Effect of apolipoprotein E genotypes on the efficacy of ezetimibe monotherapy in patients with statin induced adverse effects.

OBJECTIVE: The aim of this study was to clarify the effect of Apolipoprotein E (ApoE) polymorphism on the efficacy of cholesterol absorption inhibitor ezetimibe monotherapy on lipid parameters. METHODS: 63 hyperlipidemic patients with statin induced adverse effects were involved in the study. We examined the effect of 10 mg/day ezetimibe treatment on lipid levels after 3, 6 and 12 months of treatment in patients on a diet of only different ApoE genotypes. RESULTS: Three months of ezetimibe treatment significantly decreased the total cholesterol (TC) (-10.1%), low-density lipoprotein (LDL-C) (-12.0%) (p < 0.001) and triglyceride (Tg) (-8%) levels (p < 0.05). After 6 and 12 months of treatment reduction in TC, LDL-C and Tg levels were even more pronounced. The genotype distribution of the patients were 2/2: 4.8%, 2/3: 7.9%, 3/3: 68.3%, 3/4: 19.0%. There were no patients with 2/4 and 4/4 genotypes. In patients with 2/3, 3/3 or 3/4 genotype, the ezetimibe treatment tended to be more effective on TC and LDL-C levels than in the 2/2 group, and the efficacy of ezetimibe on Tg levels were slightly better in 2/2 carriers compared to other patients. CONCLUSIONS: The ApoE genotype does not predict the efficacy of ezetimibe treatment on serum lipid parameters.

Discriminating Low to High Adherent Type 2 Patients with Diabetes by Glycosylated Hemoglobin A1c, Eating Self-Efficacy and Other Psychosocial Determinants: Difference Between Patient and Physician Adherence Models.

Objective: Develop individual discriminant models using clinical and psychosocial variables for physicians and patients with diabetes based on their perceptions of patient adherence. Methods: This was a cross-sectional research design utilizing a discriminant analysis approach. Type 2 patients on treatment for diabetes for at least 2 years prior to research were selected. Clinical data were obtained from patient records, and psychosocial variables were collected by survey instruments filled out by patients. A final sample of 200 patients was recruited. Results: We found a positive correlation between patient and physician assessment of patient adherence behaviors. Greater adherence efforts were associated with lower HbA1c. Better quality of the patient-physician relationship was linked to better patient adherence. Increased HbA1c, longer therapy duration and higher BMI described low patient adherence for physicians. Lower HbA1c, female gender and fewer difficulties in marital adjustment characterized high adherence for patients. Dietary self-efficacy as well as emotional and social isolation discriminated mid-level adherers in both models. Conclusion: This research confirmed that patients and physicians perceived and judged patients' adherence behaviors differently. Physicians and patients associated different clinical and psychological factors with low and high adherence. Further research is recommended to clarify how the quality of the physician-patient as well as the patient-spouse relationship affect dietary efficacy and patient adherence. A randomized, controlled clinical trial approach is recommended to establish the effectiveness of interventions aiming to improve dietary self-efficacy on adherence outcomes.

Blepharophimosis mental retardation syndrome Say-Barber/Biesecker/Young-Simpson type - new findings with neuroimaging.

We report on a female patient with blepharophimosis mental retardation syndrome of Say/Barber/Biesecker/Young-Simpson (SBBYS) type. Main findings in her were marked developmental delay, blepharophimosis, ptosis, cleft palate, external auditory canal stenosis, small and malformed teeth, hypothyroidism, hearing impairment, and joint limitations. We performed diffusion tensor magnetic resonance imaging (MRI) and tractography of the brain which showed inappropriate myelination and disturbed white matter integrity. Cytogenetic analysis, subtelomeric fluorescence in situ hybridization and comparative genomic hybridization failed to identify an abnormality. It remains uncertain whether the MRI findings are specific to the present patient or form part of the SBBYS syndrome.

Whole genome transcriptional profiling identifies novel differentiation regulated genes in keratinocytes.

Keratinocyte differentiation plays a pivotal role in the epidermal barrier. Single keratinocyte differentiation genes have already been studied, but many important constituents of this process may have been missed so far. Gene expression profiling by microarray was carried out in cultured normal human epidermal keratinocytes undergoing confluence-induced differentiation to find novel differentiation genes. Candidate gene lists were established and genes of potential dermatological interest were validated by quantitative reverse transcription polymerase chain reaction and immunohistochemical analysis. Some of these points lead to the identification of counter-regulation of heme oxygenase and biliverdin reductase as well as glutaredoxin and glutathione reductase indicative of potential novel redox signaling in differentiating human keratinocytes. Others indicate a strong concert down-regulation of interleukin-1 signaling at previously unidentified levels during keratinocyte differentiation. We believe that identified genes contribute to a more comprehensive understanding of the complicated epidermal differentiation process and lead to better understanding of dermatological diseases.

Predictors of dietary self-efficacy in high glycosylated hemoglobin A1c type 2 diabetic patients.

