Does oxidative status affect serum sclerostin levels in patients with type 2 diabetes mellitus?

INTRODUCTION: Sclerostin is a glycoprotein known as a negative regulator of bone formation, predominantly expressed by mature  osteocytes. There is no causative evidence information on the role of sclerostin in the pathogenesis of type 2 diabetes mellitus (T2DM) in humans. AIM: This study aimed to investigate the relationship between serum sclerostin levels and oxidative status and biochemical parameters in T2DM patients and healthy people. MATERIALS AND METHODS: This cross-sectional study, conducted in a clinical trial center, included 45 subjects with T2DM and 45 subjects as controls. RESULTS: Serum sclerostin, total oxidative status (TOS), albumin, and ferritin levels were significantly higher in T2DM patients than in the control group (p<0.05). Total antioxidant status (TAS) was significantly higher in the control group (p<0.05). There was a weak positive correlation between sclerostin and TOS (r=0.23, p=0.03) and a weak negative correlation between sclerostin and TAS (r=-0.28, p=0.03). CONCLUSIONS: We have demonstrated that serum sclerostin levels increase in patients with T2DM and that the increased sclerostin levels are associated with oxidative stress.

An investigation of the effect of placental growth factor on intrapartum fetal compromise prediction in terminduced high risk pregnancies.

OBJECTIVES: To date, there is no available test to predict the risk of intrapartum fetal compromise (IFC) during labor, either starting spontaneously or induced due to obstetrics indications. The aim of this study was to examine the effectiveness of placental growth factor (PIGF) in identifying cases that develop intrapartum fetal compromise (IFC) in term high-risk pregnancies induced for labor. MATERIAL AND METHODS: This prospective cross-sectional study was conducted on 40 IFC+ cases and 40 IFC- cases with high-risk term pregnancy and labor induction started in the Health Sciences University Gazi Yasargil Training and Research Hospital, between January 2018 and April 2018. Comparisons were made between the groups in respect of placental growth factor (PIGF) levels, and obstetric and neonatal outcomes. RESULTS: The PIGF level was found to be statistically significantly lower in the IFC+ cases compared to the IFC- cases. For a PIGF cutoff value of 32 pg/mL for the prediction of IFC+ cases, sensitivity was 74.4%, specificity 73.2%, NPV 75% and PPV 72.5%, with a statistically significant difference determined between the groups. The IFC+ development risk increased 7.91-fold in patients with PIGF ≤ 32 pg/mL. CONCLUSIONS: The PIGF levels in cases of IFC+ high risk pregnancies were found to be statistically significantly lower than those of IFC- cases. However, further, large-scale randomized controlled research is necessary to demonstrate this relationship better.

Cordycepin prevents postoperative formation of intra-abdominal adhesion in a rat model: An experimental study.

BACKGROUND: The aim of the present study was to investigate whether cordycepin prevented adhesion formation in a rat model. METHODS: Rats were randomly assigned to 3 groups of 10 rats. CONTROL GROUP: The absence of adhesion was confirmed via laparotomy. Adhesion group: The cecum was removed from the abdomen and scraped with a dry gauze bandage until petechial hemorrhagic foci developed. Cordycepin group: The same surgical procedure was performed as in the adhesion group, and 10 mg/kg cordycepin was administered intraperitoneally. After 15 days, the rats were sacrificed humanely via cardiac blood withdrawal under anesthesia. The rats were then analyzed morphologically and histopathologically, and hydroxyproline (OH-p) and malondialdehyde (MDA) levels were measured. RESULTS: Macroscopic analysis revealed significantly less adhesion in the cordycepin group than in the adhesion group (p<0.01). Furthermore, significant histopathological improvement was also evident in the cordycepin group compared to the adhesion group (p<0.05). The levels of OH-p and MDA in blood and tissue were higher in the adhesion group than in the control group, and lower in the cordycepin group than the adhesion group. Interestingly, MDA level was significantly lower (blood: p<0.05; tissue: p<0.01) in the cordycepin group than in the adhesion group, whereas only tissue OH-p was significantly lower in the cordycepin group compared with the adhesion group (p<0.05). One rat in both adhesion group and cordycepin group died postoperatively. CONCLUSION: Results indicated that cordycepin effectively reduced adhesion in a rat abrasion model. Thus, this agent may be valuable to prevent postoperative adhesion.

Effects of Storage Temperature and Time on Stability of Serum Tacrolimus and Cyclosporine A Levels in Whole Blood by LC-MS/MS.

