Fate and function of hepatitis-C-virus-specific T-cells during peginterferon-alpha2b therapy for acute hepatitis C

BACKGROUND: Strong hepatitis C virus (HCV)-specific T-cell responses are associated with spontaneous clearance of acute hepatitis C. However, recent studies described a decline in HCV-specific CD8+ T-cells during interferon treatment, suggesting that the success of acute HCV therapy might be independent of adaptive immunity. METHODS: T-cell responses of eight human leukocyte antigen (HLA)-A2-positive, acutely infected patients treated with peginterferon-alpha2b were studied by ELISPOT and proliferation assays and flow cytometry analysis using HCV-specific tetramers. RESULTS: HCV-specific T-cells predominately declined during therapy. However, diverse patterns of CD4+ and CD8+ T-cell kinetics were observed. In patients with sustained virological response chemokine receptor 3 (CXCR-3) expression of HCV-specific CD8+ T-cells was upregulated, indicating homing to the liver. Low levels of T-cells remained detectable throughout treatment and follow up. In contrast, T-cells of a relapse patient did not upregulate CXCR-3 but displayed a higher staining for annexin-V, followed by a complete loss of peripheral virus-specific CD8+ T-cells by week 12. CONCLUSIONS: Kinetics of HCV-specific T-cell responses are heterogeneous in interferon-treated patients with acute hepatitis C. The decline of T-cells might be a consequence of both apoptosis and homing. The balance between cell death and regulation of chemokine receptors might lead to different long-term outcomes.     

Psychiatric comorbidity in medication overuse headache patients with pre-existing headache type of episodic tension-type headache.

BACKGROUND: Medication overuse headache (MOH) mostly evolves from migraine and episodic tension-type headache (ETTH). Chronic tension-type headache (CTTH) is another headache type that evolves over time from ETTH. It is well known that psychiatric comorbidity is high in MOH patients. AIM: To investigate the frequency of psychiatric comorbidity, and the intensity of depression and anxiety in MOH patients evolving from ETTH and to compare results with CTTH patients and MOH patients evolving from migraine. METHODS: Twenty-eight CTTH (Group C) and 89 MOH patients were included into the study. MOH patients were divided into two groups according to their pre-existing headache types: MOH patients with pre-existing ETTH (Group E, n = 31), and with pre-existing migraine (Group M, n = 58). All patients were interviewed with a psychiatrist and SCID-CV and SCID-II were applied. Beck Anxiety Inventory and Beck Depression Inventory scales were also performed. RESULTS: Eleven patients (39.3%) in Group C, 21 patients (67.7%) in Group E, and 31 patients (53.7%) in Group M were diagnosed to have comorbid psychiatric disorders. The psychiatric comorbidity was found significantly higher in Group E than Group C. In Group E, mood disorders were found significantly higher, but the difference between the two groups with regard to anxiety disorders was insignificant. Mean depression scores were significantly higher in Group E than Group C. The mostly diagnosed type was obsessive-compulsive personality disorder in all the three groups, and was statistically significant in Group M than Group C. CONCLUSION: Psychiatric comorbidity in MOH patients with pre-existing ETTH is common as in those with pre-existing migraine headache and MOH with regard to developing psychiatric disorders should be interpreted as a risk factor in chronic daily headache patients.     

Age-specific mumps seroprevalence of an unvaccinated population of adolescents in Ankara, Turkey

This study aimed to detect the age-specific mumps seroprevalence of an unvaccinated population of adolescents in Ankara, Turkey and to compare the prevaccination epidemiology of mumps with those of some other countries. Four hundred and forty adolescents (227 females, 213 males) aged 9 - 16 years who were admitted to the Adolescent Unit were included in this study. For each participant, a questionnaire was completed and mumps-specific IgG antibodies were screened quantitatively by enzyme-linked fluorescent assay. Of the 440 patients screened for mumps antibodies, 48 (10.9%) were seronegative. Mumps seronegativity according to sex and age groups were 13.6, 9.9, and 10.4% in females and 18, 10.2, and 6.2% in males in the age groups of 9 - 10, 11 - 13, and 14 - 16, respectively. Mumps immunization models similar to those of European countries might be acceptable for Turkey, but since a low vaccination coverage may shift mumps infection to older ages, mumps immunization of adolescents is important until a national mumps vaccination program with a high coverage could be sustained. The routine health supervision visit at ages 11 to 12 years is an ideal time to immunize unvaccinated adolescents.     

The fruit extract of three strawberry cultivars prevents lipid peroxidation and protects the unsaturated fatty acids in the Fenton reagent environment

In this study, we detected the flavonoid ingredients of three different varieties of strawberry (Fragaria ananassa Duch cultivar Camarosa, Selva and Dorit) grown in Elazig, and we researched on their effects on the radicals DPPH√ and OH√. It was detected that in the manipulation of 50-100 μl extract, it was efficient to turn the DPPH√ radical over 85% to DPPH√ OH√ form. In in vitro environment in which hydrogen peroxide and Fenton reagent were used, it was also detected that the capacity of interception of lipid peroxidation is high. When the level of Malondialdehyde (MDA)-2-thiobarbituric acid was compared with that of the Fenton R group, the level was shown to be decreased in the groups in which a quite distinct level of the extract of strawberry fruit was given (p < 0.001). Depending on the decrease in LPO formation, the amounts of oleic acid and linoleic acid that were added to the reaction environment were preserved in in vitro environment in which the extract of strawberry fruit was added (p < 0.01, p < 0.05 and p < 0.01).Consequently, it has been confirmed that the strawberry fruit that has a scavenging effect against the radicals prevents that lipid peroxidation in in vitro environment.     

