[Elevated pleural copeptin levels can distinguish to exudate from transudates]. / Yüksek plevral copeptin düzeyleri eksüdayi transüdadan ayirabilir.

INTRODUCTION: Copeptin is released simultaneously along with arginine-vasopressine as a result of different stimuli from the neurohypophysis. Physiological function of copeptin is still unclear. Increased blood copeptin levels is associated with poor prognosis in many diseases. Pleural effusion is a common clinical condition. The most common causes of pleural effusions are heart failure, parapneumonic effusion, pulmonary embolism and malignacy.Tuberculosis is one of the other major causes of pleural effusion in developing countries. In this study, we aimed to assess whether pleural copeptin level may be a new discriminative biomarker for exudates and transudates pleural effusions. MATERIALS AND METHODS: Research was done at Recep Tayyip Erdogan University School of Medicine in the Department of Chest Diseases. The concentrations of pleural copeptin and typical pleural and serum marker levels were measured in 76 subjects with pleural effusions including 22 transudates caused by congestive heart failure (CHF), and 54 exudates including 18 parapneumonic (PPE), 18 tuberculous pleural effusions (TBPEs), 18 malignant effusions (MPEs). RESULTS: Median pleural fluid copeptin levels were higher in exudates than in transudates (1936 ng/mL and 1313 pg/mL, p value < 0.001). There was no statistical significancy for pleural fluid copeptin levels with in-group exudates (n= 54). Pleural copeptin levels of exudates, with a cut off value of 1469 ng/mL, yielded a 79.6% sensitivity, 81.8% specificity, with an are a under the curve of 0.851. CONCLUSION: Pleural copeptin level is a new biomarker to separate exudates from transudates. Pleural effusion discriminative effect of copeptin is lower than plasma protein level and plasma lactat dehydrogenase (LDH). Pleural copeptin measurement is not recommended for routine clinical use. Pleural copeptin level is not contribute to different iate exudative pleural fluids from each other like PPE, TBPE and MPE.

Relationship between pulse wave velocity and serum YKL-40 level in patients with early rheumatoid arthritis.

Subclinical atherosclerosis has been demonstrated in patients with early rheumatoid arthritis (ERA) without any signs of cardiovascular disease (CVD). The aim of this study was to investigate the relationship between serum YKL-40 level and arterial stiffness in patients with ERA. Forty two patients with ERA and 35 healthy controls with no history or current sign of CVD were included in the study. ERA patients with active disease, defined as DAS28 ≥ 3.2, and symptoms onset <12 months were recruited. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (CF-PWV), and the intima-media thickness carotid (IMT-C) was measured by carotid ultrasonography. Serum YKL-40 levels were measured by an enzyme-linked immunoassay method. The mean age was 43.1 ± 5.8 years in ERA patients and 41.0 ± 5.9 years in control group. The CFPWV and IMT-C of the ERA patients were determined significantly higher than the control group (P = .001, P < .001, respectively). YKL-40 levels were significantly elevated in ERA patients than controls (P = .008). The serum levels of YKL-40 in the ERA patients showed a strong correlation with CF-PWV (r = .711, P < .001) and IMT-C (r = .733, P < .001). Multiple linear regression analysis revealed that CF-PWV could be explained by serum YKL-40 levels (adjusted R² = .493, P < .001). We have shown that patients with ERA had increased CF-PWV and serum YKL-40 levels. In addition, there was an association between CF-PWV values and serum YKL-40 levels in patients with ERA. As a result, we believe that serum YKL-40 level and CF-PWV might reflect early atherosclerosis in patients with ERA.

High serum YKL-40 level in patients with COPD is related to hypoxemia and disease severity.

