GRANULYSIN PEPTIDE AND GENE POLYMORPHISM IN THE PATHOGENESIS OF HASHIMOTO THYROIDITIS.

Background: Hashimoto thyroiditis (HT) is an autoimmune disease and the most common cause of hypothyroidism. The widespread lymphocyte infiltration in the thyroid gland and intolerance of the body against its thyroid antigens leads to the destruction of thyroid cells and impaired thyroid function. Granulysin (GNLY) is a cytolytic antimicrobial peptide that has been associated with a wide range of diseases such as various infections, cancer, transplantation, and skin problems. However, there are a few studies investigating the relationship between HT and granulysin. Aim: Our study aims to investigate whether granulysin levels and GNLY gene polymorphism contribute to the damaged immune response leading to HT. Material and Methods: 100 unrelated patients diagnosed with HT and 140 healthy individuals were included in our study. Frequencies of GNLY rs10180391 and rs7908 gene polymorphisms were determined using PCR- RFLP method and serum granulysin levels were determined using ELISA. Results: There is no statistical significance between patient and control groups in terms of genotype and allele frequencies of GNLY gene polymorphisms and serum levels of granulysin. Conclusion: In conclusion, granulysin and GNLY gene polymorphisms do not appear to relate to HT disease.

Association Between IL28B, IL29 Gene Polymorphisms and Clinical Manifestations of Behçet's Disease.

BACKGROUND: Behçet's disease (BD) is a chronic, multisystemic, inflammatory disease characterized by relapsing episodes of a wide spectrum of clinical findings. The role and mechanism of IFN-λs in BD remain unknown. The aim of this study was to investigate the relationship between IL29 and IL28B gene polymorphisms and BD or clinical manifestations. METHODS: Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, single-nucleotide polymorphisms of IL28B rs8099917 (IL28 G/T), rs12979860 (IL28 C/T) and IL29 rs30461 (IL29 T/C) were studied in 94 patients with BD and 90 healthy controls. RESULTS: Our study did not show any relationship between Behçet Disease and genotype or allele frequencies of IL28B (rs8099917, rs12979860) and IL29 (rs30461) gene polymorphisms (p > .05). We found that the TT genotype of rs12979860 (IL28 C/T) polymorphism is higher in healthy controls and patients without central nervous system (CNS) involvement compared to patients with CNS involvement (p = .014 and p = .022). CONCLUSIONS: As a result, although the relationship was found between IL28 and IL29 gene polymorphisms with some clinical manifestations of BD, it was not directly related to the predisposition of the disease. The relationship between IL-28 and IL-29 which act as regulators in inflammatory processes, with Behçet disease, needs to be investigated in further studies.

Cerebellar cognitive-affective syndrome preceding ataxia associated with complex extrapyramidal features in a Turkish SCA48 family.

SCA48 is a novel spinocerebellar ataxia (SCA) originally and recently characterized by prominent cerebellar cognitive-affective syndrome (CCAS) and late-onset ataxia caused by mutations on the STUB1 gene. Here, we report the first SCA48 case from Turkey with novel clinical features and diffusion tensor imaging (DTI) findings, used for the first time to evaluate a SCA48 patient. A 65-year-old female patient with slowly progressive cerebellar ataxia, cognitive impairment, behavioral changes, and a vertical family history was evaluated. Following the exclusion of repeat expansion ataxias, whole exome sequencing (WES) was performed. Brain magnetic resonance imaging (MRI), including DTI, and single-photon emission computed tomography (SPECT) were used to study the primarily affected tracts and regions. WES revealed the previously reported heterozygous truncating mutation in ubiquitin ligase domain of STUB1 (ENST00000219548:c.823_824delCT, ENSP00000219548:p.L275Dfs*16) leading to a frameshift. Patient's cognitive status was compatible with CCAS. Novel clinical features different from the original report include later onset chorea, dystonia, general slowness of movements, apraxia, and palilalia, some of which have been recently reported in two families with different STUB1 mutations. CCAS is a prominent and often early feature of SCA48 which may be followed years after the onset of the disease by other complex neurological signs and symptoms. DTI may be helpful for demonstrating the cerebello-frontal tracts, involved in CCAS-associated SCA48, the differential diagnosis of which may be challenging especially in its early years.

Cytokine gene polymorphism in denture stomatitis patients: A clinical study.

