Search

OBJECTIVES It has been reported that the neutrophil-to-lymphocyte ratio (NLR) can be measured relatively easily and can serve as a valuable index for much clinical pathology. The aim of this study was to investigate the association between NLR and hepatic histological findings in patients with nonalcoholic fatty liver disease (NAFLD). DESIGN AND METHODS A total of 226 consecutive patients with biopsy-proven NAFLD [nonalcoholic steatohepatitis (NASH, n=105), borderline-NASH (n=74), and simple steatosis (n=47)] were enrolled. NASH and fibrosis were diagnosed histologically using the NAFLD Clinical Research Network criteria. RESULTS Significant differences were found in aspartate aminotransferase (P

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.

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. 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.

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: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.

Visfatin, a new adipokine, facilitates adipogenesis and has insulin-mimetic properties. We aimed to investigate the plasma visfatin levels in patients with newly diagnosed and untreated type 2 diabetes mellitus (T2DM) and impaired glucose tolerance (IGT), who had no obesity or hypertension. Twenty-two patients with T2DM, 18 subjects with IGT and 40 healthy controls were enrolled. Visfatin levels were measured along with the BMI, blood pressure, lipids, glucose, insulin, adiponectin and hsCRP levels, and HOMA-IR indexes. Age, sex and BMI were similar in all groups. Visfatin levels were higher in the diabetic group than the controls (p = 0.01). There was no significant difference in the visfatin levels between the T2DM and IGT groups as well as IGT group and healthy controls. Plasma visfatin concentrations did not differ between men and women. Visfatin levels did not correlate with BMI, blood pressure, plasma adiponectin, insulin, hsCRP, glucose and lipid levels or HOMA-IR indexes in the three groups. These results indicate that hyperglycemia causes an increase in plasma visfatin levels and, as in people with T2DM but not with IGT, this increase gets more prominent as the glucose intolerance worsens.

Summary Objective There is controversy about the effects of statins on insulin resistance and plasma adiponectin. The aim of this study was to investigate the effects of fluvastatin treatment on these parameters in a group of dyslipidaemic patients who had no confounding factors for insulin resistance or alterations in plasma adiponectin. Design and patients Forty-nine patients [27 males, 22 females; mean age 47·2 ± 10·3 years; body mass index (BMI) 29·64 ± 3·2 kg/m2] with dyslipidaemia and 20 controls (six males, 14 females; mean age 45·3 ± 9·31 years; BMI 30·07 ± 4·04 kg/m2) were enrolled. All patients were treated initially with therapeutic lifestyle changes (TLC) for 6 weeks. Six out of 49 subjects were excluded from the study. Then, 24 out of 43 patients with high blood cholesterol despite TLC were allocated to fluvastatin 80 mg daily plus TLC, and the remaining 19 patients with normal cholesterol were subjected to TLC alone for additional 12 weeks. Measurements Plasma adiponectin, immunoreactive insulin levels, BMI, waist circumference, blood pressure, lipids, and glucose were determined. The insulin sensitivity index was quantified using the homeostasis model assessment (HOMA). Results TLC caused significant improvement in plasma insulin (P = 0·02) and elevation in plasma adiponectin (P = 0·02). Fluvastatin treatment decreased total cholesterol and low density lipoprotein (LDL)-cholesterol significantly (P = 0·01 and P = 0·02, respectively). No significant effect of fluvastatin was observed on plasma insulin or adiponectin or on the HOMA index. Conclusions Fluvastatin does not improve plasma adiponectin levels and insulin sensitivity, despite its beneficial effects on lipid levels. Our data, however, were limited by the fact that a more accurate method of assessing insulin sensitivity, the euglycaemic–hyperinsulinaemic glucose clamp technique, was not used.

