BACKGROUND

Some patients with Coronary Artery Disease (CAD) have no well-known risk factors of this disease, but are diagnosed with cardiovascular events. The present study aimed to assess the association between Apo A1 and ApoB and the severity of CAD and determine whether these parameters are better predictors of Ischemic Heart Disease (IHD).

METHODS

In this case control study, 271 individuals who were suspicious of having CAD and had been referred to Arak Amir-al-Momenin hospital underwent coronary angiography. Based on the results of angiography, the participants with presence or absence of coronary artery stenosis were allocated into the case and the control group, respectively. The severity of CAD involvement was determined by Gensini score. The data were entered into the SPSS statistical software and analyzed through parametric and non-parametric tests, sensitivity analysis, and logistic regression.

RESULTS

The results revealed no significant correlation between apoA-1 and severity of CAD involvement (GS) (r = 0.017, P = 0.797). However, a significant correlation was found between apoB and GS (r = 0.127, P = 0.047). Logistic regression model showed ApoB, sex, DM and, FH as the only proper predictors of IHD (P < 0.048, P < 0.002, P < 0.040, and P < 0.001, respectively). In comparison to angiography for diagnosis of CAD, ROC analysis represented ApoB as a more useful predictor (P = 0.023).

CONCLUSIONS

In addition to measurement of conventional parameters for assessing CAD high risk groups, according to the results of this study using ApoB would be resonable as well. Further investigations are recommended to clear the problem.

Pyrazinamide (PZA) causes serious hepatotoxicity, but little is known about the exact mechanism by which PZA induced liver injury. The peroxisome proliferator-activated receptors alpha (PPARα) is highly expressed in the liver and modulates the intracellular lipidmetabolism. So far, the role of PPARα in the hepatotoxicity of PZA is unknown. In the present study, we described the hepatotoxic effects of PZA and the role of PPARα and its target genes in the downstream pathway including L-Fabp, Lpl, Cpt-1b, Acaa1, Apo-A1 and Me1 in this process. We found PZA induced the liver lipid metabolism disorder and PPARα expressionwas down-regulated which had a significant inverse correlation with liver injury degree. These changeswere ameliorated by fenofibrate, the co-treatment that acts as a PPARα agonist. In contrast, short-termstarvation significantly aggravated the severity of PZA-induced liver injury. In conclusion, this study demonstrated the critical role played by PPARα in PZA-induced hepatotoxicity and provided a better understanding of the molecular mechanisms underlying PZA-induced liver injury. Copyright © 2016 John Wiley & Sons, Ltd.

PURPOSE--To evaluate if the levels of lipoprotein (a) [Lp(a)], apolipoproteins (apo) A1, B and the lipid profile (LP) differ among heart transplantation (HT) patients, with coronary artery disease (CAD) and patients without CAD (NL) and if LP discriminates patients with graft vascular disease (GVD). METHODS--A hundred and seventy patients separated in 3 groups: I) HT [n = 43 46 +/- 15 years, 24 months (median) after transplantation], of these 28 were submitted to serial angiography after the first year of transplantation subgroups with GVD (n = 9) and without GVD (NGVD) (n = 19); II) CAD (n = 72, 48 +/- 6 years); III) NL (n = 45, 50 +/- 6 years). RESULTS--HT presented higher apo A1 levels than CAD and NL (1.5 +/- 0.5 vs 1.2 +/- 0.05 vs 1.1 +/- 0.06 g/l p < 0.05 respectively). Apo B was higher on CAD than in HT and NL (1.5 +/- 0.05 vs 1.2 +/- 0.07 vs 1.3 +/- 0.09 g/l p < 0.05). Lp (a) presented a trend to higher levels in HT and CAD than in NL [25(2-97), 24(1-130) and 15 (1-100) mg/dl, p = 0.05)]. However, when individually evaluated against NL Lp(a) levels were higher in HT and CAD (p = 0.019 and 0.03 respectively). LP did not differ between GVD and NGVD. CONCLUSION--Increased Lp(a) levels after transplantation might be related to the high prevalence of GVD. The LP did not discriminate GVD.

