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Betatrophin, a liver hormone, regulates glucose and lipid metabolism. We investigated the betatrophin levels in nonalcoholic fatty liver disease (NAFLD) and searched for any relationship with histological severity and metabolic parameters. Fifty males with NAFLD [Nonalcoholic Steatohepatitis (NASH) (n = 32), non-NASH (n = 18)] and 30 healthy controls were included. Plasma betatrophin was measured by ELISA method. Insulin sensitivity was assessed by HOMA-IR index. Histological features were scored by the semi quantitative classification and combined as the NAFLD activity score (NAS). Betatrophin levels in the non-NASH group were significantly higher than the controls. Betatrophin was positively correlated to the age, waist circumference, total cholesterol, triglycerides, LDL cholesterol, glucose, insulin, HOMA-IR index and gamma glutamyl transpeptidase levels, and negatively correlated to the steatosis and NAS. In the stepwise linear regression analysis, the triglyceride (β = 0.457, p &lt, 0.001), glucose (β = 0.281, p = 0.02) and NAS (β = −0.260, p = 0.03) were the independent determinants of betatrophin. Betatrophin levels are higher in the early stages of NAFLD and tend to decrease when the disease progresses. This could be an important preliminary mechanistic finding to explain the increased frequency of glucose intolerance during the course of NAFLD.

Beta-thalassemia major is associated with the increased risk of cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA) has been implicated in the pathogenesis of endothelial dysfunction and atherosclerosis. In this study, we aimed to investigate circulating ADMA concentrations in children with beta-thalassemia major.Thirty-one beta-thalassemia major children aged between 4 and 16 year old and age, gender-matched 36 healthy controls were enrolled in the study. Plasma ADMA was measured along with the soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), P-selectin, and Pentraxin-3.Age, gender and body mass index were similar in two groups. Plasma ADMA, sVCAM-1, and sICAM-1 measurements were significantly higher in beta-thalassemia major patients than the control group (p 0.004 for ICAM-1, p 0.001 for other parameters). There were positive significant correlations between ADMA, sVCAM-1 and sICAM-1 (r = 0.437, p 0.001; r = 0.544, p 0.001; r = 0.405, p 0.001, respectively) in the whole group.The findings of the current study show us that increased plasma ADMA levels in children with beta-thalassemia major may be an early marker for endothelial dysfunction and may play a role in the development of premature atherosclerosis in beta-thalassemia major patients.

Introduction: Patients with hypogonadism are at increased risk of cardiac and metabolic diseases and osteoporosis. Vitamin D and Fibroblast growth factor-23 (FGF-23) play role in the regulation of bone mineral metabolism and endothelial functions. Low vitamin D levels are reported in hypogonadism, while there is no data about the effect of testosterone replacement therapy (TRT). We investigated the effect of TRT on vitamin D and FGF-23 levels along with endothelial functions and insulin resistance in hypogonadal patients. Material and methods: Patients with congenital hypogonadotrophic hypogonadism (CHH) (n=32, age 20.6 ±1.58 years) were enrolled. TRT was implemented in transdermal form. The demographic parameters, FGF-23, 25(OH)D3, Asymmetric dimethylarginine (ADMA) and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured both before and after TRT. Results: After a follow-up period of 3.63±1.33 months, ADMA and FGF-23 levels were significantly increased (p=0.03 and p=0.005 respectively), while the 25(OH)D3 and HOMA-IR index were not significantly changed. The body mass index and waist circumference levels of the patients were also increased (p

Transfusion of platelet suspensions is an essential part of patient care for certain clinical indications. In this pioneering study in Turkey, we aimed to assess the in vitro hemostatic functions of platelets after cryopreservation.Seven units of platelet concentrates were obtained by apheresis. Each apheresis platelet concentrate (APC) was divided into 2 equal volumes and frozen with 6% dimethyl sulfoxide (DMSO). The 14 frozen units of APCs were kept at -80 °C for 1 day. APCs were thawed at 37 °C and diluted either with autologous plasma or 0.9% NaCl. The volume and residual numbers of leukocytes and platelets were tested in both before-freezing and post-thawing periods. Aggregation and thrombin generation tests were used to analyze the in vitro hemostatic functions of platelets. Flow-cytometric analysis was used to assess the presence of frozen treated platelets and their viability.The residual number of leukocytes in both dilution groups was1x106. The mean platelet recovery rate in the plasma-diluted group (88.1±9.5%) was higher than that in the 0.9% NaCl-diluted group (63±10%). These results were compatible with the European Directorate for the Quality of Medicines quality criteria. Expectedly, there was no aggregation response to platelet aggregation test. The mean thrombin generation potential of post-thaw APCs was higher in the plasma-diluted group (2411 nmol/L per minute) when compared to both the 0.9% NaCl-diluted group (1913 nmol/L per minute) and the before-freezing period (1681 nmol/L per minute). The flow-cytometric analysis results for the viability of APCs after cryopreservation were 94.9% and 96.6% in the plasma and 0.9% NaCl groups, respectively.Cryopreservation of platelets with 6% DMSO and storage at -80 °C increases their shelf life from 7 days to 2 years. Besides the increase in hemostatic functions of platelets, the cryopreservation process also does not affect their viability rates.Amaç: Trombosit süspansiyonlarının transfüzyonu, belirli klinik endikasyonlarda hastaların tedavisinin önemli bir parçasıdır. Bu çalışma ile Türkiye’de ilk kez olmak üzere trombositlerin in vitro hemostatik fonksiyonlarının kriyopreservasyon işleminden sonra değerlendirilmesi amaçlanmıştır. Gereç ve Yöntemler: Çalışmamızda 7 ünite trombosit süspansiyonu aferez yöntemiyle elde edildi. Her aferez trombosit konsantresi (ATK) iki eşit hacime ayrıldıktan sonra %6 dimetil sülfoksit (DMSO) kullanılarak donduruldu. Dondurulmuş 14 ünite ATK -80 °C’de bir gün süre ile bekletildi. ATK’lar 37 °C’de çözdürüldükten sonra otolog plazma veya %0,9 NaCl kullanılarak dilüe edildi. ATK’ların dondurma öncesi ve çözülme işlemi sonrası; hacim, rezidüel lökosit ve trombosit sayıları incelendi. Trombositlerin in vitro hemostatik fonksiyonların incelenmesinde agregasyon ve trombin jenerasyon testleri kullanıldı. Dondurma işlemine maruz kalan ATK’lardaki trombositlerin varlığı ve bu hücrelerin canlılığını değerlendirmek için akım sitometri yöntemi kullanıldı. Bulgular: Her iki dilüsyon grubunda yer alan ATK’ların residüel lökosit sayısı 1x106’nın altındaydı. Plazma ile dilüe edilen grubun ortalama trombosit geri kazanım oranı %0,9 NaCl ile dilüe edilen gruptan daha yüksekti (%88,1±9,5’e karşılık %63±10). Bu sonuçlar Avrupa İlaç Kalite ve Sağlık Hizmetleri Direktörlüğü’nün kalite kriterlerine uygundu. Trombosit agregasyon testine beklenildiği üzere yanıt alınamadı. Dondurulup çözülerek otolog plazma ile dilüe edilen ATK’ların ortalama trombin oluşturma potansiyeli (2411 nmol/L×dakika), %0,9 NaCl ile dilüe edilenlere (1913 nmol/L×dakika) ve dondurma işlemi öncesine göre (1681 nmol/L×dakika) daha yüksek saptandı. Kriyopreservasyon işlemi sonrası plazma ve %0,9 NaCl ile dilüe edilen ATK’ların akım sitometri yöntemi ile canlılığı sırasıyla %94,9 ve %96,6 olarak bulundu. Sonuç: Trombositlerin DMSO ile kriyopreserve edilerek -80 °C saklanmaları, raf ömürlerini 7 günden 2 yıla çıkarmaktadır. Kriyopreservasyon işlemi trombositlerin in vitro hemostatik fonksiyonlarını arttırmanın yanında canlılık oranlarını da etkilememektedir.

