEPHEUS study is a multi-centre, cross-sectional observational study with the participation of Russian patients. The study participants received lipid-lowering therapy for at least 3 months (no dose modification for ≥6 weeks). The start-date and end-date of the study were Oct 22nd 2010 and Mar 22nd 2011, respectively. The cross-sectional data were collected during a single visit to the clinic.Results.The study included 1000 Russian patients. Overall, target LDL–CH levels were achieved in 34,5% (RCS criteria) and 48,2% (4JEFT criteria) of the patients who received lipid-lowering therapy in the routine clinical practice. The patients who were treated for secondary prevention of cardiovascular events (CVE) achieved target levels of LDL–CH more often than the patients treated for primary prevention: 38,2% vs. 27,0%, respectively, by the RCS criteria (odds ratio (OR) 1,67; 95% confidence interval (CI) 1,22–2,28; p=0,001) and 54,5% vs. 35,4%, respectively, by the 4JEFT criteria (OR 2,19; 95% CI 1,63–2,95; p&lt;0,001).Conclusion.Target levels of LDL–CH are achieved by &lt;50% of the Russian patients who receive lipid-lowering treatment. This percentage is even lower in patients receiving lipid-lowering treatment for primary CVE prevention.

ASSOCIATION BETWEEN THE DEGREE OF CORONARY ATHEROSCLEROSIS, RISK FACTORS, AND MARKERS OF CAROTID AND PERIPHERAL ARTERY ATHEROSCLEROSIS

Aim. To investigate the associations between the presence and degree of coronary atherosclerosis, cardiovascular risk factors, and atherosclerosis of other localisation. Material and methods. The cohort of 98 patients (61 men and 37 women; age 18–80 years) underwent an extensive clinical, biochemical, and instrumental examination, including coronary angiography. All participants were divided into three groups by the degree of coronary artery (CA) atherosclerosis: stenosis of 0–20%, 21–70%, and ≥71%. Results. There was no marked between-group difference in the non￾invasively assessed markers of the atherosclerosis of other localisation (ankle-brachial index and intima-media thickness). However, there was a significant positive correlation between CA atherosclerosis and smoking, overweight, and diabetes mellitus. The degree of CA atherosclerosis was significantly associated with hyperglycemia and positive exercise test results. The lowest levels of low-density lipoprotein cholesterol (LDL–CH) among patients with the most severe CA atherosclerosis could be due to the fact that this group also had the highest proportion of individuals who were treated with statins and achieved target LDL–CH levels. Conclusion. A further investigation is needed, with the focus on additional biochemical and other parameters, in order to identify the best determinants of the CA atherosclerosis degree and the acute complication risk for each patient.

P 17: Analysis of the relationship between parameters of total and abdominal obesity, levels of lipoproteins and occurrence of coronary heart disease in type 2 diabetes

