Protective efficacy of pirfenidone in rats with pulmonary fibrosis induced by bleomycin.

BACKGROUND: Bleomycin causes increased production of reactive oxygen species, leads to pulmonary toxicity, fibroblast activation, and fibrosis. OBJECTIVES: This study aimed to evaluate the protective effect of pirfenidone on bleomycin-induced lung toxicity in rats. METHODS: Twenty-eight adult rats were randomly divided into 3 groups; Bleomycin (B group, n=10), Bleomycin and Pirfenidone (B-PND group, n=13), and the control group (n=5). The bleomycin regimen was administered for 9 weeks. Pirfenidone was administered at 100 mg/kg daily. Total antioxidant level (TAS), total oxidant level (TOS), tumor necrosis factor (TNF-α), transforming growth factor (TGF-ß1), matrix metalloproteinase-2 (MMP-2), plasminogen activator inhibitor (PAI) levels were studied. Histopathologically, sections were stained with Hematoxylin-eosin and Masson-trichrome for grading-scoring according to the Ashcroft score. RESULTS: Stage 3 fibrosis was observed in 50% of the B group rats, stage 3 and higher fibrosis was never detected in the B-PND group and the difference was statistically significant (p=0.003). When evaluating tissue inflammation, the inflammation was higher in the B-PND group than in the other groups (p<0.001). Pleuritis was detected in all rats in group B, while was not observed in B-PND and control group (p<0.001). The TAS level was found to be significantly higher in group B than in group B-PND (p=0.034), while no difference was found between TOS, TNF-α, MMP-2, PAI, TGF-ß1. CONCLUSIONS: Pirfenidone had a statistically significant protective effect in bleomycin-induced lung fibrosis and pleuritis in rats.  Despite the presence of inflammation in the tissue, no significant changes were observed in inflammation markers in the peripheral blood. Novel serum biomarkers are needed to indicate the presence of inflammation and fibrosis in the lung.

Calcitonin Gene-Related Peptide and Adrenomedullin Levels During Ictal and Interictal Periods in Patients With Migraine.

Background Peptides related to calcitonin gene-related peptide (CGRP) have been suggested to have a role in migraine. Adrenomedullin (AM) might be a candidate molecule because it is related to pain pathways in the peripheral and central nervous systems and uses the same receptors as CGRP. Methodology In this study, we examined the serum CGRP and AM levels during unprovoked ictal and interictal periods of 30 migraine patients as well as 25 healthy controls. Another focus of this study was on the association of CGRP and AM levels with clinical features. Results Mean serum AM levels were 15.80 pg/mL (11.91-21.43 pg/mL) in the ictal and 15.85 pg/mL (12.25-19.29 pg/mL) in the interictal periods in the migraine group and 13.36 pg/mL (10.84-17.18 pg/mL) in the control group. Mean serum CGRP levels were 2.93 pg/mL (2.45-3.90 pg/mL) in the ictal and 3.25 pg/mL (2.85-4.67 pg/mL) in the interictal periods in the migraine group and 3.03 pg/mL (2.48-3.80 pg/mL) in the control group. There were no statistical differences between ictal and/or interictal AM and CGRP levels (p = 0.558 and p = 0.054, respectively) which were also comparable with the results of the control group (p = 0.230, p = 0.295, p = 0.987, p = 0.139, respectively). Ictal serum CGRP and/or AM levels did not correlate with any of the reported clinical features. Conclusions Serum AM and CGRP levels are similar in interictal and unprovoked ictal periods in migraine patients and as well in controls. These results do not indicate that these molecules do not have a role in migraine pathophysiology. Considering the broad mechanisms of action of peptides in the CGRP family, further studies are needed in larger cohorts.

Plasminogen activator inhibitor-1 levels as an indicator of severity and mortality for COVID-19.

