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Purpose: To compare the effect of two different sperm preparation techniques, including swim-up and gradient methods on sperm deoxyribonucleic acid (DNA) fragmentation status of semen samples from unexplained and mild male factor subfertile patients undergoing intrauterine insemination (IUI)., Design: A prospective randomized study was conducted in 65 subfertile patients, including 34 unexplained and 31 male factor infertility to compare basal and post-procedure DNA fragmentation rates in swim-up and gradient techniques. Sperm DNA fragmentation rates were evaluated by a sperm chromatin dispersion (SCD) test in two portions of each sample of semen that was prepared with either swim-up or gradient techniques. Sperm motility and morphology were also assessed based on WHO 2010 criteria., Results: Swim-up but not gradient method yielded a statistically significant reduction in the DNA fragmented sperm rate after preparation as compared to basal rates, in the semen samples of both unexplained (41.85 ± 22.04 vs. 28.58 ± 21.93, p < 0.001 for swim-up; and 41.85 ± 22.04 vs. 38.79 ± 22.30, p = 0.160 for gradient) and mild male factor (46.61 ± 19.38 vs. 30.32 ± 18.20, p < 0.001 for swim-up and 46.61 ± 19.38 vs. 44.03 ± 20.87, p = 0.470 for gradient) subgroups., Conclusions: Swim-up method significantly reduces sperm DNA fragmentation rates and may have some prognostic value on intrauterine insemination in patients with decreased sperm DNA integrity.

The influence of biomarkers on carcinogenesis has been investigated extensively. Whether they promote carcinogenesis or work against cancer development remains to be elucidated. To the best of our knowledge, the novel molecule cluster of differentiation 200 (CD200) has not been studied on human breast cancer subjects. The present study aimed to evaluate interleukin-1β (IL-1β), C-X-C motif chemokine ligand 8 (CXCL8), cancer antigen 15.3 (CA 15.3) and the soluble CD200 (sCD200) levels in the serum samples of breast carcinoma patients in order to predict their role in breast carcinoma. The subjects included individuals with early and advanced stage breast cancers, as well as healthy controls. Commercially available ELISA kits were used to measure the serum concentrations of sCD200, IL-1β, CXCL8, CA 15.3, C-reactive protein (CRP) and leukocyte count. A total of 130 subjects were recruited; 50 early stage cancer, 50 advanced stage and 30 control subjects. Serum sCD200, CXCL8, IL-1β and CRP levels were significantly higher in the early as well as the advanced stage breast cancer patients compared to the control group. The level of CA 15.3 was statistically different between early and advanced stage. There were significant positive correlations between IL-1β and CXCL8, and IL-1β and serum sCD200 levels in the control group. These correlations did not persist in the early or the advanced stage cancer groups except CRP and CA 15.3, but new correlations appeared between serum sCD200 level and leukocyte count for advanced stage breast cancer group. Multivariate regression correlation analysis revealed positive correlation between IL-1β and sCD200; and IL-1β and CXCL8. In conclusion, sCD200, CXCL8, CA 15.3 and IL-1β are proinflammatory molecules and their levels are influenced in breast cancer patients.

Purpose: The purpose of this study was to evaluate the soluble Apo-2L (sApo-2L) levels in the ascitic fluid and to study its potential in detecting malignant ascites and soluble CD200 (sCD200,sOX-2) levels so as to predict its clinical usage for detecting stage 4 metastatic endometrial, ovarian and breast cancer in serum samples., Methods: Ascitic fluid from 53 and blood from 25 subjects without known malignancy on admission were collected. There were 14 breast cancer (BC), 17 ovarian cancer (OC) and 19 endometrial cancer (EC) patients diagnosed later on. Blood samples for sApo-2L, sCD200, liver function tests and CEA, CA-19.9 and CA-125 were always taken and assayed in the morning., Results: Significantly low levels of sApo-2L were observed in peritoneal fluid from OC and EC patients compared to benign peritoneal fluid from control individuals. Positive correlation was observed between sApo-2L and aspartate aminotransferase (AST) in benign peritoneal fluid and sCD200, and creatinine and sCD200 and platelets in OC patients; also, sCD200 and CEA in EC patients and sCD200 and blood urea nitrogen (BUN) in healthy subjects., Conclusions: Our data indicate that low proteomics pattern of sApo-2L but not sCD200 is a good biochemical marker. Further decline in the level of sApo-2L was seen in EC compared to OC. Since higher levels of sApo-2L were seen with higher levels of AST, the liver might be involved in its metabolism. The positive correlation detected between sCD200 and creatinine, platelets, CEA and BUN needs to be elucidated.