Tacrolimus and cyclosporine A are immunosuppressant drugs with narrow therapeutic windows. The aim of this study was to investigate the stability of tacrolimus and cyclosporin A levels in whole blood samples under different storage conditions. Whole blood samples were obtained from 15 patients receiving tacrolimus and 15 patients receiving cyclosporine A. Samples were immediately analyzed and then stored at different conditions (room temperature (24°C-26°C) for 24 hours, +4°C for 24 and 48 hours, and -20°C for one month) and then analyzed again. For tacrolimus, there was a significant difference between samples analyzed immediately and those kept 24 hours at room temperature (P = 0.005) (percent change 32.89%). However, there were no significant differences between the other groups. For cyclosporine A, there was a significant difference between samples analyzed immediately and those kept 24 hours (P = 0.003) (percent change 19.47%) and 48 hours (P = 0.002) (percent change 15.38%) at +4°C and those kept 24 hours at room temperature (P = 0.011) (percent change 9.71%). Samples of tacrolimus should be analyzed immediately or stored at either +4°C or -20°C, while samples of cyclosporine A should be analyzed immediately or stored at -20°C.

Effects of antioxidant agents against cyclosporine-induced hepatotoxicity.

BACKGROUND: To investigate the potential protective antioxidant role of ursodeoxycholic acid (UDCA), melatonin, and allopurinol treatment in cyclosporine (CsA)-induced hepatotoxicity. METHODS: Hepatotoxicity was established in Sprague-Dawley rats by daily administration of CsA. Treatment groups were additionally administered UDCA, melatonin, or allopurinol treatments. Rats that received no CsA and no treatments served as a control group. Liver samples from each group were examined by histopathologic analysis to determine the effects of CsA treatment on liver morphology. Biochemical assays were also used to determine the effect of CsA treatment on liver function, in the presence or absence of UDCA, melatonin, or allopurinol. RESULTS: CsA treatment induced hepatotoxicity, resulting in sinusoidal dilatation, congestion, infiltration, hydropic degeneration, and loss of glycogen storage in the liver. From a molecular perspective, the CsA treatment increased levels of malondialdehyde (MDA) levels, decreased levels of reduced glutathione and xanthine oxidase, and decreased activities of superoxide dismutase and catalase. The CsA treatment also resulted in decreased serum total antioxidant capacity, whereas alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin levels, and total oxidant status were increased. Treatment with UDCA, melatonin, or allopurinol reduced the CsA-induced histopathologic changes, as compared with CsA-treated samples. In addition, UDCA, melatonin, or allopurinol treatment mitigated the CsA-induced effects on glutathione and MDA levels, and on superoxide dismutase and catalase activities, as well as reduced the CsA-mediated perturbations in serum levels of total antioxidant capacity, total oxidant status, and alkaline phosphatase. CONCLUSIONS: UDCA, allopurinol, and melatonin may each help to protect against CsA-induced damage to liver tissues, possibly through effects on the antioxidant system.

Investigation of dermatology life quality index and serum prolactin and serum dehydroepiandrosterone sulphate levels in patients with chronic urticaria.

BACKGROUND: Chronic urticaria (CU) is known to be one of the most disturbing diseases which significantly affect the quality of life. Prolactin (PRL) and DHEA-S (dehydroepiandrosterone sulfate) are stress-associated hormones in chronic urticaria. OBJECTIVE: In the present study, we measured DHEA-S and prolactin levels of CU patients, compared them with healthy subjects and evaluated the association between disease status and serum levels. METHODS: Plasma DHEA-S and serum PRL concentrations were measured in 48 CU patients and 31 healthy subjects. CU activity was assessed with the use of the symptom scores recommended with EAACI/GALEN/EDF guidelines. All the patients participating in this study were evaluated by means of Dermatology Life Quality Index (DLQI). With respect to DLQI and clinical activity scores, plasma DHEA-S and serum prolactin levels were compared. RESULTS: Median plasma concentration of DHEA-S was significantly lower in CU patients as compared with healthy subjects (p = 0.026). DHEA-S levels of females were significantly lower than males (p = 0.001). Mean PRL values of the patients were higher than the controls, but not statistically significant (p = 0.619) and there was a statistically signifcant inverse correlation with DHEA-S levels (p = 0.04, r = -0.298). Therewas a significant correlation between DLQI and clinical disease activity (p < 0.001, r = 0.748). CONCLUSIONS: The exact relation of hormones to CU pathogenesis remains to be determined by further clinical studies. In addition, therapies aiming to increase DHEA-S and decrease PRL may be subject to trial in CU.

Cytoprotective effects of amifostine, ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats.