Objective: The data related to association among hypertension, insulin resistance, and plasma adiponectin concentration is controversial. We aimed to evaluate the relationships among these factors in a young hypertensive group who had no confounding factors. Design and methods: Thirty newly diagnosed and formerly untreated hypertensive males (mean age 23.4±4.0 yr; body mass index: 24.9±2.2 kg/m2), and 60 healthy control subjects (mean age 22.5±3.2 yr; body mass index: 24.6±1.6 kg/m2) were enrolled. Insulin resistance was calculated by homeostasis model assessment (HOMA). Results: The two groups were similar in terms of age, body mass index, fasting glucose, total cholesterol, HDL and LDL cholesterol, adiponectin, insulin, HOMA, and hsCRP levels. Mean triglyceride levels in hypertensive patients were significantly higher than the controls (p=0.02). Conclusions: These results indicate that young, newly diagnosed, uncomplicated patients with hypertension have similar plasma adiponectin levels and insulin sensitivities when compared to healthy controls. We suggest that high blood pressure itself may not be associated with insulin resistance or low adiponectin levels in patients with new onset, uncomplicated hypertension.

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.

Malignancies account for about 20% of incidentally diagnosed venous thromboembolism. Surgery- or chemotherapy-induced risk of thrombosis is also high in patients with cancer. We report on a young male with skeletal Ewing's sarcoma who presented with deep vein thrombosis in the affected limb, which is quite a rare clinical condition. Venous thrombosis of the lower extremities in young patients should prompt the clinician to search for underlying local malignancies.

Objective Nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome (MetS) is closely associated with an increased risk of cardiovascular disease. Fetuin-A is associated with MetS and NAFLD. We investigated the relationship of circulating fetuin-A level with markers of endothelial dysfunction and presence of carotid atherosclerosis in subjects with NAFLD. Methods The consecutive 115 patients with NAFLD and age-matched 74 healthy subjects were enrolled. Plasma levels of fetuin-A and markers of endothelial dysfunction [asymmetric dimethyl arginine (ADMA) and adiponectin] were measured by ELISA method. Insulin sensitivity was determined by homeostasis model assessment of insulin resistance (HOMA-IR) index. Carotid artery intima-media thickness (cIMT) was assessed by high-resolution ultrasonography. Results Fetuin-A and ADMA were higher and, adiponectin was lower in NAFLD group than the control group (P = 0·004, P

Aims Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease. Asymmetric dimethylarginine (ADMA) is a novel marker of endothelial dysfunction and atherosclerosis. We aimed to investigate circulating ADMA concentrations in biopsy proven NAFLD and also to search its association with carotid atherosclerosis. Methods Sixty-seven nondiabetic and normotensive patients with NAFLD and 35 healthy controls were enrolled. Plasma ADMA was measured along with glucose, lipids and insulin levels. Insulin resistance (IR) was assessed by homeostasis model assessment-estimated insulin resistance (HOMA-IR) method. Carotid atherosclerosis was evaluated by carotid artery intima-media thickness (CIMT) using carotid ultrasonography. Results ADMA levels and CIMT measurements were significantly higher in NAFLD group than the controls. However, the difference regarding the CIMT disappeared when the findings were adjusted according to the metabolic parameters and insulin sensitivity. In contrast, the difference for ADMA remained significant between two groups. No significant association was found between ADMA, CIMT and histopathological findings. Conclusions Plasma ADMA levels are increased in subjects with NAFLD. This increase seems to be independent from traditional cardiovascular risk factors, insulin resistance and liver histology. Circulating ADMA may be an earlier marker of vascular damage with respect to CIMT in subjects with NAFLD.

Objectives The data regarding circulating levels of markers of platelet activation and endothelial function in people with prediabetes are scant. The aim of the present study was to search blood levels of soluble CD40 ligand (sCD40L), soluble P-selectin (sP-sel) and von Willebrand Factor (vWF) in subjects with prediabetes, along with the effects of the metabolic syndrome (MetS) on these markers. Design and methods A total of 77 prediabetic individuals and 81 age, sex and body mass index matched healthy subjects with normal glucose tolerance (NGT) were prospectively analyzed. Anthropometric parameters, fasting plasma glucose, blood d lipid profiles and insulin resistance indexes were determined. Plasma sCD40L, sP-sel and vWF levels were measured by ELISA. Results sCD40L, sP-sel and vWF levels in the prediabetic group were similar to those in the controls. However, prediabetic subjects with the MetS had significantly higher level of sCD40L compared to those without MetS. Moreover, sCD40L level correlated significantly with waist circumference, systolic blood pressure and HDL-cholesterol level in the patient group. Conclusion These data imply that MetS may contribute, at least in part, to the mechanism of platelet activation and endothelial dysfunction in people with prediabetes.