The molecular mechanisms and pathogenesis of chronic hepatitis C (CHC) infection are unclear. Innate immune cells such as natural killer (NK) cells and dendritic cells are responsible from molecular mechanism of CHC. NK cell cytotoxicity such as TRAIL expression is important pathway for viral clearance. The aim of this study was to evaluate the relationship between HCV RNA and sTRAIL levels during the first 12 weeks of Peg-IFNα and ribavirin treatment. Twelve treatment naive patients with CHC treated with Peg-INFα and ribavirin were included in this study. Circulating sTRAIL and HCV RNA levels were measured at baseline, 4th and 12th week of treatment and their correlation was investigated. sTRAIL and HCV RNA levels decreased gradually with Peg-INFα plus ribavirin treatment. The differences were significant between day 0, 4th week and 12th week of treatment. The expression of sTRAIL was correlated with HCV RNA level at baseline, at 4th and 12th week of treatment (P = 0.021 P = 0.012, P = 0.001 respectively). IFN binds to its receptor on the infected hepatocyte surface during Peg-IFNα and ribavirin treatment. So the polarized phenotype of NK cell is not displayed and NK cell cytotoxicity such as TRAIL expression is blocked. We suggest that the decreased level of circulating sTRAIL may reflect increased binding to its ligand expressed on hepatocyte and decreased TRAIL production under the influence of Peg-IFNα plus ribavirin treatment. Therefore TRAIL may be probably a immunologically predictive factor such as HCV RNA during treatment.

Pro-inflammatory factors regulated by TRAIL in vivo may lead to the development of novel therapeutic strategies for diseases as diverse as infection, autoimmunity and allergy. In this study we aimed to investigate the relationship between IFN treatment response, HCV viral load and sApo 2L levels. Eleven HCV-treatment naive HCV-infected patients were treated with pegIFN alfa-2a. Intensive serum circulating Apo 2L levels were monitored at study visits on day 0 (pretreatment), and in weeks 4, 6 and 12. HCV-RNA and sApo 2L levels decreased gradually with PegIF-alfa 2 treatment and the differences were significant between day 0 and week 4 (p 0.001, p 0.005 and p 0.01, p 0.005 respectively); between day 0 and week 12 (p 0.001, p 0.005 and p 0.001, p 0.000 respectively); between weeks 6 and 12 (p 0.01, p 0.05 and p 0.01, p 0.05 respectively). We suggest that decreased levels of circulating Apo 2L may reflect its increased binding to its ligand expressed on hepatocytes or lymphocytes under the influence of PegIFN treatment.

Purpose: To compare the efficacy of gradient and swim-up semen preparation techniques on pregnancy rates in couples undergoing intrauterine insemination (IUI) cycles with low dose gonadotropin stimulation with the diagnosis of unexplained or mild male subfertility., Methods: Two hundred and twenty three couples were randomized into swim up or gradient technique groups for sperm preperation. The clinical and on going pregnancy rates per cycle and per patient were evaluated., Results: Both clinical and ongoing pregnancy rates per cycle were significantly higher in the "gradient" group (19% and 16.9%) in comparision with the "swim up" group (9.7% and 6.9%) (p < 0.05). Clinical pregnancy and on-going pregnancy rates per patient were higher in the "gradient" group (26.1% and 23.4%) when compared to the "swim up" group (15.2% and 10.7%), (p < 0.05). In the subgroup of 191 unexplained subfertile couples with 290 cycles; the "gradient" group also revealed significantly higher clinical and ongoing pregnancy rates per cycle (21.6% and 17.9%) when compared with the "swim up" group (10.3% and 7.1%) (p < 0.05). In total of 48 treatment cycles upon 32 couples with mild male factor subfertility no significant difference were found between the two sperm preparation techniques in terms of clinical (% 5.3 vs %6.9, p > 0.05) and ongoing (% 5.3 vs %6.9, p > 0.05) pregnancy rates per cycle., Conclusion: The gradient technique significantly improves clinical outcome in IUI cycles of unexplained subfertile couples when compared to swim up technique. In male subfertile patients, both techniques yield similar clinical outcomes.