The utilization of two WHO reference materials, liquid and lyophilized, permitted international standardization of apolipoprotein measurements. We report here the results of a collaborative study between Arcol, SFBC and SFRL in order to establish reference ranges for apo A1 and B on nine standardized systems. A population of 1027 men and women supposed healthy, 4 to 60 year old, have been selected in two Centers for Preventive Medicine. The serum samples were aliquoted frozen at -20 degrees C the day of sampling and analysed by the manufacturers with IFCC standardized calibrants. A specific quality control was performed using a frozen pool of sera. For apo A1, the centile 2.5 of the reference population varies from 1.04 to 1.16 g/l. The range values for the centile 97.5 varies from 1.87 to 2.24 g/l. For apoB, the centile 2.5 varies from 0.43 to 0.57 g/l, and the centile 97.5 from 1.30 to 1.39 g/l. Only one system has a problem of dispersion with an upper limit equal to 1.20 g/l. These results improve that international standardization allowed actually a good comparability of the results, especially for apoB.

The aim of the study is to evaluate the lipids disorders in children with refractory proteinuria in acute phase and remission of the disease. The study group consist of 39 children, mean age 8.2 +/- 3.9 years with refractory nephrotic syndrome (RNS)/nephrotic proteinuria (RNP), wchich were divided in 3 groups according to RNS/RNP frequency: group A--17 children up to 3 times, group B--13 children 4-9 times, group C--9 children>> or = 10 times. Total number of relapses was 53. In all children at the start and every 3 months, the total cholesterol concentration (TC), LDL, HDL cholesterol, triglicerydes (TG), apolipoprotein A1(apoA1), apoliporotein B100 (apoB100 ) were measured. The duration of the study was 12 months.

RESULTS

Children with NS/NP in the acute phase of the disease show high levels of TC, TG, LDL-C and apolipoproteins: apo AI, apo B100, The level of HDL-C was normal. In the groups A, B, C a normalization of average levels of apo B100, was recorded after 3 month, apo AI after 3 to 6 months. With the increasing amount of relapses the time to normalization of average levels of TC and LDL-C was prolonged. Normal average levels of LDL-C were recorded in the group A after 3 months, in the group B after 9 months, in the group C was still high. TC normalization was recorded after 6 months only in the group A, in the groups B and C the level was high; TG was high during 12 months of observation in all groups.

CONCLUSIONS

The persistance of high TC, LDL-C and TG levels during the remission phase in children with higher numbers of NS/NP relapses is a risk factor of atherosclerosis developement.

1. In vivo and in vitro gene-manipulated models were used to study the metabolism of chylomicron remnants. Transgenic mice expressing human apolipoprotein (Apo) A1 or E4, gene knockout mice deficient in ApoE or low density lipoprotein (LDL) receptors and antisense gene inhibition in HepG2 cells were used to evaluate the effect of gene manipulations on the metabolism of chylomicron remnants. 2. Mice transgenic for human ApoE4 showed accelerated clearance of chylomicron-like emulsions when animals were fed a low-fat diet. When challenged by a high-fat diet, remnant clearance in ApoE4 transgenic mice was delayed, as in normal or non-transgenic controls. However, unlike normal nontransgenic controls, in ApoE4 transgenic mice high density lipoprotein (HDL)-cholesterol levels remained high after high-fat feeding, which probably protected the animals from the development of atherosclerosis. In contrast, clearance of chylomicron-like lipid emulsions was not affected by the over-expression of human ApoAI in transgenic mice. 3. Gene knock-out mice deficient in ApoE or deficient in the LDL receptor were used to show that ApoE and LDL receptors are both essential for the normal, fast catabolism of chylomicron remnants by the liver. In the absence of the LDL receptor, an alternative ApoE-dependent pathway operates to clear chylomicrons from the plasma, with significantly delayed catabolism. 4. Antisense gene inhibition techniques were used to suppress the expression of syndecan, a core protein of heparan sulfate proteoglycan, in HepG2 cells. Remnant uptake in cells transfected with the antisense oligodeoxynucleotide complementary to a 20 nucleotide sequence upstream of the initiation site of syndecan cDNA markedly reduced the uptake of chylomicron remnant.

BACKGROUND

Identifying patients with recent stroke or transient ischemic attack (TIA) at high risk of major vascular events (MVEs; stroke, myocardial infarction, or vascular death) may help optimize the intensity of secondary preventive interventions. We evaluated the relationships between the baseline Framingham Coronary Risk Score (FCRS) and a novel risk prediction model and with the occurrence of MVEs after stroke or TIA in subjects enrolled in the Stroke Prevention by Aggressive Reduction in Cholesterol Level (SPARCL) trial.