Background Apelin is a novel adipocytokine produced by white adipose tissue that binds the APJ receptor with high affinity. Insulin may have a role in regulation of apelin synthesis and secretion from the adipose tissue. Objective To investigate blood apelin concentrations in children with type 1 diabetes mellitus (T1DM) and display association of apelin with adiponectin, body mass index (BMI), lipids and insulin sensitivity. Methods Thirty patients with T1DM and 45 healthy controls were enrolled. Apelin levels were measured along with BMI, lipids, fasting plasma glucose, HbA1c and adiponectin levels. Results Plasma apelin and adiponectin levels were significantly higher in the diabetic group when compared to controls. No correlation was found between the apelin blood concentrations and adiponectin, BMI, lipids and insulin sensitivity. Conclusions Children with T1DM have significantly increased circulating apelin levels when compared to healthy controls. However, no significant relation was found between the apelin and BMI, glucose, lipids and adiponectin levels, and also insulin sensitivity.

Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity and diabetes mellitus. IL-18 is associated with obesity and metabolic syndrome. Our aim was to investigate the relationship of IL-18 with adiponectin and liver histology in subjects with NAFLD who had no additional disorder such as morbid obesity, diabetes mellitus and hypertension.Plasma levels of IL-18 and adiponectin were measured by ELISA in 96 male subjects with NAFLD [n = 65 for non-alcoholic steatohepatitis (NASH) and n = 31 for simple steatosis (SS)].IL-18 levels were not different between the two groups (p = 0.89). There was no significant association of IL-18 with adiponectin, insulin resistance and histopathological findings. Adiponectin was lower in the NASH group compared to the SS group (p = 0.02) and it was found to be negatively correlated with hepatic steatosis and fibrosis (r = -0.442, p0.001 and r = -0.292, p = 0.02, respectively).This study indicates that circulating IL-18 levels are not altered in male subjects with NAFLD. These results suggest that in the absence of metabolic risk factors, IL-18 per se may not be involved in the pathogenesis of NASH and SS.

Aim: In this study, we aimed to compare the results colonoscopy and if performed, these of histopathologic examinations in patients which are administered 18-fluoro-2-deoxyglucose positron emission tomography (FDG PET) for different reasons and diagnosed incidental colorectal metastasis. Material and Methods: 26 cases with established focally increased colorectal activity metastasis and who have been performed FDG PET for various clinical indications are included in the study. Cases are performed colonoscopy for differential diagnosis. Results: Age average of the 26 cases included in the study (9 females, 17 males) was 61.9 (38-87). Colonoscopic lesion have been established in 10 cases (38.5 %), while there was none in 16 cases (61.5 % false positive). Number of the cases which endoscopic lesions have been indicated at the localization coherent with activity metastasis in FDG PET was 9 ( 34.6 % ). However in one of the cases, colonoscopic lesion was at a different localization from the one defined in FDG PET examination.Conclusion: We have a high false positive ratio in our study. This can be due to FDG shadowing after a poor bowel lavage. For this reason, an adequate bowel lavage administration to the patients before FDG PET examination can reduce the false positive ratio. Thus we can prevent unnecessary invasive attempts. In medical practice, resection of the colonic adenomas found acceptance in protecting from colon cancer. This study showed us that incidental FDG metastasis can indicate premalign or malign lesions. Therefore, colonoscopoic examination is recommended for the cases who have been performed FDG and found increased radioactive metastasis, whether they have been administered bowel lavage or not.

The enzyme chitotriosidase (ChT) is secreted by activated macrophages and play active role in human immune response. ChT activity is increased in atherosclerosis in association to the extent of the disease. We investigated the relevance of ChT to endothelial functions and insulin resistance in patients with T2DM. Forty newly diagnosed and untreated patients with T2DM (male 17; age 47.0 ± 6.2 years) and 50 healthy volunteers (male 21; age 50.2 ± 8.8 years) were enrolled. Plasma asymmetric dimethyl arginine (ADMA) levels were determined by ELISA. ChT activity was measured by the fluorescence method. Insulin resistance was calculated by the HOMA-IR formula. The patients had higher systolic blood pressures, HOMA-IR, ADMA levels, and ChT activities (P

