Lesional activation of Tc 17 cells in Behçet disease and psoriasis supports HLA class I-mediated autoimmune responses.

BACKGROUND: Behçet disease (BD) presents with lymphocytic and neutrophilic vasculitis of unknown aetiology. HLA-B*51, the endoplasmic reticulum aminopeptidase 1 (ERAP1), and interleukin 23 receptor (IL23R)/IL12R are genetic risk factors. IL-23 regulates IL-17A, which controls the recruitment and activation of neutrophils. OBJECTIVES: To determine pathological changes in BD skin lesions related to the complex genetic predisposition. METHODS: We characterized the expression of IL-17A and IL-23A in various cell types by immunohistological double staining of sections from papulopustular skin lesions of acute attacks of BD and psoriasis vulgaris lesions, another HLA-class I-associated T-cell-mediated autoimmune disease in which excessive T-cell-derived IL-17A production promotes neutrophil activation. RESULTS: We found that in BD lesions, as in psoriasis, actively expanding CD8+ T cells were the predominant source of IL-17A. IL-17A+ CD8+ T (Tc 17) cells outnumbered infiltrating IL-17A+ CD4+ T cells. Unlike the epidermal localization of CD8+ T cells in psoriasis, Tc 17 cells in BD lesions mainly infiltrated the perivascular tissue and the blood vessel walls of dermis and subcutaneous tissue. They co-localised with a marked IL-23A expression by CD11c+ dendritic cells and CD68+ macrophages. IL-17A expression was associated with extensive recruitment of neutrophils around blood vessels that formed neutrophil extracellular traps (NETs). CONCLUSIONS: In BD, the genetic predisposition may mediate antigen-specific activation and differentiation of a Tc 17 response, possibly targeting endothelial (auto)antigens. Neutrophils recruited by IL-17A in this process may enhance tissue damage by extensive NET formation (NETosis). Thus, the IL-23/IL-17 axis presumably controls neutrophilic inflammation in BD vasculitis in the context of a predominant antigen-specific CD8+ T-cell response.

Achondrogenesis Type 2 in a Newborn with a Novel Mutation on the COL2A1 Gene.

Achondrogenesis is a group of rare and fatal disorders occurring in approximately one in every 40,000-60,000 newborns. Achondrogenesis is classified in three groups, as Achondrogenesis type 1A (Houston-Harris type or AC-G1A), Achondrogenesis type 1B (Parenti-Fraccaro type or ACG1B) and Achondrogenesis type 2 (Langer-Saldino type or ACG2), depending on clinical and radiological findings. Achondrogenesis Type 2 is a lethal skeletal dysplasia that is typically characterized by short arms and legs, a small chest with short ribs, lung hypoplasia, a prominent forehead, a small chin, and an enlarged abdomen that may accompanied by polydramnios and hydrops. This study contributes to the literature by presenting a patient who was admitted to the Level ΙΙΙ Neonatal Intensive Care Unit (NICU), Bursa, Turkey), with extremely short extremities, a small chest, abdominal distention and respiratory distress, who was diagnosed with ACG2. On the COL2A1 gene, genetic analysis with next generation sequencing (NGS), was revealed to have a heterozygous missense variation, c.2546G>A, p.Gly849Asp mutation, which is a different genetic variant that has not been previously described in the literature.

Diagnostic performances of CA125, HE4, and ROMA index in ovarian cancer.

PURPOSE OF INVESTIGATION: HE4 (human epididymis protein 4) is suggested to be used as a potential new biomarker to identify ovarian malignancies from benign adnexal masses. The aim of this study was to evaluate HE4, in comparison with CA125 and Risk of Ovarian Malignancy Algorithm (ROMA) index in benign gynecological diseases and ovarian cancer, and additionally to determine the reference range for HE4 in healthy Turkish women. MATERIALS AND METHODS: CA125 and HE4 serum levels were determined in 96 patients with benign gynecological diseases, 47 patients with ovarian cancer and 106 healthy women using a specific analyzer. CA125 and HE4 cut-offs were 35 U/ml and 70 pmol/L, respectively. RESULTS: HE4 had significantly higher concentrations in ovarian cancer than benign gynecologic disorders (p < 0.005). Tumor marker sensitivity in ovarian cancer was 78% for HE4, 63% for CA125, and 88% for ROMA index at 95% specificity. A significantly higher area under the Receiver operator characteristic (ROC) curve was obtained with HE4 and ROMA index than CA125 in the differential diagnosis of benign gynecological diseases versus ovarian cancer (0.929, 0.955, and 0.781, respectively). Reference limits for serum HE4 in healthy Turkish women was determined as 28.9-62.4 pmol/L for pre-menopausal and 23.7-152.4 pmol/L for postmenopausal women. CONCLUSIONS: In the diagnosis of ovarian cancer, HE4 had higher sensitivity, as a single tumor marker. The sensitivity of HE4 and ROMA index in postmenopausal women was higher than premenopausal women for detecting ovarian cancer.