Chronic obstructive pulmonary disease (COPD) is a major health problem with increasing morbidity and mortality throughout the world. YKL-40 is a chitin-binding glycoprotein consisting of 383 amino acids, with a molecular mass of 40 kDa, and its serum level is elevated in inflammatory diseases. YKL-40 is a newly recognized biomarker of inflammation and has not been thoroughly investigated in COPD. The aim of the study is to investigate the relationship between serum YKL-40 levels and severity of COPD. The study population consisted of 52 patients with COPD with the mean age of 60.2 ± 10.1 years. The serum YKL-40 level increased significantly with increasing age (p = 0.022, r = 0.346). In COPD patients, high serum YKL-40 level is correlated to low forced expiratory volume at 1 second (FEV1, percent of predicted) (r = -0.277, p = 0.047). Moreover, high serum YKL-40 level is correlated to low arterial oxygen pressure (PaO2, mmHg) (r = -0.387, p = 0.005). The mean serum YKL-40 level was found as 243.1 ± 129.2 ng/ml in COPD patients with desaturation during 6-minute walk test (6MWT) and this value was higher than the mean serum YKL-40 level (155.8 ± 59.1 ng/ml) of COPD patients without desaturation during 6MWT (p = 0.004). This study demonstrated that high serum YKL-40 levels were correlated to severity of COPD. We propose that circulating YKL-40 levels could be a biomarker for hypoxemia and decline in lung function.

Effects of lisinopril on NMDA receptor subunits 2A and 2B levels in the hippocampus of rats with L-NAME-induced hypertension.

Hypertension is major risk factor leading to cerebrovascular pathologies. N-methyl D-aspartate receptors (NMDARs) and renin-angiotensin system are involved in neuronal plasticity, as well as cognitive functions in the hippocampus. In this study, we examined the effects of lisinopril, an ACE inhibitor, on the levels of hippocampal NMDAR subunits; NR2A and NR2B in L-NAME (N(ε)-nitro-L-arginine Methyl Ester)-induced hypertensive rats. In addition, malondialdehyde (MDA) levels were measured as a marker for lipid peroxidation. Compared with the control group, the MDA level was significantly increased after 8 weeks in the L-NAME-treated group. Rats treated with lisinopril and L-NAME plus lisinopril were found to have significantly decreased hippocampal MDA levels. Regarding the hippocampal concentrations of NR2A and NR2B, there were no statistically significant differences between groups. We demonstrated that lisinopril treatment has no direct regulatory effect on the levels of NR2A and NR2B in the rat hippocampus. Our results showed that Lisinopril could act as an antioxidant agent against hypertension-induced oxidative stress in rat hippocampus. The findings support that the use of lisinopril may offer a good alternative in the treatment of hypertension by reducing not only blood pressure but also prevent hypertensive complications in the brain.

Effects of venlafaxine and escitalopram treatments on NMDA receptors in the rat depression model.

Depression may relate to neurocognitive impairment that results from alteration of N-methyl-D: -aspartate receptor (NMDAR) levels. Venlafaxine and escitalopram are two drugs commonly used to treat depression. The drugs may affect expression of NMDARs, which mediate learning and memory formation. The aim of the study was to examine whether the effects of venlafaxine and escitalopram treatments are associated with NMDARs in a rat model of depression. Forty male Wistar albino rats were randomly divided into four groups (n = 10) as follows: control group, chronic mild stress group (CMS), venlafaxine (20 mg/kg body weight per day) + CMS, and escitalopram (10 mg/kg body weight per day) + CMS. After induction of depression, a decrease in the concentration of NR2B was observed; venlafaxine treatment prevented the reduction of NR2B expression. Escitalopram treatment did not effect the reduced levels of NR2B resulting from depression. There was no significant difference in NR2A concentration among groups. The present data support the notion that venlafaxine plays a role in maintaining NR2B receptor in experimental depression. It may be possible that treatment with escitalopram has no effect on NMDARs in experimental depression.

Lisinopril attenuates renal oxidative injury in L-NAME-induced hypertensive rats.

