Didem Onk

Melatonin Attenuates Contrast-Induced Nephropathy in Diabetic Rats: The Role of Interleukin-33 and Oxidative Stress

Background. Inflammation and oxidative stress (OxS) contribute to the pathogenesis of diabetic kidney disease (DKD) and contrast-induced nephropathy (CIN). Patients with DKD were found to be more prone to CIN. Interleukin-33 (IL-33) is a proinflammatory cytokine, but its role in DKD and CIN is unknown. Methods. Thirty male Sprague-Dawley rats were enrolled. The first group was comprised of healthy rats (HRs), whereas the other four groups were made up of diabetic rats (DRs), diabetic rats with contrast-induced nephropathy (CIN + DRs), melatonin-treated diabetic rats (MTDRs), and melatonin-treated CIN + DRs (MTCIN + DRs). All groups except the HRs received 50 mg/kg/day streptozotocin (STZ). CIN + DRs were constituted by administrating 1.5 mg/kg of intravenous radiocontrast dye on the 35th day. MTDRs and MTCIN + DRs were given 20 mg/kg/day of intraperitoneal injection of melatonin (MT) from the 28th day for the constitutive seven days. Results. We observed increased IL-33 in the kidney tissue following induction of CIN in DRs. To determine whether MT is effective in preventing CIN, we administered MT in CIN + DRs and demonstrated that kidney tissue levels of OxS markers, inflammatory cytokines, and IL-33 were significantly diminished in MTCIN + DRs compared with other groups without MT treatment (p < 0.05). Conclusion. Inhibition of IL-33 with MT provides therapeutic potential in DKD with CIN.

Apoptosis, autophagy & endoplasmic reticulum stress in diabetes mellitus

The prevalence of diabetes mellitus (DM) is increasing secondary to increased consumption of food and decreased physical activity worldwide. Hyperglycaemia, insulin resistance and hypertrophy of pancreatic beta cells occur in the early phase of diabetes. However, with the progression of diabetes, dysfunction and loss of beta cells occur in both types 1 and 2 DM. Programmed cell death also named apoptosis is found to be associated with diabetes, and apoptosis of beta cells might be the main mechanism of relative insulin deficiency in DM. Autophagic cell death and apoptosis are not entirely distinct programmed cell death mechanisms and share many of the regulator proteins. These processes can occur in both physiologic and pathologic conditions including DM. Besides these two important pathways, endoplasmic reticulum (ER) also acts as a cell sensor to monitor and maintain cellular homeostasis. ER stress has been found to be associated with autophagy and apoptosis. This review was aimed to describe the interactions between apoptosis, autophagy and ER stress pathways in DM.

The effect of melatonin on oxidative stress and apoptosis in experimental diabetes mellitus-related ovarian injury.

Abstract We aimed to evaluate the effect of melatonin on oxidative stress and ovarian injury in rats. Twenty-four Sprague–Dawley albino rats were divided into three groups: Group 1 as nondiabetic healthy controls (n = 8), group 2 as nontreated diabetic rats (n = 8) and group 3 as melatonin-treated diabetic rats (n = 8). After overt diabetes was produced by intraperitoneal injection of streptozosin, 20 mg/kg/day of melatonin was given intraperitoneally to group 3 for a week. NF–kB and caspase-3 immunoexpressions, lipid peroxidation, the activities of antioxidative enzymes, total oxidant capacity and total antioxidant capacity were assessed. Immunoexpressions of NF–kB and caspase-3 were significantly lower in group 3 than group 2. There was a significant decrease in superoxide dismutase activity in group 2 than group 1 and a significant increase in group 3 compared with group 2. We observed a nonsignificant decrease in catalase activity between group 1 and group 2 and a nonsignificant increase between group 2 and group 3. There was a nonsignificant increase in the plasma level of total oxidant status in group 2 than group 1, but a significant decrease was observed in group 3 compared to group 2. Total antioxidant status was significantly lower in group 2 compared with group 1 and group 3. In conclusion, melatonin ameliorates the negative effects of oxidative stress on DM-related ovarian injury.