Short-term graft patency of sequential and Y-graft in open heart surgery with transit time flow measurement.

AIM: In this prospective study, we aimed to compare flow characteristics and the short term patency of sequential and y-grafts by intraoperative transit time flow measurement. METHODS: Sixty patients were selected from 1374 isolated coronary bypass operations. Group 1 (N.=36) consisted of sequential grafted, Group 2 (N.=24) consisted of y-grafted patients. Intraoperative graft flow measurement was done with a transit time flow meter at stable hemodynamic conditions. We follow up the groups at the 30th day of the operation. RESULTS: The mean flows at measurement set up were 43.2±19.7 mL/min in Group 1 and 43.6±21.7 mL/min in Group 2. After distal graft clamp removal the same values were 63.4±20.9 mL/min in Group 1 and 67.3±35.3 ml/mins in Group 2. At the 30th day of the operation no patients died, and none of them had an acute myocardial infarction. CONCLUSION: The percent of flow increase in sequential graft group was higher but the difference of the percent of flow increase between groups was not statistically significant.

Macro- and micro-strain in GaN nanowires on Si(111).

We analyze the strain state of GaN nanowire ensembles by x-ray diffraction. The nanowires are grown by molecular beam epitaxy on a Si(111) substrate in a self-organized manner. On a macroscopic scale, the nanowires are found to be free of strain. However, coalescence of the nanowires results in micro-strain with a magnitude from ± (0.015)% to ± (0.03)%. This micro-strain contributes to the linewidth observed in low-temperature photoluminescence spectra.

Reversible MRI findings of porphyric encephalopathy. A report of two cases.

We describe the magnetic resonance imaging (MRI) findings in two patients admitted to our institution with neuropsychiatric symptoms and severe abdominal pain diagnosed as acute intermittent porphyria (AIP). MRI revealed multiple lesions which regressed following treatment. We suggest reversible cerebral vasospasm underlies the MRI abnormalities and the cerebral symptoms in porphyria.

Quantitative telomerase activity in malignant, benign and normal gynecological tissues.

OBJECTIVE: The aim of this study was to evaluate quantitative telomerase activity in malignant, benign and normal gynecological tissue samples by using the Telomerase-PCR ELISA kit, and to determine a cut-off level for malignancy by this quantitative method. MATERIALS AND METHODS: Fifty gynecological tumors, 27 benign gynecological disorders and 29 normal tissues were analyzed by the Telomerase-PCR ELISA kit. All tissues were confirmed by a pathologist. A ROC (receiver operator characteristic) curve was drawn to determine a threshold level best discriminating malignant tissues from benign pathologies and normal tissues. Telomerase activity was compared in malignant, benign and normal tissues. RESULTS: The mean level of telomerase activity of the malignant tumor samples (1.03 +/- 0.53 units) was significantly (p < .001) higher than the normal tissues (0.13 +/- 0.07 units) and benign pathologies (0.37 +/- 0.25 units). The cut-off point to differentiate malignant samples from benign samples was set at 0.42 units, where the sensitivity was 93.8% and the specificity was 89.3%. Positive predictive value was 84% and negative predictive value was 89.3%. There was a significant difference in telomerase activity between malignant, benign and normal tissues within each histological group. CONCLUSION: In this preliminary study, the telomerase-PCR ELISA method was found to have a high sensitivity and specificity to differentiate malignant gynecological tissues from benign tissues.

Diagnostic implications of telomerase activity in pleural effusions.