Atherosclerosis is the commonest and the most important cause of coronary heart disease (CHD). Among the risk factors for its occurrence the key ones are diabetes mellitus, obesity and dyslipidemia. Therefore, the aim of this study was to determine the connection between the parameters of total and abdominal obesity, level of lipoproteins and the occurrence of CHD in type 2 diabetes (T2D). The research was conducted on 85 patients, 39 diabetics and 46 nondiabetics divided into the following groups: 18 patients with T2D and previously diagnosed CHD (group 1), 21 patients with T2D but without CHD (group 2), 24 nondiabetics with previously diagnosed CHD (group 3) and 22 nondiabetics without CHD (group 4). As an indicator of total obesity we calculated the body mass index (BMI). As parameters of abdominal obesity waist circumference (WC) and waist to hip ratio (WHR) were used. Total cholesterol (ch), HDL-ch, LDL-ch and Triglycerides (Tg) levels were determined by chromatography. We used also Tg/ HDL-ch ratio as an indicator of structural changes in subfractions of cholesterol particles and an independent risk factor for CHD. We found there is no difference in BMI in group 1 vs group 2 (28.09+/−0.82 vs 28.07+/−0.92 kg/m 2 , p=NS) neither in group 3 vs group 4 (27.58+/−0.97 vs 27.16+/−0.71 kg/m 2 , p=NS). WC and WHR values were significantly higher in group 1 vs group 2 (103.06+/−1.88 vs 97.60+/−1.99 cm, 0.98+/−0.01 vs 0.91+/−0.01; p<0.05 respectively) and in group 3 vs group 4 (95.15+/−2.42 vs 90.10+/−2.55 cm, 0.89+/−0.01 vs 0.83+/−0.01, p<0.05 respectively). Comparing the diabetics and nondiabetics, we have found that WC and WHR were significantly higher in diabetics (100.25+/−1.89 vs 92.50+/−2.53; 0.95+/−0.01 vs 0.86+/−0.01; p<0.05 respectively). There was no difference in levels of total ch between groups 1 and 2 (6.59+/−0.33 vs 6.32+/−0.37 mmol/L; p=NS), but total ch levels were significantly higher in group 3 compared to group 4 (6.27+/−0.20 vs 5.70+/−0.16 mmol/L, p<0.05). LDL-ch levels and Tg levels were significantly higher in group 1 vs group 2 (LDL-ch: 4.39+/−0.32 vs 3.61+/−0.24 mmol/L, p<0.05, Tg: 3.68+/−0.59 vs 3.08+/−0.60 mmol/L, p<0.05) and in group 3 vs group 4 (LDL-ch: 4.05+/−0.2 vs 3.59+/−0.17 mmol/L, p<0.05, Tg: 2.55+/−0.35 vs 1.58+/−0.16 mmol/L, p<0.05). There were no difference in HDL-ch levels between these groups (1: 1.04+/−0.06; 2: 1.14+/−0.08; 3: 1.25+/−0.08; 4: 1.25+/−0.07; 1 vs 2 and 3 vs 4 p=NS). However, Tg/HDL ratio was significantly higher in group 1 vs group 2 (4.11+/−0.88 vs 2.87+/−0.67, p<0.01) and in group 3 vs group 4 (2.18+/−0.34 vs 1.40+/−0.19, p<0.05). Also, by method of correlation, we found that in patients with CHD BMI significantly correlate with Tg and Tg/HDL ratio (r=0.338, p<0.05; r=0.388, p<0.05 respectively), while WC and WHR significantly correlate with Tg (r=0.387, p<0.05; r=0.410, p<0.01 respectively), Tg/HDL ratio (r=0.505, p<0.01; r=0.497, p<o.01 respectively) and HDL-ch (r=-0.450, p<0.01; r=-0.494, p<0.01 respectively). Our results have demonstrated that abdominal obesity disrupts cholesterol reverse path, leading to changes in the structure and composition of the HDL subfraction of cholesterol, which is one of the possible pathogenetic mechanisms of atherogenic effects of abdominal obesity. Also, this suggest that parameters of abdominal obesity could be an useful screening test for detecting people with dyslipidemia and high risk of developing CHD, especially diabetics.

P 14: Hypertriglyceridemic waist phenotype in type 2 diabetes: association with higher hs-CRP and lower antioxidative enzyme activity

Background and aim It was previously suggested that hypertriglyceridemic waist (HTgW) phenotype (waist girth ≥90 cm in men and ≥85 cm in women, and triglyceride (Tg) levels ≥2.0 mmol/l) could identify visceral obesity and higher risk for atherosclerosis, but the relationship between HTgW phenotype and different atherosclerosis risk factors has not yet been elucidated. The aim of this study was to analize (a) hs-CRP levels, (b) lipid levels and (c) antioxidant enzyme glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities in the following groups of subjects: 30 patients with type 2 diabetes (T2D) and HTgW (group A), 24 T2D patients with abdominal obesity (higher waist) and normal Tg (group B) and 20 non obese T2D patients without HTgW (group C). Methods CRP levels were detected by Elisa method, GSH-Px and SOD activity were detected by spectrophotometry, total cholesterol (Ch), HDL-Ch, LDL-Ch and Tg levels by enzymatic methods and the insulin resistance (IR) was assessed by using HOMA-IR (calculated from basal insulin levels determined by RIA and fasting glucose levels determined by glucosooxidase method). Results We found significantly higher hs-CRP level in group A compared to group B (6,97+/-2,01 vs 4,72+/-2,01 mg/l; p Conclusions Our results signify that presence of HTgW phenotype in T2D, as a marker of visceral obesity, is strongly associated with marked atherosclerosis risk profile, especially at the level of inflammation, reverse cholesterol metabolism and antioxidative enzyme activity. The results also suggest that in this phenotype detected higher IR might be exerting its atherogenic effect partly on the level of the changes in antioxidative defence.