METHODS

Data from the 4731 subjects enrolled in the SPARCL study were analyzed. Hazard ratios (HRs) from Cox regression models were used to determine the risk of subsequent MVEs based on the FCRS predicting 20% or more 10-year coronary heart disease risk. The novel risk model was derived based on multivariable modeling with backward selection. Model discrimination (c-statistics) was assessed using the areas under the receiver operating characteristic curves.

RESULTS

Of 3969 subjects with complete data, 27% had a baseline FCRS of 20% or more. In multivariable analysis, an FCRS of 20% or more was associated with twice the risk of subsequent MVEs (HR = 1.92, 95% confidence interval [CI]: 1.63-2.27). The novel model based on a multivariable analysis included age (HR = 1.37, 95% CI: 1.25-1.51 per 10 years), diabetes (HR = 1.82, 95% CI: 1.51-2.18), male sex (HR = 1.35, 95% CI: 1.12-1.61), and an apolipoprotein (APO)-B/APO-A1 ratio (HR = 1.56, 95% CI: 1.16-2.11). The c-statistic was .58 (95% CI: .55-.60) for the FCRS of 20% or more and .65 (95% CI: .63-.67) for the novel model.

CONCLUSIONS

Both a baseline FCRS of 20% or more and a novel predictive model were associated with future MVEs in SPARCL trial subjects. The novel model needs to be validated, and the benefits of using either the FCRS or the novel model in clinical practice needs to be assessed.

The objective of the study was to demonstrate the effect of pioglitazone and pioglitazone in combination with statin on East Indian patients with hyperinsulinemia and hyperlipidemia. It was a randomized, placebo-controlled, double-blind study with a parallel-group design comprising 83 patients. Patients of either sex with cardiac complications, including hyperlipidemia and (or) diabetes mellitus with or without hyperinsulinemia, were enrolled. Patients over 70 years of age, with renal or hepatic failure, or with severe diabetes mellitus (total glucose >400 mg/dL) were excluded from the study. Enrolled patients were randomly assigned to 4 groups that received placebo, pioglitazone, atorvastatin, or both. Blood samples were collected before and after treatment for analysis of serum glucose, insulin, lipid profile, apolipoprotein (apo) A1, apo B, and fibrinogen. Data were compared with that of patients with normal insulin or hyperinsulinemia. The patients with hyperinsulinemia receiving only pioglitazone showed a significant decrease in insulin levels compared with those with normal insulin levels. These patients also showed a significant increase in HDL levels. However, no significant change was observed in patients treated with both atorvastatin and pioglitazone. Pioglitazone was also found to increase significantly the apo A1 levels in patients with hyperinsulinemia, but there was no significant increase in patients given both atorvastatin and pioglitazone. Our data suggests that pioglitazone should be given preferably to the patients with hyperinsulinemia and statin should not be coadministered.

Background and aims: Reduction of atherogenic lipoproteins is often the ultimate goal of nutritional interventions, however this is complicated given that hypolipidemia is frequently observed in coronavirus disease 2019 (COVID-19) patients. We aimed to explore the association of hypolipidemia with patient outcomes in terms of immunothrombosis and multiorgan injury, focusing on specialized apolipoproteins apo A1 and apo B.

Methods: Lipid profiles of 50 COVID-19 patients and 30 sick controls presenting to the Emergency Department (ED) were measured in this prospective observational study. The primary outcome was development of severe acute kidney injury (AKI). Need for hospitalization and ICU admission were secondary outcomes. Lipoproteins were analyzed for independent association with serum creatinine (SCr) increase ratio and correlated with a wide panel of biomarkers.

Results: COVID-19 cohort had significantly lower apo A1 (p = 0.006), and higher apo B/apo A1 ratio (p = 0.041). Patients developing severe AKI had significantly lower LDL-C (p = 0.021). Apo B/apo A1 was associated with 2.25-fold decrease in serum SCr increase ratio, while LDL-C with a 1.5% decrease. Hypolipidemia correlated with low plasminogen, ADAMTS13 activity/VWF:Ag, and high inflammatory biomarkers (CRP, IL-6, IL-8, IL-10), plasminogen activator inhibitor-1 (PAI-1), ED creatinine, and SCr increase ratio.

