Overweight and obesity in polycystic ovary syndrome: association with inflammation, oxidative stress and dyslipidaemia.

Polycystic ovary syndrome (PCOS) is associated with altered lipid profile and increased small, dense LDL particles (sdLDL). Considering that paraoxonase 1 (PON1) is an antioxidative enzyme located on HDL particles, the aim of this study was to investigate the connection between oxidative stress (OS) and PON1 activity with lipoprotein subclasses in PCOS depending on obesity. In 115 PCOS patients, lipoprotein subclasses distributions were determined by gradient gel electrophoresis. OS status was assessed by total oxidative status (TOS), advanced oxidation protein products, malondialdehyde (MDA), prooxidant-antioxidant balance (PAB), total antioxidative status (TAS) and superoxide dismutase (SOD) and PON1 activity. Overweight/obese PCOS patients (n 55) had increased OS compared with normal weight patients (n 60). In addition, overweight/obese group had lower HDL size and higher proportion of HDL 3a subclasses (P < 0·05). PAB was in negative correlation with HDL 2a (P < 0·001), whereas MDA and SOD correlated positively with HDL 3 subclasses (P < 0·05). Serum PON1 activity was positively associated with proportions of PON1 activity on HDL 2b (P < 0·05) and 2a (P < 0·01), but negatively with the proportion on HDL 3 particles (P < 0·01). LDL B phenotype patients had increased TAS, SOD and PON1 activity on HDL 2b, but decreased PON1 activity on HDL 3 subclasses. OS is associated with altered lipoprotein subclasses distribution in PCOS patients. Obesity in PCOS affects the profile of HDL subclasses, reflected through the reduced proportion of PON1 activity on HDL 3 subclasses in the presence of sdLDL particles.

Cholesterol homeostasis is dysregulated in women with preeclampsia.

INTRODUCTION: The link between preeclampsia and dyslipidemia has been established. Even though lipid profile parameters have been intensively investigated in the pathology of preeclampsia, their accurate molecular mechanisms of action have not been fully decoded. OBJECTIVES: We aimed to identify the specifics of cholesterol metabolism in women affected by late-onset preeclampsia and single out potential biomarkers associated with late-onset syndrome. PATIENTS AND METHODS: A total of 90 pregnant women with a priori risk for preeclampsia were monitored at 4 time points during gestation and, based on the outcome of pregnancy, they were classified into the high-risk group (70 women) and the preeclampsia group (20 women). Cholesterol metabolic profiling was done using liquid chromatography-tandem mass spectrometry. RESULTS: The only significant change in the preeclampsia group was an increase in the lathosterol level (P = 0.001). The first-trimester lathosterol level was higher in the preeclampsia group compared with the high-risk group (P = 0.02). Further, in the preeclampsia group, positive correlations were found between desmosterol and ß-sitosterol (ρ = 0.474; P = 0.03) in the third trimester, desmosterol and campesterol changes between the second and the first (ρ = 0.546; P = 0.02), and the third and first trimesters (ρ = 0.754; P <⁠0.001), as well as between the desmosterol and ß-sitosterol differences between the third and first trimesters (ρ = 0.568; P = 0.01). No similar correlations were found in the high-risk group. CONCLUSIONS: Late-onset preeclampsia could be associated with an altered lipid profile. By studying the quantitative metabolic signatures of cholesterol, we might assume that both cholesterol synthesis and absorption are increased, that is, there is an imbalance in the cholesterol homeostasis regulation in women affected by the disease.

Increased Oxidized High-Density Lipoprotein/High-Density Lipoprotein-Cholesterol Ratio as a Potential Indicator of Disturbed Metabolic Health in Overweight and Obese Individuals.

BACKGROUND: We evaluated the qualitative characteristics of high-density lipoprotein (HDL) particles in metabolically healthy and unhealthy overweight and obese subjects. METHODS: The study involved 115 subject individuals classified as metabolically healthy and unhealthy, as in overweight and obese groups. Commercial enzyme-linked immunosorbent assay (ELISA) kits were used to measure oxidized HDL (OxHDL) and serum amyloid A (SAA) concentrations. Lipoprotein subfractions were separated using nondenaturing gradient gel electrophoresis. RESULTS: An independent association was shown between increased OxHDL/HDL-cholesterol ratio and the occurrence of metabolically unhealthy phenotype in the overweight and obese groups. The OxHDL/HDL-cholesterol ratio showed excellent and acceptable diagnostic accuracy in determination of metabolic health phenotypes (overweight group, AUC = 0.881; obese group, AUC = 0.765). Accumulation of smaller HDL particles in metabolically unhealthy subjects was verified by lipoprotein subfraction analysis. SAA concentrations did not differ significantly between phenotypes. CONCLUSIONS: Increased OxHDL/HDL-cholesterol ratio may be a potential indicator of disturbed metabolic health in overweight and obese individuals.