The Effects of Diabetes Mellitus on Ovarian Injury and Reserve: An Experimental Study.

Objective: The study aims to investigate the effects of diabetes mellitus (DM) on ovarian injury and reserve in a rat model. Study Design: In this prospective experimental study, 16 female Sprague-Dawley albino rats (12 weeks, 220-240 g) were randomly divided into 2 groups. Group 1 included 8 normal healthy rats as controls. No drug was administered to the controls. Group 2 included the other 8 rats in which diabetes was induced by intraperitoneal injections of streptozotocin (STZ). After overt DM occurred (blood glucose >250 mg/dl), all the animals were euthanized and blood samples were collected by cardiac puncture for biochemical analysis. Bilateral oophorectomy was performed for histopathological examination. Immunoexpressions of nuclear factor-kappa B (NF-kB) and caspase-3 as well as anti-Müllerian hormone (AMH) levels were assessed. Values were analyzed by t test. Results: Immunoexpressions of NF-kB and caspase-3 were significantly higher in non-treated diabetic rats than in the control group (p = 0.011 and p = 0.010, respectively). In healthy control group, AMH levels (3.22 ± 0.58 ng/ml) were significantly higher than in the non-treated diabetic group (1.41 ± 0.25 ng/dl; p = 0.024). Conclusion: Hyperglycemia causes severe ovarian injury via NF-kB pathway and caspase-3 apoptotic pathway, leading to the decrease in ovarian reserve in STZ-induced diabetic rats.

At what age range should children be circumcised

Background: Although male circumcision is a surgical intervention that is frequently performed in children, there is no consensus about the age at which it should be performed. Objectives: The purpose of this study was to determine the best age range for routine male circumcision with respect to a child’s health and the cost. Patients and Methods: This clinical trial was conducted in the affiliated hospital of the Erzincan University of Medical Sciences, Turkey, in 2014. The circumcised children were evaluated in 3 groups: < 1 year old (Group 1), 1-7 years old (Group 2), and > 7 years old (Group 3). To obtain a satisfactory Wilton sedation score, midazolam 0.1 mg/kg IV was administered first. If adequate sedation was not achieved, ketamine 2 mg/kg IV was also administered. If adequate sedation was still not achieved, general anesthesia was administered via a laryngeal mask. At the end of the surgery, the groups were compared in terms of post-anesthesia recovery duration, complications, discharging duration, and cost. Results: A total of 603 children were circumcised, 374 in Group 1, 94 in Group 2, and 135 in Group 3. Midazolam was sufficient for sedation in 364 Group 1 patients (97.3%), 6 Group 2 patients (6.3%), and 38 Group 3 patients (28.1%). The shortest post-anesthesia recovery duration after surgical intervention and time until discharge, the lowest cost, and the fewest anesthesia complications were observed in Group 1 (P < 0.05 for all). Conclusions: Although almost all of the < 1 year-old children could be sedated with midazolam alone, most of the > 1 year-old children required ketamine or general anesthesia. Performing circumcision when children are less than 1 year old decreases the risk of complications due to anesthesia and lowers the costs compared with performing the procedure on older children.