Persistent dyslipidemia in statin-treated patients: Russian real-world clinical practice data (Russian part of the DYSIS Study)

The high prevalence of persistent dyslipidemia in primary and specialized care patients treated with statins justifies the need to identify its reasons and develop the recommendations on the treatment optimization. At present, Russian studies focusing on the achievement of target lipid levels remain scarce, which emphasizes the importance of the problem and its further investigation.Aim.Cross-sectional epidemiological study which assessed the prevalence of persistent dyslipidemia in statin-treated patients and analysed the predictors of the achievement of target lipid levels.Material and methods.The lipid profile parameters were analysed in 1586 statin-treated out-patients with varied levels of cardiovascular risk, taking into account the type of lipid-lowering therapy and its doses. The assessment of the cardiovascular event (CVE) risk and the definition of target levels of low-density lipoprotein cholesterol (LDL–CH), as well as normal levels of triglycerides (TG) and high-density lipoprotein cholesterol (HDL–CH), was based on the clinical recommendations by the European Society of Cardiology (ESC 2007) and by the European Society of Cardiology and the European Atherosclerosis Society (ESC/EAS 2011).Results.The analysis based on the ESC 2007 recommendations has demonstrated that the target levels of LDL–CH (&lt;2,5 mmol/l for high-risk patients) were not achieved in 53,5% of the participants. The elevation of LDL–CH levels could be isolated or combined with the HDL–CH decrease and/or the TG increase. Low levels of HDL–CH were observed in 32,3% of the patients, while high TG levels were registered in 55,6% of the participants. The achievement of target LDL–CH levels was predicted by the higher-dose statin therapy (odds ratio 0,44). The analysis based on the ESC/EAS 2011 recommendations has shown that the prevalence of target LDL–CH levels was 12,2% in very high-risk patients (&lt;1,8 mmol/l), 30,3% in high-risk patients (&lt;2,5 mmol/l), and 53,4% in moderate-risk patients (&lt;3,0 mol/l).Conclusion.Over a half of the statin-treated patients failed to achieve target levels of LDL–CH. The lowest prevalence of target LDL–CH levels was observed in very high-risk and high-risk patients. The predictors of target LDL–CH level achievement included moderate cardiovascular risk and higher-dose statin therapy. The obtained results suggest that the correction of persistent dyslipidemia in statin-treated patients could be achieved via increasing the satin dose and combining lipid-lowering medications.

Effects of black cohosh extract on body weight gain, intra-abdominal fat accumulation, plasma lipids and glucose tolerance in ovariectomized Sprague–Dawley rats

Extracts of the black cohosh ( Actaea/ Cimicifuga racemosa (CR)) have long been used to treat estrogen deficiency symptoms in women after menopause. Recent data from randomized controlled studies have shown that CR consumption alleviates “hot flushes” and due to the lack of uterotropic effects can be a safe alternative to estrogen replacement therapy. Objective: To evaluate the effects of dietary CR extract consumption on body weight (BW) gain, intra-abdominal fat (IAF) accumulation, plasma leptin, lipids and glucose tolerance in ovariectomized rats and to compare them with the effects of 17β-estradiol. Design: Twenty-seven female Sprague–Dawley rats were ovariectomized and fed soy-free chow with the addition of estradiol-3 benzoate (E2B) (10 mg/kg, n = 10) or CR BNO 1055 extract (6.67 g/kg, n = 9). The control group ( n = 8) received soy-free chow only. Weight and food intake were recorded once a week. After 6 weeks, intra-abdominal fat was measured using computer tomography and the intraperitoneal glucose tolerance test was performed. In the seventh week of the experiment animals were sacrificed, blood was collected for plasma and uteri were removed. Results: Dietary CR BNO 1055 extract had no effects on uterine mass but significantly reduced serum lutenizing hormone (LH) levels ( P < 0.05). Although, the average weekly food consumption throughout the experiment (calculated in g/kg of BW) did not differ between our studied groups, E2B or CR BNO 1055 treated animals gained less weight and had significantly less IAF accumulation compared to control animals ( P < 0.05). E2B treatment also decreased plasma total (T-,) high-density lipoprotein (HDL-) and low-density lipoprotein (LDL)-cholesterol ( P < 0.05). Plasma T-Ch levels in CR BNO 1055 treated animals did not differ from the controls whereas LDL-Ch levels were significantly higher and plasma triglycerides (TG) significantly lower ( P < 0.05). In the glucose tolerance test, the area under the curve (AUC) was significantly smaller in the E2B treated animals compared to controls ( P < 0.05). AUC in CR BNO 1055 treated animals did not differ significantly from the controls ( P > 0.05). Nevertheless, fasting plasma insulin (FPI) levels were significantly lower in E2B and CR BNO 1055 treated animals ( P < 0.05). Conclusions: In OVX rats, CR BNO 1055 extract consumption decreases enhanced pituitary LH secretion, attenuates body weight gain and IAF accumulation, lowers FPI and has no effects on uterine mass. The effects on plasma lipids seem to be more complex and are characterized by an increase of LDL-Ch and decrease of TG levels which is in contrast to the effects of estrogen.

