A promising biomarker to distinguish benign and malignant renal tumors: ELABELA.

AIM: The aim of this study was to investigate ELABELA (ELA) expression in benign and malignant renal tissues and expression differences in different nuclear grades of clear cell carcinomas. MATERIALS AND METHODS: Patients that underwent surgery due to renal masses between the years of 2007 and 2017 were used. Control renal tissues (n = 23), papillary RCC (n = 23), clear cell RCC (CcRCC) [Fuhrman Grade1 (n = 23), Fuhrman Grade2 (n = 23), Fuhrman Grade3 (n = 23), Fuhrman Grade4 (n = 23)], and chromophobe RCC (n = 23) were included to the study. The Independent samples t-test was used for 2-point intergroup assessments and the one-way analysis of variance and posthoctukey test was used for the others. Values of P < 0.05 were considered statistically significant. RESULTS: ELA immunoreactivity was observed in proximal and distal tubules in the kidney, but not in glomeruli in control tissues. When compared with control kidney tissue, a statistically significant increase was observed in ELA immunoreactivity in renal oncocytoma. In the chromophobe RCC, ELA immunoreactivity was significantly lower than control kidney tissue, whereas papillary RCC did not show ELA immunoreactivity. However, compared with control kidney tissue, ELA immunoreactivity was not observed in Fuhrman Grade 1 and Grade 2 CcRCC. Also, there was a significant decrease at Fuhrman Grade 3 and Grade 4 CcRCC compared with control kidney tissues. In the statistical analysis of ELA immunoreactivity among the Fuhrman nuclear grades of CcRCCs, The ELA immunoreactivity was higher at Grade 4 CcRCC than Grade 1, Grade 2, and Grade 3. CONCLUSION: ELA is a usefull molecule to differentiate benign and malign renal tumors. But further broad and comprehensive studies are needed to investigate cellular and molecular mechanisms of ELAs on malign transformation.

LPS-induced Src family kinases activity mediates IL-10 production through activation of STAT3 in peripheral blood mononuclear cells of patients with Behçet's Disease.

Behçet's disease (BD) is achronic inflammatory disorder characterized by recurrent oral and genital ulcers, uveitis and skin lesions. Although,the pathogenesis of BD remains poorly understood, excessive or dysregulatedcytokine production including IL-10 is associated with BD. Revealing the key molecular mechanism by which IL-10 expression is regulated is crucial to understanding the pathogenesis of BD. The aim of this study was to investigate whether Src family kinases (SFKs) are upstream mediators of STAT3/IL-10 pathway in peripheral blood mono nuclear cells(PBMCs) of active BD patients.Twenty active BD patients and twenty healthy subjects used as control were included in the study. PBMCs were isolated from total blood by density gradient centrifugation.Western blot and ELISA methods were applied to analyzelipopolysaccharide (LPS)-induced SFKs/STAT3/IL10 signaling pathway in BD.Inhibition of SFKs activity suppressed LPS-induced IL-10 production in PBMCs fromboth controls and active BD patients. Similarly, blockage of STAT3 activation abrogated LPS-induced IL-10 production. However, LPS-induced STAT3 activation required for IL-10 production was found to be dependent on SFKs activity as LPS-induced STAT3 phosphorylation was reduced by the inhibition of SFKs activity in PBMCs of active BD patients.SFKs activity is essential for LPS-induced STAT3/IL-10 pathway in PBMCs of active BD patients. Manipulation of the SFKs activity may offer a novel therapeutic approach for BD.

Does hepcidin play a role in the pathogenesis of aphthae in Behçet's disease and recurrent aphthous stomatitis?