AIM: To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine (NAC), amifostine (AMF) and ascorbic acid (ASC) in methotrexate (MTX)-induced hepatotoxicity. METHODS: An MTX-induced hepatotoxicity model was established in 44 male Sprague Dawley rats by administration of a single intraperitoneal injection of 20 mg/kg MTX. Eleven of the rats were left untreated (Model group; n = 11), and the remaining rats were treated with a 7-d course of 50 mg/kg per day NAC (MTX + NAC group; n = 11), 50 mg/kg per single dose AMF (MTX + AMF group; n = 11), or 10 mg/kg per day ASC (MTX + ASC group; n = 11). Eleven rats that received no MTX and no treatments served as the negative control group. Structural and functional changes related to MTX- and the various treatments were assessed by histopathological analysis of liver tissues and biochemical assays of malondialdehyde (MDA), superoxide dismutase (SOD), catalase, glutathione (GSH) and xanthine oxidase activities and of serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total bilirubin. RESULTS: Exposure to MTX caused structural and functional hepatotoxicity, as evidenced by significantly worse histopathological scores [median (range) injury score: control group: 1 (0-3) vs 7 (6-9), P = 0.001] and significantly higher MDA activity [409 (352-466) nmol/g vs 455.5 (419-516) nmol/g, P < 0.05]. The extent of MTX-induced perturbation of both parameters was reduced by all three cytoprotective agents, but only the reduction in hepatotoxicity scores reached statistical significance [4 (3-6) for NAC, 4.5 (3-5) for AMF and 6 (5-6) for ASC; P = 0.001, P = 0.001 and P < 0.005 vs model group respectively]. Exposure to MTX also caused a significant reduction in the activities of GSH and SOD antioxidants in liver tissues [control group: 3.02 (2.85-3.43) µmol/g and 71.78 (61.88-97.81) U/g vs model group: 2.52 (2.07-3.34) µmol/g and 61.46 (58.27-67.75) U/g, P < 0.05]; however, only the NAC treatment provided significant increases in these antioxidant enzyme activities [3.22 (2.54-3.62) µmol/g and 69.22 (61.13-100.88) U/g, P < 0.05 and P < 0.01 vs model group respectively]. CONCLUSION: MTX-induced structural and functional damage to hepatic tissues in rats may involve oxidative stress, and cytoprotective agents (NAC > AMF > ASC) may alleviate MTX hepatotoxicity.

Determination of dermatology life quality index, and serum C-reactive protein and plasma interleukin-6 levels in patients with chronic urticaria.

INTRODUCTION: C-reactive protein (CRP) and interleukin-6 (IL-6), which is one of its most important simulators, were determined in great amounts in the sera of patients with chronic urticaria (CU). AIM: To determine the levels of IL-6 in patients with urticaria, and evaluate its relationship with urticaria activity scores and Dermatology Life Quality Index (DLQI). MATERIAL AND METHODS: Fifty-three patients with CU were included in the study successively by determining their urticaria activity scores (0-3) and DLQI (0-5). The CRP and IL-6 were measured by immune assay methods. Thirty-two healthy subjects were included as a control group. RESULTS: Serum levels of IL-6 and CRP were significantly higher in patients with CU compared to healthy controls (p < 0.001, p = 0.026 respectively). There was a statistically significant correlation among urticaria activity scores and IL-6 and CRP concentration (p = 0.004, p = 0.042). This correlation was more significant in patients who had moderate and severe disease activity scores than in those who had mild disease activity score (p < 0.001, p < 0.001, respectively). There was a statistically significant association between DLQI and IL-6 (p = 0.025). This correlation was very significant in patients who had severe and very severe disease activity scores (p < 0.001, p < 0.001, respectively). DLQI scores and serum levels of IL-6 were significantly different in the very severe group compared to healthy controls (p = 0.024). CONCLUSIONS: The levels of CRP and IL-6 are increased in patients with CU. A relationship of DLQI and urticaria activity scores with CRP and IL-6 was found. These findings support the relationship between the inflammatory process in CU and the clinical findings.

Oxytocin ameliorates remote liver injury induced by renal ischemia-reperfusion in rats.

