Aim Hyperhomocystinaemia is associated with macro- and microangiopathic diabetic complications. However, the role of homocysteine (Hcy), serum folate, and vitamin B12 level in the development of premature vascular damage in type 2 diabetic patients is not clear. The present study was designed to assess the relationship between total Hcy, folate, and vitamin B12 levels and arterial stiffness, an early marker of generalized atherosclerosis.Methods As many as 86 subjects with type 2 diabetes mellitus were studied. All participants were evaluated for glucose, HbA(1C), lipid profile, hs-CRP, endothelin, Hcy, vitamin B12, and folate. Pulse wave velocity (PWV) and augmentation index (AI) were performed as a non-invasive recording and computer analysis of the two artery sites pressure waveform using SphygmoCor (version 7.1, AtCor Medical, Sydney, Australia).Results Hcy was significantly positively associated with age, serum creatinine, and vitamin B12 levels. No association between Hcy and folate was observed. The Hcy concentration was significantly positively associated with PWV (r = 0.540, p < 0.0001) and AI (r = 0.390, p < 0.0001). In a general linear model of PWV, Hcy emerged as an independent predictor of PWV even after controlling for age, creatinine, vitamin B12, and folate levels. In a multiple linear regression analysis, the association between Hcy and arterial stiffness was independent of traditional cardiovascular risk factors. Vitamin B12 levels were significantly inversely associated with tHcy (r -0.263, p = 0.015) and marginally associated with PWV(r = -0.212, p 0.052). Significant associations between folate levels and PWV were not detected.Conclusions The results lend support to the hypothesis that elevated Hcy may have a key role in the development of atherogenesis in diabetic patients. Additionally, vitamin B12 is significantly associated with tHcy concentrations and is identified as a marginally independent correlate of PWV in diabetic patients in the absence of folate deficiency. Copyright (C) 2008 John Wiley & Sons, Ltd.

This work has two main objectives. The first objective is to carry out a statistical comparison of specific models for estimating monthly mean daily and hourly global and diffuse irradiations on a horizontal surface from the monthly average per day of the main meteorological data and to recommend the most accurate models to be used for estimating solar radiation in sites belonging to the Algerian climate areas represented by each of the three sites presented in this work. The second objective is to propose a Simulink program where the methodology allows for reconstituting daily and hourly monthly mean horizontal solar radiation data. From the 10 global radiation models proposed in several journal papers, Rietveld’s, Garg et al.’s and McCulloch’s relations are retained, respectively, for estimating the monthly mean daily global ratio for Adrar, Bouzareah and Ghardaia sites and Page and from the nine retained diffuse relations, Page’s, Liu et al.’s and Erbs et al.’s relations are used, respectively, for the same sites for calculating the monthly averages per day of diffuse irradiation. On the other hand, the models of Jain and Liu et al. are, respectively, recommended for the reconstitution of the monthly averages per hour of the global and diffuse irradiations. However, the obtained results are used to develop a Simulink program which can be used in the estimation of long-term performance of flat plate solar radiation systems.

Red blood cell (RBC) aggregation is increased in familial hypercholesterolemia, and is reduced significantly after low density lipoprotein (LDL) apheresis. The purpose of the present study was to clarify whether this reduction depends on changes in plasma composition, RBC membrane properties, or both. RBC aggregation was determined in a computerized cell flow-properties analyzer, before and after LDL apheresis. We compared RBC aggregation in autologous plasma with aggregation in a plasma-free standard solution (0.5% of dextran 500 kDa) to define the separate contributions of plasma and cellular properties to the observed RBC aggregation. RBC aggregation in autologous plasma was reduced by 35.5% after LDL apheresis (P=0.01) but was not significantly affected when measured in dextran 500. This suggests that LDL apheresis attenuated RBC aggregation by altering plasma composition rather than RBC membrane properties. These results are relevant to the understanding of hemorheological changes which follow therapeutic apheresis in hypercholesterolemic patients.