BACKGROUND: Aphthae constitute one of the major signs in Behçet's disease (BD) and recurrent aphthous stomatitis (RAS). No scientific study has yet explored the relationship of hepcidins, which have antimicrobial effects, with RAS and BD. OBJECTIVES: In this study, we aimed to evaluate by immunohistochemistry whether hepcidin is synthesized by the salivary glands and to measure levels of prohepcidin and hepcidin (an antibacterial peptide) in the serum and saliva of patients with BD and RAS. METHODS: The study included 25 BD patients and 30 RAS patients, as well as a control group comprising 25 healthy individuals. Serum and saliva samples were collected at the same time from all subjects. Levels of prohepcidin and hepcidin were measured by ELISA. The presence of hepcidin in salivary glands was assessed by immunohistochemistry. RESULTS: Hepcidin was localized in the striated ducts of the sublingual and parotid glands. Saliva prohepcidin and hepcidin levels were correlated with blood levels. Saliva prohepcidin levels were found to be lower in RAS patients than in BD patients and healthy controls (P < 0.001 and P = 0.007 respectively). In addition, RAS patients had lower saliva hepcidin levels than did the control group (P = 0.03). CONCLUSIONS: The lower serum and saliva prohepcidin and hepcidin concentrations found in RAS and BD patients indicate that hepcidin may be involved in the aetiopathogenesis of these diseases. Because it can be obtained non-invasively and easily, saliva may provide a useful alternative to serum in quantifying prohepcidin and hepcidin concentrations.

Three years prospective investigation of pituitary functions following subarachnoid haemorrhage.

Subarachnoid haemorrhage (SAH) is known to be related to pituitary dysfuntion in retrospective and short-term prospective studies. We aimed to investigate pituitary functions in patients with SAH in longer follow-up periods to demonstrate if pituitary hormone deficiencies recover, persist or new hormone deficiencies occur. Twenty patients with SAH, who were followed up for 3 years, were included in the present study. Patients were evaluated with basal hormone levels and glucagon stimulation test (GST).Serum basal cortisol and adrenocorticotropic hormone (ACTH) levels were found to be significantly elevated at 3rd year of SAH compared to 1st year. Other basal hormone levels at 3rd year did not show a significant change from the levels found at 1st year. One of the patients had ACTH deficiency at 1st year of SAH and recovered at 3rd year. Growth hormone (GH) deficiency, according to GST,was diagnosed in 4 patients. One patient with GH deficiency at first year was still deficient, 3 of them recovered and 3 patients were found to have new-onset GH deficiency 3 years after SAH. SAH is associated with anterior pituitary dysfunction and GH is the most frequently found deficient hormone in the patients. Although one year after SAH seems to be an appropriate time for the evaluation of pituitary functions, further follow-up may be required at least in some cases due to recovered and new-onset hormone deficiencies at 3rd year of SAH.

Mycophenolate mofetil and daclizumab targeting T lymphocytes in bleomycin-induced experimental scleroderma.

BACKGROUND: T lymphocytes induce the transformation of fibroblasts into myofibroblasts, the main mediators of fibrogenesis. The inosine 5'-monophosphate dehydrogenase inhibitor mycophenolate mofetil (MMF) and the anti-CD25 monoclonal antibody daclizumab (DCZ) have been reported to suppress the proliferation of T lymphocytes. AIM: To evaluate the preventive effects of MMF and DCZ in early stages of bleomycin (BLM)-induced scleroderma. METHODS: This study involved five groups of Balb/c mice (n = 10 per group). Mice in four of the groups were injected subcutaneously (SC) with BLM [100 µg/day in 100 µL phosphate-buffered saline (PBS)] for 4 weeks; the remaining (control) group received only 100 µL PBS. Three of the BLM-treated groups also received either intraperitoneal MMF 50 or 150 mg/kg/day, or SC DCZ 100 µg/week. At the end of the fourth week, all mice were killed, and blood and tissue samples were obtained for further analysis. RESULTS: In the BLM-treated group, increases were seen in inflammatory-cell infiltration, α-smooth muscle actin-positive (α-SMA+) fibroblastic cell count, tissue hydroxyproline content, and dermal thickness. Dermal fibrosis was histopathologically prominent. In BLM-treated mice also given MMF or DCZ, inflammatory-cell infiltration, tissue hydroxyproline content and dermal thickness were decreased. In the MMF groups, decreases were also noted in α-SMA+ fibroblastic cell count. CONCLUSION: In this BLM-induced dermal fibrosis model, MMF and DCZ treatments prevented the development of dermal fibrosis. Further studies are needed to evaluate whether targeting T lymphocytes is effective in resolving pre-existing fibrosis in human scleroderma.

Can renalase be a novel candidate biomarker for distinguishing renal tumors?