OBJECTIVE: Coronavirus disease-19 (COVID-19) is a multisystemic disease that can cause severe illness and mortality by exacerbating symptoms such as thrombosis, fibrinolysis, and inflammation. Plasminogen activator inhibitor-1 (PAI-1) plays an important role in regulating fibrinolysis and may cause thrombotic events to develop. The goal of this study is to examine the relationship between PAI-1 levels and disease severity and mortality in relation to COVID-19. METHODS: A total of 71 hospitalized patients were diagnosed with COVID-19 using real time-polymerase chain reaction tests. Each patient underwent chest computerized tomography (CT). Data from an additional 20 volunteers without COVID-19 were included in this single-center study. Each patient's PAI-1 data were collected at admission, and the CT severity score (CT-SS) was then calculated for each patient. RESULTS: The patients were categorized into the control group (n=20), the survivor group (n=47), and the non-survivor group (n=24). In the non-survivor group, the mean age was 75.3±13.8, which is higher than in the survivor group (61.7±16.9) and in the control group (59.5±11.2), (p=0.001). When the PAI-1 levels were compared between each group, the non-survivor group showed the highest levels, followed by the survivor group and then the control group (p<0.001). Logistic regression analysis revealed that age, PAI-1, and disease severity independently predicted COVID-19 mortality rates. In this study, it was observed that PAI-1 levels with >10.2 ng/mL had 83% sensitivity and an 83% specificity rate when used to predict mortality after COVID-19. Then, patients were divided into severe (n=33) and non-severe (n=38) groups according to disease severity levels. The PAI-1 levels found were higher in the severe group (p<0.001) than in the non-severe group. In the regression analysis that followed, high sensitive troponin I and PAI-1 were found to indicate disease severity levels. The CT-SS was estimated as significantly higher in the non-survivor group compared to the survivor group (p<0.001). When comparing CT-SS between the severe group and the non-severe group, this was significantly higher in the severe group (p<0.001). In addition, a strong statistically significant positive correlation was found between CT-SS and PAI-1 levels (r: 0.838, p<0.001). CONCLUSION: Anticipating poor clinical outcomes in relation to COVID-19 is crucial. This study showed that PAI-1 levels could independently predict disease severity and mortality rates for patients with COVID-19.

STAT3 mediated regulation of glucose metabolism in leukemia cells.

Cancer cells rewire metabolic pathways as they demand more ATP and building blocks for proliferation. Glucose is the most consumed nutrient by cancer cells and metabolized to lactate even in the presence of oxygen. This phenomenon is called 'aerobic glycolysis'. Also, glucose level is found lower in tumor environment. Leukemia is characterized by abnormal proliferation of hematopoietic cells. STAT3 a transcription factor and an oncogene is upregulated in many tumor types. Despite its well-defined functions, STAT3 has also been proposed as a metabolic regulator. In this study, we aimed to determine the role STAT3 activation in glucose limitation, in leukemia cell lines. K562, NB-4 and HL-60 cells were found sensitive to glucose limitation. In low glucose conditions, total and nuclear STAT3 protein was decreased in all cells. In mitochondria, S727 phosphorylated STAT3 (mitochondrial form) was determined slightly increased in K562 and NB-4 cells. On the other side, ectopically STAT3 expressing cells had increased glucose consumption and less proliferated in low glucose medium. This data suggests that aerobic glycolysis might be upregulated upon STAT3 expression in leukemia cells, in glucose limitation. Furthermore, in this study, it was found that GLUT3 expressing cells did not reduce STAT3 expression in low glucose medium. GLUT3 was previously determined as a molecular marker for cell sensitivity to glucose limitation, therefore, it could be hypothesized as GLUT3 expressing cells might not need to alter STAT3 expression in low glucose level. Overall, our data suggest that leukemia cells rewire glucose metabolism via STAT3 expression in glucose limitation. Elucidating pathways that cause differential phosphorylation of STAT3 and its interaction with other energy regulating pathways in cellular response to glucose limitation might be beneficial to design new drug targets such as STAT3 inhibitors for leukemia treatment.

Protective effect of liraglutide on experimental testicular ischaemia reperfusion in rats.