An experimental evaluation of the antidiabetic and antilipidemic properties of a standardized Momordica charantia fruit extract

BackgroundThe MCE, Momordica charantia fruit extract Linn. (Cucurbitaceae) have been documented to elicit hypoglycemic activity on various occasions. However, due to lack of standardization of these extracts, their efficacy remains questionable. The present study was undertaken by selecting a well standardised MCE. This study reports hypoglycemic and antilipidemic activities of MCE employing relevant animal models and in vitro methods.MethodsDiabetes was induced in Wistar rats by a s.c., subcutaneous injection of alloxan monohydrate (100 mg/kg) in acetate buffer (pH 4.5). MCE and glibenclamide were administered orally to alloxan diabetic rats at doses of 150 mg/kg, 300 mg/kg & 600 mg/kg, and 4 mg/kg respectively for 30 days, blood was withdrawn for glucose determination on 0, 7, 14, 21 and 30th days. On the 31st day, overnight fasted rats were sacrificed and blood was collected for various biochemical estimations including glycosylated haemoglobin, mean blood glucose, serum insulin, cholesterol, triglcerides, protein and glycogen content of liver. The hemidiaphragms and livers were also isolated, carefully excised and placed immediately in ice cooled perfusion solution and processed to study the glucose uptake/transfer processes. Hypolipidemic activity in old obese rats was evaluated by treating two groups with MCE (150 mg/kg & 300 mg/kg) orally for 30 days and determining total cholesterol, triglyceride and HDL-CH, LDL-CH and VLDL-CH levels from serum samples.ResultsSubchronic study of MCE in alloxan induced diabetic rats showed significant antihyperglycemic activity by lowering blood glucose and GHb%, percent glycosylated haemoglobin. Pattern of glucose tolerance curve was also altered significantly. MCE treatment enhanced uptake of glucose by hemidiaphragm and inhibited glycogenolysis in liver slices in vitro. A significant reduction in the serum cholesterol and glyceride levels of obese rats following MCE treatment was also observed.ConclusionOur experimental findings with respect to the mechanism of action of MCE in alloxan diabetic rats suggest that it enhances insulin secretion by the islets of Langerhans, reduces glycogenesis in liver tissue, enhances peripheral glucose utilisation and increases serum protein levels. Furthermore, MCE treatment restores the altered histological architecture of the islets of Langerhans. Hence, the biochemical, pharmacological and histopathological profiles of MCE clearly indicate its potential antidiabetic activity and other beneficial effects in amelioration of diabetes associated complications. Further, an evaluation of its antilipidemic activity in old obese rats demonstrated significant lowering of cholesterol and triglyceride levels while elevating HDL-cholesterol levels. Also, the extract lowered serum lipids in alloxan diabetic rats, suggesting its usefulness in controlling metabolic alterations associated with diabetes.