Hypertension and related oxidative stress are involved in the pathogenesis of any renal diseases. Angiotensin-converting enzyme inhibitors have multi-directional renoprotective effects. In this study, we aimed to investigate whether lisinopril treatment has any biochemical alterations on renal tissue in L-NAME (Nε-nitro-L-arginine methyl ester) induced hypertension model. Twenty-eight Sprague-Dawley rats were included in this study and divided into four equal groups (n = 7): control group, L-NAME treated group (75 mg/kg/day), L-NAME plus lisinopril treated group and only lisinopril treated group (10 mg/kg/day). L-NAME and lisinopril were continued for 6 weeks. Systolic blood pressures were measured by using tail cuff method. In biochemical analysis, malondialdehyde (MDA, an index of lipid peroxidation) levels, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in renal tissues were used as markers of oxidative stress-induced renal impairment. Microalbumin and N-acetyl-ß-D-glucosaminidase (NAG) in urine were determined as markers of renal tubular damage related to hypertension. Chronic L-NAME administration resulted in a significant depletion of serum nitric oxide (NO). When compared with control group, serum creatinine, microalbumin, urine NAG, renal tissue MDA level, and CAT activities were significantly high, while renal tissue SOD and GSH-Px activities low in L-NAME group. In the L-NAME plus lisinopril treated group, serum creatinine, microalbumin and urine NAG, renal MDA level and CAT activity decreased, whereas SOD, GSH-Px activities in renal tissue and serum NO levels were increased. Thus, lisinopril treatment reversed these effects. There were not any significant difference between L-NAME plus lisinopril treated group and control group concerning serum creatinine, renal tissue MDA level and SOD, GSH-Px, CAT activities. These results suggest that lisinopril could diminish biochemical alterations in L: -NAME induced hypertensive renal damage that occurs by oxidative stress.

The relationship between serum YKL-40 levels and arterial stiffness in patients with ankylosing spondylitis.

OBJECTIVE: Serum YKL-40 plays roles in inflammatory and vascular processes. Our aim was to evaluate serum YKL-40 levels in patients with ankylosing spondylitis (AS) and to investigate their potential relationship with arterial stiffness based on carotid-femoral pulse wave velocity (CF-PWV). METHODS: Forty-three patients with AS and 41 healthy controls with no history or current signs of cardiovascular disease were included in the study. All patients were administered nonsteroidal anti-inflammatory drugs (NSAIDs), and none were prescribed anti-tumor necrosis factor agents. Serum YKL-40 levels were measured. CF-PWV and intima-media thickness of the common carotid artery (IMT-C) were evaluated. RESULTS: The mean age of AS patients was 34.6 ± 10.2 years and of controls was 36.3 ± 9.0 years. CF-PWV was significantly higher in AS patients than in controls (8.2±2.7 vs.7.0±1.6 m/s, respectively; P=0.015). However, the IMT-C was not significantly different between AS patients and controls (0.6±0.3 vs. 0.5±0.2 mm, P=0.501). YKL-40 levels were significantly higher in AS patients than in controls (78.9±37.9 vs. 58.4±21.2 ng/mL, P=0.003) and were strongly correlated with CF-PWV (r=0.773, P < 0.001) and IMT-C (r=0.548, P < 0.001). A multiple linear regression analysis revealed that CF-PWV could be explained by serum YKL-40 levels and IMT-C (adjusted R²= 0.707, P=0.013 and P=0.001, respectively). AS patients with a higher disease activity score had higher YKL-40 levels, IMT-C, and CF-PWV than did those with a lower disease activity score (P < 0.001, P=0.008, and P < 0.001, respectively) Conclusion: AS patients had higher serum YKL-40 levels, CF-PWV, and IMT-C than did healthy controls. Additionally, there was an association between increased CF-PWV and serum YKL-40 levels. Therefore, we conclude that CF-PWV and YKL-40 levels may be used for early diagnosis of atherosclerosis in AS patients.

Serum levels of homocysteine, asymmetric dimethylarginine and nitric oxide in patients with Parkinson's disease.

OBJECTIVES: Endothelial dysfunction has been implicated as a crucial event in the development of several neurodegenerative diseases. The aim of this study was to investigate the serum homocysteine, asymmetric dimethylarginine (ADMA) and nitric oxide (NO) levels in patients with Parkinson's disease (PD) and to compare the results with data from healthy controls. METHODS: A total of 132 subjects, including 82 idiopathic PD patients who were newly diagnosed and untreated (47 males, 35 females, mean age of 60.8 ± 7.1 years) and 50 healthy controls (28 males, 22 females, mean age of 60.2 ± 6.7 years) were enrolled in this study. The serum ADMA and NO levels were determined using enzyme-linked immunosorbent assay (ELISA), while the homocysteine levels were determined by chemiluminescent microparticle immunoassay. RESULTS: The ADMA and NO levels of the PD patients were significantly higher than those of the healthy controls. The serum ADMA levels were 0.70 ± 0.15 µmol/L in the PD patients and 0.50 ± 0.12 µmol/L in the healthy controls (p < 0.001). The serum NO levels were 78.7 ± 10.3 µmol/L in the PD patients and 59.9 ± 9.5 µmol/L in the healthy controls (p < 0.001). In addition, the ADMA and NO levels were significantly correlated with the serum homocysteine levels in patients with PD (r = 0.874, p < 0.001, r = 0.803, p = 0.005, respectively). CONCLUSION: In our study, the high ADMA and NO levels of patients with PD indicate endothelial dysfunction, and this dysfunction may play a role in PD pathogenesis. Larger studies, including randomised clinical trials in humans and animal studies, are needed to validate our findings and help in developing a better understanding of the pathogenesis of PD.