This study was performed to evaluate the effect of liraglutide on experimental testicular ischaemia reperfusion in rats in terms of biochemistry, histopathology and immunohistochemistry. A total of 28 male Wistar-Albino rats were divided randomly into 4 groups: control (7), sham (7), ischaemia-reperfusion (7) and ischaemia-reperfusion + liraglutide (7). Biochemically, Nitric Oxide, Malondialdehyde, Superoxide dismutase, Glutathione peroxidase and Catalase levels were measured in the testis. Apoptosis protease activating factor-1 and inducible nitric oxide synthase activity were evaluated immunohistochemically as well. Statistical analyses were made via the Kruskal-Wallis and Mann-Whitney U tests. In the reperfusion group, CAT and SOD values were increased (p > .05), NO and MDA values were decreased (p < .05) after administration of liraglutide. In addition, GPx values were significantly increased in ischaemia reperfusion + liraglutide administered group compared to reperfusion group (p < .05). Apaf-1 and iNOS activity were significantly decreased with the addition of liraglutide treatment to the ischaemia-reperfusion group (p < .05). First of all, we would like to say that liraglutide treatment is moderately preventive against I/R injury in testicular torsion. The anti-inflammatory, antioxidant and antiapoptotic properties of liraglutide are create a moderately protective effect as we show in this study.

Association of Serum Paraoxonase 1 Activities, Polymorphisms and Oxidative Stress in Breast Cancer Patients with Type 2 Diabetes Mellitus.

BACKGROUND: The aim of the study was to investigate the association of paraoxonase 1 (PON1) polymorphism, PON1/arylesterase (ARE) activity and oxidative stress index (OSI) in breast cancer (BC) patients with type 2 diabetes (DM). METHODS: Our study group consisted of 30 healthy women (HV group) and 66 female BC patients. The BC patients were divided into two groups: those with (n=37) and without DM (n=29) (BDM and NBDM group). Genotyping of PON1 Q192R and L55M polymorphisms were done by polymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP) method. Serum PON1/ARE enzyme activities, total oxidant status (TOS) and total antioxidant status (TAS) were analysed by spectrophotometric method. The ratio of TOS to TAS was accepted as the oxidative stress index (OSI). RESULTS: PON1 Q192R genotype frequency distribution was significantly different in the BDM group compared to the NBDM group (p=0.021). When alleles distribution was examined, R and L alleles were significantly lower, Q and M alleles were significantly higher in the BDM group than in the NBDM group (p<0.001). TOS and OSI were statistically higher in BC patients than HV group (p<0.001). CONCLUSIONS: Our results suggest that PON1 gene Q and M alleles may be the risk factors predisposing formation of BC due to increased oxidant damage seen in DM. However, these statements require further confirmation with screening PON1 polymorphism in a greater number of patients with DM, and also wide range follow-up studies are necessary for the same purpose.

Comparative Performance Analysis of Urised 3 and DIRUI FUS-200 Automated Urine Sediment Analyzers and Manual Microscopic Method.

OBJECTIVE: Microscopic examination of urine sediment is necessary for evaluation of renal and urinary tract diseases. In this study, we evaluated and compared analytic and diagnostic performances of DIRUI FUS-200 and a new image-based automated urine sediment analyzer Urised 3. METHOD: A total of 440 urine samples, submitted to our laboratory, were evaluated by two automated urine sediment analyzers and a standardized manual microscopy. Precision, linearity and method comparison studies were performed according to CLSI guidelines. RESULTS: Considering the red blood cell (RBC) and white blood cell (WBC) counts, strong correlations existed between FUS-200 and manual microscopy (r=0.993 vs 0.861), Urised 3 and manual microscopy (r=0.962 vs 0.818), FUS200 and Urised 3 (r=0.961 vs 0.961). Clinical non-concordance ranged from 7% to 14.16% among all methods. CONCLUSIONS: The concordance between the analyzers and manual microscopy for WBC was better than that of RBC. The concordance between the two analyzers was better for WBC and RBC, with respect to the manual microscopy. Although the Urised 3, FUS-200 and manual microscopy counts were in agreement; confirmation of the results of automated analyzers with manual microscopy is particularly helpful, for pathological samples with near cut-off values.