INTRODUCTION:Military aircrew men represent an elite group of relatively young, fit, and healthy people. The effectiveness of statin treatment in reducing low-density lipoprotein cholesterol (LDL-C) according to the current National Cholesterol Education Program (NCEP) guidelines, its safety, and compliance in this group of people has not yet been determined.METHODS:We prospectively evaluated 84 military aircrew men (mean age 43 +/- 7 yr) with LDL-C above the current NCEP guidelines. The patients were divided into two groups according to their coronary risk factors: Group 1, LDL-C goal < 160 mg x dL(-1); Group 2, LDL-C goal < 130 mg dL(-1). All patients received statins in addition to therapeutic lifestyle changes and were followed for a mean of 3 +/- 1 yr according to a simple flow chart. Lipoprotein levels, liver function tests, creatinine phosphokinase, and subjective adverse reactions were checked periodically.RESULTS:LDL-C significantly declined by 32% (p < 0.0001) within the first month of treatment and 99% of subjects achieved their LDL-C goal within 114 +/-35 d from statin therapy initiation. The Framingham estimated 10-yr coronary risk showed a reduction at an average of 12 mo after statin therapy initiation from a baseline value of 6.54% to 3.95% (p = 0.003). No subjects were grounded or disqualified from duty, there were no cardiovascular events during follow-up, and compliance to therapy was high [82/84 (98%)].DISCUSSION:Statin treatment in this highly select, relatively young group of aircrew men significantly and safely lowered LDL-C cholesterol levels.

LDL-apheresis lowers the LDL level in patients with severe hypercholesterolemia. The present study compared three apheresis methods--DSA, DALI, and plasma exchange--for effectiveness in removal of LDL and effect on various blood parameters involved in atherogenesis. The study group included 6 patients with primary hypercholesterolemia unresponsive to maximal drug therapy. All were treated first with 4 consecutive plasma exchange sessions followed by 4 DSA sessions; in four out of six, an additional 4 sessions of DALI were then performed. Levels of lipoproteins, apoproteins, CRP, homocysteine, fibrinogen, and blood count were determined before and after each session. All 3 procedures yielded a significant reduction in total cholesterol and ApoB-containing lipoproteins, with DALI being the most effective. Also, a significant reduction in triglycerides, HDL, and ApoA1 was observed with all the methods. The reduction in HDL-C with DSA and DALI was greater than previously reported. The LDL/HDL-cholesterol ratio decreased significantly with DSA and DALI and increased with plasma exchange. There was a significant decrease in CRP, fibrinogen, and platelets with all three methods, and a significant decrease in homocysteine only with DSA and DALI. All three procedures effectively reduced the concentration of various compounds involved in atherosclerosis. Plasma exchange is nonselective and cannot be recommended as the procedure of choice.

Objective: To determine the degree of correlation between red blood cell (RBC) aggregation on peripheral blood glass slides (PBGS) as determined by image analysis and the inter-erythrocytic cohesive forces as determined in a computerized cell flow properties analyzer (CFA). Study design: RBC aggregation was assessed using both systems simultaneously in healthy volunteers, obese patients and hypercholesterolemic individuals before and following LDL apheresis. Results: A significant (r=0.5, p<0.001) correlation was noted between the flow-dependent average aggregate size (AAS) obtained in the CFA and the degree of RBC aggregation on peripheral blood glass slides. Moreover, the enhanced RBC aggregation on the slides was positively associated with the appearance of larger aggregates in the CFA (r=0.5, p<0.001) and inversely with the formation of smaller aggregates (r=−0.27, p<0.04). A similar reduction in RBC aggregation following LDL apheresis was noted in both systems. Conclusions: The phenomenon of RBC aggregation on peripheral blood glass slides is governed by significant inter-erythrocytic cohesive forces and is not a result of a mere coincidental superimposition of cells. The slide test offers a rapid and simple method of evaluating rheologically significant RBC aggregation, and may allow stratification of patients at risk for atherothrombosis.

The purpose of this study was to compare the degree of erythrocyte adhesiveness/aggregation (EAA) reduction of two low-density lipoprotein (LDL) apheretic procedures, namely direct adsorption of lipoproteins (DALI) and dextran sulfate adsorption (DSA). A significant (P < 0.001) reduction of EAA was noted in six hypercholesterolemic patients who underwent a total of 40 apheretic sessions and no difference was noted in the degree of EAA reduction by the two techniques. Thus, being a real-time and point-of-care test, the erythrocyte adhesiveness/aggregation test can be applied in relevant situations of acute ischemia, where therapeutic LDL apheresis could improve the hemorheology of individuals with increased concentrations of cholesterol and inflammatory sensitive proteins.

