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.

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.

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.

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.

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.

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.

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 56 µmoL/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.

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.

Serum cytokine levels in patients with colorectal cancers according to tumor stages and VEGF gene polymorphism.

BACKGROUND/AIMS: Colorectal cancers are the most common cancers of the gastrointestinal system. A significant relationship was detected between the metastasis and tumor angiogenesis of colorectal cancer. The aim of the present study was to investigate the association between some cytokines and tumor stages. Additionally, association between VEGF gene polymorphisms and colorectal cancer was studied. METHODS: In this study, we measured serum IL-18, IL-2, VEGF, endothelin (ET), and nitric oxide (NO) levels in 44 patients with colorectal cancer and 44 healthy controls. Also we investigated VEGF G634C (rs2010963) and VEGF C936T (rs3025039) polymorphisms of VEGF gene in these groups by using a PCR-RFLP method. Data were analyzed statistically. RESULTS: Serum levels of IL-18, VEGF, IL-2 and NO were significantly higher in patients with colorectal cancer when compared to controls (p<0,05). Serum ET levels were found to be similar in colorectal cancer patients and healthy controls. When we compared the two subgroups constituted by tumor stages (Stage 1-2 and Stage 3-4) with each other, serum VEGF levels were found significantly higher in stage 3-4 group than stage 1-2 group (p<0,05). No significant difference was found between subgroups with regard to other parameters. We found that investigated VEGF G634C and VEGF C936T polymorphisms were not associated with the severity of colorectal cancer. (P=0.228 for VEGF G­634-C; P= 0.484 for VEGF C­936-T) CONCLUSION: In the future, serum levels of IL-18, VEGF, IL-2 and NO may be a useful marker for diagnosis of patients with colorectal cancer. Additionally we consider that serum VEGF levels can be used as a tumor marker to predict prognosis of cancer. However, larger studies with long-term follow-up are necessary to clarify this hypothesis. On the other hand, there is necessity for the new studies for determination of association between VEGF gene polymorphism and colorectal cancer.

Correlation of Cystatin-C and radionuclidic measurement method of glomerular filtration rate in patients with lung cancer receiving cisplatin treatment.

OBJECTIVE: Cisplatin is a chemotherapeutic agent which affects renal functions adversely. The best indicator of renal functions is glomerular filtration rate (GFR) measurement. Cystatin-C appears to be a good alternative to existing methods of measuring GFR. However, it is controversial whether Cystatin-C demonstrates GFR correctly for patients receiving chemotherapy. This study aimed to investigate the correlation between GFR values calculated by Cystatin-C based formulas, radionuclidic method (multiple blood sampling) and blood Cystatin-C values in patients with lung cancer, receiving cisplatin treatment in both pre-treatment and post-treatment periods. MATERIALS AND METHODS: Thirty-six patients with lung cancer who were going to receive cisplatin treatment were included in this study. However, the evaluation was performed with 20 patients since 16 of them could not complete the treatment. Blood Cystatin-C values, GFR values calculated via Cystatin-C based formulas, and radionuclidic method were investigated before and after the cisplatin treatment. RESULTS: After treatment significant decreases were detected in GFR values, obtained via radionuclidic measuring method. However, there was no significant difference in Cystatin-C values between pre-treatment and post-treatment periods. Also GFR values obtained by Cystatin-C based formulas were not significantly different in pre-treatment and post-treatment periods. There were meaningful correlations between radionuclidic method and Cystatin-C values and Cystatin-C based formulas before treatment. However, all correlations disappeared after the treatment. CONCLUSION: GFR values, calculated by Cystatin-C may not be reliable in following renal functions in patients receiving chemotherapy. When reliable monitoring of the renal functions is necessary radionuclidic method may be preferred in these patients.

Protective effect of hydrogen sulfide on gentamicin-induced renal injury.