The aim of the present study was to investigate the diagnostic efficacy of telomerase activity for discrimination of malignant and benign pleural effusions. Pleural effusions were collected from 109 consecutive patients in whom the diagnosis was confirmed with cytological and/or histological examinations. Cytological samples were classified as malignant (n=63) and benign (n=46). Telomerase activity was determined with the polymerase chain reaction-based telomeric repeat amplification protocol assay. Telomerase activity was detected in 52 (82.5%) and nine (19.6%) samples from the malignant and benign groups, respectively, which was a significant difference. The sensitivity rate of cytological examination when combined with telomerase activity (92.1%) was significantly greater than that of cytological examination alone (53.9%). The sensitivity and specificity of telomerase activity were 82.5 and 80.4%, respectively. Diagnostic accuracy of telomerase activity was 81.6%. Telomerase activity is a highly sensitive diagnostic biomarker for malignancy and may be used as an adjunct to cytological findings in determining malignant pleural effusions.

Plasma and erythrocyte lipid peroxide levels in workers with occupational exposure to lead.

The plasma and erythrocyte lipid peroxide levels were measured in a group of male subjects occupationally exposed to lead for an average period of 17 yr, and compared to those from an age-matched control group living in the same city in a similar socioeconomical environment. The blood lead and plasma zinc levels were measured by atomic absorption spectroscopy. The plasma and erythrocyte lipid peroxide levels were established by the malondialdehyde determination method. Significant differences were found in the blood lead levels in lead-exposed workers, 15.00 +/- 10.15 microg/dL as compared to controls, 2.37 +/- 0.89 microg/dL. The plasma (2.67 +/- 0.69 microM) and erythrocyte (27.53 +/- 6.28 nmol/g Hb) lipid peroxide levels in workers with occupational exposure to lead were significantly higher than controls, 1.23 +/- 0.61 microM and 14.35 +/- 2.08 nmol/g Hb, respectively. There were no significant differences of the zinc levels in both groups. The blood lead levels had a statistically significant positive correlation with age and with duration of exposure in both groups, but showed no relationship to the corresponding blood zinc levels. The results presented in this study indicate that the increase of plasma and erythrocyte lipid peroxide levels in workers exposed to lead may be related to the lead concentration, age and duration of exposure. Index Entries: Blood lead; lipid peroxides; malondialdehyde.

Oxidant and antioxidant status in larynx squamous cell carcinomas.

In this study we reviewed 20 patients with laryngeal squamous cell carcinoma to evaluate the oxidant and antioxidant status on tissue level. Superoxide Dismutase (SOD) and Catalase levels, two important antioxidant enzymes, and Malondialdehyde (MDA) levels, a valuable index of lipid peroxidation, were compared in cancerous and normal tissues of the patients. In cancerous tissue SOD activities were significantly lower than in the normal tissue, while there was no significant difference in MDA levels and Catalase activities. It was also observed that SOD activities significantly decreased as the histopathologic malignancy grades increased in cancerous tissue. These changes in oxidant and antioxidant status in carcinomatous tissue of the larynx are considered to be of great interest.

A model of hypoxia-induced necrotizing enterocolitis: the role of distension.

BACKGROUND/PURPOSE: This study was performed to investigate additional effects of intestinal distension in the damage to the gut caused by hypoxia-reperfusion. METHODS: Five groups each consisting of ten 1-day-old Wistar albino rat pups were studied; Group 1, hypoxia-reoxygenation; Group 2, hypoxia-reoxygenation and distension; Group 3, distension and hypoxia-reoxygenation; Group 4, distension; and Group 5, control. Hypoxia was induced by placing the rat pups in a 100% carbon dioxide chamber for 5 minutes. After the hypoxia, the pups were exposed to 100% oxygen for reoxygenation for 5 minutes. The intestinal distension was carried out with a fine 21-gauge SILASTIC cannula via rectal route. The rats were killed on the third day, and all the intestine were harvested from duodenum to sigmoid colon. Malondialdehyde (MDA) levels were determined as an index of lipid peroxidation related to free radical reaction in the intestine. The histopathologic investigation was carried out by light microscopy in a blinded fashion. RESULTS: The MDA levels of Group 3 animals were significantly higher than those in Group 1, 4, and the control group (P < .05). The MDA level of Group 2 did not differ significantly from that of the Group 3 (P > .05). All MDA levels of the study groups also were significantly higher than the control group (P < .05). CONCLUSION: The results demonstrated that intestinal distension increased the damaging effects of hypoxia-reoxygenation in the gut.