Investigation of surfactant protein-D and interleukin-6 levels in patients with blunt chest trauma with multiple rib fractures and pulmonary contusions: a cross-sectional study in Black Sea Region of Turkey.

OBJECTIVE: Multiple rib fractures (RFs) and pulmonary contusions (PCs), with resulting systemic lung inflammation, are the most common injuries caused by blunt chest trauma (BCT) in motor vehicle accidents. This study examined levels of the inflammation marker interleukin (IL)-6 and those of the acute-phase reactant surfactant protein (SP)-D in patients with BCT. DESIGN: Prospective, cross-sectional, observational study. SETTING: Single-centre, tertiary care hospital in the Black Sea Region of Turkey. PARTICIPANTS: The study included 60 patients with BCT who were hospitalised in our thoracic surgery department. PARAMETERS MEASURES: The SP-D and IL-6 serum levels of patients with RFs (two or more RFs) (n=30) and patients with PCs (n=30) were measured after 6 hours, 24 hours and 7 days, and compared with those of age-matched and gender-matched healthy participants. RESULTS: The 6-hour serum SP-D levels of the RFs (p=0.017) and PCs (p<0.001) groups were significantly higher than those of the healthy controls. The 24-hour and 7-day SP-D levels of both groups were also higher than the control group. The serum IL-6 levels of both groups were significantly higher than those of the control group. We have found Injury Severity Score to be independently related to 6-hour IL-6 (ß=1.414, p<0.001) and 24-hour IL-6 levels (ß=1.067, p<0.001). The development of complications was independently related to 6-hour SP-D level (ß=0.211, p=0.047). CONCLUSIONS: RFs and PCs after BCT lead to local and systemic inflammation due to lung injury. The levels of the systemic inflammation marker IL-6 and those of the acute-phase reactant SP-D were elevated in the present study. The SP-D level may be used as a marker in the follow-up of BCT-related complications.

Infliximab Modulates Cisplatin-Induced Hepatotoxicity in Rats.

BACKGROUND: Cisplatin (Cis) is one of the most commonly used antineoplastic drugs. It is used as chemotherapy for many solid organ malignancies such as brain, neck, male and female urogenital, vesical and pulmonary cancers. Infliximab blocks tumor necrosis factor alpha (TNF-α). Several studies have reported that infliximab ameliorates cell damage by reducing cytokine levels. AIMS: We aimed to investigate whether infliximab has a preventive effect against cisplatin-induced hepatotoxicity and whether it has a synergistic effect when combined with Cis. STUDY DESIGN: Animal experimentation. METHODS: Male Wistar albino rats were divided in three groups as follows: Cis group, infliximab + Cis (CIN) group and the control group. Each group comprised 10 animals. Animals in the Cis group received an intraperitoneal single-dose injection of Cis (7 mg/kg). In the CIN group, a single dose of infliximab (7 mg/kg) was administered 72 h prior to the Cis injection. After 72 h, a single dose of Cis (7 mg/kg) was administered. All rats were sacrificed five days after Cis injection. RESULTS: TNF-α levels in the Cis group were significantly higher (345.5±40.0 pg/mg protein) than those of the control (278.7±62.1 pg/mg protein, p=0.003) and CIN groups (239.0±64.2 pg/mg protein, p=0.013). The Cis group was found to have high carbonic anhydrase (CA)-II and low carbamoyl phosphate synthetase-1 (CPS-1) levels. Aspartate transaminase (AST) and alanine transaminase (ALT) levels were lower in the CIN group as compared to the Cis group. Total histological damage was greater in the Cis group as compared to the control and CIN groups. CONCLUSION: Cis may lead to liver damage by increasing cytokine levels. It may increase oxidative stress-induced tissue damage by increasing carbonic anhydrase II (CA-II) enzyme levels and decreasing CPS-1 enzyme levels. Infliximab decreases Cis-induced hepatic damage by blocking TNF-α and it may also protect against liver damage by regulating CPS-1 and CA-II enzyme levels.