Renalase (RNLS) is synthesized mainly in renal tissues. The function of RNLS in cancerous renal tissues has not been investigated. We investigated the synthesis of RNLS in chromophobe renal cell carcinoma, papillary renal cell carcinoma and clear cell renal cell carcinoma with Fuhrman grades (FG): FG1, nucleoli are absent or inconspicuous and basophilic; FG2, nucleoli are conspicuous and eosinophilic and visible but not prominent; FG3, nucleoli are conspicuous and eosinophilic; FG4, extreme nuclear pleomorphism, multinucleate giant cells, and/or rhabdoid and/or sarcomatoid differentiation. We used 90 tissue samples including 15 healthy controls, 15 chromophobe renal cell carcinoma tissues and 10 papillary renal cell carcinoma renal tissues: 12 FG1, 14 FG 2, 14 FG 3 and 10 FG4. RNLS in the tissue samples was measured using enzyme linked immunosorbent assay and immunostaining of RNLS in these tissues. RNLS was significantly greater in the chromophobe renal cell carcinoma and papillary renal cell carcinoma tissues than the control. The least amount of RNLS was found in the renal tissues of clear cell renal cell carcinoma FG1; the amount of RNLS increased as the FG grades increased. Because RNLS increased significantly in renal tissues due to cancer, except for clear cell renal cell carcinoma FG1, RNLS may be useful biomarker for distinguishing grades of renal cancer. Because RNLS increases cell survival, anti-RNLS preparations may be useful for treating cancer in the future.

Effects of iloprost and sildenafil treatment on elabela, apelin-13, nitric oxide, and total antioxidant and total oxidant status in experimental enzyme-positive acute coronary syndrome in rats.

Despite significant advances in medicine, mortality due to cardiovascular disease is not yet preventable. We investigated the amounts of elabela (ELA) and apelin, synthesized by cardiomyocytes, and changes of these compounds in cardiac tissue and circulation after administration of iloprost (ILO) and sildenafil (SIL) in rats with induced myocardial ischemia (MI). We also investigated a connection with circulating troponin-I, creatine kinase (CK), creatine kinase-myocardial band (CK-MB) and nitric oxide (NO), and total anti-oxidant (TAS)/total oxidant status (TOS). We established eight study groups of five rats each. Group 1, sham, was given only physiologic serum; group 2, ILO; group 3, SIL; group 4, ILO + SIL; group 5, MI; group 6, MI + ILO; group 7, MI + SIL; group 8, MI + ILO + SIL. Troponin-I, CK, CK-MB and TAS-TOS were investigated using an autoanalyzer. NO, ELA and apelin were analyzed by ELISA. Tissue apelin and ELA expressions and localizations were determined by immunohistochemistry. The MI group compared to the control (sham) group showed that ELA, apelin, troponin-I, CK, CK-MB, NO and TOS levels were elevated significantly. Concentrations of these factors increased in MI, but decreased after ILO and SIL administration. The largest decrease of TOS was identified in the ILO + SIL group. ELA and apelin may be novel indicators of MI and administration of ILO and SIL, individually or together, may be useful for treating MI.

Reversal of glycogen storage disease type IIIa-related cardiomyopathy with modification of diet.

Glycogen storage disease type III (GSD III) is caused by a deficiency in debranching enzyme, which leads to an accumulation of abnormal glycogen called limit dextrin in affected tissues. Muscle and liver involvement is present in GSD type IIIa, while the defect is limited to the liver only in GSD type IIIb. Besides skeletal muscle involvement, a cardiomyopathy resembling idiopathic hypertrophic cardiomyopathy is seen. Management consists of maintaining normoglycaemia by supplementation with cornstarch therapy and/or protein. While studies are lacking regarding the best treatment for skeletal muscle disease, a high-protein diet was previously reported to be beneficial. No cases of improvement in cardiomyopathy have been reported. Our patient presented in infancy with hypoglycaemia and hepatomegaly. His prescribed management consisted of cornstarch supplementation and a high-protein diet providing 20% of his total energy needs. At 16 years of age, he developed a severe cardiomyopathy with a left ventricular mass index of 209 g/m(2). The cardiomyopathy remained stable on a protein intake of 20-25% of total energy. At age 22 years, the diet was changed to increase his protein intake to 30% of total energy and minimize his cornstarch therapy to only what was required to maintain normoglycaemia. Dramatic improvement in the cardiomyopathy occurred. Over one year, his left ventricular mass index decreased from 159.7 g/m(2) to 78 g/m(2) (normal 50-86 g/m(2)) and the creatine kinase levels decreased from 455 U/L to 282 U/L. Avoidance of overtreatment with carbohydrate and a high-protein diet can reverse and may prevent cardiomyopathy.