OBJECTIVE: This clinical study investigated the association between cytokine gene polymorphism and Candida growth in denture stomatitis (DS) patients. SUBJECTS AND METHODS: Saliva and blood samples of 160 complete denture wearers (80 healthy controls and 80 with DS) were collected for mycological and gene polymorphism testing, respectively. Salivary Candida growth and TNF-α, TGF-ß, IL-6, and IL-10 genotypes were investigated. Data were analyzed using Student's t test, Mann-Whitney U test, chi-square analysis, and continuity (yates) correction tests (p < .05). RESULTS: Candida albicans colony counts in saliva were significantly higher in the DS group and in the TNF-α GG genotype (p < .05). TGF-ß TC GG and TGF-ß CC GG haplotypes were significantly higher in DS and control groups, respectively (p < .05). C. albicans colony counts were significantly higher in control group in the TGF-ß TC GG haplotype (p < .05). Candida glabrata colony counts were significantly higher in the DS group than the control group in IL-6 GG genotype (p < .05). The difference between DS types in IL-6 genotypes was significant with lower expression level in DS type 3 than DS type 1 and also type 2 (p ≤ .01). CONCLUSION: The significant differences in some genotypes of the TNF-α, TGF-ß, and IL-6 in DS patients are promising in understanding the host defense in DS.

Selenoproteins are involved in antioxidant defense systems in thalassemia.

Thalassemia major (TM) is a hereditary blood disease that affects the production of hemoglobin, resulting in severe anemia. Iron overload because of repeated blood transfusion and increased intestinal iron absorption and hemolysis are the major causes of increased oxidative stress in these patients. Growth and maturational delay, cardiomyopathy, endocrinopathies, and osteoporosis are the complications of thalassemia, secondary to anemia and iron overload. The human body has endogenous defense mechanisms to help protect against free radical-induced cell damage. Selenoproteins are important enzymes involved in these antioxidant defense mechanisms. In thalassemia patients, selenoproteins are essential because of their potential defense against oxidative damage due to iron overload and hemolysis. The aim of this review is to provide an overview of data regarding selenoproteins including glutathione peroxidase, thioredoxin reductase and iodothyronine deiodinases in TM patients. We also underline some complications of thalassemia that may be associated with selenoproteins.

The antifungal activity and cytotoxicity of silver containing denture base material.

OBJECTIVE: Denture base materials are susceptible to fungal adhesion, which is an important etiological issue in the pathogenesis of denture stomatitis. The purpose of this in vitro study was to evaluate the antifungal activity and cytotoxicity of denture base material containing silver microparticles. MATERIALS AND METHODS: The polymethyl methacrylate (PMMA) denture base material was used, and silver microparticles were added to the polymer powder in different concentrations by volume (0%, 0.25%, 0.5%, and 1%). Their antifungal activity against Candida albicans was assessed in terms of colony-forming units. PMMA disc specimens containing silver microparticles were eluted with culture medium for 1, 2, and 5 days. The cytotoxicity of the eluates to cultured L929 mouse fibroblast cells was evaluated using a real-time cell analysis (RTCA) system and the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. RESULTS: The antifungal effect against C. albicans increased with the percentage of silver microparticles (P < 0.05). For both tests, both RTCA and the MTT assay, no time- or silver-dependent cytotoxicity of PMMA denture base material containing silver microparticles was observed. CONCLUSIONS: PMMA denture base material containing silver microparticles have antifungal activity and no cytotoxic effect.

Thalassemia major patients using iron chelators showed a reduced plasma thioredoxin level and reduced thioredoxin reductase activity, despite elevated oxidative stress.

In the present study, we aimed to investigate plasma levels of peroxiredoxin 2 (Prx2) and thioredoxin 1 (Trx1), and the activity of thioredoxin reductase (TrxR), in thalassemia major (TM) patients living in the Antalya region, Turkey. The patients were divided into three groups, according to chelators - the deferoxamine group (DFO, n = 20), the deferasirox group (DFX, n = 20), and the deferiprone group (DFP, n = 20), to compare any possible effect of chelators on antioxidative and oxidative stress parameters. A control group (n = 20) was selected from healthy volunteers. The activities of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and TrxR, as well as the concentrations of Prx2, Trx1, glucose-6-phosphate dehydrogenase (G-6-PD), reduced glutathione (GSH), hydrogen peroxide (H2O2), and malondialdehyde (MDA) were measured in the plasma samples of TM patients and the controls. The activity of CAT and the levels of H2O2 and MDA in the TM patients were significantly higher than those in the controls, while the levels of GPx, Trx1, TrxR, and GSH were lower. The concentrations of ferritin, GSH, H2O2, and MDA, as well as the activities of GR, CAT and TrxR, showed significant differences among the chelator groups. Although TrxR activity showed an increase in TM patients due to an elevated iron overload, both TrxR activity and Trx1 level were lower in the patient groups compared with the cases in the control group. As a result, because Trx1 level and TrxR activity were measured at a low level in the patients, increasing the levels of Trx1 and TrxR in TM patients will be a target of future treatment.

