The Association between Melatonin Levels and Sleep Quality in Patients with Pruritus: A Potential Biomarker on a Candidate Future Treatment.

Background: Melatonin is a hormone that regulates the sleep-wake cycle and has immunomodulatory and anti-inflammatory roles. Aims: The aim of this study is to assess melatonin levels and investigate the association with pruritus severity, sleep quality, and depressive symptoms in dermatoses with nocturnal pruritus. Methods: The study was a prospective study with 82 participants, including 41 patients and 41 healthy volunteers. The visual analog scale (VAS), Pittsburg Sleep Quality Index (PSQI), and Beck Depression Inventory (BDI) were recorded for each patient. To assess the melatonin levels, urinary 6-sulfatoxymelatonin levels in the first urine in the morning were measured. Results: Melatonin concentrations were significantly lower (P = 0.007), while the BDI (P = 0.001) and PSQI (P = 0.001) scores were significantly higher in the patients with pruritus than in the healthy control subjects. There was an inverse correlation between melatonin levels and PSQI scores (r = -0.355, P = 0.023), and a positive correlation was detected between BDI scores and PSQI scores (r = 0.631, P = 0.001) in the pruritus group. Conclusion: Melatonin levels were found to decrease in relation to sleep quality in nocturnal pruritus patients. Low melatonin levels in these patients may be associated with sleep disorders and pruritus.

Are Salivary Gland Ultrasonography Scores Associated with Salivary Flow Rates and Oral Health-related Quality of Life in Sjögren Syndrome?

OBJECTIVE: Major salivary gland ultrasonography (SGUS) is a widely used imaging technique to evaluate salivary gland involvement in primary Sjögren syndrome (pSS). The aim of this study was to evaluate the relationship between SGUS, salivary flow rate (SFR) as an objective measure of the gland function, and oral health-related quality of life (OHRQOL) as a patient-reported outcome measure (PROM) in a pSS cohort. METHODS: Sixty-six patients with pSS were examined by SGUS according to Hocevar and Milic scoring systems. Patients with inhomogeneity/hypoechoic areas with scores ≥ 2 in parotid and submandibular glands were classified separately as "severe glandular involvement." Further, oral health, SFR, and Oral Health Impact Profile-14 (OHIP-14) for OHRQOL were assessed. RESULTS: Both total Hocevar and Milic scores were higher in 21 pSS patients with low unstimulated whole salivary flow rate (U-WSFR) than 45 pSS patients without low U-WSFR (P = 0.001 and P < 0.0001, respectively). Increased scores of homogeneity, hypoechoic areas and glandular border visibility were observed in patients with low U-WSFR (P < 0.05). Among these variables, homogeneity score was found to be an independent risk factor for low U-WSFR in pSS according to logistic regression analysis (OR 1.586, P = 0.001). Moreover, a higher OHIP-14 score was observed in severe parotid involvement compared to nonsevere cases (23.26 ± 21.19 vs 8.32 ± 13.82, P = 0.004). CONCLUSION: High Milic and Hocevar SGUS scores are associated with reduced SFR and poor OHRQOL as a PROM. The inhomogeneity component of the SGUS score is associated with low U-WSFR and is an indicator of severely affected gland function.

Immune and inflammatory gene expressions are different in Behçet's disease compared to those in Familial Mediterranean Fever.

OBJECTIVE: The immune classification of Behçet's disease (BD) is still controversial. In this study, we aimed to compare the immune/inflammatory gene expressions in BD with those in familial Mediterranean fever (FMF), an autoinflammatory disorder with innate immune activation. MATERIAL AND METHODS: CD4+ T cells and CD14+ monocytes were isolated from the peripheral blood mononuclear cells of Behçet's disease patients (n=10), FMF (n=6) patients, and healthy controls (n=4) with microbeads, and then, the mRNA was isolated. The expressions of 440 genes associated with immune and inflammatory responses were studied with a focused DNA microarray using a chemiluminescent tagging system. Changes above 1.5-fold and below 0.8-fold were accepted to be significant. RESULTS: In BD patients, in the CD4+ T-lymphocyte subset, interleukin 18 receptor accessory protein (1.7-fold), IL-7 receptor (1.9-fold), and prokineticin 2 (2.5-fold) were all increased compared to those in FMF patients, whereas chemokine (C-X3-C motif ) receptor-1 (CX3CR1) (0.7-fold) and endothelial cell growth factor-1 (0.6-fold) were decreased. In the CD14+ monocyte population, the V-fos FBJ murine osteosarcoma viral oncogene homolog (1.5-fold), Interleukin-8 (IL-8) (2.1-fold), and Tumor Necrosis Factor alpha (TNF-α) (1.8-fold) were all increased, whereas the chemokine (C-C motif ) ligand 5 (CCL5) (0.6-fold), C-C chemokine receptor type 7 (0.6-fold), and CX3CR1 (0.7-fold) were decreased, again when compared to those in FMF. Compared to healthy controls in the CD4+ T-lymphocyte population, in both BD and FMF patients, pro-platelet basic protein and CD27 had elevated expression. In BD and FMF patients, 24 and 19 genes, respectively, were downregulated, with 15 overlapping genes between both disorders. In the CD14+ monocytes population, chemokine (C-C motif ) receptor-1 (CCR1) was upregulated both in BD and FMF patients compared to that in the controls, whereas CCL5 was downregulated. CONCLUSION: Immune and inflammatory gene expressions seem to be variable in both the innate (CD14+) and adaptive (CD4+) immune responses in BD and FMF patients compared to those in controls, suggesting differences in immune regulation between the two disorders.