Nonalcoholic fatty liver disease (NAFLD) is linked to an increased risk of cardiovascular disease. We aimed to research whether the levels of soluble P-selectin (sP-selectin) and soluble CD40 ligand (sCD40L), markers of endothelial function, are altered in subjects with NAFLD having no confounding factors for atherosclerosis. sCD40L, sP-selectin, and high-sensitivity C-reactive protein (hsCRP) levels, and homeostasis model assessment of insulin resistance (HOMA-IR) indexes were measured in 50 NAFLD subjects and 30 healthy controls. sCD40L, sP-selectin, and hsCRP levels were not significantly different between two groups (P = 0.48, 0.51, and 0.34, respectively). Body mass index, waist circumference, and insulin levels and HOMA indexes were significantly higher in subjects with NAFLD (all P < 0.001). The present data show that sCD40L and sP-selectin may not contribute to the accelerated atherogenesis associated with this clinically relevant condition.

To the Editor: Huang et al. reported some interesting data regarding a relation between metabolic syndrome (MetS) and nonalcoholic steatohepatitis (NASH) in severely obese subjects [1]. Although most clinicians believe that an association is already present, the study is important because it provides scientific information on this clinically relevant condition. However, we think that some points should be discussed. First, as stated in the text and shown in Table 1, some of the subjects with and without NASH have overt diabetes. However, no information about the glucose tolerance of other subjects can be seen. Although both diabetes mellitus (DM) and impaired glucose tolerance (IGT) are among the components of MetS [2], plasma insulin and adipokine levels differ according to the degree of glucose dysregulation [3, 4]. The same is true for hypertension or elevated blood pressure and dyslipidemia [5, 6]. Lastly, circulating adipokines and measures of insulin sensitivity are easily affected from the medications started for the underlying conditions [7, 8]. The authors state in their article that the participants were accepted as having MetS according to predefined criteria [2]. The diagnostic criteria can be used clinically with success; however, while designing clinical studies to display mechanistic associations, we have to give ultimate effort to exclude possible confounders that might interfere with the results. Finally, we would like to ask the authors whether they can present some additional data by categorizing their patients with MetS and NASH according to metabolic confounders such as DM, IGT, blood pressure, lipid profile, and medication. This would certainly provide the readers clearer information about the association between MetS and NASH.

Unlike diabetes mellitus and impaired glucose tolerance, it is not clear whether the subjects with impaired fasting glucose (IFG) are at increased risk of atherosclerosis and cardiovascular diseases. The CD40-CD40 ligand interaction is involved in the mechanism of atherosclerosis. We investigated whether soluble CD40L (sCD40L) as well as high sensitive C-reactive protein (hsCRP) levels are increased in subjects with IFG having no confounding factors for inflammation or atherosclerosis. Twenty four IFG subjects with no additional disorders and 40 appropriate healthy controls were studied. sCD40L and hsCRP levels in the IFG and control groups were similar. Blood pressures, total and LDL-cholesterol, and triglyceride levels were also similar, whereas HDL-cholesterol was lower and HOMA-IR indexes were higher in the IFG group. Though the sample size was small, the present data show that sCD40L seems not to alter in subjects with IFG suggesting that it might not be an independent risk factor for atherosclerosis.

Smoking is closely associated with insulin resistance, though the mechanism is not clear. Adiponectin, a novel anti-atherosclerotic and anti-inflammatory adipose tissue product, which is closely associated with insulin resistance, was reported to be low in smokers with cofactors for atherosclerosis. However, the effects of smoking on circulating adiponectin levels in otherwise healthy people are unknown. In this study, a case control design was implemented to search for the effect of smoking on plasma adiponectin and insulin sensitivities in healthy people. Sixty-four healthy male smokers, with no family history of hypertension and diabetes mellitus were compared with appropriate 36 age and body mass index matched controls. Both the patients and controls were the soldiers of a troop with regular daily physical activity. Plasma adiponectin, high sensitive C-reactive protein (hsCRP), insulin and lipid levels, and insulin sensitivity as assessed by homeostasis model assessment index (HOMA) of the smokers were measured and compared with those of the controls. The plasma adiponectin, hsCRP, insulin levels and HOMA indexes of the two groups were similar. These parameters were not affected by the amount of cigarettes per day. HDL-cholesterol levels were lower (p = 0.01) and systolic blood pressures were higher (p = 0.02) in the smokers. These results indicate that smoking may not affect plasma adiponectin and insulin levels in young and healthy men with high exercise capacity.