Does systemic clarithromycin therapy have an inhibitory effect on tympanosclerosis? An experimental animal study.

OBJECTIVE: To demonstrate the inhibitory effects of clarithromycin on in vitro tympanosclerosis. METHOD: Twenty-eight rats were divided into three groups: a clarithromycin group, a non-clarithromycin group and a negative control group. Those in the first two groups were injected with Streptococcus pneumoniae following a myringotomy, and tympanosclerosis was experimentally induced. Oral clarithromycin therapy was administered in the clarithromycin group. The other groups received no medical treatment. RESULTS: All eardrums in the clarithromycin and non-clarithromycin groups developed myringosclerosis, but there was only one eardrum, in the clarithromycin group, with very severe myringosclerosis. In the clarithromycin group, 11 ears showed no inflammation and there were no ears with severe inflammation. In the non-clarithromycin group, there were 11 ears with severe inflammation. The mean eardrum thickness in the clarithromycin group was 20.93 µm and in the non-clarithromycin group it was 42.71 µm. CONCLUSION: Acute otitis media and myringotomies induced tympanosclerosis, but clarithromycin reduced the severity of tympanosclerosis.

Mucopolysaccharidosis: Otolaryngologic findings, obstructive sleep apnea and accumulation of glucosaminoglycans in lymphatic tissue of the upper airway.

OBJECTIVE: The aim of this study is to evaluate otolaryngologic problems (upper airway obstruction, obstructive sleep apnea, restriction of mouth opening, middle ear effusion, hearing and breathing problems) and their treatments on mucopolysaccharidoses (MPS) patients and to investigate accumulation of glucosaminoglycans (GAG) in the upper airway biochemically and pathologically. METHODS: 76 MPS patients were evaluated. Forty-two MPS patients underwent polysomnography (PSG) for obstructive sleep apnea (OSA). Pre- and postoperative PSG results of 18 patients were compared. The success and complications of treatments for OSA in MPS were evaluated. Biochemical and histopathological accumulation of GAG in tonsil and adenoid tissue and middle ear effusion were analyzed and compared with the control group. RESULTS: Forty patients out of 42 tested with PSG had OSA (95%). Adenoid grade, Mallampati grade, restricted mouth opening, rate of difficult intubation were significantly different among MPS subtypes. MPS types III and IV had significantly lower Mallampati scores; type VI had significantly worse mouth opening; and type III had significantly better mouth opening and higher rate of easy intubation when compared to other MPS types. There was no significant difference between MPS subtypes according to tonsil grade, adenoid grade, rate of otitis media with effusion and OSA severity. Statistically significant difference was found between GAG accumulation in adenoid tissue and middle ear effusion of MPS and control group (p<0.05). However, GAG accumulation in tonsil was not significantly different between MPS and control group. There was a statistically significant improvement in postop Apnea-Hypopnea Index (AHI) compared to preop AHI (p<0.05). CONCLUSIONS: Most MPS patients have airway obstruction and OSA due to adenotonsillar hypertrophy. Most of these children benefit from adenotonsillectomy, after which OSA significantly improves. They experience high recurrence rate after adenoidectomy; though this is not clinically problematic. They also suffer from conductive hearing loss due to OME, which has to be treated with ventilation tube insertion. However, such operations are usually complicated by difficult endotracheal intubation and restricted mouth opening. Sometimes tracheotomy may be necessary. Tracheotomy is also highly complicated in MPS patients. Significant accumulation of GAG in middle ear fluid and adenoid tissue is present; however, GAG appears not to accumulate in tonsillar tissue.

Comparing two deep brain stimulation leads to one in refractory tremor.