In vitro antioxidant effect of Ginkgo biloba extract (EGb 761) on lipoperoxidation induced by hydrogen peroxide in erythrocytes of Behçet's patients.

Excessive superoxide radical production and an impaired antioxidant mechanism in both the neutrophils and plasma of patients with Behçet's disease (BD) have been reported. To provide clinical support for the earlier data, erythrocyte membrane integrity was investigated by measuring malondialdehyde (MDA, a marker of lipid peroxidation) levels in the erythrocytes of BD patients. In addition, the antioxidant effect of Ginkgo biloba extract (EGb 761) at 25 and 250 microg/ml concentrations on lipoperoxidation induced by hydrogen peroxide (H2O2) in erythrocyte obtained from BD patients was examined in in vitro conditions. When compared to healthy controls, basal erythrocyte MDA levels were found to be higher in BD patients. In the in vitro study, there was also a significant increase in H2O2-induced MDA production in the medium containing no EGb 761 in the patient group, whereas significant decreases in MDA levels were observed in the mediums containing EGb 761 both in the patient and control groups. The decrease in MDA production was found to be related to EGb 761 concentration. These data indicate that an oxidative damage is present in erythrocytes obtained from Behçet's patients, and EGb 761, which may strengthen the antioxidant defense system, may contribute to the treatment of BD.

Oxidative stress in hemodialyzed patients and the long-term effects of dialyzer reuse practice.

OBJECTIVES: To investigate the existence of an altered oxidant/ antioxidant balance in patients on regular hemodialysis treatment (RHT) and whether there is any effect of dialyzer reuse on oxidative damage and antioxidative mechanism. DESIGN AND METHODS: Malondialdehyde (MDA) levels and glutathione peroxidase (GPx) activities in both plasma and erythrocytes, plasma selenium (Se) levels, and erythrocyte superoxide dismutase (SOD) activities of RHT patients were determined at the beginning and end of 4-month reuse period. RESULTS: When compared to healthy controls, both plasma and erythrocyte MDA levels were found to be significantly higher in RHT patients before the dialyzer reuse practice; whereas both plasma and erythrocyte GPx activities, erythrocyte SOD activity, and also plasma Se levels were lower in the same patient group than those of controls. When statistical comparison was made on RHT patients between before and after the reuse period, the decreases in MDA levels but increases in the enzyme activities and also an increase in plasma Se levels were observed after the reuse period. However, erythrocyte SOD activities and plasma Se levels measured after the reuse period were not found to be statistically different from the control values; MDA levels still remained elevated above the control values, and GPx activities were not attained to those of controls, after the reuse practice. In addition, positive correlations were found between activities of erythrocyte SOD and GPx enzymes, between GPx and Se levels and negative correlations between the activities of both enzymes and MDA levels in erythrocytes of patients on RHT. CONCLUSION: These findings may indicate that dialyzer reuse may provide, at least partly, an improvement on oxidative stress in patients on RHT.

The effects of dialyzer reuse on plasma antioxidative mechanisms in patients on regular hemodialysis treatment.

The effects of antioxidative mechanism are known to be reduced in patients on regular hemodialysis treatment (RHT). The data about the effects of reuse on antioxidative mechanisms are limited. Twelve patients on RHT (age range: 16-50 years) were included in the study. The basal and after 4 months of dialyzer reuse period, plasma antioxidant activity (AOA), myeloperoxidase (MPO) activity, ceruloplasmin (Cp), copper (Cu), transferrin (TF), and sulphydryl group (SH) levels were detected. The basal plasma AOA (110.92 +/- 17.19 microliters), TF (1.23 +/- 0.23 g/l), and SH (307.11 +/- 51.81 mumol/l) levels were lower than the levels of the control subjects (73.75 +/- 9.07 microliters, 2.38 +/- 0.25 g/l, 690.59 +/- 84.18 mumol/l) (p < .001). The basal Cp (0.47 +/- 0.08 g/l) and MPO activity (86.31 +/- 9.57 U/l) levels were higher than the levels of the control subjects (0.34 +/- 0.07 g/l and 65.90 +/- 7.28 U/l) (p < .001). The basal Cu levels (1.19 +/- 0.24 mg/l) were similar to the levels of the control subjects (1.11 +/- 0.13 mg/l) (p > .05). The difference between plasma AOA (83.33 +/- 14.71 microliters), Cp (0.38 +/- 0.08 g/l), and MPO activity (64.43 +/- 10.01 U/l) after the reuse period and the control values were not statistically significant (p > .05). The TF (1.87 +/- 0.15 g/l) levels after the reuse period were significantly lower than the control values (p < .001), although the levels were increased after the reuse period. Our findings may indicate some beneficial effects of hemodialyzer reuse process on plasma antioxidative mechanisms in patients on RHT.