M.483 Molecular genetics of familial hypercholesterolemia in Morocco

Obesity is a serious health problem that increases the risk of many complications, including diabetes and cardiovascular disease. This study aims to evaluate, for the first time, the effects of oxaziridine 3 on lipoprotein lipase activity in the serum of rats fed with a high-fat diet (HFD) on body weight, lipid profile and liver-kidney functions. The administration of oxaziridine 3 to HFD-rats lowered body weight and inhibited the lipase activity of obese rats leading to notable decrease of T-Ch, TGs and LDL-Ch levels accompanied with an increase in HDL-Ch concentration in serum. Moreover, the findings of this study revealed that oxaziridine 3 helped to protect liver tissue from the appearance of fatty cysts. Additionally, oxaziridine 3 administration to HFD-rats induces antioxidant activity proven by the increase of superoxide dismutase (SOD) and catalase (CAT) activities and the decrease in Thiobarbituric acid reactive substances (TBARS) levels. It also induces the protection of liver-kidney functions confirmed by a decrease in the levels of toxicity parameters in blood.

Hypocholesterolemic activity of calcic and magnesic-sulphate-sulphurous spring mineral water in the rat

We have studied the influence of hydropinic treatment with calcic and magnesic-sulphate-sulphurous spring mineral water (IDCS water) on plasma cholesterol (T-Ch), low density lipoprotein (LDL-Ch) and high density lipoprotein (HDL-Ch) levels, in experimental animals made hypercholesterolemic with a high cholesterol diet, and investigated possible mechanisms involved in lipoprotein metabolism. Ad libitum intake of IDCS water, during the 120 days of a hypercholesterolemic diet, produced an increase in the T-Ch/LDL-Ch ratio, compared to that of hypercholesterolemic animals treated with tap water. This datum indicates that after treatment with spring mineral water the LDL-Ch plasma concentration increases less than that of T-Ch. Vice versa, the T-Ch/HDL-Ch ratio was lower. Considering that the HDL-Ch levels in hypercholesterolemic rats treated with IDCS water were not significantly different than those of control animals, the very low T-Ch/HDL-Ch ratio recorded indicates that IDCS water intake during a hypercholesterolemic diet induces a lower increase of the T-Ch and LDL-Ch levels by increasing lipoprotein metabolism, which leads to reduced bile acid absorption both through precipitation in the intestinal lumen and increased excretion via the feces.

Significance of platelet-activating factor acetylhydrolase in patients with non-insulin-dependent (type 2) diabetes mellitus.

Non-insulin dependent diabetes mellitus (NIDDM) represents an independent risk factor for cardiovascular diseases (CVD), being characterized by a continuous low-grade inflammation and endothelial activation state. Plasma platelet - activating factor - acetylhydrolases (PAF-AHs) are a subgroup of Ca(2+)-independent phospholipase A(2) family (also known as lipoprotein-associated phospholipases A(2)) that hydrolyze and inactivate the lipid mediator platelet-activating factor (PAF) and/or oxidized phospholipids. This enzyme is considered to play an important role in inflammatory diseases and atherosclerosis. The present study aims to investigate the relations between the levels of PAF-AH activity and LDL-cholesterol / HDL-cholesterol (LDL-ch / HDL-ch) ratio in NIDDM patients as compared to controls. serum PAF-AH activity was measured in 50 patients with dyslipidemia, in 50 NIDDM patients and in 50 controls (normal lipid and glucose levels). Total cholesterol, LDL-ch, HDL-ch, triglyceride and blood glucose were determined in all subjects. All NIDDM patients display hiperlipidemia, with increased LDL-ch and triglyceride levels. There is a significant correlation between LDL-ch levels (especially LDL-ch / HDL-ch ratio) and PAF-AH activity in dyslipidemic and NIDDM patients. Diabetic and dyslipidemic patients have an increased plasma PAF-AH activity correlated with their LDL-ch levels and mainly with LDL-ch / HDL-ch ratio. Plasma PAF-AH high levels appear to be important as a risk marker for endothelial dysfunction in patients with NIDDM.

Metabolic effects of Captopril in hypertensive patients with noninsulin-dependent diabetes mellitus and hyperlipidemia