BACKGROUND:It is not clear what is the relative importance of fibrinogen, immunoglobulins, highly sensitive C-reactive protein (hs-CRP), cholesterol and triglyceride concentrations on the appearance of aggregated red blood cells in the peripheral blood.DESIGN:Six hypercholesterolaemic patients undergoing regular LDL apheresis that were examined repeatedly before and following the procedure.RESULTS:We determined the degree of erythrocyte adhesiveness/aggregation in relation to the concentration of the above-mentioned macromolecules in 80 samples. In a linear logistic regression the respective R2 values for fibrinogen, total cholesterol, triglycerides, hs-CRP, IgG, IgM and IgA were 0.45 (P<0.0001), 0.2 (P<0.0001), 0.02 (P=0.02), 0.001 (P=NS) and 0.002 (P=NS), respectively. We further analyzed the potential of ApoA, ApoB and Lpa to participate in red cell adhesiveness/aggregation and found them to be not significant.CONCLUSIONS:In a milieu of adhesive macromolecules, lipids and inflammation-sensitive proteins including fibrinogen, total cholesterol, triglycerides, hs-CRP and immunoglobins G, M and A, fibrinogen has a dominant role in maintaining the red blood cell adhesiveness/aggregation in the peripheral venous blood. These findings are relevant for the research directed at finding new apheretic modalities to reduce the degree of red blood cell adhesiveness/aggregation in the peripheral blood.

BACKGROUNDThe beneficial effect of 3-hydroxy-3-methylglutyaryl co-enzyme A reductase inhibitors on cardiovascular risk reduction has been clearly established. Concerns have been raised that lowering blood cholesterol by other hypolipidemic drugs or by a non-pharmacologic approach may have deleterious effects on psychopathologic parameters. Garlic is one of the most commonly used herbal remedies and is considered to have hypocholesterolemic as well as other cardioprotective properties. Its effect on psychopathologic parameters has never been reported.OBJECTIVETo evaluate the effect of garlic on lipid parameters and depression, impulsivity, hostility and temperament in patients with primary type 2 hyperlipidemia.METHODSIn a 16 week prospective double-blind placebo-controlled study, 33 patients with primary hypercholesterolemia and no evidence of cardiovascular disease were randomly assigned to receive either garlic or placebo. Garlic in the form of alliin 22.4 mg/day was given to 13 patients, and placebo to 20. Both groups received individual dietary counseling. The changes in lipid profile and the various psychopathologic parameters were determined at the beginning and end of the trial. The differences in lipid parameters were evaluated by Student's t-test. The psychological data were analyzed by one-way analysis of variance (ANOVA) with repeated measures and Neuman-Keuls test.RESULTSNo significant changes were observed in levels of total cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol and triglycerides, or in the psychopathologic parameters evaluated.CONCLUSIONShort-term garlic therapy in adults with mild to moderate hypercholesterolemia does not affect either lipid levels or various psychopathologic parameters.

BACKGROUND:Decreased elasticity of the aorta is associated with aging and several risk factors of atherosclerosis. The data regarding this phenomenon in patients with familial hypercholesterolemia are rather sparse.OBJECTIVES:To evaluate non-invasively the elasticity of the proximal ascending aorta of 51 heterozygous FH patients compared to 42 normal age and gender-matched controls.METHODS:Aortic elasticity was estimated by transthoracic echocardiography using the "pressure-strain" elastic modulus and aortic strain formulas.RESULTS:The elastic modulus score was higher in the FH group than in the controls (1.12 +/- 0.91 10(6) dynes/cm2 vs. 0.65 +/- 0.46 10(6) dynes/cm2 respectively, P = 0.01). This was consistent in both the pediatric (0.5 +/- 0.2 10(6) dynes/cm2 vs. 0.4 +/- 0.1 10(6) dynes/cm2 respectively, P = 0.009) and adult subgroups (1.3 +/- 1.0 10(6) dynes/cm2 vs. 0.8 +/- 0.5 10(6) dynes/cm2 respectively, P = 0.0004). Aortic strain was significantly lower in patients with FH than in controls (6 +/- 4% vs. 9 +/- 5% respectively, P = 0.0002). These findings reflected decreased elasticity of the proximal ascending aorta in the FH patients. In multivariate analysis, age, serum cholesterol level and serum triglycerides level were the independent predictors of the elastic modulus score, whereas age was the predictor of aortic strain.CONCLUSIONS:The elasticity of the proximal ascending aorta is decreased in heterozygous FH patients.