OBJECTIVE: We evaluated the potential protective effect of hydrogen sulfide (H2S) against GEN-induced nephrotoxicity in rats. MATERIALS AND METHODS: Twenty-four rats were randomly divided into four groups, each consisting of six animals as follows: (1) the rats were control, (2) intraperitoneally injected with GEN 14 consecutive days (100 mg/kg/day), (3) treated with GEN plus %0.9 saline intraperitoneally for 14 days and (4) treated with GEN plus sodium hydrogen sulfide (NaHS)-exogenous H2S donor (56 µmol/kg/day) for 14 days. After 15 days, rats were sacrificed and their kidneys were taken and blood analysis was performed. Twenty-four hours urine collections were obtained in standard metabolic cages a day before the rats were sacrificed. Tubular necrosis 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. Statistical analyses were made by the chi-squared test and one-way analysis of variance. RESULTS: Serum urea and creatinine levels were significantly higher in rats treated with GEN alone, than the rats in control and GEN + NaHS groups. The GSH levels in renal tissue of only GEN-treated rats were significantly lower than those in control group, and administration of NaHS to GEN-treated rats significantly increased the level of GSH. The group that was given GEN and NaHS had significantly lower MDA and NO levels in kidney cortex tissue than those that was given GEN alone. In rats treated with GEN + NaHS, despite the presence of mild tubular degeneration and tubular necrosis are less severe, and glomeruli maintained a better morphology when compared with GEN group. DISCUSSION: We can say that H2S prevent kidney damage with antioxidant and anti-inflammatory effect.

Pomegranate extract attenuates gentamicin-induced nephrotoxicity in rats by reducing oxidative stress.

Nephrotoxicity is a major complication of gentamicin (GEN), which is widely used in the treatment of severe Gram-negative infections. Reactive oxygen species are important mediators of GEN-induced nephrotoxicity. Because of the strong antioxidant properties of pomegranate extract (PE), we evaluated the protective effect of PE against GEN-induced nephrotoxicity. Thirty-two adult male rats were randomly divided into four equal groups: (1) controls; (2) treated with GEN for 14 consecutive days (100 mg/kg/day); (3) treated with GEN plus distilled water; and (4) treated with GEN plus PE (100 µL). After 15 days, the rats were killed and their kidneys were taken, and blood analysis was performed. Tubular necrosis and interstitial fibrosis scores were determined histopathologically; and biochemically, nitric oxide (NO), malondialdehyde (MDA), and reduced glutathione (GSH) levels in kidneys were determined. Urea, creatinine, Na(+), and K(+) levels were investigated in the blood analysis. Statistical analyses were made by the chi-square test and analysis of variance. Serum urea and creatinine levels were significantly higher in rats treated with GEN alone than rats in the control and the GEN + PE-treated groups. The GSH level in renal tissue of only GEN-treated rats was significantly lower than those in the control group, and administration of PE to GEN-treated rats significantly increased the level of GSH. The group that was given GEN and PE had significantly lower MDA levels in kidney cortex tissue than those given GEN alone. There was no significant difference of NO levels between the groups. In rats treated with GEN + PE, despite the presence of mild tubular degeneration and tubular necrosis is less severe, and glomeruli maintained a better morphology when compared with the GEN-treated group. We think that PE prevents kidney damage by decreasing oxidative stress in kidney.

Protective effect of montelukast which is cysteinyl-leukotriene receptor antagonist on gentamicin-induced nephrotoxicity and oxidative damage in rat kidney.