Twelve patients with mild and 3 with severe hypereholesterolemia were stabilized with an isocaloric diet containing less than 300 mg cholesterol daily with a P/S ratio of 1.8, and placebo period of 4 weeks. They were administered 1000 mg probucol daily for 12 weeks, followed by placebo for 6 weeks. In patients with mild disease, a significant cholesterol reduction was achieved in serum, LDL, and HDL (maximum decrease, 17%, 13%, and 31%, respectively). While HDL3 cholesterol was reduced significantly throughout the period (P < 0.001), HDLZ cholesterol showed a significant decrease only at the 4th week of treatment (P < 0.001), and returned to basal levels at the 8th and 12th treatment weeks.Serum apo B levels decreased only slightly, but the HDL-apo A-I fall was significant with a reduction in the HDL-CH/HDL-apo A-I ratio throughout the treatment period.In 3 patients with severe disease, cholesterol decrease in serum and in VLDL, LDL and HDL fractions varied, but on the whole was lower than in patients with mild disease. A decrease in VLDL-CH and HDL-CH was present in all 3, but LDL-CH levels were only slightly lowered in 2 patients, and unchanged in the third.Serum probucol levels fell 66% from the 4th to the 12th treatment week, and in parallel, the percentage of lipoprotein-bound drug increased about 2-fold. It is suggested that these changes in pharmacokinetics as well as the cholesterol-lowering effect of the drug may be due to a change in lipoprotein composition or structure.

Westernized food habits and concentrations of serum lipids in the Japanese

To investigate the association of westernized food habits and concentrations of serum lipids in the Japanese, we studied 1200 healthy Japanese living in Hiroshima prefecture and 1483 ethnic Japanese from Hiroshima prefecture living in the Hawaii Islands and Los Angeles. The nutritional assessments were made by the same dietitians. No major difference was observed in the total energy intake between the Japanese and the Japanese-Americans in both males and females. However, the intake of animal fat and simple carbohydrates (especially fructose) were markedly greater, and that of complex carbohydrates lower, in the Japanese-Americans compared with the Japanese. The mean serum cholesterol (CH), LDL-CH and serum triglyceride (TG) levels were significantly higher in the Japanese-Americans in both sexes. The mean HDL-CH concentration was similar between the two groups in males, but it was approximately 7 mg/dl higher in Japanese-American females. Using the 75 percentile values of CH and TG in the Japanese in Hiroshima, the frequency of WHO types IIa and IIb hyperlipidemia was about twice as high in the Japanese-Americans. These results suggest that westernized food habits in the Japanese include qualitative changes in animal fat, simple carbohydrate and complex carbohydrate diet rather than an increase in the total energy intake. These changes are associated with marked increases in the concentrations of serum CH and TG and increased prevalence of types IIa and IIb hyperlipidemia.

Diagnosis and Management of Abnormal Plasma Lipids

Four classes of lipoproteins transport the lipids found in human plasma during the fasting state: very low density (VLDL), intermediate density (IDL), low density (LDL), and high density lipoprotein (HDL). These lipoproteins all undergo extensive modifications as they circulate. Consequently, there is considerable heterogeneity among the particles within each lipoprotein class. Triglycerides comprise 50 to 65% of the mass of VLDL which is synthesized primarily in the liver and metabolized in the circulation first to IDL and finally to form LDL. LDL is the major carrier of cholesterol and cholesteryl esters, which together account for about half of its mass. HDL, originating as a nascent particle in both liver and intestine, contains about 50% protein in its mature form. Chylomicrons transport dietary fat from the intestine and are cleared so rapidly that they are never present in normal individuals after an overnight fast. The major protein components in the lipoproteins are apolipoprotein B48 in chylomicrons, Bioo in VLDL, IDL, and LDL, and Al in HDL (1). Numerous epidemiologic studies and animal experiments have clearly shown that LDL is an atherogenic lipoprotein and that increased levels of cholesterol and LDL cholesterol (LDLCh) are associated with an increased risk of coronary artery disease (CAD). Small dense LDL particles are especially atherogenic. Epidemiologic data have also shown an association between low levels of HDL and excessive CAD. In most studies, elevated triglycerides were an independent risk factor for CAD only in women. However, hypertriglyceridemia can contribute indirectly to CAD because it is almost always accompanied by low levels of HDL cholesterol (HDLch) and increased amounts of small dense LDL. Extremely high triglyceride levels (>1000 mg/dl) can trigger attacks of acute pancreatitis. Before the mid 1980s, aggressive treatment of plasma lipid abnormalities was limited by the lack of proven benefits from lowering LDL or raising HDL levels. Two intervention studies, the Coronary Primary Prevention Trial (CPPT) and the Helsinki Heart Study, have now demonstrated that improving the levels of these lipoproteins significantly reduced the number of coronary events. Another clinical trial used repeat coronary angiography to show that lowering LDL and raising HDL slowed the progression of lesions in coronary arteries and bypass grafts. Treatment did not decrease overall mortality in these trials, a result predictable from their relatively small size and the short periods of follow-up. However, men treated 15 yr earlier with nicotinic acid for 6 yr in the Coronary Heart Project had an 11% lower overall mortality than the control group. Taken together with the serious consequences of CAD, these findings dictate aggressive efforts to identify and treat abnormalities of plasma lipids and lipoproteins. Because the fall in LDLCn was considerably greater than the rise in HDLCh in the CPPT, the benefits were attributed primarily to the reduced LDLch levels. The drugs used in the other studies decreased triglycerides and increased HDLCh significantly, but LDLch also fell by 10% or more. Thus, no study has unequivocally proven the benefits of raising HDLch alone. However, sophisticated statistical analyses of the data from the Helsinki Heart Study suggested that the 10% increase in HDLch levels was the major contributor to the smaller number of coronary events in the treatment group. These trials were all done in men between the ages of 35 and 59, and there is no direct evidence that improving LDL or HDL levels will decrease coronary events in women or men who are younger or older than those studied. Since complications of CAD are the major cause of death in women, albeit at an older age than in men, it is likely that women will also benefit from improved levels of LDL and HDL. Control of abnormal levels should be especially protective in younger individuals who have less atherosclerosis at the outset and a longer period of potential treatment to slow its progression. Guidelines for detection and treatment of elevated LDL levels