KISA, Ucler/0000-0002-8131-6810; Sonmez, Alper/0000-0002-9309-7715; Turan, Mustafa/0000-0003-4782-8596 WOS: 000239297400006 PubMed: 16865300 T cells are involved in the pathogenesis of atherosclerosis. We aimed to search for any association between the peripheral T-cell activities and atherogenic risk factors in healthy subjects. Fifty male volunteers (age 22.0 +/- 2.4 years) were enrolled. No subject had any chronic disease or was under any drug treatment. Lymphocytes were isolated from heparinized venous blood and the proliferative responses to phytohemagglutinin (PHA) were measured from the amount of radioactive thymidine uptake by the lymphocyte DNA. T-cell activity responses of patients with a family history of coronary events were compared with others. The activity responses of smokers were compared with nonsmokers. Subjects with a positive family history of coronary events had higher PHA stimulated T-cell response and delta cpm (P < 0.05 for each). Total and low-density lipoprotein cholesterol levels of the subjects with a positive family history of cardiovascular events were positively correlated with the PHA-activated T-cell responses (P = 0.022, r = 0.604 and P = 0.015, r = 0.635, respectively). There was no significant difference between the T-cell activity responses of smokers and nonsmokers. No correlation was found between the biochemical parameters and T-cell activities in these groups. Peripheral T-cell activity responses to PHA are higher in the asymptomatic relatives of patients with coronary events. This may be a clue for the familial tendency of atherosclerotic diseases. Further follow-up studies are necessary to investigate the relationship.