Diffusion-weighted MR imaging of thyroid nodules.

INTRODUCTION: The purpose of our study was to determine the diagnostic role of diffusion-weighted imaging (DWI) in the differentiating of malignant and benign thyroid nodules by using fine needle aspiration biopsy cytology criteria as a reference standard. The apparent diffusion coefficient (ADC) values of the normal-looking thyroid parenchyma were also evaluated both in normal patients and in patients with nodules. METHODS: Between March 2007 and February 2008, 76 consecutive patients with ultrasound-diagnosed thyroid nodules and 20 healthy subjects underwent diffusion-weighted MR imaging by using single-shot spin echo, echo planar imaging. A total of 93 nodules were included in the study using the following b factors 100, 200, and 300 mm(2)/s. ADC values of thyroid nodules and normal area in all subjects were calculated and compared using suitable statistical analysis. RESULTS: Mean ADC values for malignant and benign nodules were 0.96+/-0.65 x 10(-3) and 3.06+/-0.71 x 10(-3)mm(2)/s for b-100 factor, 0.56+/-0.43 x 10(-3) and 1.80+/-0.60 x 10(-3)mm(2)/s for b-200, and 0.30+/-0.20 x 10(-3) and 1.15+/-0.43 x 10(-3)mm(2)/s, for b-300, respectively. Mean ADC values of malignant nodules were lower than benign nodules. There were significant differences in ADC values between benign and malignant nodules. ADC values among normal-appearing thyroid parenchyma of patients and normal-appearing thyroid parenchyma of healthy subjects were insignificant at all b factors. CONCLUSION: Benign nodules have higher ADC values than malignant ones. DWI may be helpful in differentiating malign and benign thyroid nodules.

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.

Lamivudine and interferon-alpha combination treatment of childhood patients with chronic hepatitis B infection.

BACKGROUND: The aim of our study was to compare the efficacy of combined interferon-alpha and lamivudine in children with chronic hepatitis B infection and two durations of treatment (6 and 12 months). METHODS: Combination of interferon-alpha 2b (10 MU/m2 of body surface) and lamivudine 4 mg/kg (maximum, 100 mg) were given synchronously to 30 patients for 6 months (Group 1) and to 27 patients for 12 months (Group 2). Biochemical, virologic and serologic features were compared between two groups at the end of therapy and 6 months after therapy. RESULTS: Hepatitis B e antigen clearances were 33 and 59% at the end of treatment and 37 and 56% 6 months after therapy in Groups 1 and 2, respectively (P > 0.05). Hepatitis B virus DNA clearances were 97 and 100% at the end of treatment and 97 and 96% 6 months after therapy in Groups 1 and 2, respectively (P > 0.05). In both groups normalization of alanine aminotransferase was maintained at the end of therapy and 6 months after therapy (P < 0.05). Sustained complete responses were obtained in 20 and 37% of patients at the end of therapy and 6 months after therapy, respectively (P = 0.07). CONCLUSIONS: When the combination of large dosage interferon-alpha 2b and lamivudine therapy in children was compared at the end of therapy and 6 months after therapy, normalization of alanine aminotransferase and the clearances of hepatitis B e antigen and hepatitis B surface antigen in both groups were directly proportional to the duration of treatment. However, the higher complete response rate at 12 months of combination therapy was not statistically different from that at 6 months.

The ultra-low resistance Groningen voice prosthesis: clinical experiences.

The performance of the ULR Groningen prosthesis was assessed in 21 laryngectomees. The intratracheal phonatory pressures (PITP), voice parameters (speech rate, maximal phonation time, maximal vocal intensity, dynamic vocal intensity range), device lifetime and patient's subjective acceptances were recorded and compared to identical parameters for other prostheses reported in the literature and to data obtained from an age-matched group of normal laryngeal speakers. The low airflow resistance of the ULR Groningen voice prosthesis objectively (PITP = 2.7 kPa) and subjectively leads to a low effort to phonate. Compared to "normals" maximal phonation time shows no significant difference, but speech rate, maximal vocal intensity and dynamic vocal intensity range show a significant worse outcome. The mean device lifetime of the ULR Groningen prosthesis is more than 13.6 weeks, which is comparable to other indwelling voice prostheses. In conclusion, the ULR Groningen voice prothesis enables easier tracheoesophageal phonation than the low-resistance Groningen type.