Genes critical for fertility are highly conserved in mammals. Interspecies DNA sequence variation, resulting in amino acid substitutions and post-transcriptional modifications, including alternative splicing, are a result of evolution and speciation. The mammalian follicle-stimulating hormone receptor (FSHR) gene encodes distinct species-specific forms by alternative splicing. Skipping of exon 2 of the human FSHR was reported in women of North American origin and correlated with low response to ovarian stimulation with exogenous follicle-stimulating hormone (FSH). To determine whether this variant correlated with low response in women of different genetic backgrounds, we performed a blinded retrospective observational study in a Turkish cohort. Ovarian response was determined as low, intermediate or high according to retrieved oocyte numbers after classifying patients in four age groups (<35, 35-37, 38-40, >40). Cumulus cells collected from 96 women undergoing IVF/ICSI following controlled ovarian hyperstimulation revealed four alternatively spliced FSHR products in seven patients (8%): exon 2 deletion in four patients; exon 3 and exons 2 + 3 deletion in one patient each, and a retention of an intron 1 fragment in one patient. In all others (92%) splicing was intact. Alternative skipping of exons 2, 3 or 2 + 3 were exclusive to low responders and was independent of the use of agonist or antagonist. Interestingly, skipping of exon 3 occurs naturally in the ovaries of domestic cats--a good comparative model for human fertility. We tested the signaling potential of human and cat variants after transfection in HEK293 cells and FSH stimulation. None of the splicing variants initiated cAMP signaling despite high FSH doses, unlike full-length proteins. These data substantiate the occurrence of FSHR exon skipping in a subgroup of low responders and suggest that species-specific regulation of FSHR splicing plays diverse roles in mammalian ovarian function., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: CD200 (OX-2) is a novel immune-effective molecule, existing in a cell membrane-bound form, as well as in a soluble form in serum (s OX-2), which acts to regulate inflammatory and acquired immune responses., Material and Methods: We planned this study to evaluate the sOX-2 levels of type 2 diabetic foot (group B), and compare it with that of healthy controls (group A). The patient group had the following values: DM period: 27.9±10.3 year [mean ±SD], HbA1c: 9.52±2.44% [mean ±SD]., Results: Blood samples for sCD200 measurement were always taken in the morning between 8 and 10 A.M.. The results were reported as means of duplicate measurements. Concentrations of sOX-2 in the serum samples were quantified using an ELISA kit. Serum hs-CRP levels were measured using an hs-CRP assay kit. The sOX-2 level in group B was 173.8±3.1 and in group A was 70.52±1.2 [p<0.0001). In subgroup analysis of T2DM-DFI patients, we noticed that sOX-2 levels were higher in WGS (Wagner grading system) I and II patients than in WGS III and IV patients. The HbA1c, BUN, creatinine, hs-CRP levels, and sedimentation rates were higher in the patient group (p<0.0001, p<0.001, p<0.001, p<0.005, and p<0.0001, respectively)., Conclusions: We suggest that there are vascular, immunologic, and neurologic components in DFI, whereas autoimmune diseases and inflammatory skin disorders have only an immunologic component. This is possibly evidence of a pro-inflammatory effect seen in DFI as a vascular complication.