Conclusion: Although favored in dietetics, findings of a low LDL-C in COVID-19 patients should be alarming in light of our observations. Low apo B/apo A1 ratio and LDL-C are predictive of renal deterioration in COVID-19 patients, and low LDL-C in particular may potentially serve to indicate COVID-19 related AKI driven by disrupted fibrinolysis and a secondary thrombotic microangiopathy-like process.

Keywords: Acute kidney injury; Apolipoproteins; Coronavirus disease 2019; Hypolipidemia; Thrombotic microangiopathy.

Arsenic (As) is a toxic environmental contaminant and potential human carcinogen. Chronic intake of arsenic-contaminated water and food leads to arsenicosis, a major public health problem in many parts of the world. Early detection of arsenic toxicity would greatly benefit patients; however, the detection of arsenicosis needs to be done early before onset of severe symptoms in which case the tools used for detection have to be both sensitive and reliable. In this context, the present study investigated plasma proteome changes in arsenic-exposed Labeo rohita, with the aim of identifying biomarkers for arsenicosis. Changes in the plasma proteome were investigated using gel-based proteomics technology. Using quantitative image analysis of the 2D proteome profiles, 14 unique spots were identified by MALDI-TOF/TOF MS and/or LC-MS/MS which included Apolipoprotein-A1 (Apo-A1) (6 spots), α-2 macroglobulin-like protein (A2ML) (2 spots), transferrin (TF) (3 spots) and warm-temperature acclimation related 65kDa protein (Wap65). The proteome data are available via ProteomeXchange with identifier PXD003404. Highly abundant protein spots identified in plasma from arsenic-exposed fish i.e. Apo-A1 (>10-fold), A2ML (7-fold) and Wap65 (>2-fold) indicate liver damage. It is proposed that a combination of these proteins could serve as useful biomarkers of hepatotoxicity and chronic liver disease due to arsenic exposure.

The synthetic estrogen diethylstilbestrol is used to prevent miscarriages and as a therapeutic treatment for prostate cancer, but it has been reported to have adverse effects on endocrine homeostasis. However, the toxicity mechanism is poorly understood. Recently, we reported that diethylstilbestrol impairs adrenal steroidogenesis via cholesterol insufficiency in adult male rats. In the present study, we found that the adrenal cholesterol level was significantly reduced without of the decrease in other precursors in the adrenal steroidogenesis 24 h after a single dose of diethylstilbestrol (0.33 μg/g body mass). The serum HDL/cholesterol level was also reduced only 12 h after the diethylstilbestrol exposure. The level of Apo E, which is indispensable for HDL/cholesterol maturation, was decreased in both the HDL and VLDL/LDL fractions, whereas the level of Apo A1, which is an essential constituent of HDL, was not altered in the HDL fraction. Because the liver is a major source of Apo E and Apo A1, the secretion rates of these proteins were examined using a liver perfusion experiment. The secretion rate of Apo A1 from the liver was consistent between DES-treated and control rats, but that of Apo E was comparatively suppressed in the DES-treated rats. The disruption of adrenal steroidogenesis by diethylstilbestrol was caused by a decrease in serum HDL/cholesterol, which is the main source of adrenal steroidogenesis, due to the inhibition of Apo E secretion from the liver.

OBJECTIVE

To determine the biochemical and clinical response of two patients with homozygous familial hypercholesterolemia to three different schedules of low-density lipoprotein apheresis compared with plasmapheresis.

METHODS

Two female patients aged 17 years, both affected by homozygous familial hypercholesterolemia, underwent low-density lipoprotein apheresis using a dextran-sulfate/cellulose affinity column on successive twice-weekly, weekly, and biweekly schedules. Plasmapheresis was carried out only at biweekly intervals. Plasma lipids and apolipoproteins A1 and B were assayed before and after each procedure. Cardiac status was assessed before and after the study.