Renal ischemia-reperfusion (IR) causes remote liver damage. Oxytocin has anti-inflammatory and antioxidant effects. The main purpose of this study was to evaluate the protective function of oxytocin (OT) in remote liver damage triggered by renal IR in rats. Twenty four rats were randomly divided into four different groups, each containing 8 rats. The groups were as follows: (1) Sham operated group; (2) Sham operated+OT group (3) Renal IR group; (4) Renal IR+OT group. OT (500µg/kg) was administered subcutaneously 12 and 24 hours before and immediately after ischemia. At the end of experimental procedure, the rats were sacrificed, and liver specimens were taken for histological assessment or determination of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), paraoxonase (PON-1) activity and nitric oxide (NO). The results showed that renal IR injury constituted a notable elevation in MDA, TOS, Oxidative stress index (OSI) and significantly decreased TAS, PON-1 actvity and NO in liver tissue (p<0.05). Additionally renal IR provoked significant augmentation in hepatic microscopic damage scores. However, alterations in these biochemical and histopathological indices due to IR injury were attenuated by OT treatment (p<0.05). These findings show that OT ameliorates remote liver damage triggered by renal ischemia-reperfusion and this preservation involves suppression of inflammation and regulation of oxidant-antioxidant status.

Effect of pneumatic tube delivery system rate and distance on hemolysis of blood specimens.

BACKGROUND: We evaluated the effects of pneumatic tube system (PTS) transport rates and distances on routine hematology and coagulation analysis. PTS effects on centrifuged blood samples were also examined. METHOD: The study was completed at Dicle University Hospital, which has the longest pneumatic tube system in Turkey. Blood samples were collected at three different locations within the hospital and an emergency department, and delivered to the central laboratory by the PTS or a human carrier. Samples were transported at different rates and over varying distances. Each specimen's potassium (K) and lactic dehydrogenase (LDH) levels, in both the serum and plasma, were tracked to monitor hemolysis. Measurements of LDH and K were obtained using heparin or citrate. RESULT: A positive correlation was observed between distance and hemolysis in serum samples transported at 4.2 m/sec, and at 3.1 m/sec for more than 2200 m (r = 0.774 and r = 0.766, respectively). Distance and hemolysis were also correlated in non-centrifuged samples (r = 0.871). The alterations in plasma LDH and K levels at different rates and PTS lengths were not statistically significant. CONCLUSION: The rate of hemolysis in PTS transported samples, dependent on PTS length and rate, may seriously affect routine tests of non-centrifuged samples.

Increased asymmetric dimethylarginine and nitric oxide levels in patients with migraine.

Asymmetric dimethylarginine (ADMA) has been found as correlated with endothelial dysfunction and oxidative stress. There are few studies regarding ADMA and nitric oxide (NO) levels in patients with migraine and alterations of ADMA and NO levels during migraine attack are not well-known. Therefore, in present study, we aimed to measure NO and ADMA levels in patients with migraine and compare them with the control group to investigate the correlation between migraine, oxidative stress and endothelial dysfunction. The migraine group consisted of 59 patients, including 22 suffering from migraine with aura and 37 suffering from migraine without aura. The control group consisted of 31 healthy volunteers without headache. The patients in migraine group were divided into subgroups based on whether attack period was present or not and whether it was migraine with or without aura. Plasma ADMA levels were measured using an enzyme-linked immunosorbent assay method. Migraine patients had higher concentrations of NO (35.6±7.7, 31.0±6.2 µmol/L, respectively, p=0.005) and ADMA (0.409±0.028, 0.381±0.044 µmol/L, respectively, p = 0.001) levels when compared with the healthy controls. During migraine attack, NO and ADMA levels were found to be significantly higher in migraine group as compared to control group (respectively, p=0.015, p=0.014). Similarly, NO and ADMA levels in the patients with migraine in the interictal period were found to be significantly higher as compared to control group (p=0.011, p=0.003). In conclusion, higher ADMA and NO levels of patients with migraine supported that oxidative stress and endothelial dysfunction may have a role in migraine pathogenesis.

Complement activation in acute coronary syndromes.