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, type 2 diabetes mellitus, and dyslipidemia. It is well known that the presence of visceral fat increases the risk for metabolic complications of obesity, especially NAFLD. The visceral adiposity index (VAI), a novel marker of visceral fat dysfunction, shows a strong association with insulin resistance and also cardiovascular and cerebrovascular events. However, there is conflicting data regarding the association between VAI and NAFLD. Our aim was to assess the relationship between VAI, insulin resistance, adipocytokines, and liver histology, in nondiabetic subjects with NAFLD.A total of 215 male patients with biopsy-proven NAFLD were included. Among this group, serum levels of adiponectin, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP) were measured in 101 patients whose blood samples were available.High gamma-glutamyl transferase (GGT), high total cholesterol (TC), high triglycerides (TGs), low high-density lipoprotein cholesterol (HDL-C), and presence of metabolic syndrome were significantly associated with higher VAI, although only higher GGT and TC were independent factors on multiple linear regression analysis. On the other hand, no significant association was found between VAI and adiponectin, TNF-α, IL-6, and hsCRP levels. The multivariate analysis of variables in patients with (n=124) and without (n=91) fibrosis showed that only higher homeostasis model assessment of insulin resistance value was independently associated with liver fibrosis.Our findings suggest that VAI is not related to the severity of hepatic inflammation or fibrosis in nondiabetic patients with NAFLD. The lack of association between the adipocytokines and VAI also implies that the VAI may not be a significant indictor of the adipocyte functions.

The study aims to evaluate the changes between body mass index (BMI) and ghrelin levels after laparoscopic Nissen fundoplication (LNF). Twenty-four consecutive patients with gastroesophageal reflux disease who were scheduled for LNF consented to participate in the study. The participants’ age, sex, preoperative (phase 0), postoperative 1st week (phase 1) and postoperative 4th week (phase 2) dysphagia scores, plasma ghrelin levels, and BMI were recorded. Compared to the preoperative level (phase 0), ghrelin was decreased in both phase 1 and phase 2. A strong correlation in the changes in the ghrelin values and BMI between phase 0 and phase 2 was detected. There was a strong, statistically significant difference in the changes in the BMI values between phase 1 and phase 2. Total plication of the fundus impairs its ghrelin-secreting functions for up to 4 weeks and is accompanied by weight loss.

Background: Sepsis is a state of augmented oxidative stress and diminished antioxidant capacity. High den- sity lipoprotein (HDL) particles were shown to possess antioxidant and anti-inflammatory properties, as well as Paraoxonase 1 (PON1), which is an enzyme that is also protective against HDL oxidation. Previous stud- ies suggested a possible role of decreased PON1 activ- ity or HDL levels in sepsis patients. Aims: The present study was designed to test a hypoth- esis that higher PON1 activity and HDL-cholesterol levels could predict a better survival in sepsis patients. Study Design: Observational study. Methods: Venous blood samples were collected from sepsis patients for HDL-cholesterol levels, PON1 ac- tivity and cytokine assays (TNF-α and IL-6) and Acute Physiologic and Chronic Health Evaluation II (APACHE II) scores were calculated in order to weight patients’ disease severity on the day of sepsis diagnosis. Patients were followed-up until the 28th day for any cause intra- hospital mortality. Data were statistically analyzed for effects of study parameters on patients’ survival. Results: In total, 85 patients with sepsis were included in the study. The mean age was 65.2±17.9 years and 48 were male; at the end of the 28-day follow-up pe- riod, 46 survived. TNF-α (86.9±10.5 vs 118.6±16.4) and IL-6 levels (906.7±82.7 vs 1323.1±54.3) were sig- nificantly higher in non-survivors, while PON1 activity (140.7±42.3 vs 66.7±46.6) and HDL-cholesterol lev- els (43.6±8.1 vs 34.5±8.9) were significantly higher in survivors (p