RESULTS

On schedule 1 of apheresis, the immediate post-procedure low-density lipoprotein cholesterol levels declined to 60 mg/100 dL plasma. Quasi-steady-state values of low-density lipoprotein cholesterol and apolipoprotein B were also markedly reduced, with levels approaching the upper limits of normal for age and sex. This response was attenuated as the intervals between procedures were prolonged. No advantage of low-density lipoprotein apheresis over plasmapheresis was observed during the biweekly protocol except that after plasmapheresis high-density lipoprotein cholesterol levels declined by 50% or more compared with less than 10% after apheresis. The latter procedure, especially on schedules 1 and 2, caused an increase in the quasi-steady-state concentrations of both high-density lipoprotein cholesterol and apolipoprotein A1. Thus, mean low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and apolipoprotein B/apo A1 ratios were reduced by more than three- to four-fold during twice-weekly apheresis. Other laboratory parameters remained stable throughout except for iron and hemoglobin levels, which were reduced with both plasmapheresis and apheresis. Xanthomas regressed significantly in the one patient who had not been treated prior to the current trial. Cardiac changes were minor in both patients.

CONCLUSIONS

Low-density lipoprotein apheresis proved safe and effective on an accelerated protocol as well as during more conventional schedules. Owing to its simplicity, selectivity, and safety, apheresis using a dextran-sulfate/cellulose column is possibly the optimum means currently available for the extracorporeal removal of low-density lipoprotein cholesterol.

BACKGROUND

Some results exist on fetuin-A as marker for vascular disease in type 2diabetes. We examined the relationship between serum fetuin-A with some factors, in patients with type 2 diabetes mellitus (T2DM).

METHODS

From October 2012 to June 2013, a total of 131 T2DM patients were recruited and evaluated for various parameters including HOMA-IR, Apo-A1, Apo-B100, body fat percentage and waist circumference. Serum fetuin-A levels were measured by enzyme-linkedimmunosorbent assay (ELISA), and Serum glucose with a Cobas MIRA analyzer by enzymatic method. Apo-B100 and apo-A1 were measured by immunoturbidimetry with a Cobas MIRA analyzer. HOMA-IR was calculated by the following formula: [fasting insulin (uIU/mL) × fasting blood glucose (mmol/L)]/22.5.

RESULTS

The mean levels of HOMA-IR were significantly increased progressively across fetuin-A tertiles (p for trend=0.04) in women but not men. Fetuin-A had just a significant positive correlation with Apo- A1(r=0.22, p=0.02).

CONCLUSIONS

This present study showed that levels of serum fetuin-A are significantly associated with insulin resistance in women with T2DM.

The aims of this study were: the identification of proteins differentially represented in the serum proteome of dogs with leishmaniosis after treatment and the verification of one selected protein as a possible biomarker for treatment monitoring. Serum samples from five dogs with leishmaniosis, before and after treatment were pooled into two groups and analysed using 2-dimensional electrophoresis followed by mass spectrometry analysis (MS). The MS analysis allowed the identification of 8 proteins differently expressed. APO-A1 was selected and an immunoturbidimetric assay was validated for its measurement in dogs. Significantly decreased concentrations of APO-A1 in dogs with leishmaniosis and a significant increase after a good response to the treatment were observed, suggesting that APO-A1 could be a potential biomarker of treatment monitoring with the advantages of an automated measurement.

It has been shown that mouse 24p3 protein is a dexamethasone-inducible secretory protein which suggests the involvement of an autocrine mechanism in the L929 cell line. The aim of this study was to investigate the possibility of this mechanism in L929 cells and to also demonstrate further processing of this protein after association with L929 cells. We have characterized the internalization of 24p3 protein in L929 cells with fluorescein isothiocyanate- and Alexa555-labeled protein supplement instead of secreted 24p3 protein. As endocytotic inhibitors could reveal the inhibition of protein internalization, we confirmed the existence of receptor-mediated 24p3 protein internalization in L929 cells by carrying out an inhibition test. Plus-chase experiment of L929 cells with biotinylated 24p3 protein demonstrated a release of internalized 24p3 protein into the extracellular region. The protein recycling inhibitor, bafilomycin A1, arrests the transport of 24p3 protein by accumulating in early endosome, but no effect could be observed in protein release from early to late endosome by nocodazole. These results provide the first evidence on recycling of apo-24p3 protein in L929 cells.