Dear Editor With great interest we have read the article by Arinc et al. (1). In this study, the relationship of liver enzymes with endothelial dysfunction and carotid atherosclerosis was evaluated in subjects with biopsy-proven non-alcoholic steatohepatitis (NASH). Patients with NASH had impaired flow-mediated dilatation (FMD) and higher carotid intima-media thickness (CIMT) when compared with healthy controls. In addition, serum concentrations of gamma glutamyl transferase (GGT) and alanine amino transferase (ALT) were found to be associated with FMD and CIMT. Consequently, they suggested that serum GGT and ALT concentrations might have a predictive value to demonstrate the presence of endothelial dysfunction and carotid atherosclerosis in subjects with NASH. The major strengths of this study were the use of liver biopsy, which is the gold standard method for the diagnosis of non-alcoholic fatty liver disease (NAFLD), and the use of FMD and CIMT, which are well known and accepted methods to assess endothelial dysfunction and carotid atherosclerosis. However, we would like to share our thoughts and experiences with Arinc et al. Obesity and NAFLD are both well-known metabolic risk factors for prediabetes and diabetes mellitus (DM) (2). Keeping in mind that both macrovascular and microvascular complications can occur in patients with prediabetes, they should be examined carefully in terms of cardiovascular disease (CVD) risk assessment (3). In the article by Arinc et al., body mass index values were in the range of overweight or obesity in most subjects with NASH. Despite being specified that there were no diabetic subjects with NASH, these data were obtained using only the results of fasting plasma glucose (FPG), and standard oral glucose tolerance tests (OGTT) were not performed. OGTT is currently the gold standard method for the diagnosis of DM. In several studies conducted in patients with NAFLD and no history of DM, it is stated that the use of the measurement of FPG alone is not sufficient to assess glucose tolerance and OGTT is recommended for routine evaluation of this clinically relevant condition (4,5). Moreover, it has been reported that 120-min OGTT results were independent risk factors for advanced stages of liver fibrosis in patients with NAFLD (5).Therefore, we think that the presence of prediabetes should be investigated both in terms of cardiovascular risk management and prognosis of liver disease in patients with NAFLD. Increased CIMT is associated with cardiovascular risk factors, and also CVD. In addition, CIMT is an important marker in the evaluation of subclinical atherosclerosis and a well-known predictor in the development of cardiovascular events (independent of other cardiovascular risk factors) (6). CIMT levels were reported to be higher in patients with NAFLD compared with healthy controls in many studies, as well as in the study of Arinc et al. In addition, in patients with NASH, CIMT levels were higher than in patients with simple steatosis (SS) and healthy controls. Moreover, there was a relationship between CIMT and the degree of liver damage (independent of the presence of insulin resistance, traditional risk factors, and MetS) in some of these studies (7). On the other hand, contrary to these findings, Petit et al. were unable to find any relationship between hepatic steatosis and CIMT in patients with DM (8). This finding also accords with our previous observations, which showed no association between CIMT and histological severity in NAFLD (9). We consider a number of possible explanations regarding the different reports on the relationship between carotid atherosclerosis and NAFLD. Firstly, most studies that investigate the association of CIMT with NAFLD were performed in subjects with ultrasonographically diagnosed fatty liver. Although there is a well-known correlation with the histological findings of fatty infiltration, liver ultrasonography is not sufficiently sensitive to detect liver inflammation and fibrosis. Secondly, when the above-mentioned studies were analysed separately, it can be seen that some of the patients with NAFLD had metabolic confounders like morbid obesity, DM, and hypertension. In addition, some of these subjects were using medications related to these metabolic problems. It has been reported that CIMT levels may be affected by these metabolic risk factors and also medications (6). Thirdly, it is well known that there is a strong and independent relationship between age and CIMT. Moreover, differences as small as 0.1 mm of CIMT were found in longitudinal studies after 20 years when a combination of adverse risk factors clustered together (10). In light of these data as well as our own findings (9,11), we think that age may be an important determinant for the development of carotid atherosclerosis in NAFLD, and a longer exposure time to fatty liver may be required to develop higher CIMT. Thus, a recent study reported no association between CIMT and NAFLD in children and adolescents (12). Lastly, CIMT may not reflect all components of cardiovascular risk, and other markers of endothelial function such as asymmetric dimethylarginine and flow-mediated dilatation may be more useful indexes of early vascular changes (13). In light of these data, we suggest that NAFLD may have no direct impact on carotid atherosclerosis and it may contribute to CVD by acting in concert with metabolic abnormalities. In agreement with this hypothesis, a recent cross-sectional study found NAFLD to be associated with CIMT only in people with MetS (14).

Afghanistan is one of the endemic regions of chloroquine resistant P. falciparum. Mefloquine and doxycycline are among the recommended prophylactic regimes. The aim of the study was to compare the efficacy and tolerability of the two regimes on the Turkish soldiers settled in Kabul, Afghanistan.A total number of 1400 soldiers were subjected to prophylactic regimes with either doxycycline 100 mg/day (n=986) or mefloquine 250 mg/week (n=414). Prophylaxis lasted about 12 weeks. The side effects and compliances were investigated by questionnaires. All soldiers were monitored up to 6 months after returning home.No malaria case was observed and there was no severe side effect in either group. The total side effects in doxycycline group were significantly higher (P0.001). The compliance of mefloquine takers was better than the doxycycline takers (P0.05).The tolerability of the mefloquine regime is better than the doxycycline regime in malaria prophylaxis.

We read with great interest the recently published article by Dalmas et al. (1) in which the authors investigated the arterial intima-media thickness (IMT) and its association with systemic inflammation and adipose tissue in severely obese subjects. They concluded that IMT increased with severe obesity but was not influenced by the degree of systemic inflammation or adipose tissue macrophage accumulation. The results seem important regarding the role of adipokines, cytokines, and inflammatory mediators in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, we think that there are some points that should be emphasized about the study. First, it was stated that …