Beneficial effects of Oltipraz, nuclear factor - erythroid - 2 - related factor 2 (Nrf2), on renal damage in unilateral ureteral obstruction rat model

ABSTRACT Introduction: We investigated whether Oltipraz (OPZ) attenuated renal fibrosis in a unilateral ureteral obstruction (UUO) rat model. Materials and Methods: We randomly divided 32 rats into four groups, each consisting of eight animals as follows: Rats in group 1 underwent a sham operation and received no treatment. Rats in group 2 underwent a sham operation and received OPZ. Rats in group 3 underwent unilateral ureteral ligation and received no treatment. Group 4 rats were subjected to unilateral ureteral ligation plus OPZ administration. Transforming growth factor beta-1 (TGF-β1), E-cadherin, nitric oxide (NO) and hydroxyproline levels were measured. Histopathological and immunohistochemical examinations were carried out. Results: TGF-β1, NO and E-cadherin levels in the UUO group were significantly higher than the sham group and these values were significantly different in treated groups compared to the UUO group. In rats treated with UUO + OPZ, despite the presence of mild tubular degeneration and less severe tubular necrosis, glomeruli maintained a better morphology when compared to the UUO group. Expressions of α-SMA in immunohistochemistry showed that the staining positivity decreased in the tubules of the OPZ-treated group. Conclusions: While the precise mechanism of action remains unknown, our results demonstrated that OPZ exerted a protective role in the UUO-mediated renal fibrosis rat model highlighting a promising therapeutic potency of Nrf2-activators for alleviating the detrimental effects of unilateral obstruction in kidneys.

Beneficial effects of Oltipraz, nuclear factor - erythroid - 2 - related factor 2 (Nrf2), on renal damage in unilateral ureteral obstruction rat model.

INTRODUCTION: We investigated whether Oltipraz (OPZ) attenuated renal fibrosis in a unilateral ureteral obstruction (UUO) rat model. MATERIALS AND METHODS: We randomly divided 32 rats into four groups, each consisting of eight animals as follows: Rats in group 1 underwent a sham operation and received no treatment. Rats in group 2 underwent a sham operation and received OPZ. Rats in group 3 underwent unilateral ureteral ligation and received no treatment. Group 4 rats were subjected to unilateral ureteral ligation plus OPZ administration. Transforming growth factor beta-1 (TGF-ß1), E-cadherin, nitric oxide (NO) and hydroxyproline levels were measured. Histopathological and immunohistochemical examinations were carried out. RESULTS: TGF-ß1, NO and E-cadherin levels in the UUO group were significantly higher than the sham group and these values were significantly different in treated groups compared to the UUO group. In rats treated with UUO + OPZ, despite the presence of mild tubular degeneration and less severe tubular necrosis, glomeruli maintained a better morphology when compared to the UUO group. Expressions of α-SMA in immunohistochemistry showed that the staining positivity decreased in the tubules of the OPZ-treated group. CONCLUSIONS: While the precise mechanism of action remains unknown, our results demonstrated that OPZ exerted a protective role in the UUO-mediated renal fibrosis rat model highlighting a promising therapeutic potency of Nrf2-activators for alleviating the detrimental effects of unilateral obstruction in kidneys.

Effects of Tadalafil 5 mg Dosed Once Daily in Men with Premature Ejaculation.

PURPOSE: In this study, we evaluated the effect of 5 mg tadalafil once daily in men with premature ejaculation (PE). METHODS: Thirty married men with lifelong PE and 30 healthy men as control group were included in this study. All the patients received 5 mg tadalafil once a day for a month. The international index of erectile function questionnaire and intravaginal ejaculatory latency times (IELTs) and PE profile were recorded before and after treatment. Plasma samples were collected before and after treatment. RESULTS: The mean baseline IELTs was 40.8 ± 8.1 s in the PE group and 196.5 ± 26.2 s in the control group. After treatment in the PE group, the mean IELTs values showed a statistically significant improvement from the baseline values. At the end of 4 weeks, in the PE group, the mean IELT values showed a statistically significant improvement from the baseline values. Baseline serum nitric oxide (NO) levels were 27.3 ± 1.7 in the PE group and in the 31.1 ± 1.4 healthy control groups. After treatment, NO levels were increased from baseline. CONCLUSION: We consider that 5 mg tadalafil once daily is safety and effective for the treatment of PE.

Low serum Insulin Like Growth Factor - 1 in patients with Stress Urinary Incontinence.