This work studies the relationship between a common genetic marker in our population, sickle-cell trait, and atherogenic risk factors. One hundred and twenty-two healthy subjects were studied. Forty-six subjects had normal haemoglobin (HB-AA) while 76 had sickle-cell trait Hb-AS. Mean cholesterol level was higher in subjects with sickle-cell trait (2.82 +/- 0.21 g/I) than in subjects with normal haemoglobin (2.08 +/- 0.40 g/I) used as controls. The difference was statistically significant (p < 0.05). HDL cholesterol levels remained in the normal range in controls (Hb-AA) (0.560 +/- 0.10 g/I) while subjects with Hb-AS had high HDL-c levels (0.618 +/- 0.30 g/I). Mean LDL cholesterol levels in Hb-AS subjects were about 57% higher than those in controls (1.84 +/- 0.10 g/I and 1.17 +/- 0.30 g/I, respectively) (p < 0.05). Apolipoprotein A1 levels of Hb-AS subjects were lower (1.37 +/- 0.10 g) than those of Hb-AA subjects (1.98 +/- 0.15 g/I), (p < 0.05) while apolipoprotein B concentrations of Hb-AS subjects were higher (1.70 +/- 0.27 g/I) than in controls (1.30 +/- 0.10 g/I) (p < 0.05). The atherogenicity index given by the Apo-B/Apo-AI ratio was higher in Hb-AS subjects (1.24) than in those with normal haemoglobin (0.65). We conclude that Hb-AS subjects are at high atherogenic risk if subsequent diet management is not undertaken.

Three groups of hyperlipoproteinemia patients have been submitted to long term treatment (18 months) with bezafibrate, gemfibrate and fenofibrate evaluating efficacy and tolerability of the three drugs. A global improvement of lipemic profile with an increase in protective (HDL, APO-A1) and a reduction in atherogenic factors (TC, LDL, APO-B, TG) has been shown, particularly at the end of the 18 months of therapy. No pathological changes have been observed in SGOT, SGPT, GGT values. Echotomography of biliary tract excluded the development of gallstones during treatment. The Authors can conclude with a positive judgement about use of these drugs in long term treatment of primary hyperlipoproteinemias, resistant to diet alone.

OBJECTIVE

The objective of this study was to examine the relationship between amino acid (AA) intake and serum lipid profile in European adolescents from eight European cities participating in the cross-sectional (2006-2007) HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) study, and to assess whether this association was independent of total fat intake.

METHODS

Diet, skinfold thickness, triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), TC/HDL-c ratio, low-density lipoprotein cholesterol (LDL-c), apolipoprotein B (Apo B), apolipoprotein A1 (Apo A1) and Apo B/Apo A1 ratio were measured in 454 12.5- to 17.5-year-old adolescents (44% boys). Intake was assessed via two non-consecutive 24-h dietary recalls. Data on maternal education and sedentary behaviors were obtained via questionnaires. Physical activity was objectively measured by accelerometry.

RESULTS

Alanine, arginine, asparaginic acid, glycine, histidine, lysine and serine intakes were inversely associated with serum TG concentrations in both boys and girls. Intake of other AA like alanine and/or arginine was also inversely associated with serum TC, LDL-c and Apo B/Apo A1 ratio only in girls. An inverse association was observed between intakes of alanine, isoleucine, leucine, methionine, serine, tryptophan, tyrosine and valine and TC/HDL-c ratio among female adolescents. Similar results were found in males for serine and tryptophan intakes. It is noteworthy, however, that associations were no longer significant in both genders when total fat intake was considered as a confounding factor.

CONCLUSIONS

In this sample of adolescents, the association between AA intakes and serum lipid profile did not persist when dietary fat was considered. Therefore, dietary interventions and health promotion activities should focus on fat intake to improve lipid profile and potentially prevent cardiovascular disease.

OBJECTIVE

The purpose of this study was to evaluate the efficacy and safety of LIVALO tablets (pitavastatin) in Japanese male children with heterozygous familial hypercholesterolemia (FH).

METHODS

A multicenter, randomized, double-blind, parallel study was conducted in 14 male children 10-15 years of age with heterozygous FH. Pitavastatin (1 mg/day or 2 mg/day) was administered orally for 52 weeks.The primary endpoint was the percent change in the LDL-cholesterol (LDL-C) concentrations from baseline to endpoint (repeated measures ANCOVA at Weeks 8 and 12). Secondary endpoints included the percentage of patients who achieved the target LDL-C concentration and percent changes in the levels of lipoprotein and lipid parameters at the visit performed at 52 weeks.