Role of Capsaicin-Sensitive Nerves in Gastric and Hepatic Injury Induced by Cold-Restraint Stress

The role of capsaicin-sensitive afferent fibers on cold-restraint stress-induced gastric and hepatic injury was examined at the macroscopic and ultrastructural levels. Wistar albino rats were treated with capsaicin either locally (intragastric, perivagal, and periceliac) or systemically (neonatal, intraperitoneal). Perineural and neonatal treatment with capsaicin was used to denervate afferent fibers, while intragastric capsaicin treatment would have activated mucosal afferent fibers just before the stress exposure. Capsaicin decreased significantly the formation of macroscopic gastric lesions caused by stress in all treatment groups. At the electron microscopic level, however, denervation of vagal afferent fibers with capsaicin was most effective in prevention of cellular injury in gastric mucosa. In the liver, systemic denervation of afferent fibers completely inhibited stress-induced cellular damage, while denervation of afferent fibers in vagus and splanchnic nerve was partially effective. Central neural pathways sensitive to capsaicin may mediate formation of both gastric and hepatic injury resulting from stress.     

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.     

The prevalence of manifest and latent celiac disease in type 1 diabetes mellitus.

BACKGROUND/AIMS: Celiac disease and type 1 diabetes mellitus are both autoimmune diseases which have a common genetic predisposition. The aim of this study was to determine the prevalence of manifest and latent celiac disease in type 1 diabetic patients. METHODS: Anti-endomysium IgA was tested by indirect immunofluorescence using sections of human umbilical cord for screening in 100 adult patients with type 1 diabetes mellitus and in 80 age and sex matched controls with no known disease. Distal duodenal biopsy, human leukocyte antigen typing, urinary D-xylose excretion test, stool analysis, biochemistry profile, blood counts, serum ferritin level and small intestinal radiography were performed in anti-endomysium IgA positive cases. Small bowel biopsy specimens consistent with celiac disease were defined as manifest celiac disease, while positive antiendomysium IgA and normal intestinal histology with the presence of human leukocyte antigen class II antigens consistent with the disease were defined as latent celiac disease. RESULTS: Anti-endomysium IgA was positive in eight diabetic patients, while it was negative in all controls. Celiac disease was found in a total of six (6%) patients, four with manifest and two with latent disease. Only one patient had symptoms. CONCLUSIONS: The prevalence of celiac disease is increased in patients with type 1 diabetes mellitus. Since many patients may be asymptomatic, it is suggested that all diabetic patients should be screened for this disease.     

Arthritis in children with familial Mediterranean fever

The clinical spectrum of arthritis in 124 children with well-documented familial Mediterranean fever (FMF) was investigated in a retrospective study. Seven mutations in the FMF gene (MEFV) were also screened using restriction enzyme digestion and amplification refractory mutation system techniques in 110 patients. Mean age at the onset of FMF arthritis was 5.93+/-3.50 years, 75% of the patients being under 10 years of age. Arthritis in the lower extremities, upper extremities, and small joints of the hands and feet was noted in 122 (98%), 17 (14%), and 15 (12%) patients, respectively. Three patients had atypical arthritis involving temporomandibular, sacroiliac, and sternoclavicular joints. Although most of the arthritic attacks resolved within a few weeks, 12 (10%) patients developed protracted arthritis persisting for months. Amyloidosis was demonstrated in 17 (14%) patients who had not received colchicine treatment. Mutation analysis confirmed the diagnosis of FMF in 77 (62%) children. The clinical presentations of arthritis in FMF may be an important source of diagnostic confusion in FMF. Mutation analysis is of value in situations of diagnostic uncertainty.     

Cold-restraint- and TRH-induced ulcer models demonstrate different biochemical and morphological manifestations in gastric and hepatic tissues in rats

In the present study, two ulcer models—central thyrotropin-releasing hormone (TRH) injection and cold-restraint stress (CRS) application—were compared. Animals were treated either with salmon calcitonin (sCT) or saline intracerebroventricularly (ICV) before CRS exposure or ICV TRH injection. In both models, besides ultrastructural properties, ulcer indexes and lipid peroxidation (LP) and glutathione (GSH) levels of liver and stomach were determined. While TRH treatment did not affect GSH and LP levels of the stomach and led to a slight decrease in hepatic GSH levels. CRS induced a marked reduction in gastric and hepatic GSH and an increase in LP levels of both tissues. sCT pretreatment prevented the reduction of gastric and hepatic GSH levels and morphological damage of both tissues in the CRS group. However, the same treatment did not prevent the TRH-induced reduction of hepatic GSH levels and, interestingly, it worsened the ultrastructural disturbances in the liver. Although sCT prevented macroscopic ulcer formation in both models, it did not totally reverse the microscopic effects of TRH.