Caspase-cleaved fragments of cytokeratin 18 in patients with chronic hepatitis B.

BACKGROUND: During hepatocyte apoptosis, intermediate filament protein cytokeratin 18 is cleaved by caspases at Asp396 which can be specifically detected by the monoclonal antibody M30 (M30-antigen). In this study, we sought to determine whether serum M30-antigen levels can serve as a useful biomarker of liver injury in the clinical spectrum of HBV infection. METHODS: Serum M30-antigen levels were measured in inactive HBV carriers (n=54), patients with HBeAg-negative chronic hepatitis B (CHB, n=47), patients with HBeAg-positive CHB (n=42) and healthy controls (n=29). All subjects were treatment-naïve. RESULTS: There were significant differences in serum M30-antigen levels across the study groups (P<0.001; Kruskal-Wallis test). Post hoc analyses revealed that M30-antigen levels did not differ significantly between inactive HBV carriers (median 109.6 U/L) and healthy controls (median 106.1 U/L). However, both patients with HBeAg-negative (CHB, median 182.9 U/L, P<0.001) and HBeAg-positive CHB (median 158.3 U/L, P<0.001) had significantly higher levels of M30-antigen compared with inactive HBV carriers. CONCLUSIONS: Hepatocyte apoptotic activity--as reflected by serum M30-antigen levels--is increased in chronic active hepatitis B, but is not associated with the HBeAg status. In contrast, apoptosis does not appear to be a prominent feature of inactive HBV carriers.

The prevalence of the mutation in codon 249 of the P53 gene in patients with hepatocellular carcinoma (HCC) in Turkey.

UNLABELLED: Hepatocellular carcinoma (HCC) is one of the most common cancers in the worldwide. Aflotoxins, products of Aspergillus Flavus found in the high humidity environments induce HCC in humans by causing mutations in oncogenes such as codon 249 mutation of p53 in hepatocytes. In turkey, aflatoxins are found to be increased in some foods in certain areas, such as Istanbul which have high humidity. In present study we aimed to look for the prevalence of codon 249 mutation of p53 in patients with HCC, cirrhosis and chronic hepatitis B (CHB). METHODS: DNA was extracted from plasma and mutation was detected by PCR-RFLP method. RESULTS: the codon 249 mutation of p53 is found one out of 50 HCC (2%) patients. In conclusion, although codon 249 mutation of p53 gene has been found very rare but it exists showing the effect of aflatoxins in HCC patients in Turkey.

Serum levels of adipokines in patients with chronic HCV infection: relationship with steatosis and fibrosis.

BACKGROUND AND AIMS: Hepatic steatosis and fibrosis are common histological findings in patients with chronic hepatitis C virus (HCV) infection. In this study we sought to determine whether serum levels of three adipokines (leptin, adiponectin and resistin) show any biochemical correlation with hepatic steatosis and fibrosis in patients with chronic HCV infection. METHODS: We examined a total of 51 patients with chronic HCV infection (22 males and 29 females, mean BMI: 27.4+/-5kg/m(2)) and 24 healthy control subjects (10 males and 14 females, mean BMI: 23.2+/-3kg/m(2)). Liver steatosis and fibrosis were scored on biopsies. Serum levels of leptin, adiponectin and resistin were determined by ELISA. RESULTS: HCV genotypes were 1b in 41 patients (80.4%), 3a in three patients (5.9%), 2a in two patients (3.9%), 1a in two patients (3.9%), 1c in one patient (2%), and 2b in one patient (2%). Serum levels of leptin, resistin, and the leptin-to-adiponectin ratio were significantly higher in patients with chronic HCV infection than in controls. Steatosis and fibrosis were detected in 33.3% and 70.5% of chronic HCV patients, respectively. No significant association with serum adipokine levels and degree of steatosis was evident. Low serum levels of resistin were associated with the presence of fibrosis independently of potential confounders. CONCLUSIONS: Patients with chronic HCV infection display elevated levels of adipokines in their sera. Reduced concentrations of resistin may be a biochemical marker of fibrosis in this patient group.

Determination of hepatitis B genotypes in patients with chronic hepatitis B virus infection in Turkey.

BACKGROUND/AIMS: There are significant variations in the geographic distribution of hepatitis B virus genotypes throughout the world, and some genotypes are associated with different clinical outcomes. Eight genotypes of human hepatitis B virus (designated A-H) have been described to date. To determine the hepatitis B virus genotypes in Turkish patients with chronic liver disease and compare the results with clinical characteristics of the patients. METHODS: Fifty-four (pediatric: n=25 and adult: n=29) patients with chronic hepatitis B virus infection and with an hepatitis B virus DNA level above 5 pg/ml were entered into the trial. Restriction fragment length polymorphism method was used to determine hepatitis B virus genotype and their restriction fragment length polymorphism patterns. Hepatitis B virus DNA samples of 13 patients were sequenced automatically for further confirmation of restriction fragment length polymorphism results. RESULTS: Genotype D was the dominant genotype in all of our cases. Among six restriction fragment length polymorphism patterns of genotype D reported in the literature, three (D1, D2, D6) were present in our series and D2 was the most frequent restriction fragment length polymorphism pattern (81.5%). No significant differences were observed among different genotype D restriction fragment length polymorphism patterns with respect to patients' serum ALT, AST, and hepatitis B virus DNA titer, but D2 restriction fragment length polymorphism pattern was significantly more common in younger adults compared to D1 restriction fragment length polymorphism pattern. CONCLUSION: Genotype D with D2 restriction fragment length polymorphism pattern is the dominant hepatitis B virus genotype in all age groups in Turkey.