The Protective Effect of Adalimumab on Renal Injury in a Model of Abdominal Aorta Cross-Clamping.

BACKGROUND: Adalimumab (ADA) is a potent inhibitor of tumor necrosis factor (TNF-α). ADA treatment suppresses proinflammatory cytokines, leading to a decrease or inhibition of the inflammatory process. OBJECTIVES: The aim of this study was to investigate the possible protective effects of ADA on oxidative stress and cellular damage on rat kidney tissue after ischemia/reperfusion (I/R). MATERIAL AND METHODS: A total of 30 male Wistar albino rats were divided into three groups: control, I/R, and I/R plus ADA (I/R + ADA); each group comprised 10 animals. The control group underwent laparotomy without I/R injury. After undergoing laparotomy, I/R groups underwent two hours of infrarenal abdominal aortic cross ligation, which was followed by two hours of reperfusion. ADA (50 mg/kg) was administered as a single dose, intraperitoneally, to the I/R + ADA group, 5 days before I/R. RESULTS: The I/R group's TNF-α (1150.9 ± 145.6 pg/mg protein), IL-1ß (287.0 ± 32.4 pg/mg protein) and IL-6 (1085.6 ± 56.7 pg/mg protein) levels were significantly higher than those of the control (916.1 ± 88.7 pg/mg protein, p = 0.003; 187.5 ± 37.2 pg/mg protein, p < 0.001; 881.4 ± 57.1 pg/mg protein, p < 0.001, respectively) and I/R + ADA groups (864.2 ± 169.4 pg/mg protein, p = 0.003; 241.4 ± 33.4 pg/mg protein, p = 0.010; 987.7 ± 66.5 pg/mg protein, p = 0.004, respectively). To date, a few histopathological changes have been reported regarding renal I/R injury in rats due to ADA treatment whereas I/R caused severe histopathological injury to kidney tissue. CONCLUSIONS: ADA treatment significantly attenuated the severity of kidney I/R injury, inhibiting I/R-induced oxidative stress and renal damage. Because of its anti-inflammatory and antioxidant effects, ADA pretreatment may have protective effects on experimental kidney injury.

Evaluation of the effects of fasting associated dehydration on maternal NGAL levels and fetal renal artery Doppler parameters.

OBJECTIVE: The aim of this study was to evaluate maternal neutrophil gelatinase-asssociated lipocalin (NGAL) levels and fetal renal artery (fRA) Doppler flow indices in pregnant women fasting in Ramadan in respect of dehydration in long hot summer days as a marker of hypoperfusion and early renal injury. METHODS: A cross-sectional observational study was carried out at a University Hospital. Fasting pregnant women and non-fasting age, gravidity and gestational age-matched women were evaluated for hematologic, blood biochemistry and urine parameters in the first and fourth weeks of the Ramadan. Umbilical artery and fRA Doppler flows were studied in each evaluation. RESULTS: Blood urea nitrogen, potassium and hematocrit levels, blood and urine NGAL levels were significantly higher, and fRA Doppler indices increased in fasting women (p < 0.05) during the second visit in the last week of the Ramadan, while non-fasting women had no significant alterations in each evaluation (p > 0.05). CONCLUSIONS: Adequate maternal vascular volume is essential for the maintenance of healthy pregnancy. Fasting during the long and hot summer days leads to fluid deprivation and dehydration which was found to be related to subclinical maternal renal dysfunction and increased fRA Doppler indices.

Is resveratrol a potential substitute for leuprolide acetate in experimental endometriosis?