RESULTS

The percent change in LDL-C from baseline (mean 258 mg/dL for all patients) to the endpoint was -27.3% (95%CI; -34.0, -20.5) and -34.3% (95%CI; -41.0, -27.5) in the patients receiving 1 mg and 2 mg of pitavastatin, respectively. Stable reductions in the total cholesterol (TC), non-HDL cholesterol (non-HDL-C), apolipoprotein B (Apo-B) and LDL-C levels and non-HDL-C/HDL-C and Apo-B/Apo-A1 ratios were observed up to 52 weeks in both groups. One patient in each dose group (14%) reached the treatment target level of 130 mg/dL.Adverse events were observed in seven (100%) patients receiving 1 mg and five (71%) patients receiving 2 mg of pitavastatin, although none were considered related to the study treatment. One patient in the 1 mg group reported a musculoskeletal AE; however, it was attributed to recent excessive exercise.

CONCLUSIONS

Pitavastatin significantly reduced the LDL-C levels and was well tolerated when administered at usual adult doses in 14 male children 10-15 years of age with heterozygous FH. Pitavastatin is a promising therapeutic agent for pediatric dyslipidemia with few safety concerns.

Serum concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), and triglyceride (TG) were measured and that of low density lipoprotein cholesterol (LDL-C) calculated in blood samples obtained from mentally handicapped women undergoing therapeutic amenorrhea (TA) induced by 5-10 mg of peroral lynestrenol, some receiving, some not receiving simultaneous anticonvulsant therapy (phenytoin, carbamazepine or barbiturate, alone or in combination). In addition, these analyses were carried out in women receiving only anti-convulsants and in controls (mentally handicapped women not receiving any of the above-mentioned medications). Significantly lower HDL-C, Apo A1, TG and cholesterol concentrations were measured in TA patients receiving lynestrenol only, than in those receiving anticonvulsants only, or in controls (p less than 0.001). With regard to HDL-C and Apo A1, patients receiving both lynestrenol and anticonvulsants were intermediate between lynestrenol only patients and controls, but the HDL-C/LDL-C and Apo A1/Apo B ratios were similar to those observed in lynestrenol only patients. Addition of 8 or 12 mg of estriol succinate to the lynestrenol regimen was virtually without an effect. However, halving of the lynestrenol dose resulted in a significant increase in HDL-C and in the HDL-C/LDL-C and Apo A1/Apo B ratios (p less than 0.001 or p less than 0.01), respectively. The lynestrenol dose was thus the most important determinant of lipoprotein pattern and should be kept as small as possible in order to reduce cardiovascular risk.

UNASSIGNED

Type 2 diabetes mellitus (T2DM) is one of the most common diseases worldwide and insulin insufficiency and insulin resistance are two main metabolic issues connected with it. The dyslipidemia associated with insulin resistance and T2DM is characterized by higher triglycerides (TGs), higher very-low-density lipoprotein cholesterol and lower apo A1. Pioglitazone, a member of the thiazolidinedione class, with a proven antihyperglycemic effect, is known to positively influence insulin sensitivity and β-cell function and to have the potential to alter the lipid profile.

UNASSIGNED

The aim of our meta-analysis is to summarize and determine the influence of pioglitazone on the glycemic profile and lipoprotein metabolism as well as on weight and BMI in order to highlight the benefit of pioglitazone therapy in patients with T2DM. A comprehensive literature search was conducted through the electronic databases PubMed, MEDLINE, Scopus, PsyInfo, eLIBRARY.ru (from 2000 until February 2016) to identify studies that investigate the effect of pioglitazone on the glycemic and lipid profile and on the weight and BMI. We chose the random-effects method as the primary analysis. Forest plots depict estimated results from the studies included in the analysis and funnel plots are used to evaluate publication bias. Sensitivity analyses were performed in order to evaluate the degree of influence of the consequent elimination of each individual study on the final result.

UNASSIGNED

Of the 1536 identified sources only 15 randomised trials were included in the meta-analysis. Pioglitazone treatment was associated with improvement in the glycemic profile. It reduced FPG levels by a mean of 1.1-2 mmol/l and HbA1c by a mean of 0.9-1.3%. Our results reaffirmed the hypothesis that pioglitazone has a positive influence on the lipid profile of T2DM patients with increase in TC and HDL, no significant changes in LDL and notable decrease in TGs. Results also showed that pioglitazone therapy led to increase in both weight and BMI (WMD 1.755, 95% CI 0.674 to 2.837 and 1.145, 95% CI 0.389 to 1.901 respectively).

