Asprosin, visfatin and subfatin as new biomarkers of obesity and metabolic syndrome.

OBJECTIVE: Metabolic syndrome (MetS) and obesity are important public health problems associated with adipose tissue mass. Asprosin, visfatin, and subfatin are new members of which fate in MetS and obesity has not been fully revealed yet. Thus, this study was to investigate the association between asprosin, visfatin, subfatin, and biochemical values, demographic data, and body composition measurement values in MetS patients with and without obesity. PATIENTS AND METHODS: Blood samples were taken from a total of 90 people, including 31 MetS patients with obesity, 29 MetS patients without obesity, and 30 healthy (control). Asprosin, visfatin, and subfatin were studied by the ELISA method. RESULTS: There was a negative correlation between asprosin and Body Mass Index (BMI) in the MetS + Obese group. The correlations between asprosin and urea and fasting insulin (FI) levels in the MetS group were positive and statistically significant (p < 0.05). While there was a statistically significant negative correlation (p < 0.05) between visfatin and BMI in the MetS + Obese group, the correlation with waist circumference in the MetS + Obese and MetS groups was statistically significant and negative (p < 0.05). There was a statistically significant negative relationship (p < 0.05) between aspartate aminotransferase value and visfatin. The results between visfatin values and asprosin and subfatin in all groups were significant (p < 0.05). CONCLUSIONS: There is a direct relationship between circulating amounts of asprosin, visfatin, and subfatin hormones and age, weight, height, diastolic blood pressure, high-density lipoprotein-cholesterol, aspartate aminotransferase, alanine transaminase, and creatinine. Therefore, asprosin, visfatin, and subfatin hormones are the new biomarkers of metabolic turbulence.

Prevalence of hepatitis delta virus (HDV) infection in chronic hepatitis B patients in eastern Turkey: still a serious problem to consider.

Hepatitis delta virus (HDV) is a serious cause of liver-related morbidity and mortality. Coexistent infection with HDV tends to aggravate the course of hepatitis B virus (HBV)-associated liver disease. The aim of this study was to determine the prevalence of HDV infection among patients chronically infected with HBV in the Elazig region, which is in eastern Turkey. A group of 282 patients infected with chronic HBV were investigated for the study. Anti-HDV seropositivity was evaluated in all patients. The anti-HDV-positive patients were further tested for HDV RNA. Severity of liver disease was assessed by liver biopsy. Regression analysis was used to determine the relationship between independent variables and HDV positivity. Of 282 chronic HBV patients, 192 were men (68.1%) and 90 were women (31.9%). The mean age was 43.8 ± 12.7 (between 18 and 73 years). Anti-HDV was positive in 45.5% of the patients (128/282). Among the 128 anti-HDV-positive patients, 116 were checked for HDV RNA and 56.9% were found positive (66/116). Chronic HDV infection rate was therefore present in at least 23.4% of the whole study group (66/282). There were 83 patients with cirrhosis (29.4%) in the study group. Anti-HDV seroprevalence and HDV RNA presence were higher in those with cirrhosis (61.4% and 42.2%, respectively). No significant relationship was found between anti-HDV seropositivity and demographic factors such as age, sex and operation or transfusion history except family history. HDV-RNA-positive patients had significantly higher ALT and lower albumin levels when compared to HDV-RNA-negative patients. HDV-RNA-positive patients also had a significantly higher fibrosis stage. In conclusion, these findings demonstrated that HDV infection is endemic and still a serious problem in the Elazig region of eastern Turkey. HDV infection is significantly related to the family exposure and increases the risk of severe liver fibrosis in this region.

Heterotopic gastric mucosa (inlet patch): endoscopic prevalence, histopathological, demographical and clinical characteristics.

OBJECTIVE: Heterotopic gastric mucosa (HGM) is found in the cervical oesophagus, just below the upper oesophageal sphincter, and has generally been overlooked by endoscopists. The objective of the present study is to determine endoscopic prevalence and histopathological and clinical characteristics of HGM and to classify patients according to their clinicopathological features. METHOD: A total of 911 consecutive patients (436 M and 475 F) who were admitted to our Endoscopy Unit were examined. HGM type and the presence of Helicobacter pylori (Hp) either in the stomach or in the HGM were histopathologically evaluated. RESULTS: Of the 911 patients, 33 (25 M and 8 F) were found to have HGM. HGM prevalence was determined to be 3.6%. On the basis of HGM patients' symptoms, only dysphagia was significantly correlated with the size of HGM (p < 0.05). Hp was positive in 29.2% of HGM. Clinicopathological classification of the patients showed that 20 patients were HGM type 1 and 13 were HGM type 2. None of the patients had HGM type 3, 4 or 5. CONCLUSION: Prevalence of HGM was 3.6%. Dysphagia was found related with the size of HGM. This may be associated with larger HGMs' causing more acid secretion.

