Differential expression of ABC transporters (MDR1, MRP1, BCRP) in developing human embryos.

Three ABC transporters (MDR1, MRP1, BCRP), belonging to the family of multidrug resistance (MDR) proteins, play a crucial role in the protection mechanisms during embryogenesis and mediate drug resistance in cancer cells. The distribution of these transporters in the series of human embryonal/fetal intestine, liver and kidneys of various stages of intrauterine development (IUD) by indirect two-step immunohistochemical method was investigated. The organ- and age-specific expression patterns of these transporters were depicted and compared with the expression in adult organs. The evaluation of intestine and liver samples demonstrate differences in expression pattern of ABC transporters during IUD. On the contrary, in kidneys the age-specific localization was not observed. However, the increasing positivity from the kidney surface towards deeper, more differentiated parts was found. Hopefully, our study may contribute to elucidation of the role of multidrug resistance (MDR) pathways during IUD in man.

Treatment with atorvastatin reduces serum adipocyte-fatty acid binding protein value in patients with hyperlipidaemia.

BACKGROUND: Adipocyte-fatty acid binding protein (A-FABP) is a circulating protein expressed in adipocytes and macrophages. Several recent studies demonstrated that A-FABP might be involved in the pathogenesis of metabolic syndrome, particularly in dyslipidaemia, insulin resistance and atherosclerosis. The aim of this study was to investigate the influence of atorvastatin treatment (20 mg day(-1) for 3 months) on serum A-FABP value in subjects with hyperlipidaemia. MATERIALS AND METHODS: Anthropometric and serum analyses were performed for body mass index, A-FABP, triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, uric acid, alanine aminotransferase (ALT), aspartate aminotransferase (AST), high sensitive C-reactive protein (hs-CRP), creatine kinase (CK) and glucose on 26 subjects (BMI 30.3 +/- 6.0, mean age 62 +/- 10 years) with hyperlipidaemia who met the criteria: total cholesterol > 5.2 mmol L(-1), LDL cholesterol > 3.3 mmol L(-1) and triglycerides < 3 mmol L(-1). RESULTS: After the 3-month therapy, a significant reduction in total cholesterol (P < 0.001), LDL cholesterol (P < 0.001), glucose (P < 0.001), A-FABP (from 44.6 +/- 26.2 to 38.6 +/- 19.3 g L(-1), P < 0.01), uric acid (P < 0.05), AST (P < 0.05) and triglycerides (P < 0.05) values was observed. No difference was found in BMI, CK, ALT, hs-CRP, or HDL cholesterol values. A significant difference in the serum A-FABP value before and after the therapy remains after the correction for total cholesterol value (P < 0.001). A positive correlation between serum A-FABP and glucose was found (P < 0.05). CONCLUSIONS: In conclusion, our study confirmed in vivo that atorvastatin reduces serum A-FABP by a pleiotropic mechanism and supports the hypothesis that A-FABP is involved in atherosclerotic actions.

[Healthy persons versus patients with diabetes mellitus type 2--choosen parameters in serum and subcutaneous abdominal adipose tissue]. / Zdravé osoby versus pacienti s diagnózou diabetes mellitus 2. typu--vybrané parametry v séru a v subkutánní abdominální tukové tkáni.

UNLABELLED: Endocrinal products of adipocytes (PPARgamma, A-FABP, E-FABP, leptin, adiponectin and others) modulate insulin tissue sensitivity enabling them to participate in the ethiopathogenesis of diabetes mellitus type 2 (DM2T). Persons with DM2T are characterised by typical changes in lipid spectrum (lower HDL-cholesterol and higherTAG) and in the endocrinal function of subcutaneous adipose tissue; adipocytes produce more PPARgamma, A-FABP and E-FABP and less adiponectin. AIMS OF THE STUDY: To measure chosen markers of metabolic syndrome (MS) in serum and in abdominal subcutaneous adipose tissue in healthy persons and patients with DMT2, to determine basic statistical characteristics of investigated parameters and to discus their role in the genesis and progress of the MS. METHODS: Samples of blood and abdominal subcutaneous adipose tissue were collected from each participant (healthy: 7 men and 8 women; diabetics: 18 men, 11 women) to investigate the levels of HDL, TAG, insulin, C-peptide, glycaemia and the concentrations of A-FABP, E-FABP, leptin, adiponectin, resistin, PPARgamma and TNFalpha. RESULTS: In most cases the average concentration of investigated parameters in serum was higher in persons with DM 2 regardless of gender. Lower values were only found for HDL and adiponectin. The same situation prevailed in the subcutaneous adipose tissue. Values of most other parameters (A-FABP, E-FABP, and PPARgamma) were also higher in patients. The values of measured parameters not only differed in healthy and in sick persons but depended on gender. The increase/decrease in concrete parameters was greater in diabetic women than diabetic men. CONCLUSION: Higher concentrations of A-FABP, E-FABP in serum and in subcutaneous adipose tissue in diabetic persons also higher concentrations of PPARgamma in subcutaneous adipose tissue suggest that these investigated parameters are closely associated with obesity and MS. We can assume that in the near future these parameters will be used in clinical work for diagnosis of this syndrome.

Gender differences in tumor necrosis factor alpha and leptin secretion from subcutaneous and visceral fat tissue.

Tumor necrosis factor alpha (TNFalpha) and leptin concentrations were determined in the abdominal subcutaneous and visceral (omental) adipose tissue of patients undergoing elective open-abdominal surgery and compared with their body mass index. The concentration of leptin did not differ significantly between women and men, being high in subcutaneous fat tissue and low in visceral fat tissue. TNFalpha concentration in subcutaneous fat tissue was approximately the same in both genders, but it was significantly lower in visceral fat tissue of women and unchanged in visceral fat tissue of men. A significant correlation between BMI and leptin was found in the two fat tissue compartments of both genders, but the correlation between BMI and TNFalpha was found only in subcutaneous fat tissue of women.

[Tumor necrosis factor alfa (TNFalpha) and insulin resistance]. / Tumor nekrotický faktor alfa (TNFalpha) a inzulinová rezistence.

Obesity and diabetes mellitus type 2 belong among the most frequent illnesses and are categorized among the dominant risk factors for cardiovascular disease in all developed countries. There is a causal relation between insulin resistance and the origin of these risk factors of the cardiovascular morbidity and mortality. Numerous studies have attemted to identify the mechanisms linking obesity with insulin resistance and type 2 diabetes. Numbers of factors have been suggested as having a role in pathogenesis of obesity-related insulin resistance. One of these factors is tumor necrosis factor alfa (TNFalpha).