UNASSIGNED

Our results prove that the PPAR γ agonist pioglitazone has the potential to be beneficial to patients with T2DM.

The leaf and bark paste of Holoptelea integrifolia is traditionally used for the treatment of obesity in Asian countries. However, no scientific studies have been undertaken to reveal the actual mechanism of action. The present study aimed to investigate the hypolipidaemic effect of H. integrifolia and its mechanism in diet-induced obese rat model. After 4 weeks of oral administration, blood samples were collected for the estimation of serum lipids, lecithin: cholesterolacyltransferase (LCAT) apolipoproteins (apo) and liver for HMG-CoA reductase (HMGR) assay. The faecal samples were also collected to estimate the faecal fat content. The H. integrifolia treatment markedly lowered body weight, serum lipids and apo B and increase high-density lipoprotein-cholesterol and apo A1 concentrations. In this study, HMGR activity was enormously reduced, which helps to reduce cholesterol biosynthesis and an increase in LCAT activity was also observed. The detailed faecal analysis showed a remarkable increase in faecal lipids, which indicates the ability to inhibit intestinal fat absorption. The methanol fraction of H. integrifolia on LC-MS and tandem mass spectrometry analysis shows the presence of a compound, 3-(7-ethoxy-4-methyl-2-oxo-2H-chromen-3-yl)propanoate (C1). The result showed that the significant hypolipidaemic effect of H. integrifolia may be linked to its ability to inhibit HMGR activity and block intestinal fat absorption.

Polycythemia vera (PV) is a myeloproliferative disorder (MPD) characterized by an acquired gain-of-function mutation of the JAK2 protein (JAK2 V617F). Allele-specific quantitative PCR has showed a JAK2 V617F dosage effect on haematological and clinical parameters of PV at diagnosis, but it is unknown whether the level of certain serum proteins might correlate with the proportion of mutated JAK2. Taking into account that such proteins could represent useful prognostic marker, we investigated the serum protein profile of PV patients by SELDI-TOF MS. We identified apolipoprotein A1 (Apo-A1) as a serum marker correlated to the percentage of JAK2 V617F alleles; Apo-A1 expression being the highest for PV patients with more than 75% of mutated alleles. Immuno-assay on an automated random immuno-analyser confirmed the correlation between Apo-A1 concentrations and JAK2 V617F percentages, and showed that serum Apo-A1 assay allowed the specific discrimination of PV patients with high levels of mutated alleles (≥75%). These data suggest that Apo-A1 assay could be a useful assay for the stratification of PV patients at diagnosis.

Metabolic factors such as cholesterol appear to play an important role in the development of Achilles tendinopathy. There is, however, no morphologic proof explaining the link between high cholesterol and tendinopathy. As apolipoprotein A1 (Apo-A1) is essential for reverse cholesterol transport, it may be related to cholesterol overload in tendon. Nothing is known about Apo-A1 expression in tendon tissue. We examined the distribution of Apo-A1 protein in biopsies from normal and tendinopathy-affected human Achilles tendons, and APOA1 mRNA production from cultured human hamstring tenocytes. Specific immunoreactions for Apo-A1 were detected. The tenocytes showed specific Apo-A1 immunoreactions. These reactions were usually distinct in the tendinopathy specimens. While the tendinopathy specimens often showed granular/small deposit reactions, the slender tenocytes of control specimens did not show this pattern. The magnitude of Apo-A1 immunoreactivity was especially marked in the tendinopathy specimens, as there is a high number of tenocytes. Reactions were also seen in the walls of blood vessels located within the tendon tissue proper of both the normal and tendinopathy tendons and within the peritendinous/fatty tissue of the tendinopathy tendons. The reactions were predominantly in the form of deposit reactions within the smooth muscle layer of the vessel walls. Cultured hamstring tenocytes produced APOA1 mRNA. We demonstrated the presence of Apo-A1 in human tendon tissue. This suggests there may be a link between Achilles tendinopathy and cholesterol metabolism. We hypothesize that Apo-A1 may be important for tenocyte and blood vessel function within tendons.