OBJECTIVE: SUI, involuntary loss of urine, occurs when intra abdominal pressure exceeds urethral pressure in women. Recent animal study has shown that there are therapeutic effects of Insulin-like growth factors (IGF-1) on stress urinary incontinence in rats with simulated childbirth trauma. IGF-1 is an important mediator of cell growth, differentiation and transformation in various tissues and stimulates fibroblast proliferation and enhances collagen synthesis. The purpose of the current study was to determine the association between IGF-1 levels and SUI. MATERIALS AND METHODS: All patients were evaluated for SUI and divided into two groups: 116 women with SUI and 76 women without SUI. Diagnosis of SUI was based on the International Consultation on Incontinence Questionnaire-Short Form (ICIQSF). Levels of IGF-1 were measured in serum by enzyme-linked immunosorbent assay. The relationship between IGF-1 levels and SUI in patients was evaluated statisticaly. RESULTS: The mean age of patients wiyh SUI was 49.9±8.6 and 48.7±7.8 in control group. Plasma IGF-1 levels were significantly lower in SUI than in control group (106.5±26.4 and 133.3±37.1ng/mL, respectively, P <0.001). Body mass indexes were higher in women with SUI than women without SUI. CONCLUSION: In this study lower serum IGF-1 levels were found to be associated with SUI. Serum IGF-1 level appears to be a specific predictor of SUI, and it may be used in early prediction of SUI in female population.

Perifollicular blood flow and its relationship with endometrial vascularity, follicular fluid EG-VEGF, IGF-1, and inhibin-a levels and IVF outcomes.

PURPOSE: The aim of this study is to investigate the association of perifollicular blood flow (PFBF) with follicular fluid EG-VEGF, inhibin-a, and insulin-like growth factor-1 (IGF-1) concentrations, endometrial vascularity, and IVF outcomes. METHODS: Forty women with tubal factor infertility were included in a prospective cohort study. Each woman underwent IVF/ICSI procedure. Individual follicles of ≥16 mm (n = 156) were evaluated by power Doppler analysis and categorized as well-vascularized follicles (WVFs) or poorly vascularized follicles (PVFs). WVFs referred to those with perifollicular vascularity of 51-100 %. Each follicular fluid (FF) was individually aspirated and FF/serum EG-VEGF, inhibin-a, and FF IGF-1 levels were evaluated. Zones III-IV endometrial vascularity was classified as a well-vascularized endometrium (WVE). The presence of a WVE and mature oocytes, in addition to the embryo quality and clinical pregnancy rate (CPR), were recorded for each follicle. The main outcome measures were FF serum EG-VEGF, inhibin-a, IGF-1 levels, and WVE and IVF outcome per PFBF. RESULTS: For WVFs, the level of FF EG-VEGF (p = 0.008), oocyte quality (p = 0.001), embryo quality (p = 0.002), a WVE (p = 0.001), and CPR (p = 0.04) increased significantly. The pregnant group was characterized by increased numbers of WVFs (p = 0.044), a WVE (p = 0.022), and increased levels of FF IGF-1 (p = 0.001) and serum EG-VEGF (p = 0.03). FF IGF-1 >50 ng/mL (AUC 0.72) had 75 % sensitivity and 64 % specificity for predicting CPR. CONCLUSIONS: WVFs yield high-quality oocytes and embryos, a WVE, increased FF EG-VEGF levels, and increased CPRs.

Low serum Insulin Like Growth Factor - 1 in patients with Stress Urinary Incontinence

ABSTRACT Objective: SUI, involuntary loss of urine, occurs when intra abdominal pressure exceeds urethral pressure in women. Recent animal study has shown that there are therapeutic effects of Insulin-like growth factors (IGF-1) on stress urinary incontinence in rats with simulated childbirth trauma. IGF-1 is an important mediator of cell growth, differentiation and transformation in various tissues and stimulates fibroblast proliferation and enhances collagen synthesis. The purpose of the current study was to determine the association between IGF-1 levels and SUI. Materials and Methods: All patients were evaluated for SUI and divided into two groups: 116 women with SUI and 76 women without SUI. Diagnosis of SUI was based on the International Consultation on Incontinence Questionnaire-Short Form (ICIQSF). Levels of IGF-1 were measured in serum by enzyme-linked immunosorbent assay. The relationship between IGF-1 levels and SUI in patients was evaluated statisticaly. Results: The mean age of patients wiyh SUI was 49.9±8.6 and 48.7±7.8 in control group. Plasma IGF-1 levels were significantly lower in SUI than in control group (106.5±26.4 and 133.3±37.1ng/mL, respectively, P <0.001). Body mass indexes were higher in women with SUI than women without SUI. Conclusion: In this study lower serum IGF-1 levels were found to be associated with SUI. Serum IGF-1 level appears to be a specific predictor of SUI, and it may be used in early prediction of SUI in female population.