Patients with hypogonadism have poor cardiovascular and metabolic outcomes, and the effect of testosterone replacement therapy (TRT) is not clear. We investigated the presence of inflammation, insulin resistance and endothelial dysfunction in an unconfounded population of congenital hypogonadotrophic hypogonadism (CHH) and the effect of TRT on these subjects. A total of 60 patients with CHH (mean age 21.82±2.22 years) and 70 healthy control subjects (mean age 21.32±1.13 years) were enrolled. The demographic parameters, Asymmetric dimethylarginine (ADMA), TNF-like weak inducer of apoptosis (TWEAK), high sensitive C reactive protein (hs-CRP) and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured before and after TRT. The patients had higher Waist Circumferences (WC) (p=0.009), Diastolic Blood Pressures (p=0.02), Triglycerides (p=0.03), ADMA, insulin and HOMA-IR levels (p

Background/Aims: Fetuin-A, a glycoprotein with anti-inflammatory properties, plays an important role in counter-regulating inflammatory responses. It has also been associated with insulin resistance and metabolic syndrome. We aimed to investigate circulating concentrations of fetuin-A and its possible association with hepatic and systemic inflammation in nondiabetic subjects with nonalcoholic fatty liver disease (NAFLD). Patients and Methods: We included 105 nondiabetic male subjects with NAFLD [nonalcoholic steatohepatitis (NASH, n = 86) and simple steatosis (SS, n = 19)]. Plasma levels of fetuin-A and markers of inflammation [high-sensitive C reactive protein (hsCRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and adiponectin] were measured by enzyme-linked immunosorbent assay method. Insulin sensitivity was determined by homeostasis model assessment of insulin resistance (HOMA-IR) index. Results: Fetuin-A was negatively correlated with age (r = −0.27, P = 0.006), however there was no association between fetuin-A and body mass index, waist circumference (WC), glucose, insulin, HOMA-IR, lipid parameters, and inflammatory markers. In addition, no significant association was observed between fetuin-A and histological findings including liver fibrosis. Conclusion: This study demonstrated that plasma fetuin-A levels are not correlated with the hepatic histology and systemic markers of inflammation in nondiabetic subjects with NAFLD. Our data also suggested that age is significantly associated with fetuin-A in this clinically relevant condition.

Background: The effect of the timing of the second laparotomy on wound healing is not clear. In an experimental study in rats, we aimed to investigate the effect of timing on wound healing after reoperations on the same surgical site. Material and methods: Forty-eight rats were divided into four groups. The control group (GC) didn't have another laparotomy whereas the relaparotomies on the same surgical site were performed either on the 3rd, 15th or the 30th postoperative days in the three study groups (G3, G15, G30 respectively). The midline tension pressure, collagen types I, III and, histological analysis were performed from the specimens in order to assess the wound healing and strength. Results: The tensile strength was the highest in GC and decreased gradually in G3, G15 and G30, the difference between the groups did not reach statistical significance. Higher collagen levels, increased fibrosis, and large defects were observed in relaparotomy groups than CG. The musculoaponeurotic gap was shortest in GC when compared to other three relaparotomy groups (P

Cardiometabolic disorders and osteoporosis are prevalent in patients with hypogonadism. Osteoprotegerin (OPG) and fibroblast growth factor-23 (FGF-23), are co-secreted from bones and vascular endothelium, regulating bone mineral metabolism and vascular functions. Vitamin D is another hormone with dual effects on bone and vascular metabolism. The aim of this study was to search for any difference between the serum levels of OPG, FGF-23, and vitamin D in patients with hypogonadism and the healthy controls. We also aimed to search for any relationship between these parameters and endothelial dysfunction or insulin resistance. Forty-nine male patients with congenital hypogonadotropic hypogonadism (CHH) (mean age 20.71 ± 1.75 years) and 43 BMI matched healthy male subjects (mean age 21.37 ± 1.04 years) were enrolled. OPG, FGF-23, vitamin D, and asymmetric dimethylarginine (ADMA) levels were measured from the fasting serum samples. The insulin sensitivity was estimated by homeostatic model assessment-insulin resistance (HOMA-IR) formula. Triglycerides, insulin, HOMA-IR, and ADMA levels in the patient group were significantly higher than the values of the control group (p = 0.014, p = 0.002, p = 0.003, p < 0.001, respectively). The OPG, FGF-23, and vitamin D levels of the patients were not significantly different from the healthy controls. In addition, these markers were not correlated to ADMA or HOMA-IR levels. The results show that young and treatment naive subjects with CHH have endothelial dysfunction and insulin resistance when compared to their healthy counterparts. However, the OPG, FGF-23, and vitamin D levels were similar in the 2 groups. In addition, these parameters are not significantly related to the endothelial functions or insulin resistance in these subjects.

Purpose: Diabetes mellitus (DM) and coronary artery disease (CAD), seen frequently in the general population, are major causes of morbidity and mortality. DM, controllable through treatment, is one of the most important risk factors for the development of cardiovascular diseases. Material and Method: Our study included patients who had undiagnosed glucose metabolism disorders and had undergone an angiography under elective conditions. To diagnose the glucose metabolism disorders, these patients were given the oral glucose tolerance test (OGTT) (75 g) within 5-10 days after angiography. Results: In our study, 24.5% (n=79) of patients had isolated impaired fasting glucose, 9.3% (n=30) had isolated impaired glucose tolerance, 21.1% (n=68) had both impaired fasting glucose and impaired glucose tolerance, and 5% (n=16) had DM. None of these patients knew about their condition beforehand. Only 40.1% (n=129) of patients had normal OGTT results. Discussion: If patients with suspected CAD found to have blocked arteries after an angiography are screened for DM, glucose metabolism disorders can be diagnosed early. When caught early, the long-term complications can be avoided, resulting in significant savings for health care costs. Turk Jem 2013; 17: 111-5