Effect of probucol treatment on lipoprotein cholesterol and drug levels in blood and lipoproteins in familial hypercholesterolemia

Twelve patients with mild and 3 with severe hypereholesterolemia were stabilized with an isocaloric diet containing less than 300 mg cholesterol daily with a P/S ratio of 1.8, and placebo period of 4 weeks. They were administered 1000 mg probucol daily for 12 weeks, followed by placebo for 6 weeks. In patients with mild disease, a significant cholesterol reduction was achieved in serum, LDL, and HDL (maximum decrease, 17%, 13%, and 31%, respectively). While HDL 3 cholesterol was reduced significantly throughout the period ( P < 0.001), HDLZ cholesterol showed a significant decrease only at the 4th week of treatment ( P < 0.001), and returned to basal levels at the 8th and 12th treatment weeks. Serum apo B levels decreased only slightly, but the HDL-apo A-I fall was significant with a reduction in the HDL-CH/HDL-apo A-I ratio throughout the treatment period. In 3 patients with severe disease, cholesterol decrease in serum and in VLDL, LDL and HDL fractions varied, but on the whole was lower than in patients with mild disease. A decrease in VLDL-CH and HDL-CH was present in all 3, but LDL-CH levels were only slightly lowered in 2 patients, and unchanged in the third. Serum probucol levels fell 66% from the 4th to the 12th treatment week, and in parallel, the percentage of lipoprotein-bound drug increased about 2-fold. It is suggested that these changes in pharmacokinetics as well as the cholesterol-lowering effect of the drug may be due to a change in lipoprotein composition or structure.

正常ウサギの大動脈壁脂質およびリポ蛋白脂質に及ぼすインスリンの影響

The effect of insulin on a lipid content of the aorta and lipid distribution of the lipoprotein was studied in normal rabbits.The study was performed on 12 male rabbits, being divided into two groups; one group (7 animals) was injected long acting insulin (1 unit/kg daily) (insulin-group) and the other (5) was used as control (control-group). The food (commercial rabbit pellet) intake was limited 200g daily.Three months later, the blood collected in the fasting state for the determination of blood sugar, IRI and lipoprotein, thereafter the aorta was removed for the determination of cholesterol (Ch) and cholesterol ester (Ch-E) in the wall of the aorta.There were no significant differences between two groups in weight gain, blood sugar and IRI. Ch content in the aorta was higher in insulin-group (2.96±0.28mg/g wet weight) than in controlgroup (2.28±0.12mg/g wet weight), though the difference was not significant. Ch-E content in the aorta was higher in insulin-group than in controlgroup, too. HDL-Ch levels were similar in two groups. LDL-Ch levels in insulin-group (12.8±1.4mg/dl) were significantly higher (p<0.05) than that in control-group (7.3±1.5mg/dl).As a result of this study, it is suggested that insulin may have atherogenic action in the normal rabbit, probably by means of an increment of LDL-Ch.