OBJECTIVE: Resveratrol, a phytoalexin polyphenol, has anti-angiogenic, antioxidant, anti-inflammatory properties. We aimed to compare the anti-inflammatory and anti-angiogenic effects of resveratrol and leuprolide acetate (LA) in an experimental endometriosis model. STUDY DESIGN: A prospective experimental study was conducted in a University Surgical Research Center. Thirty-three non-pregnant female Sprague-Dawley rats, in which experimental model of endometriosis were surgically induced were randomly divided into four groups. Group 1 was administered 30 mg/kg resveratrol i.m. for 14 days, group 2 was given 1mg/kg s.c. single dose LA, group 3 was administered both resveratrol and LA, and group 4 had no medication. After two weeks medication rats were sacrificed and size, histopathology and immunreactivity to matrix metalloproteinase (mmp)2, mmp9, vascular endothelial growth factor (VEGF) of the endometriotic implants were evaluated. Plasma and peritoneal fluid levels of interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) were analyzed. RESULTS: The endometriotic implant volumes, histopathological grade and immunreactivity to mmp2, mmp9 and VEGF were significantly reduced (p<0.001), and plasma and peritoneal fluid levels of IL-6, IL-8 and TNF-α were significantly decreased in group 1 and group 2 in comparison to group 3 and group 4 (p < 0.001). CONCLUSION: Resveratrol alone is a potential agent for the treatment of endometriosis and may be an alternative to LA. In contrast, the combination of LA and resveratrol decreased the anti-inflammatory and anti-angiogenic effects of each agent. Since resveratrol is widely used as an alternative therapy for a variety of conditions, it can undermine the effectiveness of LA. Therefore, caution should be exercised when used in combination with other agents.

Soluble urokinase-type plasminogen activator receptor is a novel biomarker predicting acute exacerbation in COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory condition, and progresses with acute exacerbations. (AE). During AE, levels of acute phase reactants such as C-reactive protein (CRP) and inflammatory cells in the circulation increase. Soluble urokinase-type plasminogen activator receptor (suPAR) levels increase in acute viral and bacterial infections and in diseases involving chronic inflammation. The purpose of this study was to investigate the effectiveness of suPAR in predicting diagnosis of AE of COPD (AE-COPD) and response to treatment. METHODS: The study population consisted of 43 patients diagnosed with AE-COPD and 30 healthy controls. suPAR, CRP, and fibrinogen levels were measured on the first day of hospitalization and on the seventh day of treatment. RESULTS: We found that fibrinogen (P<0.001), CRP (P<0.001), and suPAR (P<0.001) were significantly higher in patients with AE-COPD than in healthy controls. Fibrinogen (P<0.001), CRP (P=0.001), and suPAR (P<0.001) were significantly decreased by the seventh day of treatment. However, the area under receiver operator characteristic curve showed that suPAR is superior to CRP and fibrinogen in distinguishing AE-COPD. There was a correlation between fibrinogen, CRP, and suPAR. However, only fibrinogen was a powerful predictor of suPAR in multiple linear regression. In multiple logistic regression, only suPAR and fibrinogen were strong predictors of AE-COPD (P=0.002 and P=0.014, respectively). Serum suPAR was negatively correlated with forced expiratory volume in 1 second (r=-478, P=0.001). CONCLUSION: suPAR is a marker of acute inflammation. It is well correlated with such inflammation markers as CRP and fibrinogen. suPAR can be used as a predictor of AE-COPD and in monitoring response to treatment.

Protective effect of infliximab on methotrexate-induced liver injury in rats: unexpected drug interaction.

AIMS: Although methotrexate (mtx) is a widely used agent to treat cancer and inflammatory diseases, its hepatotoxic effect limits for clinical utility. We aimed to investigate whether infliximab (inf), an inhibitor of tumor necrosis factor-alpha (TNF-α) has a protective effect against mtx-induced hepatotoxicity. MATERIALS AND METHODS: For mtx group, the animals received an intraperitoneal single dose injection of mtx at a dose of 20 mg/kg. For inf group, the animals received an intraperitoneal single dose injection of inf at a dose of 7 mg/kg. For mtx + inf group, the single dose of inf at a dose of 7 mg/kg was given 72 h prior to mtx injection. After 72 h, a single dose of mtx 20 mg/kg was given. All rats were sacrificed 5 days after mtx injection. RESULTS: TNF-α and nitric oxide (NO) levels of mtx group was significantly higher than the control (P < 0.001), inf (P < 0.001) and mtx + inf (P < 0.001) groups. Total score of histological damage was higher in the mtx group when compared with the mtx + inf group. Arginase and carbamoyl phosphate synthetase 1 (CPS-1) of mtx group was suppressed in comparison with the control group and was markedly increased in mtx + inf group. CONCLUSION: Inf may partially prevent mtx-induced hepatic damage in rats. However, the combined usage of mtx and inf increases arginase and CPS-1 enzyme activities and at the same time blocks TNF-α. This combination especially in cancer patients may lead to cancer cell invasion and metastasis.