Molecular and Clinical Aspects of Angelman Syndrome.

The Angelman syndrome is caused by disruption of the UBE3A gene and is clinically delineated by the combination of severe mental disability, seizures, absent speech, hypermotoric and ataxic movements, and certain remarkable behaviors. Those with the syndrome have a predisposition toward apparent happiness and paroxysms of laughter, and this finding helps distinguish Angelman syndrome from other conditions involving severe developmental handicap. Accurate diagnosis rests on a combination of clinical criteria and molecular and/or cytogenetic testing. Analysis of parent-specific DNA methylation imprints in the critical 15q11.2-q13 genomic region identifies 75-80% of all individuals with the syndrome, including those with cytogenetic deletions, imprinting center defects and paternal uniparental disomy. In the remaining group, UBE3A sequence analysis identifies an additional percentage of patients, but 5-10% will remain who appear to have the major clinical phenotypic features but do not have any identifiable genetic abnormalities. Genetic counseling for recurrence risk is complicated because multiple genetic mechanisms can disrupt the UBE3A gene, and there is also a unique inheritance pattern associated with UBE3A imprinting. Angelman syndrome is a prototypical developmental syndrome due to its remarkable behavioral phenotype and because UBE3A is so crucial to normal synaptic function and neural plasticity.

Evaluation of liver hemangiomas using three different b values on diffusion MR.

PURPOSE: To determine which diffusion-weighted MR technique (i.e., b-100, b-600, b-1000 s/mm(2)) is most useful in depicting liver hemangiomas. We also aimed to assess the effect of lesion size on apparent diffusion coefficient (ADC) values. MATERIALS AND METHODS: Diffusion-weighed MR (DWMR) was performed for 61 hemangiomas in 32 patients. DWMR images were obtained before contrast administration using three different b values of 100, 600, and 1000 s/mm(2). ADCs were measured for each lesions and compared with normal liver parenchymal ADCs on different b values. Hemangiomas were subdivided according to lesion size (less than 3 cm and 3 cm or greater). Data were analyzed using SPSS software by analysis of variances (ANOVA) and post hoc values were tested using HSD Tukey test. RESULTS: There was no significant relation between lesion size and ADC values on different b values. Lower ADC values were obtained for higher b values in normal liver tissue and hemangiomas. Although there is significant difference between normal liver tissue and hemangiomas; this is more apparent on b-1000 images (p=0.022 on b-100, p=0.003 on b-600, and p=0.000 on b-1000 images). Variance analysis revealed hemangiomas had higher ADC values than normal liver tissue on b-1000 images. CONCLUSION: Mean values for ADCs of hemangiomas were lower than ADCs of the normal liver except for b-1000 value. Higher b values are useful for the differentiation between normal liver tissue and hemangiomas. Lesion size does not affect ADC measurement on different b values.

Is inflammatory bowel disease a risk factor for early atherosclerosis?

OBJECTIVES: Chronic inflammatory diseases are associated with an accelerated atherosclerotic process. Recent studies have discussed whether inflammatory bowel diseases (IBDs) can predict early atherosclerosis. We investigated this possibility. METHODS: The study consisted of IBD cases (group 1, n = 40) and healthy persons (group 2, n = 40). The IBD group was selected so as not to have vascular disease or the presence of established major cardiovascular risk factors. RESULTS: Group 1 cases showed a significant increase in carotid intima media thickness (cIMT; P = .01). Carotid artery stiffness was impaired in group 1 (P = .03) and high-sensitivity C-reactive protein (hsCRP), homeostasis model assessment of insulin resistance (HOMA-IR), and homocysteine (Hyc) were higher in group 1 patients (P = .02, P = .03, P = .05). CONCLUSIONS: Inflammatory bowel disease patients have an increased risk of early atherosclerosis as shown by greater values of cIMT, carotid artery stiffness, Hyc, hsCRP, and insulin resistance.