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.

Adiponectin: a therapeutic target in the antiphospholipid syndrome?

The antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of the IgG and/or IgM isotypes of the antiphospholipid antibodies, thrombosis and/or recurrent pregnancy losses. Various markers of inflammation are associated with clinical and/or laboratory features of APS. Adiponectin (Ad) is a member of the adipocytokines that exert its roles by binding to its receptors (AdR). Peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonists induced Ad production. The aged Pparg null-mice represented the first animal model that spontaneously develops APS and this model emphasized the importance of PPAR-gamma signaling in the development of APS. Recombinant Ad (rAd) application was beneficial for the improvement of glucose, insulin and lipid levels in mice. Orally active AdR agonist exerted similar effects to Ad in mice. Due to the re-occurrence of thrombotic episodes in APS patients (despite life-long anticoagulation), administration of PPAR-gamma agonists, rAd, or AdR agonists should be further tested in experimental models of APS, which eventually, will provide more data for novel therapeutic strategies that will ameliorate clinical manifestations of the APS.

25(OH) vitamin D deficiency in lymphoid malignancies, its prevalence and significance. Are we fully aware of it?

INTRODUCTION: Vitamin D has a role in cellular differentiation, proliferation, apoptosis, and angiogenesis and therefore is studied as a prognostic factor in cancer. The aim of our study was to assess the prevalence and significance of 25(OH)D deficiency in patients with lymphoid malignancies. METHODOLOGY: Between January 2014 and June 2016 at the Clinic for Hematology, Clinical Center of Serbia, Belgrade, the pretreatment serum level of 25(OH)D was determined in 133 (62 women/71 men, median age 58 (18-84) years) previously untreated patients with lymphoid malignancy using a chemiluminescent immunoassay. From their medical records, we noted the age, clinical stage, Eastern Cooperative Oncology Group Performance Scale (ECOG PS), nutritional status using the Nutritional Risk Score 2002 (NRS2002), the time of year, comorbidity index, progression, and progression-free survival (PFS) for a median of 20 (1-32) months. The optimal cutoff point for prediction of outcome was determined using the Maximally Selected Rank Statistics. RESULTS: There were 37 (27.8%) patients with the severe 25(OH)D deficiency ≤ 25 nmol/l, 80 (60.2%) with 25(OH)D deficiency 25-50 nmol/l, and 16 (12%) with 25(OH)D insufficiency 50-75 nmol/l. None of the patients had the desired normal level. There were significant differences between groups in regard to ECOG PS, NRS2002, type of lymphoma, and progression. The severely 25(OH)D-deficient patients had a shorter mean time until progression (P = 0.018). Cox regression analysis showed that 25(OH)D < 19.6 nmol/l remained the only significant parameter for PFS (HR = 2.921; 95% CI 1.307-6.529). CONCLUSION: The prevalence of 25(OH)D deficiency in the analyzed group of patients with lymphoid malignancies is high and greater in malnourished individuals. Patients with pretreatment serum 25(OH)D < 19.6 nmol/l had a significantly shorter PFS.

Urinary prostate-specific antigen: predictor of benign prostatic hyperplasia progression?

INTRODUCTION: Urinary prostate-specific antigen (uPSA) can be used as additional parameter of benign prostatic hyperplasia (BPH) progression. MATERIALS AND METHODS: From January 2001 to December 2011, uPSA was determined in 265 patients with benign prostate. Based on total prostate volume (TPV), the patients with benign prostate were divided in two groups: TPV < 31 mL and TPV ≥ 31 mL. Additional three groups were formed upon MTOPS study criteria: non- progressive BPH group (TPV < 31 mL, PSA < 1.6 ng/mL, age < 62 yrs), intermediate group (one, or two parameters {TPV, PSA, age} increased) and progressive BPH group (TPV ≥ 31 ml, PSA ≥ 1.6 ng/mL, age ≥ 62 yrs). RESULTS: Average uPSA values in the groups TPV < 31 mL and TPV ≥ 31 mL were 119.3 ± 124.5 and 255.5 ± 204.9 ng/mL, respectively and they were significantly different (p < 0.0001). Average uPSA values in the non- progressive BPH group, intermediate group and progressive BPH group were 86.8 ± 82.4 ng/mL, 166.6 ± 164.9 ng/mL and 274.9 ± 208.3 ng/mL, respectively and they were significantly different (p < 0.0001). The level of uPSA correlated significantly with TPV (r = 0.32, p < 0.0001). The cut off uPSA level of 150 ng/mL discriminates the patients with non-progressive BPH and progressive BPH with specificity of 0.83 and sensitivity of 0.67. CONCLUSION: The level of uPSA reflects prostatic hormonal activity and correlates with TPV, PSA and age. UPSA level ≥ 150 ng/mL can be used as additional predictive parameter of BPH progression.

Correlation of bone alkaline phosphatase and iPTH with some basic biochemical markers in predialysis and dialysis patients.