Ghrelin is an orexigenic peptide that stimulates food intake, whereas peptide YY (PYY) and cholecystokinin (CCK) are anorexigenic gut hormones. Patients with polycystic ovary syndrome (PCOS) appear to have alterations in appetite regulation.We aimed to determine whether fasting or meal-stimulated ghrelin, PYY, CCK, and satiety responses are different between lean PCOS patients and healthy women. We also aimed to assess the potential effect of oral contraceptive use on these hormones and satiety response.We conducted a prospective observational study in a university practice.Eighteen lean PCOS patients and 18 healthy control women matched for age and body mass index underwent measurements of circulating ghrelin, PYY, CCK, and satiety index (SI) before and after a standardized mixed meal at 0, 15, 30, 45, 60, 90, 120, and 180 minutes.For PCOS patients who were treated with ethinyl estradiol 30 μg/drospirenone 3 mg for 3 months, measurements were repeated.We measured ghrelin, PYY, and CCK levels and SI.At baseline, fasting ghrelin, PYY, CCK, and SI values in PCOS patients were not different from controls. Meal-stimulated PYY, CCK, and SI were also not different between the groups, whereas PCOS patients had significantly lower meal-stimulated ghrelin levels compared to controls (P = .04). Ghrelin, PYY, CCK, and SI did not show a significant change after treatment with ethinyl estradiol/drospirenone for 3 months.Basal and stimulated hunger and satiety hormones in lean PCOS patients are not different from lean healthy women, except for a lower meal-stimulated ghrelin response. Short-term use of a low-dose oral contraceptive does not have an effect on appetite regulation of PCOS.

Background. Visfatin is a proinflammatory and insulin-mimetic adipokine contributing to whole body glucose and lipid metabolism. Studies to date are conflicting regarding the relationship between visfatin and non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the relationship of circulating visfatin with NAFLD. Material and methods. The study included 114 NAFLD patients and 60 healthy non-diabetic controls. Plasma visfatin, adiponectin, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels were measured by ELISA. High sensitive C-reactive protein (hsCRP) levels were measured by immunoturbidimetric fixed rate method. Insulin sensitivity determined by homeostasis model assessment (HOMA-IR) index. Results. TNF-α, IL-6 and hsCRP levels were higher and, Adiponectin levels were lower in NAFLD group when compared to healthy controls (p < 0.001, for all). However, no difference was found regarding to visfatin levels between two groups. Different histologic subgroups of NAFLD had a significantly higher TNF-α, IL-6 and hsCRP, and lower adiponectin levels than those with controls (p < 0.001, for all). On the other hand, no statistically significant difference was found regarding to visfatin levels among different histologic groups. Visfatin was found to be negatively correlated with TNF-α (r = −0.236, p = 0.011) in NAFLD group. However, no association was found between visfatin and histological findings. Conclusion. Our findings show that plasma visfatin levels are not altered in the early stages of NAFLD. However, it is inversely associated with TNF-α. These findings suggest a role for visfatin in protection against liver injury in this widespread disease.

Metabolic disorders and cardiovascular events are increased in hypogonadism. Serum HDL composition is a better cardiovascular predictor than the HDL counts. However, there is no information about the HDL subfractions in patients with hypogonadism. We designed a prospective study to investigate the HDL subfractions in treatment naïve subjects with hypogonadism and the effects of 2 different testosterone replacement regimens on the HDL subfractions. Seventy young male patients with congenital hypogonadotropic hypogonadism (CHH) and 70 age and BMI-matched healthy males were enrolled in the present study. The patients were assigned to receive intramuscular injections of testosterone esters 250 mg every 3 weeks and transdermal testosterone applications 50 mg daily. Biochemical investigations including HDL subfractions and insulin resistance were done. Patients with CHH had higher levels of insulin, HOMA-IR, WC, triglyceride, and diastolic blood pressure. Although, the HDL cholesterol concentrations were similar in both groups, hypogonadal patients had lower HDL2 and higher HDL3 levels. The total testosterone levels were independent determinants of the HDL2 subfractions. During the follow-up, a significant increase in the BMI and WC values and a significant decrease in the levels of total cholesterol, HDL cholesterol, and HDL3 were observed. No difference was present between the 2 treatment arms. These results show that patients with hypogonadism have unfavorable HDL compositions in addition to the other dysmetabolic features. However, testosterone replacement for about six months neither improves the metabolic problems nor the HDL composition. Mechanistic studies are warranted to better understand the cardiovascular effects of unfavorable HDL compositions in hypogonadism.

There is limited and contradictory information regarding the role of serum ischemia-modified albumin (IMA) in obstructive sleep apnea (OSA). In this study we examine the effects of OSA and obesity on IMA and interleukin-6 (IL-6), and detect whether IMA and IL-6 may be potential biomarkers in OSA.Fifty-one males who underwent all night polysomnography test were included into the study. Body-mass index (BMI) and apnea-hypopnea index (AHI) of all patients were determined. Serum IMA and IL-6 levels, erythrocyte sedimentation rate (ESR), complete blood count, routine blood biochemistry and thyroid function tests were performed.Mean IMA [0.36 (± 0.04) U/ml, 0.89 (± 0.15) U/ml], mean IL-6 [1.01 (± 0.19) pg/ml, 2.02 (± 1.19) pg/ml] and mean ESR [4.14 (± 2.5) mm/h, 14.35 (± 13.7) mm/h] levels showed significant difference between non-OSA and OSA groups (P = 0.005, P 0.001, P 0.001, respectively). Sensitivity of IMA in distinction of non-OSA/OSA was equal to IL-6 and higher than ESR. IMA was also a stronger predictive factor than IL-6 and ESR in the evaluation of OSA groups (severe/mild/moderate OSA and non-OSA). IMA was the sole distinctive biomarker in assessment of obese and non-obese cases. IMA correlated with IL-6, AHI and ESR.Serum IMA may be a valuable oxidative stress indicator for OSA and could act as a better biomarker than IL-6 for reflecting the presence and the severity of OSA.