The complement system is part of the host defence response. However, considerable evidence suggests that complement plays an important role in the pathophysiology of ischemic heart disease. The aim of this study was to evaluate complement activation in patients with all forms of acute coronary syndromes (ACS) and to examine the relationship between the degree of complement activation and myocardial injury. The study population included 152 subjects (26 females): 82 with ACS (35 acute myocardial infarction (AMI), 22 non-Q wave MI (NQMI), 25 unstable angina (UAP)) (Group A), 35 stable angina (SA) (Group B), and 35 healty control subjects (Group C). Complement 3 (C3), Complement 4 (C4), C-reactive protein (CRP), troponin I (TnI) as well as creatine kinase MB (CK-MB) were evaluated. Patients' blood samples were taken on admission (day 1) and after 2, 3 and 7 days in group A. However, only one measurement was performed in the groups B and C. Plasma C3 and C4 peak levels were significantly higher in patients with AMI (141+/-29 and 35+/-11 mg/dl) and NQMI (136+/-13 and 35+/-7 mg/dl) than in patients with SA (128+/-14 and 27+/-10 mg/dl) and the control subjects (114+/-22 and 22+/-7 mg/dl) (p<0.03). Also, C3 and C4 serum levels in patients with SA and UAP (126+/-16 and 31+/-7 mg/dl) were significantly higher than those in control subjects (p<0.01, p<0.03, respectively). At 1-week follow-up, there were no significant differences between the plasma levels of C3 and C4 in patients with UAP (p>0.05). However, plasma levels of C3 and C4 were significantly different between days in patients with AMI and NQMI (p<0.0001). Plasma C3 and C4 levels in ACS showed a relationship with peak CK-MB and Tn I levels (p<0.01). Plasma CRP level in ACS showed positive correlation with C3 (p<0.01) and C4 (p<0.001). In this study, we determined that plasma C3 and C4 levels were elevated in ACS and SA. Although C3 and C4 were higher in ACS and SA, the systemic levels of inflammatory markers in patients with SA and UAP were lower than those found in the AMI and NQMI groups. The relationship between C3, C4 levels and ACS further suggests that the complement activation is related to necrosis within the myocardium.

The serial changes in plasma homocysteine levels and it's relationship with acute phase reactants in early postmyocardial infarction period.

OBJECTIVE: We aimed to study the change in the plasma homocysteine concentration in the early stage of acute myocardial infarction and its relationship with the acute phase reactants. METHODS: We included into the study 33 patients who were admitted to the hospital with acute myocardial infarction within the first three hours after the onset of symptoms. The plasma samples were obtained on admission (within 3 hours onset of symptom) and at 6, 12, 24 hours and 2, 4, 7, 30 and 90th day after admission. RESULTS: The serial homocysteine measurements were as following: 11.87+/-0.71 micromol/L, 11.89+/-0.62 micromol/L, 11.37+/-0.83 micromol/L, 10.96+/-0.93 micromol/L, 11.37+/-0.89 micromol/L, 11.24+/-0.66 micromol/L, 13.09+/-0.64 micromol/L, 12.85+/-0.71 micromol/L, and 12.19+/-0.91 micromol/L, respectively (p=0.05). Statistically significant difference was found only between the hour 24 and the day 7 (p=0.04). However, there was no statistically significant difference between the admission level and none of the other time points. No correlation was identified between acute phase reactants and lipid parameters that were measured serially at the same time periods and homocysteine levels. CONCLUSION: Although homocysteine plasma values obtained during the sixth and twelfth hours of acute myocardial infarction provide reliable results as a risk markers, timing of blood sampling during the myocardial infarction does not have significant role since plasma values of homocysteine did not affect acute phase reactants.

The association between NT-proBNP levels, functional capacity and stage in patients with heart failure.

OBJECTIVE: Amino-terminal probrain natriuretic peptide (NT-proBNP), a biologically inactive derivative of BNP, is clinically more useful owing to its longer half-life, higher plasma concentrations, lesser variation among individuals, and higher in vitro stability. In this regard, NT-proBNP may be a better indicator of the severity of ventricular dysfunction. In this study, the association of NT-proBNP levels with functional capacity and stage of heart failure was explored in patients with CHF. Also, we particularly focused on the presence and significance of neurohormonal activation in the group of patients classified as stage-A according to ACC/AHA guidelines. METHODS AND RESULTS: 64 patients with CHF (31 men, 33 women; mean age 58.26 +/- 10.59 y) and 36 healthy controls (24 men, 12 women; mean age 57.47 +/- 10.83) were included in this study. The New York Heart Association (NYHA) classification system (I, II, III, IV) was used to define the functional capacity; and the stage of the heart failure was based on the ACC/AHA guidelines (A, B, C, D). Healthy female participants had higher NT-proBNP levels compared to their male counterparts (p < 0.001). Left ventricular ejection fraction (LVEF) did not correlate significantly with functional capacity and stage of the disease. CHF patients had higher NT-proBNP compared to controls (p < 0.001). There was a positive correlation between NT-proBNP and functional capacity in patients, and NT-proBNP increased significantly with each increasing class of the disease. Similarly, a positive correlation existed between the stage of heart failure and NT-proBNP levels, which increased significantly with increasing stages of the disease. Patients with NYHA I and stage A disease had higher NT-proBNP levels compared to controls (p = 0.04). CONCLUSIONS: The severity of CHF can be objectively assessed by measuring the circulating levels of NT-proBNP. Even in NYHA I and stage A disease, NT-proBNP levels are higher compared to controls (p = 0.04). NT-proBNP can provide objective information regarding the severity of the disease and also aid in treatment decisions in patients with CHF.