Background: Soluble CD200 (sCD200) is a novel immuno-effective molecule, which acts to regulate inflammatory and acquired immune responses. Recently, our study group showed that sCD200 was present in serum and blister fluid in a patient with bullous pemphigoid and a patient with toxic epidermal necrolysis. We therefore planned this study to evaluate the sCD200 levels of autoimmune and inflammatory skin disorder patients and to compare them with that of healthy controls., Material/methods: Our study included 30 consecutive patients with psoriasis vulgaris, 15 with pemphigus vulgaris, and 15 healthy controls. Clinical examination and laboratory tests were performed on the same day. Psoriasis patients were also assessed with the Psoriasis Area and Severity Index (PASI) and pemphigus patients were assessed using the Pemphigus Disease Area Index (PDAI). Levels of sCD200 in the serum samples were quantified using ELISA kits., Results: The serum sCD200 level was observed to be statistically significantly higher in patients with psoriasis vulgaris (96.7±15.8) compared to patients with pemphigus vulgaris (76.2±14.6), (p<0.001) and healthy controls (26.8±7.0) (p<0.001). The serum sCD200 levels were observed to be statistically significantly higher in patients with pemphigus vulgaris compared with that in healthy controls (p<0.001). In addition, there was a statistically significant correlation between serum sCD200 levels and PDAI (r=0.987, p=0.001). Nevertheless, there was no statistically significant correlation between serum sCD200 levels and PASI (r=0.154, p=0.407)., Conclusions: sCD200 might play a role in immune response in the pathogenesis of autoimmune and inflammatory skin disorders. However, it remains to be fully elucidated how sCD200 can orchestrate inflammatory response in psoriasis and pemphigus.

Background: Hyperglycemia is among the potent factors that may induce or facilitate apoptosis. TNF-Related Apoptosis-Inducing Factor (TRAIL) is known for its apoptotic and immunomodulatory effects that have recently been correlated with diabetes. We examined serum-soluble TRAIL (sTRAIL) and high-sensitivity CRP (hs-CRP) levels and their association with various distinct parameters in type 2 diabetic nephropathy patients with diabetic foot disease., Material/methods: Twenty-two diabetic nephropathy patients with foot ulcers were enrolled in our study. Patients had been diagnosed with diabetes at age 24±10.58 years. Circulating sTRAIL and Hs-CRP levels were compared with control values, and possible correlations were investigated with parameters such as age, Wagner's Grade (WG), BMI, HbA1c, and creatinine., Results: Serum sTRAIL levels were significantly reduced in the patient group, compared to healthy subjects. High HsCRP levels correlated with age, and WGS correlated with BMI and creatinine levels., Conclusions: Significantly suppressed sTRAIL levels in diabetic nephropathy patients with foot ulcers compared to healthy controls suggest a protective role for TRAIL in the disease setting.

Background: Lung cancer is the leading cause of cancer mortality in the world. Many factors can protect against or facilitate its development. A TNF family member TRAIL, has a complex physiological role beyond that of merely activating the apoptotic pathway in cancer cells. Vitamin D is converted to its active form locally in the lung, and is also thought to play an important role in lung health. Our goal was to investigate the possible clinical significance of serum sTRAIL and 1,25-dihydroxyvitamin D(3) levels in patients with non-small cell lung cancer (NSCLC)., Materials and Methods: Totals of 18 consecutive adenocarcinoma and 22 squamous cell carcinoma patients with stage-IV non-small cell lung cancer referred to our institute were included in this study. There were 12 men and 6 women, with ages ranging from 38 to 97 (mean 60.5) years with adenocarcinoma, and 20 men and 2 women, with ages ranging from 46 to 80 (mean 65) years with squamous cell carcinoma. Serum levels of sTRAIL and 1,25-dihydroxyvitamin D(3) were measured in all samples at the time of diagnosis., Results: sTRAIL levels in NSCLC patients were higher than in the control group. Although there was no correlation between patient survival and sTRAIL levels, the highest sTRAIL levels were correlated with age and cigarette smoking in the adenocarcinoma patients. sTRAIL level in healthy individuals were correlated with serum 1,25-dihydroxyvitamin D(3)., Conclusions: Serum sTRAIL concentrations were increased in NSCLC patients, and correlated with age and smoking history, but not with overall survival.