Nephrotoxicity is a major complication of gentamicin (GEN). We aimed to evaluate the potential protective effect of montelukast (MK) against GEN-induced nephrotoxicity in rats. Thirty-two rats were randomly divided into four groups, each consisting of eight animals as follows: (1) the rats were control; (2) intraperitoneally injected with GEN 14 consecutive days (100 mg/kg/day); (3) treated with GEN plus distilled water via nasogastric gavage for 14 days; and (4) treated with GEN plus MK (10 mg/kg/day) for 14 days. After 15 days, rats were killed and their kidneys were taken and blood analysis was performed. Twenty-four hours urine collections were obtained in standard metabolic cages a day before the rats were killed. Tubular necrosis 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. Statistical analyses were made by the chi-square test and analysis of variance. Serum urea and creatinine levels were significantly higher in rats treated with GEN alone, than the rats in control and GEN + MK groups.The GSH levels in renal tissue of only GEN-treated rats were significantly lower than those in control group, and administration of MK to GEN-treated rats significantly increased the level of GSH. The group that was given GEN and MK had significantly lower MDA and NO levels in kidney cortex tissue than those that was given GEN alone. In rats treated with GEN + MK, despite the presence of mild tubular degeneration and tubular necrosis are less severe, and glomeruli maintained a better morphology when compared with GEN group. We can say that MK prevents kidney damage with antioxidant effect, independently of NO.

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.

Nitric oxide: a new biomarker of Doxorubicin toxicity in children?

Doxorubicin (DOX) has been used in the treatment of childhood cancers, but its usage is limited because of cardiotoxicity. There are many studies on the role of nitric oxide (NO) in several cardiac diseases. However, to the authors' knowledge, no studies have investigated the plasma levels of total nitrite, a stable product of NO, in children that received DOX. The authors determined plasma total nitrite levels in 29 children who received DOX and investigated the correlations between these and other clinical and laboratory findings. All patients were in remission during the study period. Plasma total nitrite levels and cardiac functions were determined prospectively. The mean cumulative DOX dose was 310.0 ± 90.9 mg/m(2). In echocardiographic evaluation, 3 patients (10.3%) had a pathological value for ejection fraction (EF) and/or fractional shortening (FS), whereas 11 patients (37.9%) had a threshold value. Total nitrite levels were higher in patients than in matched controls (75.24 ± 39.4 vs 43.14 ± 10.58 µmol/L, respectively, P < .001). It was also found to be higher in patients who had a pathological/threshold value of EF and FS than in patients who had a physiological value of EF and FS (92.35 ± 50.36 vs 59.26 ± 13.56 µmol/L, respectively, P = .038). A negative correlation was found between FS and plasma total nitrite level (r = -.42, P = .023). The authors speculate that increased NO may be a sign of subclinical cardiotoxicity of DOX.

Association between documented coronary artery disease and urinary albumin, albumin to creatinine ratio.

BACKGROUND: The aim of this study was to investigate whether the amount of urinary albumin concentration (UAC) or urinary albumin to creatinine ratio (UACR) is more strongly associated with angiographically documented coronary artery disease (CAD). MATERIAL/METHODS: A total of 199 consecutive patients [11 9(60%) male, 80 (40%) female, mean age =57±10] undergoing diagnostic coronary angiography were included in the study. Significant coronary artery disease was defined as a stenosis equal to or above 50% in the main coronary artery or in one of the other branches. UAC and UACR were calculated from the urine. Baseline clinical parameters, UAC and UACR were compared between subjects with and without CAD. Factors predicting CAD were evaluated by multivariate analysis. RESULTS: Baseline clinical and laboratory characteristics of patients with and without CAD were not different except for a slightly male predominance in patients with CAD. Patients with CAD had significantly higher UACs and UACRs than patients without CAD (32.14±31.27 mg/day vs. 15.61±16.70 mg/day, p=0.01; 9.11±7.42 mg/g vs. 4.80±3.28 mg/g, p=0.009). A positive correlation was found between Gensini score and UACR (p=0.01), whereas no correlation was found between Gensini and UAC. UACR was the only significant parameter for the presence of CAD in the multivariate analysis adjusted for age, sex, other well known CAD risk factors, UAC and UACR. CONCLUSIONS: Our preliminary results suggest that UACR is more closely associated with angiography documented CAD than is the level of UAC itself, but UACR maybe more significantly associated with angiography documented CAD than with the levels of UAC.