The role of hypoxia at primary dysmenorrhea, utilizing a novel hypoxia marker--SCUBE1.

STUDY OBJECTIVE: To determine the SCUBE1 levels in adolescents with primary dysmenorrhea. DESIGN: A prospective cross-sectional study. SETTING: A university hospital outpatient clinic, Rize, Turkey. PARTICIPANTS: A total of 40 adolescent girls, 15 on menses and 25 not on menses. INTERVENTIONS AND MAIN OUTCOME MEASURES: Demographic features and menstrual history of the participants were assessed and blood samples were obtained for detecting the platelet volume, platelet counts, and SCUBE1 levels of the participants. RESULTS: No difference was detected between the 2 groups in mean platelet volume, platelet count, and SCUBE1 levels. CONCLUSION: Future trials are required to investigate the relation between SCUBE1 levels and primary dysmenorrhea.

Protective effects of erdosteine, vitamin E, and vitamin C on renal injury induced by the ischemia-reperfusion of the hind limbs in rats.

BACKGROUND/AIM: To compare the protective efficacy of erdosteine and vitamins C and E against renal injury caused by hind limb ischemia-reperfusion (I/R). MATERIALS AND METHODS: Rats were split into 4 groups: group I as the control, group II as I/R, group III as I/R + erdosteine, and group IV as I/R + vitamins C and E. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities and malondialdehyde (MDA) tissue levels were determined. RESULTS: MDA levels were found comparable with the control group in groups II and III. However, they were considerably decreased in group IV when compared to group II (P < 0.01). Additionally, SOD, CAT, and GSH-Px activities were considerably (P < 0.05) decreased in group II. While CAT and GSH-Px activities were restored (P <0.01) by vitamin E and C treatment, SOD activity was not significantly affected. While GSH-Px activities were higher (P < 0.05) with erdosteine administration, SOD and CAT activities were unchanged. CONCLUSION: The protective effect of vitamins C and E is higher than that of erdosteine treatment in reducing the oxidative stress after renal ischemia in this animal model.

The relationship of plasma catestatin concentrations with metabolic and vascular parameters in untreated hypertensive patients: Influence on high-density lipoprotein cholesterol.

OBJECTIVE: Catestatin has several cardiovascular actions, in addition to diminished sympatho-adrenal flow. Decreased plasma catestatin levels may reflect a predisposition for the development of hypertension and metabolic disorders. We planned to investigate the possible roles of catestatin in untreated hypertensive patients. As a secondary objective, we compared catestatin concentrations of healthy subjects with those of hypertensive patients in order to understand whether catestatin is increased reactively or diminished at onset. METHODS: Our study was cross-sectional and observational. The patient group, comprising 109 consecutive untreated hypertensive patients without additional systemic or coronary heart disease, underwent evaluations of plasma catestatin, waist circumference, lipid parameters, left ventricular mass, carotid intima-media thickness, and flow-mediated dilation of the brachial artery. Additionally, we measured catestatin concentrations of 38 apparently healthy subjects without any disease using a commercial enzyme-linked immunosorbent assay kit. RESULTS: We documented increased catestatin concentrations in previously untreated hypertensive patients compared to healthy controls (2.27±0.83 vs. 1.92±0.49 ng/mL, p=0.004). However, this association became insignificant after adjustments for age, gender, height, and weight. Within the patient group, catestatin levels were significantly higher in females. Among all study parameters, age, high-density lipoprotein cholesterol (HDL-C) correlated positively to plasma catestatin, whereas triglycerides, hemoglobin, and left ventricular mass correlated negatively to plasma catestatin. We could not detect an association between vascular parameters and catestatin. Catestatin levels were significantly elevated with increasing HDL-C (1.91±0.37, 2.26±0.79, and 3.1±1.23 ng/mL in patients with HDL-C <40, 40-60, and >60 mg/dL, respectively). Multiple linear regression analysis revealed age (beta: 0.201, p=0.041) and HDL-C (beta: 0.390, p<0.001) as independent correlates of plasma catestatin concentration. Additionally, male gender (beta:-0.330, p=0.001) and plasma catestatin (beta: 0.299, p=0.002) were significantly associated with HDL-C concentrations. CONCLUSION: We documented that plasma catestatin is an independent predictor of high-density lipoprotein cholesterol. In addition to antihypertensive effects, catestatin appears to be related to improved lipid and metabolic profiles. Coexistence of low catestatin levels with low HDL-C may provide a probable mechanism for the predictive value of low HDL-C for increased hypertension and cardiovascular events.