Background: Allergic rhinitis is a common health problem affecting the immune system. The homeostasis of the immune system is regulated by apoptosis. In this study, serum circulating soluble TRAIL levels of allergic rhinoconjunctivitis patients before and after allergen-specific immunotherapy were evaluated., Material/methods: The sTRAIL levels of pre- and post-treated allergic rhinoconjunctivitis patients (n=25) were compared to age- and sex-matched healthy individuals (n=25). sTRAIL levels were measured by ELISA. The skin prick test (SPT) results were recorded before and after treatment., Results: The sTRAIL levels between the pre-treated and control groups were significantly different (p<0.0001). However, there was no significant difference between the post-treated group and healthy individuals (p=0,801). SPT was a statistically significant difference between the values of the research group before and after immunotherapy (grasses mixture, barley mixture, Oleaauropeae, D. Pteronyssinus, D. farinae)., Conclusions: The sTRAIL levels were decreased after allergen-specific immunotherapy to healthy levels and may be of use as a marker of efficacy of immunotherapy in allergic rhinoconjunctivitis patients.

Background: Trimetazidine (TMZ) has been used in cardiology practice for protection from ischemiareperfusion injury. But its effects on intestinal mucosa are not well known. Our aim was to investigate the protective effect of TMZ on intestinal mucosa and on damaged kidney due to thermal injury in rats., Material and Methods: Total of 30 male Sprague-Dawley rats were used in the study of intestinal mucosa damage and 24 female Sprague-Dawley rats in renal injury model. Back regions were shaved and taken into 99°C water for about 10 seconds in order to have a thermal injury. All rats were sacrificed 5 hours after the burn injury. Tissue malondialdehyde (MDA), myeloperoxidase (MPO) and glutathione (GSH) levels were measured. In order to show the tissue edema resulting from microvascular circulatory impairment, unbiased stereological technique, Cavalieri's volume estimation applied to each kidney., Result: TMZ decreased MPO levels, but no effect on GSH/oxidized glutathione (GSSG) and MDA levels. MPO levels were significantly lower in TMZ group than burnt-control group (p<0.05). There were statistically significant differences in the kidney volumes between TMZ group and sham group (p<0.05)., Conclusion: In this study, TMZ seems to be protective on intestinal mucosa and prevented kidney damage originated from thermal injury.

This study determined the allelic frequency and genotypic distribution of an angiotensin-converting enzyme (ACE) polymorphism and serum ACE activity in Turkish patients with obstructive sleep apnea syndrome (OSAS). A colorimetric assay measured serum ACE activity in 73 of 97 subjects. Frequencies for II, ID, and DD genotypes were 19.6, 53.6, and 26.8% in the OSAS group and 15, 38, and 47% in the control group, respectively (P = 0.02). The I allele frequency was higher in the OSAS group than in the healthy control group (P = 0.02). Carrying the I allele (II or ID genotypes) increased OSAS risk 2.41 times in the Turkish population. Mean ACE activity was significantly lower in patients with the II genotype than in the DD genotype (P = 0.011), and ACE activity was significantly lower in patients with severe OSAS than in those with mild OSAS (P = 0.006). Our results suggest that II and ID genotypes of the ACE gene increase the risk of developing OSAS in the Turkish population.

Introduction: A chemiluminescence (CL) technique, which determines the glucose-6-phosphate dehydrogenase (G-6-PD) activities in healthy, heterozygous, and completely enzyme-deficient individuals was applied., Methods: CL intensities were detected for 4 h at 15-min intervals in each sample with or without addition of G-6-PD substrates into the reaction mixture., Results: The results revealed an inverse correlation to the reference UV method (Zinkham method; r=-0.80). Furthermore, the CL assay was able to detect G-6-PD activities as low as 0.2 IU/gHb, which was not possible by the UV method., Discussion: In conclusion, we believe that this method offers a new diagnostic tool for the detection of G-6-PD activities in enzyme-deficient individuals and, because of its increased sensitivity, makes it amenable for determining the effects of different pharmaceutical agents on G-6-PD activity in tissue or cell cultures.