Low serum insulin-like growth factor-1 in patients with erectile dysfunction.

OBJECTIVE: Endothelial dysfunction and microvascular damage play a crurical role in the pathogenesis of erectile dysfunction (ED). Insulin-like growth factor-1 (IGF-1) is one of the growth factors that have a wide range of biologic effects. IGF-1 is an important mediator of cell growth, differentiation and transformation in various tissues. The purpose of the current study was to determine the association between IGF-1 levels and ED. MATERIALS AND METHODS: All men were evaluated for ED and divided into two groups: 80 patients suffering from ED for > 1 year and 80 subjects without ED were enrolled as a control group in this study. Diagnosis of ED was based on the International Index of Erectile Function Score-5. IGF-1 levels were measured in serum by an automated chemiluminescence immunoassay. The relationship between IGF-1 levels and ED scores in patients was statistically evaluated. RESULTS: The mean age of patients in ED group was 60.4 ± 11.3 years and 55.4 ± 9.6 in control group. The plasma IGF-1 levels were significantly lower in ED than in control group (96.5 ± 38.3 and 132.5 ± 53.3 ng/ mL, respectively, P < 0.001). The IGF-1 levels were positively correlated with ED score (r = 0.623, P < 0.01). CONCLUSION: In this study serum IGF-1 levels were found to be associated with endothelial dysfunction that predicts ED. Serum IGF-1 level appears to be a specific predictor of ED, and it might be used in early prediction of ED in male population.

OBJECTIFS: La dysfonction endothéliale et les altérations vasculaires jouent un rôle crucial dans la pathogenèse de la dysfonction érectile (DE). L'Insulin-like Growth Factor-1 (IGF-1) est l'un des facteurs de croissance qui ont un vaste champ d'effets biologiques. IGF-1 est un médiateur important de la croissance, différentiation et transformation cellulaires dans différents tissus. Le but de la présente étude était de rechercher une association entre les taux d'IGF-1 et la dysfonction érectile. MATÉRIEL ET MÉTHODES: La dysfonction érectile a été évaluée chez tous les hommes, constitués en 2 groupes : 80 patients souffrant de DE depuis plus d'un an, et 80 sujets sans DE recrutés comme groupe témoin dans l'étude. Le diagnostic de DE était basé sur le score 5 de l'Index International de la Fonction Erectile. Les taux d'IGF-1 ont été mesurés par immunodosage automatisé par chemiluminescence. La relation entre les taux d'IGF-1 et le score de la DE a été statistiquement évaluée. RÉSULTATS: L'âge moyen des patients du groupe DE était de 60.4±11.3 ans et de 55.4±9.6 dans le groupe témoin. Les taux plasmatiques d'IGF-1 étaient significativement plus bas dans le groupe DE que chez les témoins (respectivement 96.5±38.3 et 132.5±53.3 ng/mL, P < 0.001). Les taux d'IGF-1 étaient positivement corrélés au score de la DE (r = 0.623, P < 0.01). CONCLUSIONS: Nos résultats indiquent que les taux sériques d'IGF-1 sont associés à une dysfonction endothéliale qui prédit la DE. L'IGF-1 sérique apparaît être un prédicteur spécifique de la DE, et il pourrait être utilisé pour une prédiction précoce de la DE dans la population masculine.

The effects of serum leptin levels on thrombocyte aggregation in peritoneal dialysis patients.