Patients with hypogonadism are at increased risk of cardiac and metabolic diseases and osteoporosis. Vitamin D and Fibroblast growth factor-23 (FGF-23) play role in the regulation of bone mineral metabolism and endothelial functions. Low vitamin D levels are reported in hypogonadism, while there is no data about the effect of testosterone replacement therapy (TRT). We investigated the effect of TRT on vitamin D and FGF-23 levels along with endothelial functions and insulin resistance in hypogonadal patients.Patients with congenital hypogonadotrophic hypogonadism (CHH) (n=32, age 20.6 ±1.58 years) were enrolled. TRT was implemented in transdermal form. The demographic parameters, FGF-23, 25(OH)D3, Asymmetric dimethylarginine (ADMA) and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured both before and after TRT.After a follow-up period of 3.63±1.33 months, ADMA and FGF-23 levels were significantly increased (p=0.03 and p=0.005 respectively), while the 25(OH)D3 and HOMA-IR index were not significantly changed. The body mass index and waist circumference levels of the patients were also increased (p0.001 and p=0.02) along with a significant decrease in the HDL cholesterol levels (p=0.006).The results show that a short term TRT increases plasma FGF-23 and ADMA levels, in young, treatment naive patients with CHH. Whether this is an early implication of TRT related adverse effects in this very young and treatment naïve population of CHH is not clear. Future prospective studies are required to find out the long-term effects of TRT on cardio-metabolic morbidity and mortality in this specific population.

Objective:Gilbert’s syndrome (GS), is a benign condition characterized by unconjugated hyperbilirubinemia related to a decreased hepatic glucuronidating activity without symptoms and signs of liver disease or overt hemolysis. In the present study, we aimed to assess circulating levels of asymmetric dimethylarginine (ADMA), pentraxin-3 (PTX-3) and high sensitivity C-reactive protein (hs-CRP) between patients with GS and controls and determine the correlation of unconjugated bilirubin (UCB) levels with these molecules as prognostic factors for vascular risk stratification and endothelial dysfunction.Methods:Forty two patients with GS and 37 age and sex matched control subjects were enrolled in this study. The diagnosis of GS was made by unconjugated hyperbilirubinemia (1 mg/dL or >17.1 μmol/L) on at least two occasions with normal values of other liver function tests, normal hepatic imaging, and absence of hemolysis.Results:Serum ADMA, PTX-3 and hs-CRP levels were significantly lower in GS than the healthy controls (p=0.037, p=0.025 and p=0.040, respectively). In correlation analysis, UCB was negatively correlated with ADMA, PTX-3 and hs-CRP (r=−0.239, p=0.034; r=−0.280, p=0.012 and r=−0.224, p=0.047, respectively).Discussion and conclusion:The present study showed for the first time that decreased levels of ADMA, PTX-3 and hs-CRP may prove the protective effects of hyperbilirubinemia on the endothelial dysfunction.

Measurement of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) has recently become more popular as a means of assessing oxidative stress in the human body. The aim of this study is to compare the levels of urine 8-OHdG in patients with type 2 diabetes with and without nephropathy and to evaluate its role as a biochemical marker for distinguishing these patients from healthy and patients without complications.For this purpose, 52 patients with type 2 diabetes mellitus (32 with nephropathy (DMN), 20 without nephropathy (DM)) and 20 healthy control subjects (C) were included in this study. The urine concentrations of 8-OHdG were measured by modified LC-MS/MS method and compared with the first morning voiding urine albumin/creatinine ratio (UACR) and HbA1c values of the same patients.The concentrations of urine 8-OHdG in DMN and DM patients were higher than those of the control subjects (3.47 ± 0.94, 2.92 ± 1.73, 2.1 ± 0.93 nmol/mol creatinine, respectively). But there was no statistical difference between DMN and DM (p = 0.115). There is significant correlation between urinary 8-OHdG and UACR (r = 0.501, p 0.001). According to ROC analysis, the AUC value of HbA1c was higher than the value of the AUC of 8-OHdG (0.882 and 0.771, respectively).This study shows that the urine 8-OHdG levels increase in diabetic patients. However, urinary 8-OHdG is not a useful clinical marker, compared with UACR, to predict the development of diabetic nephropathy in diabetic patients.

Polycystic ovary syndrome (PCOS) is described as a low-grade chronic inflammatory state where the macrophage infiltration increased in visceral fat play the major role. The aim of this study was to assess chitotriosidase (ChT) activity (an activated macrophage marker) in women with PCOS and controls and to evaluate its correlation with anthropometric and biochemical parameters.Seventy-nine women with PCOS and 60 healthy controls were included in the study. PCOS and controls were divided into two subgroups according to body mass indexes (BMIs) as normoweight (25 kg/m(2)) and overweight (≥25 kg/m(2)). ChT activity, biochemical (free testosterone, luteinizing hormone, insulin resistance index, etc.) and clinical parameters [BMI, waist-to-hip ratio, modified Ferriman-Gallwey scores (mFG)] were analyzed according to groups.Serum ChT activity was significantly (p0.001) higher in women with PCOS than controls (normoweight, 87.1 ± 90.1 vs. 18.4 ± 9.0 nmol/ml/h; overweight, 92.0 ± 96.7 vs. 17.9 ± 12.1 nmol/ml/h PCOS and controls, respectively). No statistically significant difference was noted between ChT activity of normoweight and overweight PCOS subgroups. A positive correlation was found between ChT activity and PCOS status (r 0.598, p0.001), mFG scores (r 0.525, p0.001), free testosterone (r 0.402, p 0.001) and total testosterone (r 0.168, p 0.048) for the combined groups (PCOS + controls). In multivariant linear regression analysis participants' PCOS status (presence or absence) and LH levels were the main predictors of ChT activity in the whole study population (p 0.002 and p 0.041, respectively).ChT activity elevates in PCOS independent of obesity. Our findings support the concept of PCOS is a state of low-grade chronic inflammation where the macrophages could play the major role. Hyperandrogenism might also be related to this inflammatory state and can be a subject of further trials.