Early diagnosis of pancreatic cancer: neutrophil gelatinase-associated lipocalin as a marker of pancreatic intraepithelial neoplasia.

Pancreatic cancer is a highly lethal malignancy with a dismal 5-year survival of less than 5%. The scarcity of early biomarkers has considerably hindered our ability to launch preventive measures for this malignancy in a timely manner. Neutrophil gelatinase-associated lipocalin (NGAL), a 24-kDa glycoprotein, was reported to be upregulated nearly 27-fold in pancreatic cancer cells compared to normal ductal cells in a microarray analysis. Given the need for biomarkers in the early diagnosis of pancreatic cancer, we investigated the expression of NGAL in tissues with the objective of examining if NGAL immunostaining could be used to identify foci of pancreatic intraepithelial neoplasia, premalignant lesions preceding invasive cancer. To examine a possible correlation between NGAL expression and the degree of differentiation, we also analysed NGAL levels in pancreatic cancer cell lines with varying grades of differentiation. Although NGAL expression was strongly upregulated in pancreatic cancer, and moderately in pancreatitis, only a weak expression could be detected in the healthy pancreas. The average composite score for adenocarcinoma (4.26+/-2.44) was significantly higher than that for the normal pancreas (1.0) or pancreatitis (1.0) (P<0.0001). Further, although both well- and moderately differentiated pancreatic cancer were positive for NGAL, poorly differentiated adenocarcinoma was uniformly negative. Importantly, NGAL expression was detected as early as the PanIN-1 stage, suggesting that it could be a marker of the earliest premalignant changes in the pancreas. Further, we examined NGAL levels in serum samples. Serum NGAL levels were above the cutoff for healthy individuals in 94% of pancreatic cancer and 62.5% each of acute and chronic pancreatitis samples. However, the difference between NGAL levels in pancreatitis and pancreatic cancer was not significant. A ROC curve analysis revealed that ELISA for NGAL is fairly accurate in distinguishing pancreatic cancer from non-cancer cases (area under curve=0.75). In conclusion, NGAL is highly expressed in early dysplastic lesions in the pancreas, suggesting a possible role as an early diagnostic marker for pancreatic cancer. Further, serum NGAL measurement could be investigated as a possible biomarker in pancreatitis and pancreatic adenocarcinoma.

The value of alpha-SMA in the evaluation of hepatic fibrosis severity in hepatitis B infection and cirrhosis development: a histopathological and immunohistochemical study.

AIMS: To investigate the value of alpha-smooth muscle actin (alpha-SMA), an indicator of stellate cell activation, in predicting fibrosis in chronic hepatitis B (CHB) patients. METHODS AND RESULTS: The liver biopsy specimens of 30 patients with a clinical diagnosis of CHB were obtained before treatment and scored by Knodell's histological activity index. The specimens were then immunohistochemically stained with alpha-SMA and semiquantitatively evaluated. Fibrosis and the immunoreactivity of alpha-SMA in the periportal, perisinusoidal and pericentral areas were compared. Fibrosis and necroinflammatory activity in CHB patients were significantly correlated (P =0.022). Furthermore, the degree of alpha-SMA expression and the scores of fibrosis (in periportal, perisinusoidal and pericentral areas) were highly correlated (P =0.000, 0.001, 0.000, respectively). CONCLUSIONS: In liver biopsy samples, alpha-SMA may prove to be a valuable marker in the evaluation of stellate cell activation and fibrosis progression and an early indicator of the development of fibrosis.

The value of ultrasonography and computerized tomography in estimating the histopathological severity of nonalcoholic steatohepatitis.