OBJECTIVE: Serum leptin levels of chronic kidney disease patients have been detected higher than normal population. The aim of this study was to investigate the effects of serum leptin levels on thrombocyte aggregation in peritoneal dialysis patients. METHODS: Fourty three peritoneal dialysis patients were included in the study. Thrombocyte aggregation was calculated from the whole blood subsequently the effects of different concentrations of human recombinant leptin on thrombocyte aggregations were investigated. Four test cells were used for this process. While leptin was not added into the first test cell, increasing amounts of leptin was added into the second, third and fourth test cells to attain the concentrations of 25, 50 and 100 ng/ml respectively. RESULTS: Thrombocyte aggregation was inhibited by recombinant leptin in peritoneal dialysis patients. Thrombocyte aggregation mean values were found statistically significantly higher in first test cell when compared to leptin groups in peritoneal dialysis patients. For leptin groups we could not find any statistically significant differences for thrombocyte aggregation mean values between any of the groups. CONCLUSION: Further studies with larger number of peritoneal dialysis patients are required to prove the action of leptin on thrombocyte aggregation.

Urinary nerve growth factor and a variable solifenacin dosage in patients with an overactive bladder.

INTRODUCTION AND HYPOTHESIS: We evaluated changes in urinary nerve growth factor (NGF) and NGF/creatinine (NGF/Cr) levels after increasing the dosage of solifenacin in overactive bladder patients. METHODS: The study groups included 59 overactive bladder (OAB) patients and 20 healthy subjects as controls. We measured NGF at baseline for the patients and controls, and used the Overactive Bladder Awareness Tool (OAB-V8) to evaluate urinary symptoms. All patients received a treatment of solifenacin 5 mg for 6 weeks. The responders to treatment served as group 1 and nonresponders received solifenacin 10 mg for an additional 6 weeks. Responders and nonresponders to the 10-mg treatment were defined as groups 2 and 3 respectively. NGF was measured after each treatment using the ELISA method and normalized by the urinary creatinine levels (NGF/Cr). RESULTS: There were 21, 22 and 16 patients in groups 1, 2, and 3 respectively. At baseline, the NGF and NGF/Cr levels were higher in groups 1, 2, and 3 compared with the controls. After the solifenacin 5 mg treatment, the NGF and NGF/Cr levels of group 1 individuals decreased to those of the control level. After increasing the dosage of solifenacin to 10 mg in group 2, the NGF and NGF/Cr levels decreased to normal levels. In group 3 (patients who did not responded to any treatment), these levels remained unchanged. CONCLUSIONS: Our results suggest that urinary NGF could be a potential biomarker for monitoring the treatment of symptoms in OAB patients who are treated with solifenacin.

Soluble Programmed Death 1 (PD-1) Is Decreased in Patients With Immune Thrombocytopenia (ITP): Potential Involvement of PD-1 Pathway in ITP Immunopathogenesis.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by dysregulation of T cells. Programmed death (PD) 1 and programmed death 1 ligand 1 (PD-L1) are cosignaling molecules, and the major role of the PD-1 pathway is the inhibition of self-reactive T cells and to protect against autoimmune diseases. We measured levels of serum soluble PD 1 (sPD-1) and serum soluble PD-L1 (sPD-L1) in 67 patients with ITP (24 newly diagnosed ITP [ndITP], 43 chronic ITP [cITP]) and 21 healthy controls (HCs). We determined decreased serum sPD-1 levels both in patients with ndITP and in patients with cITP when compared to HC. Moreover, there was a positive correlation between sPD-1 levels and platelet counts. The sPD-L1 levels were decreased in patients with ndITP when compared to patients with cITP. This is the first study investigating PD-1 signaling pathway in ITP. Decreased sPD-1 levels may have a role in ITP pathogenesis as without the inhibitory regulation of PD-1, sustained activation of T cells may cause inflammatory responses which is the case in ITP.

Protective effect of hydrogen sulfide on renal injury in the experimental unilateral ureteral obstruction

Introduction/Objective: Ureteral obstruction is a common pathology and causes kidney fibrosis and dysfunction at late period. In this present study, we investigated the antifibrotic and antiinflammatory effects of hydrogen sulfide on kidney damage after unilateral ureteral obstruction (UUO) in rats. Materials and Methods: 24 rats were divided into four groups. Group 1 was control, group 2 was sham, group 3 included rats with UUO and group 4 rats with UUO which were given sodium hydrogen sulfide (NaHS)-exogenous donor of hydrogen sulfide (intraperitoneally 56μmoL/kg/day). After 14 days, rats were killed and their kidneys were taken and blood analysis was performed. Tubular necrosis, mononuclear cell infiltration and interstitial fibrosis were determined histopathologically in a part of the kidneys; nitric oxide (NO), malondialdehyde (MDA) and reduced glutathione (GSH) levels were determined in the other part of the kidneys. Urea-creatinine levels were investigated by blood analysis. Statistical analyses were made by the Chi-square test and one-way analysis of variance (ANOVA). Results: There was no significantly difference for urea-creatinine levels among groups. Pathologically, there was serious tubular necrosis and fibrosis in group 3 and there was significantly decreasing of tubular necrosis and fibrosis in group 4 (p<0.005). Also, there was significantly increase of NO and MDA levels and decrease of GSH levels in group 3 compared to other groups (p<0.005). Conclusions: hydrogen sulfide prevents kidney damage with antioxidant and antiinflammatory effect.