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance. Chronic low-grade inflammation has been anticipated to play role in the pathogenesis of both insulin resistance and atherosclerosis. Pentraxin 3 (PTX3) is an inflammatory mediator synthesized in a variety of cells and tissues including heart, vascular endothelial cells, macrophages and adipocytes. In the present study, serum PTX3 level and its relationship with insulin resistance were investigated in patients with PCOS.Forty patients with PCOS and 40 age- and body mass index (BMI)-matched healthy controls were enrolled in the study. PTX3 and high-sensitivity C-reactive protein (hs-CRP) levels were determined by enzyme immunoassay (EIA). Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula.Plasma levels of PTX3, hs-CRP and HOMA-IR scores were all significantly higher (p = 0.021, p = 0.002 and p = 0.0001, respectively) in women with PCOS compared with healthy controls. Blood PTX3 level correlated positively with hs-CRP, BMI, waist-to-hip ratio (WHR), HOMA-IR and negatively with high-density lipoprotein cholesterol level (p 0.05, for all). After adjustment for age and BMI, PTX3, total testosterone levels and BMI remained as independent predictors of HOMA-IR scores (p 0.05, for all).PTX3 level is increased in patients with PCOS in concordance with insulin resistance.

The amount of epicardial adipose tissue (EAT), a component of body visceral adiposity, has been linked to the presence and severity of cardiovascular disease through multiple mechanisms. Polycystic ovary syndrome (PCOS) is characterized by insulin resistance and subclinical inflammation, which participate in the mechanism of atherosclerosis. We searched if the patients with PCOS have increased EAT thickness (EATT), along with its relation to the measures of adiposity and insulin sensitivity. A total of 41 subjects with PCOS and 46 age and body mass index (BMI) matched healthy controls were enrolled. EAT was measured by echocardiography above the free wall of the right ventricle. Insulin resistance was assessed by homeostasis model assessment of insulin resistance (HOMA-IR) formula, and plasma adiponectin level was measured by ELISA. Compared to healthy controls EATT and HOMA-IR score were significantly higher (p=0.0001 for both) while plasma adiponectin concentration was significantly lower (p=0.048) in women with PCOS. EATT correlated positively with total cholesterol, triglyceride, luteinizing hormone (LH) and negatively with sex hormon binding globuline (p

Non-alcoholic steatohepatitis (NASH) is closely associated with components of metabolic syndrome. Vaspin is a novel adipocytokine that may link obesity, insulin resistance (IR), and type 2 diabetes mellitus. We aimed to investigate circulating vaspin levels in subjects with NASH and also to search for the association of vaspin with IR, adiponectin, and histological findings.A total of 50 male patients with NASH and 30 healthy male controls were enrolled. Vaspin and adiponectin were measured with ELISA method. Insulin sensitivity determined by homeostasis model assessment (HOMA-IR) index.Plasma vaspin levels were higher and adiponectin levels were lower in NASH group compared with controls (p0.01 and p0.001, respectively). However, in multivariate analysis adjusted for glucose and lipid parameters, and HOMA-IR indexes, the difference in vaspin concentrations was disappeared. Nonetheless, the difference regarding the adiponectin levels remained significant between groups (p = 0.03). Vaspin was negatively correlated with low-density lipoprotein cholesterol (r = -0.32, p = 0.03) in subjects with NASH.This study indicates that circulating vaspin levels are not altered in male subjects with NASH. These results suggest that in the absence of metabolic risk factors, vaspin per se may not be involved in the pathogenesis of NASH.

Objective To investigate the role of small dense low density lipoprotein cholesterol (sd-LDL-C) in the mechanism of decreased incidence of cardiovascular disease in Gilbert's syndrome (GS). Design and methods sd-LDL-C, ox-LDL, and high sensitive C reactive protein (hs-CRP) levels were investigated in subjects with GS ( n = 42) and compared to healthy controls ( n = 52). Results Age, gender and body mass index (BMI) distributions were similar between the two groups. sd-LDL-C, ox-LDL and hs-CRP levels were lower in GS than the healthy controls ( p p p = 0.001, respectively). Unconjugated bilirubin was negatively correlated with sd-LDL-C, ox-LDL and hs-CRP ( r = −0.594, p r = −0.249, p = 0.016 and r = − 0.373, p r = 0.307, p = 0.003). Conclusions The findings of this preliminary study suggest that reduced sd-LDL-C, ox-LDL and hs-CRP levels may have a role in preventing atherosclerosis in subjects with GS.

Background Non-alcoholic fatty liver disease (NAFLD) is linked to an increased risk of cardiovascular disease. Mean platelet volume (MPV), a determinant of platelet activation, is an emerging risk factor for atherothrombosis. Aims The aim of this study was to investigate the levels of MPV in subjects with NAFLD having no confounding factors for atherosclerosis such as obesity, diabetes mellitus, and hypertension. In addition, the possible relationship between MPV and carotid artery intima media thickness (CIMT), a well known marker of subclinical atherosclerosis, was also studied. Methods MPV and CIMT levels were measured in 60 biopsy-proven NAFLD subjects and 54 healthy controls. Age and sex were similar between two groups. Results Body mass index and waist circumference levels were higher in the NAFLD group when compared to the controls. There were no differences between the two groups regarding LDL cholesterol levels, whereas HDL cholesterol levels were lower in the NAFLD group. MPV and CIMT levels were not different between the two groups. According to the correlation analyses, CIMT levels were positively correlated to age in patients with NAFLD. However, no significant correlation was found between MPV and CIMT levels. Conclusions The results of this study do not show any difference in MPV levels between subjects with NAFLD and controls. These finding suggests that in the absence of other metabolic risk factors, MPV might not be involved in the mechanism(s) of increased cardiovascular risk in NAFLD.