The effect of acute ligation of the rabbit appendix on antioxidant enzymes.

The role of oxygen free radicals (OFR) in the pathogenesis of many diseases is known. This experimental study was planned to investigate the role of OFR in acute abdominal inflammation. In this study, 20 adult rabbits were used. They were divided into two groups with 10 rabbits in each. In the study group, blood samples were taken from peripheral and mesenteric veins and then their appendices were ligated; after 24 h, blood samples were taken again and the appendices were resected. The same procedures were carried out in the control group, except for ligation of the appendices. Superoxide dismutase,catalase and glutathione peroxidase (GPX) activities were measured in all blood samples. The activities of catalase and GPX were increased postoperatively in peripheral and mesenteric blood samples in the experimental group. The catalase activity was increased in the control group. These results suggest that OFR increased sufficiently to activate the enzymatic defense system in acute appendicitis.

Plasma selenium levels in rheumatoid arthritis.

The plasma selenium (Se) levels were determined in patients with rheumatoid arthritis (RA) and healthy controls. Plasma Se levels in 60 patients were found to be significantly lower than those in 60 normal, healthy controls (p < 0.001). Similar significant differences were determined in sex-matched comparisons between patients and controls (p < 0.001) but there was no significant difference in plasma Se levels in sex-matched comparisons in both groups (p > 0.05). Our results suggest that Se is an important factor in RA.

The effect of vitamin E on ipsilateral and contralateral testis following unilateral testicular torsion in rats.

An experimental study was conducted to investigate the role of lipid peroxidation in ipsilateral and contralateral testicular reperfusion injury following unilateral testicular torsion (TT) and the effect of vitamin E in the management of this injury. Fifty adult male Sprague-Dawley rats were divided into five equal groups. Bilateral orchiectomy was performed immediately in group 1, and 3 h after unilateral TT in group 2. In group 3, both testes were harvested 3 h after a sham operation. In groups 4 and 5, unilateral TT, detorsion after 3 h and bilateral orchiectomy after 6 h were performed. Vitamin E was given before detorsion in group 4 and after detorsion in group 5. The levels of malondialdehyde (MDA) were measured as an index of lipid peroxidation in all testes. There were no significant differences between right and left testes within groups or between right or left testicular MDA values in different groups. The results suggest that lipid peroxidation does not play an important role in ipsilateral and contralateral testicular injury following unilateral TT and that vitamin E given before or after detorsion of testes is not useful in preventing testicular reperfusion injury.

Changes in platelet monoamine oxidase and plasma dopamine-beta-hydroxylase activities in lithium-treated bipolar patients.

The activity of monoamine oxidase (MAO) and dopamine-beta-hydroxylase (DBH), enzymes involved in monoamine metabolism, were studied in 29 bipolar patients (mean age = 33.12 years, SD = 7.27) who were treated with lithium carbonate and in 20 healthy volunteers (mean age = 30.05 years, SD = 6.04). Platelet MAO activity was higher after lithium withdrawal, whereas plasma DBH activity was lower in remitted euthymic bipolar patients compared with normal volunteers. During lithium treatment, platelet MAO activity decreased and plasma DBH activity increased compared with the lithium-withdrawal values. It was also observed that the activities of these enzymes in the bipolar patients during lithium treatment did not differ from those in the volunteers. Thus, platelet MAO and plasma DBH activities differed in unmedicated patients with bipolar affective disorder from those of healthy subjects. Treatment with lithium appeared to have a normalizing effect on MAO and DBH activity levels.