Effect of infliximab on renal injury due to methotrexate in rat.

INTRODUCTION: Methotrexate, an antagonist of folic acid used in the treatment of many cancers and inflammatory diseases, is associated with side effects that limit its usage. Infliximab has been reported to have a protective effect against nephrotoxicity induced by some drugs and ischemic reperfusion. We aimed to investigate whether infliximab has a protective effect against methotrexate-induced nephrotoxicity. MATERIALS AND METHODS: We administered methotrexate at a dose of 20 mg/kg as a single intraperitoneal injection in 10 rats (methotrexate group). Another group of 10 rats received a single dose of infliximab, 7 mg/kg, intraperitoneally (infliximab group). The methotrexate and infliximab group received a similar single injection of infliximab 72 hours prior to methotrexate injection. After 72 hours a single dose of methotrexate, 20 mg/kg, was administered intraperitoneally. Five days after methotrexate injection, blood samples were collected and the kidney tissues were removed for biochemical and histological examination. RESULTS: The methotrexate group had significantly higher tissue levels of tumor necrosis factor-α (P = .008), interleukin-1ß (P = .04), nitric oxide (P < .001), and adenosine deaminase (P < .001) than the methotrexate and infliximab group after the 5-day study. The methotrexate group also had significantly higher total histological scores (P < .001) and carbonic anhydrase-II activity (P < .001) when compared to the methotrexate and infliximab group. CONCLUSIONS: Infliximab has a strong protective effect against methotrexate-induced nephrotoxicity by suppressing cytokines release. It may decrease methotrexate-induced nephrotoxicity by regulating carbonic anhydrase-II enzyme activities and slowing down purine metabolism.

Nesfatin-1 and Vitamin D levels may be associated with systolic and diastolic blood pressure values and hearth rate in polycystic ovary syndrome.

Obesity, insulin resistance (IR), inflammation, and hyperandrogenism may lead to polycystic ovary syndrome (PCOS) and hypertension. Nesfatin-1 (N1) may be related to IR, obesity, and hypertension. Furthermore, a vitamin D (VD) deficiency is associated with hypertension and PCOS. We aimed to investigate N1 and VD levels in PCOS that have an effect on systolic and diastolic blood pressure (BP) and heart rate (HR).This study included 54 patients with PCOS and 48 age-body mass index (BMI)-matched healthy controls. PCOS was diagnosed according to clinical practice guidelines. Ferriman-Gallwey scores (FGS) were calculated, while N1, VD, and other hormonal and biochemical parameters were measured for all subjects. Systolic and diastolic BP was measured as well. HR was calculated using an electrocardiogram.The levels of N1 (p < 0.001), high-sensitivity C-reactive protein (hs-CRP) (p = 0.036), homeostasis model assessment as an index of insulin resistance (HOMA-IR) (p < 0.001), systolic (p < 0.001) and diastolic (p < 0.001) BP and HR (p < 0.001) in the PCOS group were significantly higher than in the control group. However, the VD levels of the PCOS group were lower than the control group (p = 0.004). N1 had a strong positive correlation with BMI, HOMA-IR, hs-CRP, luteinizing hormone, systolic and diastolic BP, and HR. VD levels were negatively correlated with HOMA-IR and luteinizing hormone.Elevated N1 and decreased VD levels may be related to the presence of high-normal BP or hypertension in PCOS subjects.  N1 level may be associated with an increased BP due to its relation to inflammation and IR.