The effect of thiamine and its metabolites on peripheral neuropathic pain Induced by cisplatin in rats

Thiamine pyrophosphate (TPP) is the active metabolite of thiamine. This study aimed to investigate the effects of thiamine and TPP on cisplatin-induced peripheral neuropathic pain (PNP). Male albino Wistar type Rattus norvegicus were divided into six groups (n=6) that received 2 mg/kg cisplatin (CIS), 25 mg/kg thiamine (TM), 2 mg/kg cisplatin+25 mg/kg thiamine (CTM), 25 mg/kg TPP (TPP), 2 mg/kg cisplatin+25 mg/kg TPP (CTPP), or distilled water (healthy group; HG) for 8 days intraperitoneally. Analgesic effect was measured with a Basile Algesimeter. IL-1β, malondialdehyde (MDA), total glutathione (tGSH), thiamine, and TPP were determined in blood samples. Histopathological examinations were performed on removed sciatic nerves. The percent analgesic effects of the CTM and CTPP groups were calculated to be 21.3% and 82.9%, respectively. Increased production of IL-1β and MDA by cisplatin was inhibited by TPP, while it was not inhibited by thiamine. Conversion of thiamine to TPP significantly decreased in the CIS group. Histopathological and biochemical investigations demonstrated that hyperalgesia and sciatic nerve damage developed in the CIS and CTM groups with low TPP levels. These results indicate that cisplatin inhibits the formation of TPP from thiamine, leading to severe PNP. This finding suggests that TPP may be more beneficial than thiamine for the treatment of cisplatin-induced PNP.

The Effect of Anakinra on Paclitaxel-Induced Peripheral Neuropathic Pain in Rats

OBJECTIVE Paclitaxel is used in the treatment of cancer, and it may cause interleukin-1 beta (IL-1β)-related peripheral neuropathic pain. While our primary aim was to investigate the analgesic efficacy of an IL-1β antagonist, a secondary outcome was to assess whether a correlation exists between analgesic effects and antioxidant activity. METHODS A total of 24 albino Wistar male rats were divided into the following groups: paclitaxel-control, paclitaxel+50 mg kg-1 anakinra, paclitaxel+100 mg kg-1 anakinra and healthy group (HG). After the normal paw pain threshold in all animal groups was measured using a Basile algesimeter, a single dose of 2 mg kg-1 paclitaxel was intraperitoneally administered on the 1st, 3rd, 5th and 7th days. Anakinra was intraperitoneally administered following the final paclitaxel administration. The paw pain thresholds in the groups were measured before and seven days after paclitaxel administration and at the 1st and 3rd hours after anakinra administration. After the third hour of measurement, the rats were killed with high doses of ketamine, and the paw tissues were removed. Malondialdehyde, myeloperoxidase and total glutathione levels were measured in claw tissues, and IL-1β gene expression was determined. The biochemical results were compared with the results of the HG; in the meanwhile the claw pain threshold results were compared with the results obtained after the last paclitaxel and the results obtained from the 1st and 3rd hours after the anakinra application. RESULTS The claw paw pain threshold of the rats decreased one and three hours after anakinra administration. Further, 100 mg kg-1 anakinra had greater analgesic activity than 50 mg kg-1 anakinra. A correlation was found between the antioxidant and analgesic activities of 100 mg kg-1 anakinra. CONCLUSION Anakinra may be useful to reduce paclitaxel-induced neuropathic pain; further, 100 mg kg-1 anakinra may have greater analgesic and antioxidant activities.

Effects of Fentanyl and Morphine on Shivering During Spinal Anesthesia in Patients Undergoing Endovenous Ablation of Varicose Veins

Background We sought to investigate the effect of morphine and fentanyl on shivering when used adjunctively with bupivacaine during spinal anesthesia in patients undergoing varicose vein surgery on an outpatient basis. Material/Methods The study included a total of 90 patients, aged 25–45 years, ASA I–II, scheduled to undergo endovenous laser ablation under spinal anesthesia for lower extremity venous insufficiency/varicose vein disease. Patients were randomly allocated into 3 groups: Group M (morphine group) received 5 mg 0.5% hyperbaric bupivacaine + 0.1 mg morphine, Group F (fentanyl group) received 5 mg 0.5% hyperbaric bupivacaine + 25 μg fentanyl, and Group C (control group) received 5 mg 0.5% hyperbaric bupivacaine + physiologic saline. The level of sensory blockade was assessed with pin-prick test and the level of motor blockade was assessed with Bromage scale at 5-min intervals. Shivering grade and time to first postoperative analgesic requirement was recorded. Results Level and time of sensory block showed a slight but insignificant increase in the Morphine Group and Fentanyl Group. Time of postoperative analgesic requirement was significantly longer in patients who received morphine (p<0.05). Shivering was significantly less common in patients who received morphine and fentanyl than in patients who are in the Control Group (p<0.02). Conclusions Morphine or fentanyl may be used as adjunctives to spinal anesthesia to prevent shivering in patients undergoing venous surgery.