Both apelin and asymetric dymethyl arginine (ADMA) regulate blood pressures. Low apelin and high ADMA levels have been reported in several cardiometabolic disorders. However, there is no data about ADMA and apelin levels in essential hypertension and any relationship between them. We investigated a group of newly diagnosed and untreated 30 young hypertensive men and 30 healthy controls. Apelin levels were significantly lower and the ADMA levels were significantly higher in the patients (p = 0.04 for both). Both ADMA and apelin were related to the systolic blood pressures (SBP) (beta = -0.393, p = 0.003; beta = 0.285, p = 0.03, respectively). Future studies are necessary in order to clearly define the role of ADMA and apelin in the pathogenesis of essential hypertension.

Objective To investigate the role of CD40 ligand and P-selectin in the mechanism of decreased incidence of cardiovascular disease in Gilbert's syndrome (GS). Design and methods The soluble forms of CD40 ligand (sCD40L) and P-selectin (sP-selectin), and high sensitive C reactive protein (hs-CRP) levels were investigated in subjects with GS (n = 25) and compared to healthy controls (n = 53). Results sCD40L and hs-CRP levels were significantly lower in GS compared to the controls (0.33 ± 0.27 vs 0.71 ± 0.37 ng/mL, p

There is little evidence in the literature about circulating asymmetric dimethylarginine (ADMA) levels in Behcet’s syndrome (BS). The aim of the present study was 1. to measure the levels of ADMA in male patients with BS, 2. to compare ADMA levels with healthy volunteers, and 3. to evaluate whether there is any difference between patients both with/without thrombosis and in active/inactive stage. In patients with BS, CRP levels were higher than controls. The mean ADMA and C-reactive protein (CRP) levels were significantly higher in active stage patients and patients with thrombosis than in patients during the inactive stage and without thrombosis. In conclusion, we did not find any significant difference in ADMA levels between patients with BS and healthy controls. Serum ADMA concentrations, however, were higher in active patients and patients with thrombosis than in patients during the inactive stage and patients without thrombosis.

There is a little information in literature about circulating asymmetric dimethylarginine (ADMA) concentrations in polycystic ovary syndrome (PCOS) and the results reported are discrepant. In this study, therefore, we aimed (1) to determine the circulating ADMA concentrations in 44 women with PCOS and 22 age- and BMI-matched healthy controls, (2) to evaluate its correlations with insulin resistance, gonadotrophins, and androgen secretion, and (3) to compare effects of metformin and ethinyl estradiol-cyproterone acetate (EE/CPA) treatments on circulating ADMA concentrations. In conclusion, our data indicate that circulating ADMA concentrations in non-obese, non-hypertensive and young women with PCOS are significantly higher than healthy controls and they improved by a 3-month course of metformin and oral contraceptive treatments.

Objective: To investigate blood apelin concentrations in patients with newly diagnosed and untreated type 2 diabetes mellitus (T2DM) who had no additional disorder and to investigate the association of apelin with adiponectin, body mass indexes (BMI) and insulin sensitivity. Methods: Forty patients with T2DM and 40 healthy controls were enrolled. Apelin levels were measured along with BMI, lipids, glucose, insulin and adiponectin levels, and HOMA-IR indexes. Age, sex and BMI were similar in the two groups. Results: Plasma apelin and adiponectin levels were significantly lower in the diabetic group compared to controls (p

Angiogenesis is the process of generating new blood vessels from preexisting vessels and is considered essential in many pathological conditions. Bilberry has been traditionally used as a folk medicine for some countries. The purpose of the present study was to evaluate the effect of bilberry in chick chorioallantoic membrane angiogenesis model in vivo. In this well characterized model, bilberry inhibited angiogenesis in a concentration-dependent manner. Compared with the normal group, bilberry group has significant decreased vessels proliferation. These results provide evidence that bilberry inhibits angiogenesis and may be useful for treating angiogenesis-dependent human diseases.