Nonalcoholic fatty liver disease associated with increased risk of cardiovascular mortality. Carotid artery intima media thickness is a reliable index of subclinical atherosclerosis. There are contradictory reports about relationship between nonalcoholic fatty liver disease and carotid atherosclerosis. In this study, we aimed to investigate carotid artery intima media thickness levels and its association with histological findings in biopsy proven nonalcoholic fatty liver disease. 113 male patients and 57 healthy male controls were enrolled. Patients and control groups mean ages were 31.7± 5.7 and 30.1± 5.5 respectively. Body mass index, Waist circumference, glucose, lipids and insulin levels, and HOMA-IR were determined. Carotid atherosclerosis evaluated by carotid artery intima media thickness using high resolution carotid ultrasonography. Carotid artery intima media thickness levels were higher in patient group than the control group. This difference was disappeared when the findings were adjusted according to the body mass index, waist circumference, glucose and lipid levels, and HOMA-IR indexes. In addition, no significant association was observed between carotid artery intima media thickness and liver histology. However, there was a significant association between age and carotid artery intima media thickness in patients and controls. Our study does not support an association between carotid atherosclerosis and nonalcoholic fatty liver disease. Otherwise, it can be speculated that a longer exposure to the disease is required to determine significant differences in carotid atherosclerosis.

In a recent issue, we read with great interest the article by Yilmaz et al [1] reporting microalbuminuria and its association with liver fibrosis in nondiabetic patients with nonalcoholic fatty liver disease (NAFLD). The results are interesting and likely to contribute to our understanding of the relationship between microalbuminuria and NAFLD. However, we have some concerns about the data presented by the authors. Firstly, many studies have suggested the relationship of microalbuminuria with NAFLD in patients with different glucose disorders [2,3]. Although it was stated in the article that diabetic patients were excluded from the study, there is no information regarding the glucose tolerance status of the subjects. We think that this is an important issue because NAFLD is associated with prediabetes [4] and microalbuminuria is strongly associated with prediabetes in subjects with NAFLD [2]. Secondly, as mentioned by the authors in the article, it has been suggested that there is an association between microalbuminuria and the components of metabolic syndrome (MetS) [5-7]. It is well known that insulin resistance and the MetS have been associated with an increased incidence of chronic kidney disease and microalbuminuria [7,8]. In addition, NAFLD is strongly associated with obesity, insulin resistance, hypertension, and dyslipidemia and is now regarded as a liver manifestation of the MetS. However, no data could be seen in the text regarding the proportion of subjects with MetS and the relationship of microalbuminuria and the components of MetS. Finally, the measurement of urine total protein and albumin is central to the diagnosis and management of subjects with kidney disease and in assessing the cardiovascular risk. For this reason, accurate assessment is vital to enable detection and management of patients with proteinuria. The measurement of albumin in a spot urine sample is an accurate, easy-toperform, and recommended method in the clinical setting [9] However, all abnormal test results must be confirmed in 2 of 3 samples collected over a 3to 6-month period because of the known day-to-day variability in urinary albumin excretion [10].

To the Editor: Nazal et al. reported some interesting data regarding a relation between plasma adiponectin concentrations and liver histology in morbidly obese patients [1]. Although most clinicians believe that an association is already present [2], the study is important because it provides scientific information on this clinically relevant condition. However, we think that some points should be discussed. Firstly, as stated in the text and shown in Table 1, there are significant differences regarding the body mass index, highdensity lipoprotein cholesterol and triglyceride levels, and also the proportions of subjects with hypertension and diabetes mellitus (DM). It is well known that all these parameters affect circulating adiponectin concentrations [3]. Secondly, apart from DM, no information about the glucose tolerance of other subjects can be seen in the text. We know from previous studies that hypoadiponectinemia occurs not only in diabetes but also in people with impaired glucose tolerance (IGT) [4], which is a condition with insulin resistance as well. Obesity is a strong risk factor for the development of DM and also IGT. In light of these clear data, we think that some of the study participants may still have overt glucose dysregulation or DM without implementation of the glucose tolerance test. This issue is important because non-alcoholic fatty liver disease (NAFLD) is associated with prediabetes and circulating adiponectin and insulin concentrations are altered in subjects with disordered glucose metabolism [5]. Lastly, no information about the drug use of the subjects could be seen in the text. We know that adiponectin blood levels and measures of insulin sensitivity may be affected from the medications started for the metabolic problems mentioned above [6, 7]. Finally, we would like to ask the authors whether they can present some additional data by categorizing their patients with metabolic syndrome and NAFLD according to metabolic confounders such as DM, IGT, blood pressure, lipid profile, and medication. This would certainly provide the readers clearer information about the association between adiponectin and liver histology in patients with morbid obesity.