Risk Factors for Acute Kidney Injury after Coronary Artery Bypass Surgery and Its Detection Using Neutrophil Gelatinase-Associated Lipocalin

Introduction: Acute kidney injury (AKI) is an important complication of cardiac surgery due to its high mortality. The aim of the present study was to detect the factors leading to AKI in patients who underwent coronary artery bypass surgery (CABS) and also to determine the optimal timing for detecting AKI using the biomarker neutrophil gelatinase-associated lipocalin (NGAL). Materials and Methods: The records of 375 patients who underwent CABS were reviewed in this case-control study. Ejection fraction (EF), common carotid artery intima-media thickness (CCA-IMT) and cross-clamp (C-C) time of the patients were recorded. Blood samples were taken from all patients on preoperative day 1 as well as 6, 12, 24, 36, 48 h and 7 days after operation. Biochemical parameters were studied in patients with and without AKI. Results: According to the Risk Injury Failure Loss End Stage criteria, 24 patients had renal risk, 17 had injury and 4 had failure. Postoperative 24-hour serum creatinine levels indicated the risk of renal dysfunction for only 4 patients in the AKI group. CCA-IMT, C-C time, haematocrit (HCT) and preoperative interleukin-6 levels were significantly higher in the AKI group than in the non-AKI group. Postoperative 6- and 12-hour NGAL levels in the AKI group correlated with postoperative 36-hour serum creatinine levels. The optimal cut-off values for postoperative 6- and 12-hour NGAL test were 310 and 283 ng/ml, respectively. The area under the curve was higher in the 12-hour NGAL test (p < 0.0086). Conclusion: The number of stenotic coronary arteries, EF, CCA-IMT and HCT are all important risk factors. Early postoperative NGAL results were highly specific for the early recognition of AKI.

Comparison of TIVA and Desflurane Added to a Subanaesthetic Dose of Propofol in Patients Undergoing Coronary Artery Bypass Surgery: Evaluation of Haemodynamic and Stress Hormone Changes

Introduction. Increased levels of stress hormones are associated with mortality in patients undergoing coronary artery bypass grafting (CABG). Aim. To compare total intravenous anaesthesia (TIVA) and desflurane added to a subanaesthetic dose of propofol. Material and Methods. Fifty patients were enrolled in this study. Fentanyl (3–5 mcg/kg/h) was started in both groups. Patients were divided into two groups. The PD group (n = 25) received 1 minimum alveolar concentration (MAC) desflurane anaesthesia in addition to propofol infusion (2-3 mg/kg/h), while P group (n = 25) received propofol infusion (5-6 mg/kg/h) only. Biochemical data, cortisol, and insulin levels were measured preoperatively (T0), after initiation of CPB but before cross-clamping the aorta (T1), after removal of the cross-clamp (T2), and at the 24th postoperative hour (T3). Results. Systolic, diastolic, and mean arterial pressure levels were significantly higher in PD group than those in P group in T1 and T2 measurements (p ≤ 0.05). CK-MB showed a significant decrease in group P (p ≤ 0.05). When we compared both groups, cortisol levels were significantly higher in PD group than P group (p ≤ 0.05). Conclusion. Stress and haemodynamic responses were better controlled using TIVA than desflurane inhalation added to a subanaesthetic dose of propofol in patients undergoing CABG.