Neuroprotective effect of edaravone in experimental glaucoma model in rats: a immunofluorescence and biochemical analysis.

AIM: To evaluate the neuroprotective activity of systemically administered edaravone in early and late stage of experimental glaucoma in rats. METHODS: In this study, 60 Wistar albino rats were used. Experimental glaucoma model was created by injecting hyaluronic acid to the anterior chamber once a week for 6wk in 46 of 60 subjects. Fourteen subjects without any medication were included as control group. Edaravone administered intraperitoneally 3 mg/kg/d to the 15 of 30 subjects starting at the onset of glaucoma induction and also administered intraperitoneally 3 mg/kg/d to the other 15 subjects starting at three weeks after the onset of glaucoma induction. The other 16 subjects who underwent glaucoma induction was administered any therapy. Retinal ganglion cells (RGCs) have been marked with dextran tetramethylrhodamine (DTMR) retrograde at the end of the sixth week and after 48h, subjects were sacrificed by the method of cardiac perfusion. Alive RGC density was assessed in the whole-mount retina. Whole-mount retinal tissues homogenized and nitric oxide (NO), malondialdehyde (MDA) and total antioxidant capacity (TAC) values were measured biochemically. RESULTS: RGCs counted with Image-Pro Plus program, in the treatment group were found to be statistically significantly protected, compared to the glaucoma group (Bonferroni, P<0.05). The neuroprotective activity of edaravone was found to be more influential by administration at the start of the glaucoma process. Statistically significant lower NO levels were determined in the glaucoma group comparing treatment groups (Bonferroni, P<0.05). MDA levels were found to be highest in untreated glaucoma group, TAC levels were found to be lower in the glaucoma induction groups than the control group (Bonferroni, P<0.05). CONCLUSION: Systemic administration of Edaravone in experimental glaucoma showed potent neuroprotective activity. The role of oxidative stress causing RGC damage in glaucoma was supported by this study results.

Beneficial effects montelukast, cysteinyl-leukotriene receptor antagonist, on renal damage after unilateral ureteral obstruction in rats.

INTRODUCTION: Ureteral obstruction is a common pathology and caused kidney fibrosis and dysfunction at late period. In this present, we investigated the antifibrotic and antiinflammatory effects of montelukast which is cysteinyl leukotriene receptor antagonist, on kidney damage after unilateral ureteral obstruction(UUO) in rats. MATERIALS AND METHODS: 32 rats divided four groups. Group 1 was control, group 2 was sham, group 3 was rats with UUO and group 4 was rats with UUO which were given montelukast sodium (oral 10 mg/kg/day). After 14 days, rats were killed and their kidneys were taken and blood analysis was performed. Tubular necrosis, mononuclear cell infiltration and interstitial fibrosis scoring were determined histopathologically in a part of kidneys; nitric oxide(NO), malondialdehyde(MDA) and reduced glutathione(GSH) levels were determined in the other part of kidneys. Urea-creatinine levels were investigated at blood analysis. Statistical analyses were made by the Chi-square test and one-way analysis of variance (ANOVA). RESULTS: There was no difference significantly for urea-creatinine levels between groups. Pathologically, there was serious tubular necrosis and fibrosis in group 3 and there was significantly decreasing for tubular necrosis and fibrosis in group 4(p<0.005). Also, there was significantly increasing for NO and MDA levels; decreasing for GSH levels in group 3 compared the other groups(p<0.005). CONCLUSION: We can say that montelukast prevent kidney damage with antioxidant effect, independently of NO.