A sizable proportion of medication refractory tremor patients may not respond satisfactorily to deep brain stimulation (DBS) to the ventralis intermedialis nucleus of the thalamus (Vim). Implanting a second DBS lead ipsilaterally to the first one is thought to be beneficial based on scarce and unblinded data. This article aims to report a double-blind assessment of five patients with a second DBS lead for refractory tremor. Tremor was assessed by two blinded movement disorder specialists using a videotaped tremor rating scale (TRS) evaluation of each patient in four conditions: both leads OFF, Vim ON/2nd lead OFF, Vim OFF/2nd lead ON, and both leads ON. Paired t-test was used to determine if double stimulation was different than stimulation of Vim alone or than stimulation of the 2nd lead alone. Each hypothesis was tested with the total TRS as well as the contralateral upper limb score and the contralateral hemibody score. Tremor was secondary to multiple sclerosis in two patients and to essential tremor in three. The second lead was in the ventralis oralis anterior nucleus of the thalamus in three patients and in the prelemniscal radiations in two patients. There was improvement with the 2nd lead or double ON in four patients compared to stimulating the Vim alone. However, when taken as a group, the results were not statistically significant. These results were constant with the three different ratings used. The lack of overall statistically significant improvement might be secondary to the small size and the heterogeneity of our sample. However, four patients had 17 to 60 % tremor improvement after the implant of the 2nd lead on double-blinded evaluation. We report objective improvement after addition of a second DBS lead in patients with tremor refractory to Vim DBS. Larger studies are needed to confirm these results.

Resveratrol ameliorates methotrexate-induced hepatotoxicity in rats via inhibition of lipid peroxidation.

Hepatotoxicity is one of the major complications of methotrexate (MTX) therapy. This study was carried out to evaluate the possible protective effect of resveratrol (trans-3,5,4'-trihydroxystilbene, RVT) against MTX-induced hepatotoxicity. Rats were randomly divided into four groups as control, MTX treated (7 mg/kg/day, intraperitoneally (i.p.), once daily for 3 consecutive days), MTX + RVT treated (20 mg/kg/day, i.p.), and RVT treated. First dose of RVT was administrated 3 days before the MTX injection and continued for 3 days. Histopathology of liver was evaluated by light microscopy. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were used as biochemical markers of MTX-induced hepatic injury. The levels of thiobarbituric acid reactive substances (TBARS, a marker of lipid peroxidation) and activities of hepatic antioxidant enzymes such as catalase (CAT) and glutathione-S-transferase (GST) were used to analyze the oxidative stress-mediated lipid peroxidation in liver sections. Our results showed that MTX administration significantly increased ALT, ASP, and ALP levels. TBARS, CAT, and GST levels were also markedly increased in liver after MTX administration. RVT treatment significantly prevented MTX-induced hepatotoxicity, as indicated by AST, ALT, and ALP levels and liver histopathology. Moreover, administration of RVT significantly decreased the elevated levels of TBARS and activities of CAT and GST in the liver compared to MTX-treated group. These results revealed that RVT may have a protective effect against MTX-induced hepatotoxicity by inhibiting oxidative stress-mediated lipid peroxidation. Consequently, RVT treatment might be a promising strategy against MTX-induced hepatotoxicity.

Frequency of juvenile fibromyalgia syndrome in children with familial Mediterranean fever: effects on depression and quality of life.

OBJECTIVES: To determine the prevalence of juvenile fibromyalgia syndrome (JFMS) in children with familial Mediterranean fever (FMF) and to evaluate quality of life (QoL) and depression. METHODS: Ninety-one FMF patients (M/F: 44/47) who fulfilled the Livneh criteria and 60 healthy children (M/F: 27/33) were enrolled in the study. Yunus and Masi's criteria were used for diagnosis of JFMS. Depression was assessed with Children's Depression Inventory (CDI) and QoL was evaluated with child and parent reports of Paediatric Quality of Life Inventory 4.0 (PedsQL™). RESULTS: While 20 (21.9%) of 91 FMF patients fulfilled JFMS criteria, 2 (3.3%) of the control group met the diagnostic criteria of JFMS (p=0.002). PedsQL™ scores (child self-report and parent-report) of the FMF patients were significantly lower and the depression scores were significantly higher than the healthy controls (p<0.001 for all). When the FMF patients were assigned to two groups as FMF with or without JFMS, patients with JFMS were found to have a higher depression score (p=0.007) and child and parent reports of PedsQL™ 4.0 were lower in the children with JFMS than in the patients without JFMS (p=0.001, p=0.003, respectively). CONCLUSIONS: We have determined that JFMS frequency was higher in children with FMF and patients with FMF and JFMS had a poor QoL and were more susceptible to depression. FMF patients with widespread and persistent pain should be evaluated for JFMS in order to avoid unnecessary investigations and inappropriate treatment.