We applied an erythrocyte adhesiveness/aggregation test (EAAT) to a model of plasma exchange in individuals with familial and primary hypercholesterolemia. The significant (p < 0.0001) reduction in the concentration of fibrinogen by 56%, globulins by 48%, and cholesterol by 53% corresponded to the expected significant (p < 0.0001) reduction in the degree of erythrocyte adhesiveness/aggregation in the peripheral venous blood. By virtue of its being a real-time, simple, very-low-cost, and essentially bedside technique, the EAAT might have the potential of disclosing information of rheological relevance immediately before, during, as well as following apheretical procedures administered to patients with an impaired rheological profile.

Weight reduction is recommended for the treatment of subjects with insulin resistance (IR) syndrome; however, the relative importance of the decrease in body fat or the negative energy balance achieved during a hypo-energetic diet in the improvement of this metabolic syndrome is still debated. Therefore, we undertook to study their relative impact on amelioration of the metabolic abnormalities associated with IR in obese subjects. Twelve obese subjects (six males and six females, mean+/-s.d. body mass index 36.1+/-4.7 kg/m(2)) aged 38-57 years were investigated. During the first phase they were fed a hypo-energetic diet for 6 weeks (week 0-6). During the second phase, lasting 4 weeks (week 6-10) they consumed an iso-energetic diet. During the third phase (week 10-16) the subjects were put again on a hypo-energetic diet. Insulin sensitivity (SI) was assessed by an insulin-enhanced, frequently sampled i.v. glucose tolerance test with minimal model analysis. All subjects reduced weight during both hypo-energetic periods: 5.49+/-0.75 and 2.32+/-0.37%, means+/-s.e.m., P<0.005, week 0-6 and 10-16 respectively. One-third of this loss was achieved within the first week of each period. SI increased by 353+/-121 and 147+/-38% (P<0.005), means+/-s.e.m., at the end of both hypo-energetic periods (week 6 vs 0 and 16 vs 10 respectively). Two-thirds of this improvement were observed within the first week of each period (week 1 vs 0 and 11 vs 10 respectively). During the iso-energetic weight-maintaining period (week 10 vs 6), SI decreased by 43.5+/-7.9% (P<0.002). Serum levels of leptin and triglyceride followed a similar pattern, but to a lesser extent. It may be concluded that negative energy balance is more effective when compared with maintaining a stable lower weight in achieving an improvement in the metabolic parameters of the IR syndrome.

HERSHCOVICI, TIBERIU M.D.; MEKHMANDOROV, SERGEI M.D.; BEIGEL, YITZHAK M.D.; HARDOFF, RUTH M.D., D.Sc. Author Information

Background: Although the cessation of smoking reduces the increased risk for ischemic heart disease, it is associated with marked weight gain and presumably insulin resistance, both of which heighten the risk of coronary heart disease.Hypothesis: We investigated the isolated effect of nicotine on body weight and insulin resistance during smoking cessation.Methods: Eleven healthy, middle-aged heavy smokers were studied. Insulin sensitivity was assessed by an insulin-enhanced, frequently sampled intravenous glucose tolerance test with minimal model analysis. The subjects were studied at baseline (last day of smoking) (phase 1), at the end of the 6-week nicotine replacement program (phase 2), and after 8 weeks without smoking or nicotine replacement (phase 3).Results: The subjects started to gain weight during nicotine replacement (phase 2) (0.3 +/- 0.2 kg/week, mean +/- standard deviation) and continued to do so at a steady rate after nicotine replacement was stopped (0.2 a 0.2 kg/week) (p = 0.3). Insulin sensitivity decreased by 14 +/- 2.6% luring nicotine replacement but increased by 16 +/- 5.1% (compared with phase 2) during phase 3, even though the weight gain continued (p = 0.047; 95% confidence interval: 0.05-5.73).Conclusions: Smoking cessation is associated with weight gain and improvement in insulin resistance. Nicotine is the main ingredient in cigarette smoke causing insulin resistance, but the withdrawal of another, unknown ingredient in cigarette smoke is responsible for the weight gain associated with smoking cessation.

A 43-year-old man was hospitalized because of a three-day history of epigastric pain, pain in the right upper quadrant, and constipation. The pain was intermittent and not associated with nausea, vomiting, fever, or eating.The patient had been born in Israel to parents of Libyan origin. His job as a merchant often took him abroad, especially to Spain and Egypt. He had had type 2 diabetes mellitus for six years, for which he took 5 mg of glyburide per day. Approximately 13 months before the present admission, he had been hospitalized at another facility for several days for . . .