BACKGROUND: Bone alkaline phosphatase (BALP) is a direct and independent indicator of impaired bone turnover. We intended to find out whether there are any significant changes in BALP and iPTH levels, in comparison to total Ca, total Mg, inorganic P, total alkaline phosphatase (ALP), and tartrate resistant acid phosphatase (TRAP) in predialysis and dialysis patients. METHODS: Out of 266 patients investigated, 114 were on continuous ambulatory peritoneal dialysis, 112 were on maintenance haemodialysis, while 40 predialysis patients had end stage renal disease. The parameters were analysed according to the manufacturers' instructions. RESULTS: Correlations were established for the bone marker concentrations analysed among the studied groups. The largest ranges were determined for BALP and iPTH. Predialysis and dialysis patients showed very low levels of BALP. Dialysis patients had lower levels of iPTH (p < 0.001), while in predialysis patients the levels were significantly higher (p < 0.05) than recommended for low bone turnover, according to K/DOQI. CONCLUSIONS: The observations made in this study identify BALP as a good indicator of decreased bone turnover in predialysis and dialysis patients. However, in order to reveal a difference between bone activity and the level of parathyroid activity and its effect on bone turnover, it is always necessary to observe both BALP and iPTH levels.

Antiphospholipid antibodies in healthy Serbian middle-aged subjects: Preliminary data.

Background: The investigation of the prevalence of the IgG and the IgM isotypes of anticardiolipin (aCL) and antib2glycoprotein I (ab2gpI) Abs in healthy Serbian middleaged subjects was the main goal of our study. In addition, we analyzed the potential associations of above-mentioned Abs with serum proteins and lipids/lipoproteins. Methods: Forty healthy subjects were included in our study. Obesity (BMI 30 kg/m2) was present in 8/40 (20%) subjects. Titers of analyzed Abs were measured by ELISA. Results: The prevalence of IgG and IgM ab2gpI Abs was 5% and 12.5%, respectively, while the prevalence of IgM aCL was 10%. The IgG ab2gpI Abs were significantly different between subjects with normal triglycerides levels and those with hypertriglyceridemia (Mann-Whitney, P = 0.014). The significant difference in hsCRP concentrations was observed between subjects with the increased levels of the IgM isotype of aCL Abs and those with normal IgM aCL values (Mann-Whitney, P = 0.028). Conclusions: Dyslipidemia and BMI ≥30 were associated with aPL Abs and therefore, the correction of BMI and lipid status might be beneficial in reduction or elimination of predisposing factors that might trigger thrombotic events in otherwise healthy middle-aged subjects. Larger national study is necessary to confirm our findings.

Antiphospholipid antibodies in patients with Graves' orbitopathy: preliminary data.

PURPOSE: Graves' orbitopathy (GO) is an inflammatory autoimmune disorder of the orbit and while the antiphospholipid antibodies (aPL) Abs were associated with the markers of inflammation in the antiphospholipid syndrome (APS), there is no literature that investigate the presence of aPL Abs in GO. We analyzed the prevalence of aPL Abs and the differences between aPL (+) and aPL (-) subgroups of GO patients. METHODS: Study included consecutive patients with GO (66 with Graves' (GD), 10 with Hashimoto (HD), and 8 were euthyroid). Anticardiolipin (aCL) and anti-beta 2glycoprotein I (aß2gpI) Abs were measured by ELISA. RESULTS: aPL Abs were present in 9/84 (10.71%) patients. The IgM aß2gpI Abs were present in 8/66 and in 1/10 patients with GD and HD. The IgG aCL Abs were present in one GD patient, and IgM aCL were present in 3/66 GD and in 1/10 patients with HD. In GD group, anti-Tg Abs were in positive correlation with aß2gpI IgG (p = 0.000) and with anti-TPO Abs (p = 0.016). In HD group, anti-Tg Abs were in positive correlation with IgM aCL (p = 0.042), while anti-TPO Abs were in positive correlation with aß2gpI IgM (p = 0.014). CONCLUSION: This study is the first report of the aPL Abs presence in GO patients. The anti-thyroid Abs were linked to aPL suggesting that their presence is not the sole consequence of hyperstimulation of autoreactive B-lymphocytes. Larger studies are necessary to confirm potential cause-effect relations.

Pancreatic Elastase Levels in Feces As A Marker of Exocrine Pancreatic Function in Patients With Diabetes Mellitus.

OBJECTIVE: The measurement of pancreatic elastase (PE) in feces is used widely to screen for pancreatic exocrine insufficiency. The aim of our study was to evaluate the relationship of PE with residual beta cell secretion and metabolic control in patients with diabetes mellitus. METHOD: We determined the presence of PE in specimens via enzyme-linked immunosorbent assay (ELISA), whereas serum fasting glucose, C-peptide, amylase, lipase, triglycerides, total 25(OH)-vitamin D, C-reactive protein (CRP), and hemoglobin A1c (HbA1c) concentrations were assayed using routine laboratory tests. RESULTS: PE values in 48 patients with diabetes were significantly lower than in 24 healthy volunteers (P = 001). In one-third of participants with diabetes mellitus, PE were less than 200 µg per g, indicating pancreatic functional insufficiency. Among the patients in the cohort, PE correlated positively with C-peptide levels (P = 04), lipase (P = 009), CRP (P = 04), sex (P = 03), and BMI (P = 02) but not significantly with duration of diabetes (P = 81) or levels of HbA1c(P = 87), amylase (P = 06), total 25(OH)-vitamin D (P = 16), or triglycerides (P = 52). CONCLUSION: Our results demonstrated a strong association of diabetes with low PE levels.