BACKGROUND & AIMS: Liver biopsy is the gold standard for the diagnosis of non-alcoholic steatohepatitis (NASH), but is an invasive method. There is a need for non-invasive methods that can reflect the histopathological severity of NASH. The aim of this study was to compare the ultrasonography and computerized tomography findings with the histopathological severity in patients with NASH. MATERIAL AND METHODS: Twenty-two consecutive patients with biopsy proven NASH and 20 age- and sex-matched healthy individuals were enrolled. Clinical and demographic data were collected at the time of liver biopsy. Histopathological grading and staging were made by an expert pathologist. Each patient underwent ultrasonography and computerized tomography. RESULTS: Liver ultrasonographic findings were not correlated with histopathological grade and stage (r: 0.134, P > 0.05; r: 0.130, P > 0.05). Mean liver densities obtained by computed tomography of NASH patients were lower than that of controls (P < 0.05) and liver/spleen density ratios were lower than that of controls (P < 0.05). These results were significantly correlated with histopathological grade (r: -0.716, P < 0.001; r: -0.663, P: 0.001), but not with the histopathologic stage (r: -0.416, P: 0.05; r: -0.356, P: 0.1). CONCLUSIONS: Ultrasonography findings do not reflect histopathological severity in patients with NASH. Computed tomography attenuation of the liver is significantly correlated with histopathologic grade but not with histopathological stage.

Levels of serum vitamin A, alpha-tocopherol and malondialdehyde in patients with non-alcoholic steatohepatitis: relationship with histopathologic severity.

The aims of our study were to estimate serum levels of malondialdehyde (MDA), serum levels of vitamin A and alpha-tocopherol as antioxidants and determine relationship of these with histopathologic severity in patients with non-alcoholic steatohepatitis (NASH). Twenty-nine patients with biopsy-proven NASH were included to study. NASH were histopathologically scored for grading and staging. Serum MDA and vitamin A levels were increased in patients with NASH and simple steatosis as compared to healthy control group. Serum alpha-tocopherol levels measured in simple steatosis and NASH were significantly lower than in healthy control group. There was no significant difference between grade/stage 0-1 and grade/stage 2-3 in terms of MDA, vitamin A and alpha-tocopherol levels. Serum MDA and vitamin A levels are increased in simple steatosis and NASH. MDA, vitamin A and alpha-tocopherol levels in NASH were not associated with the histopathologic severity.

Diabetes mellitus: a risk factor for pancreatic cancer?

The relationship between pancreatic cancer (PC) and diabetes is controversial. While some investigators assume that type II diabetes is a predisposition to PC, recent data argue that diabetes and altered glucose metabolism are a consequence of PC, and yet, the clinical presentation of the altered glucose metabolism in these patients varies considerably. Around 70% of patients with PC have impaired glucose tolerance (IGT) or frank diabetes. Of these, nearly 60% show an improvement of IGT or diabetes after surgery, whereas the rest show only mild or no improvement. It appears that biologically there are three types of PC: (1) PC not associated with IGT or diabetes; (2) PC associated with IGT or diabetes in which the abnormality improves postoperatively; (3) PC associated with IGT or diabetes in which the abnormality does not improve postoperatively. Based on our own studies, we suggest that the reason for impaired glucose metabolism in most patients is the alteration of islet cells either by the carcinogen directly, or by diabetogenic substances released by cancer cells. The extent of the islet alteration (i.e. focal or diffuse) may determine whether the removal of tumor alone can improve the metabolic alteration. The elucidation of the mechanism is of immense importance for providing an early tumor marker and for developing preventative or therapeutic modalities.

Effect of elevated calcium levels on segmental tubular sodium reabsorption in normal man.

The aim of the present study was to assess the effect of calcium infusion on segmental tubular reabsorption in humans using lithium clearance, along with creatinine and free water clearances during maximal water diuresis. In 8 healthy volunteers, a 20-min 5 mg/kg calcium infusion that increased serum calcium levels from 2.27 +/- 0.07 to 2.87 +/- 0.07 mmol/l (p < 0.01) was followed by a 60-min 3 mg/kg infusion for maintenance. During the experimental period, blood pressure did not change. Maximal urine flow increased from 15.6 +/- 2.4 to 20.8 +/- 2.8 ml/min (p < 0.01), while clearance of sodium increased from 1.5 +/- 0.4 to 3.7 +/- 0.9 ml/min (p < 0.001). Lithium clearance showed an increase of 7.4 ml/min, pointing to a suppression of proximal reabsorption. Free water clearance also increased from 11.5 +/- 3.7 to 14.4 +/- 3.9 ml/min, indicating an increase in TALH reabsorption which was attributed to increased sodium and water reaching this segment. Time control studies showed no significant changes in the parameters measured except for potassium excretion. Potassium excretion during calcium infusion was somewhat lower than during the control studies. The data support the view that an increase in serum calcium concentration leads to a decrease in proximal tubular reabsorption as indicated by lithium clearance while a decrease in reabsorption in the collecting duct could well add to the diuretic properties of calcium.