OBJECTIVE: To predict dietary self-efficacy behaviors in high glycosylated hemoglobin A1c (HbA1c) patients using type D personality (TDP) and other psychosocial measures. METHODS: A cross-sectional, predictive research design was implemented. Participants were type 2 diabetes mellitus patients diagnosed more than 2 years prior to the study. Data were collected for demographics, dietary self-efficacy and psychological measures. Spearman's rank-order correlation was used to test for relationships, the Mann-Whitney test was used to test for differences and multiple linear regression was used to examine predictors of dietary self-efficacy. RESULTS: Lower dietary self-efficacy was strongly correlated with greater social isolation (r = 0.93) and moderately correlated with more mental health problems (r = 0.20) and higher TDP scores (r = 0.17). Higher HbA1c was inversely related to self-reported physical health (r = -0.19). Social and emotional isolation and time since diagnosis predicted dietary self-efficacy (greater isolation was associated with more dietary management difficulties). CONCLUSIONS: Regression outcomes suggested that a 10% decrease in social isolation improves dietary self-efficacy by 30%, a significant boost to therapeutic adherence. We recommend assessment of social isolation to improve dietary self-efficacy and achieve better patient adherence to therapy.

Reference genes for quantitative real time PCR in UVB irradiated keratinocytes.

Real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) is a sensitive and highly reproducible method often used for determining mRNA levels. To enable proper comparison of gene expression genes expressed at stabile levels within the cells in the studied experimental system need to be identified and used as reference. Ultraviolet B (UVB) radiation is an exogenous carcinogenic stimulus in keratinocytes, and UVB elicited changes have extensively been studied by qRT-PCR, yet a comparison of commonly used reference genes in UVB treatment is lacking. To find the best genes for compensating slight inter-sample variations in keratinocytes in UVB experiments and to understand the potential effects of improper reference gene (RG) selection we have analyzed the mRNA expression of 10 housekeeping genes in neonatal human epidermal keratinocytes (NHEK) after UVB treatment. The biological effect of the used UVB light source was validated by trypane blue exclusion, MTT and comet assays. 20-40mJ/cm(2) dose was chosen for the experiments. The stability of the 10 RGs was assessed by the GeNorm and Normfinder software tools. Regardless of their slightly different algorithm the programs found succinate dehydrogenase complex subunit A (SDHA) to be the best individual RG and SDHA and phosphoglycerate kinase-1 (PGK1) as the most suitable combination. Analysis of the expression of tumor necrosis factor alpha (TNFalpha) and vascular endothelial growth factor (VEGF) found that while the perception of changes in TNF-alpha, a gene undergoing marked upregulation after UVB irradiation is independent of the used RG, changes seen in the more modestly upregulated VEGF are greatly effected by reference gene selection. These findings highlight the importance of reference gene selection in UVB irradiation experiments, and provide evidence that using SDHA or the combination of SDHA and PGK1 as standards could be a reliable method for normalizing qRT-PCR results in keratinocytes after UVB treatment.

[The role of transmembrane lipidtransporter molecules in the atherosclerotic process]. / A transzmembrán lipidtranszporter molekulik szerepe az érelmeszesedés kialakulásában.

The role of transmembrane lipidtransporter molecules in the atherosclerotic process. The protective effect of high-density lipoprotein in the atherosclerotic process has been mainly attributed to its role in reverse cholesterol transport. Identification of mutations in the ATP-bindig casette transporter-A1 (ABCA1) as the genetic defect in genetic high-density lipoprotein-deficiency (Tangier disease) and selected patients with familiar hypoalphalipoproteinemia has generated interest in discovering the role of this lipid transporter molecule in the reverse cholesterol transport. It is well established, that the ABCA1 mediates cellular cholesterol efflux through transfer of phospholipids and cholesterol from the inner to the outer layer of the cell membrane, thus enabling the bindig to apolipoproteins. Previous studies showed that the ABCA1 is critically involved in cellular trafficking of cholesterol and phospholipids in total body of lipid homeostasis. In Tangier disease, the loss of the function of ABCA1, leads to an impaired formation of nascent high-density lipoprotein particles by preventing the release of cellular phospholipids and cholesterol to the acceptor apolipoprotein A1. This rare genetic disorder is characterized by a severe high-density lipoprotein deficiency, cholesterol deposition in macrophages and premature atherosclerosis. These findings implicate the ABCA1 as an important therapeutic target for preventing diseases that are associated with accelerated atherogenesis. The present review summarizes the current knowledge of the ABCA1, its pivotal role in the cholesterol homeostasis and preventing atherosclerosis.

Obesity abrogates the concentration-dependent effect of leptin on endogenous cholesterol synthesis in human monocytes.

Leptin the cytokine-like hormone is involved not only in local inflammations, but it regulates cholesterol biosynthesis in human monocytes. Since, monocyte-membrane composition in obesity shows considerable difference from control cells, our aim was to elucidate the concentration dependence of the effect of leptin in OW monocytes, and the downstream signaling of high and low leptin concentrations. Control and OW monocytes were stimulated with leptin in the presence or absence of different inhibitors. Our results are as follows: a concentration-dependent biphasic effect could only be detected in control monocytes whereas in OW cells only elevated cholesterol synthesis was found. The signal pathway of 50 ng/mL leptin stimulation involves Ca(2+) signal, activation of PI3K, MAPK and HMG CoA reductase. In the 500 ng/mL leptin-stimulated control monocytes the suppression of cholesterol synthesis was dependent on the Ca(2+) signal, the H-7 sensitive cPKC and PI3K activation, whereas in OW monocytes only PI3K was involved in increased cholesterol synthesis. We conclude that leptin-signaling in OW monocytes is characterized by Ca(2+) influx, abrogation of H-7 sensitive cPKC activation, and by PI3K mediated PKC activation.