Floating-Harbor syndrome: case report.

Floating-Harbor syndrome is a rare disorder which is clinically characterized by short stature, retarded speech development, delayed bone ages, triangular face, bulbous nose and thin lips. We described two cases with Floating-Harbor syndrome and briefly reviewed the relevant literature.

Papillon-lefevre syndrome with congenital hepatic fibrosis.

Papillon Lefevre syndrome (PLS) is a rare autosomal recessive disorder, which is characterized by palmar-plantar hyperkeratosis, periodontitis, and premature loss of dentition. We report a 16 years old girl with PLS. The patient presented at 08 years of age with complaints of corn on the feet and hands, and failure to thrive. On examination, her upper primarily canines were loose, she had severe periodontitis, eruption of permanent teeth, diffuse eritematous and hyperkeratotic palms and soles that suggested the syndrome. During the follow-up, the patient was diagnosed to have congenital hepatic fibrosis (CHF) when she was 16 years old, while she was being investigated for the etiology of her splenomegaly and pancytopenia. We report a patient with PLS associated with CHF, an association that has not been previously described. Abbreviations-HbsAg: Hepatitis B virus surface antigen, Anti Hbs: Antibody against Hepatitis B surface antigen, Anti Hbc IgM: Antibody against Hepatitis B cor antigen immunglobulin M, Anti dsDNA: Antibody against double stranded deoksiribonucleic acid, Anti HCV: Antibody against Hepatit C virus, Anti HIV: Antibody against human immun deficiency virus, AST: Aspartat amino transferase, ALT: Alanin amino transferase, Gamma-GT: Gamma glutamyl transferase, LDH: Lactate dehydrogenase & MRI: Magnetic resonance imaging.

Lack of platelet activation reflected by circulating soluble glycoprotein V in pre-eclampsia.

Pre-eclampsia (PE) is a human pregnancy-specific disorder of unknown aetiology. Although the quantitative relationship between platelet aggregation in PE is not clearly defined yet, we aimed to investigate the possible relationship between PE and platelet glycoprotein V (GPV), which is an integral platelet membrane protein involved in the function of the GPIb-V-IX receptor. Fifty patients with PE and 37 normotensive pregnant women (controls) were enrolled in this study. Fasting blood samples were collected and soluble GPV (sGPV) levels were determined using a commercially available enzyme immunoassay. No statistically significant difference in sGPV was found between PE patients and control subjects. There was no correlation between sGPV and platelet counts or between pregnancy duration and platelet counts. Further clinical and experimental investigations are needed to elucidate the pathological processes involved in the development of PE in complicated pregnancies.

Audiologic findings in children with biotinidase deficiency in Turkey.

OBJECTIVE: Biotinidase deficiency is an autosomal recessively inherited disorder characterized by neurological and cutaneous features, including sensorineural hearing loss. Although many features of the disorder are reversible following treatment with biotin, the hearing loss appears to be irreversible. In the present study, hearing status of patients with biotinidase deficiency is characterized in a Turkish population. METHODS: Subjective and objective audiologic tests were performed on 20 children with profound biotinidase deficiency. RESULTS: Sensorineural hearing loss occurs in approximately 55% of the children with biotinidase deficiency. The hearing loss varies in severity from mild to profound hearing loss. In children diagnosed immediately after birth because they had an older sibling with the disorder, statistically significant differences were found between ABR results and age of diagnosis (p<0.05). Greater prolongation in ABR latencies were observed in the late-diagnosed children compared to that in the early-diagnosed children (p<0.05). CONCLUSION: Early diagnosis is important to prevent peripheral and central hearing loss. Children with biotinidase deficiency who have hearing loss are likely at increased risk for having speech and language problems. If hearing aids do not provide sufficient amplification, cochlear implantation may be indicated in these children. Therefore, it is important to test the hearing thresholds of these children with hearing aids and evaluate their language development.