Telomerase stability and evaluation of real-time telomeric repeat amplification protocol.

Telomerase is RNA directed polymerase which acts as reverse transcriptase based on its own RNA component. It is considered to be involved in the pathology of many diseases and is recognized as a potential biomarker. The aims were to determine the sample storage conditions and the time frame for samples analysis, then to prove reliability of enzyme activity measurement with real-time telomeric repeat amplification protocol (TRAP) and to evaluate the suitable standard samples for telomerase activity measurements. Samples used for stability and freeze-thaw study were peripheral blood leukocytes, obtained from apparently healthy persons, patients with diagnosed cancer and cell lines. Telomerase activity was measured using TRAP method, while standard evaluation was done using nuclear magnetic resonance (NMR) technique. Storage at -20 °C preserved telomerase activity in samples from cancer patients for at least 14 days (21.46 ± 0.135 versus 21.84 ± 0.357, p = .756), while samples obtained from healthy persons should be stored at -80 °C. We observed significant decrease of telomerase activity at freeze thaw cycle 5 in cancer patients' samples (21.46 ± 0.135 versus 23.09 ± 0.316, p < .05), and in healthy persons' ones already at cycle 3 (22.74 ± 0.107 versus 24.85 ± 0.151, p < .05). Telomerase activity from cell lines samples showed overall greater stability regarding the storage period and freeze-thaw cycles and it was considered for standard sample, which was confirmed by NMR analysis. Telomerase enzyme had adequate stability while efficacy, linearity, and reproducibility of TRAP method were acceptable for bio-analytical methods. All this indicated that telomerase could be a reliable biomarker.

Effects of total fibre or resistant starch-rich diets within lifestyle intervention in obese prediabetic adults.

PURPOSE: Starting from the evidence-based health benefits that resistant starch (RS) shows when added to the diet, our aim in this study was to evaluate the effects of increased fibre intake with two different levels of RS coming from regular daily consumed foods on normalization of glycaemia within lifestyle intervention in the population with risk factors for developing diabetes. METHODS: Study included 47 overweight and obese men and women with disordered glucoregulation and dyslipidaemia, aged between 45-74, divided into RS and Fibre group. Participants were subjected to the lifestyle and dietary intervention with low-fat and high-fibre (>25 g/day) diet for 12 months and were offered two different dietary advices aimed at increasing total fibre intake in Fibre group and at increasing RS intake in RS group. RESULTS: The intake of macronutrients and total fibre was similar between groups at the end of the study, but achieved RS intake was two times higher in the RS group. Decrease in total cholesterol and non-HDL-cholesterol was more pronounced in RS group in comparison with Fibre group (p = 0.010, p = 0.031, respectively), whereas in Fibre group, a more pronounced effect on glucoregulation was observed: significant fall in glycaemia after 2-h oral glucose tolerance test (7.93 vs 6.96 mmol/L, p = 0.034). CONCLUSION: At the end of the study, RS-rich diet failed to affect glycaemic control in prediabetic obese individuals in contrast to the regular fibre-rich diet, which indicated that fibre profile could be an important determinant of the effect of dietary intervention.

Association of moderate alpha-1 antitrypsin deficiency with lung cancer in the Serbian population.

BACKGROUND: Alpha-1 antitrypsin (AAT) is an important serine protease inhibitor in human plasma. Its major physiological role is to inhibit neutrophil elastase (NE) in the lower respiratory tract and protect lung tissue from destruction. Recent studies indicated an etiological role of NE in lung cancer development. The aim of this study was to investigate the association of alpha-1 antitrypsin deficiency (AATD) with lung cancer in patients with four different histological types of cancer: squamous cell carcinoma, adenocarcinomas, large cell carcinoma and small cell carcinoma. METHODS: Phenotyping was carried out by isoelectric focusing (pH 4.2-4.9). We compared the frequency of AATD phenotypes in 186 lung cancer patients with the value obtained in our previous study in a healthy Serbian population (3.7%) using the Fisher exact test. RESULTS: Allele frequencies in patients were Pi *M 0.9677, Pi *Z 0.0215, Pi *S 0.0081 and Pi *other rare 0.0027. Eleven of the 186 lung cancer patients (5.9%) were AATD heterozygotes with moderate deficiencies (PiMZ and PiMS). When this value was compared with AATD heterozygote frequency obtained in the healthy individuals (3.7%), the difference was close to the level of significance (p = 0.055). However, individuals with AATD phenotypes had a higher risk of developing squamous cell lung cancer then those with non-deficient AAT variants (OR = 4.51, 95% CI = 1.66-12.29). CONCLUSIONS: Our findings provide evidence of an association between AAT phenotypes with moderate deficiency and squamous cell lung cancer.