OBJECTIVE Decreased effects of smoking on serum high-density lipoprotein cholesterol (HDL-c) were demonstrated in subjects smoking more than 20 cigarettes a day. We aimed to evaluate the effects of non-heavy smoking (< or =20 cigarettes a day) on HDL-c in young, healthy men who are similar in terms of age, physical activity and diet. METHODS A total of 1012 male students between 19 and 25 years old (21.4 +/- 1.5) in a military college who do not smoke or smoking < or =20 cigarettes a day were enrolled. Subjects who were consuming alcohol were excluded. Smoking levels (0: nonsmoker, 1: 1-5 cigarettes, 2: 6-10 cigarettes, 3:11-20 cigarettes a day) and duration were obtained by a questionnaire. Blood samples were taken after an over-night fasting. Blood pressure and anthropometric measurements were reported. RESULTS HDL-c showed a stepwise decrease as the level of smoking increased (49 +/- 9 mg/dL in level 0, 47 +/- 7 mg/dL in level 1, 46 +/- 8 mg/dL in level 2, 45 +/- 7 mg/dL in level 3, p < 0.001). Total cholesterol, triglycerides and low-density cholesterol were not different among the smoking levels. Body mass index (BMI) and waist/hip ratio were found to be slightly decreased in smokers. In a multivariate regression model including smoking level, duration, BMI, systolic and diastolic blood pressures, smoking level was the only predictor of HDL-c (B = -1.407, p < 0.001). CONCLUSION Smoking, even in relatively low levels, has a negative stepwise relationship with HDL-c in a homogeneous population of healthy young men in whom other major non-genetic factors that are known to affect HDL-c levels are identical.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with increased cardiometabolic risk. Although dyslipidemia represents a key factor in this disease, its impact on serum levels of distinct lipoprotein subfractions is largely unknown.OBJECTIVE: To assess the full low-density lipoprotein (LDL) and high-density lipoprotein (I-EDL) profiles in patients with NAFLD.METHODS: Seven LDL and 10 HDL subfractions were assessed by gel electrophoresis (Lipoprint, Quantimetrix Corporation, USA) in men with biopsy proven NAFLD (simple steatosis [n = 17, age, 34 7 years] and nonalcoholic steatohepatitis [NASH; n = 24, age, 32 +/- 6 years]). Exclusion criteria included robust alcohol consumption, infection with hepatitis B or C virus, body mass index >= 40 kg/m(2), diabetes mellitus, and hypertension. RESULTS: Compared with simple steatosis, NASH patients had similar body mass index, homeostasis model assessment of insulin resistance index and plasma lipids, with increased levels of.both aspartate aminotransferase and alanine transaminase. NASH subjects had lower levels of larger LDL1 (10 4 vs 13 4%, P =.010) and increased smaller LDL3 and LDL4 particles (9 5 vs 5 5%, P =.017 and 3 3 vs 1 2%, P =.012, respectively). No changes were found in the HDL subclass profile. By multiple regression analysis, we found that NASH was associated only with increased levels of LDL3 (P =.0470).CONCLUSIONS: The increased levels of small, dense LDL3 and LDL4 in NASH may help to at least partly explain the increased risk for atherosclerosis and cardiovascular diseases in these patients. (C) 2015 National Lipid Association. All rights reserved. Background Nonalcoholic fatty liver disease (NAFLD) is associated with increased cardiometabolic risk. Although dyslipidemia represents a key factor in this disease, its impact on serum levels of distinct lipoprotein subfractions is largely unknown. Objective To assess the full low-density lipoprotein (LDL) and high-density lipoprotein (HDL) profiles in patients with NAFLD. Methods Seven LDL and 10 HDL subfractions were assessed by gel electrophoresis (Lipoprint, Quantimetrix Corporation, USA) in men with biopsy proven NAFLD (simple steatosis [n = 17, age, 34 ± 7 years] and nonalcoholic steatohepatitis [NASH; n = 24, age, 32 ± 6 years]). Exclusion criteria included robust alcohol consumption, infection with hepatitis B or C virus, body mass index ≥40 kg/m2, diabetes mellitus, and hypertension. Results Compared with simple steatosis, NASH patients had similar body mass index, homeostasis model assessment of insulin resistance index and plasma lipids, with increased levels of both aspartate aminotransferase and alanine transaminase. NASH subjects had lower levels of larger LDL1 (10 ± 4 vs 13 ± 4%, P =.010) and increased smaller LDL3 and LDL4 particles (9 ± 5 vs 5 ± 5%, P =.017 and 3 ± 3 vs 1 ± 2%, P =.012, respectively). No changes were found in the HDL subclass profile. By multiple regression analysis, we found that NASH was associated only with increased levels of LDL3 (P =.0470). Conclusions The increased levels of small, dense LDL3 and LDL4 in NASH may help to at least partly explain the increased risk for atherosclerosis and cardiovascular diseases in these patients.

Blood gas analyzers (BGAs) are important in assessing and monitoring critically ill patients. However, the random use of BGAs to measure blood gases, electrolytes and metabolites increases the variability in test results. Therefore, this study aimed to investigate the correlation of blood gas, electrolyte and metabolite results measured with two BGAs and a core laboratory analyzer.A total of 40 arterial blood gas samples were analyzed with two BGAs [(Nova Stat Profile Critical Care Xpress (Nova Biomedical, Waltham, MA, USA) and Siemens Rapidlab 1265 (Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA)) and a core laboratory analyzer [Olympus AU 2700 autoanalyzer (Beckman-Coulter, Inc., Fullerton, CA, USA)]. The results of pH, pCO₂, pO₂, SO₂, sodium (Na⁺), potassium (K⁺), calcium (Ca⁺²), chloride (Cl⁻), glucose, and lactate were compared by Passing-Bablok regression analysis and Bland-Altman plots.The present study showed that there was negligible variability of blood gases (pCO₂, pO₂, SO₂), K⁺ and lactate values between the blood gas and core laboratory analyzers. However, the differences in pH were modest, while Na⁺, Cl⁻, Ca²⁺ and glucose showed poor correlation according to the concordance correlation coefficient.BGAs and core laboratory autoanalyzer demonstrated variable performances and not all tests met minimum performance goals. It is important that clinicians and laboratories are aware of the limitations of their assays.

We aimed to investigate the diagnostic utility of serum DPP-IV enzyme activity, urinary GAG/Cre ratio, chitotriosidase activity, total adenosine deaminase (ADA) and ADA-1 isoenzyme activity in the diagnosis of MPS. 31 MPS patients which were previously diagnosed by clinical and enzymatic analysis and 31 healthy controls matched with age and gender were included in this study. Serum DPP-IV enzyme activity, urinary GAG/Cre ratio, total ADA and ADA-1 isoenzyme activity were significantly higher in patients than in controls (p0.001, p0.001, p=0.038 and p=0.006, respectively). There were significant correlations between serum DPP-IV enzyme activity and urinary GAG/Cre ratios, ADA-1 activity, ADA-1/total ADA (r=0.498, p0.001; r=0.348, p=0.006; r=0.270, p=0.034, respectively). Area under ROC curve for DPP-IV enzyme activity was 0.988, p0.001 and for urinary GAG/Cre ratio was 0.986, p0.001. DPP-IV enzyme activity and urinary GAG/Cre ratio were the most significant parameters according to the univariate logistic regression analysis (p=0.001 and p0.001, respectively). The measurement of serum DPP-IV enzyme activity can be used complementary to the urinary GAG/Cre ratio for first-line MPS screening, since it is more less prone to age and hydration related interferences.

Sir: In a recent issue of The Scandinavian Journal of Clinical & Laboratory Investigation, Wium and colleagues [1] investigated the relationship between diabetes and adipose tissue distribution in ...