Ensari Guneli

Effect of Melatonin on Testicular Damage in Streptozotocin-Induced Diabetes Rats

Background: It is well known that diabetes mellitus is associated with impairment of testicular function. In the present study, we aimed to demonstrate the effect of melatonin on testicular damage in male rats with streptozotocin (STZ)-induced diabetes. Methods: Male Wistar rats were divided into 4 groups: (1) control group, (2) melatonin-treated nondiabetic group, (3) diabetic group and (4) melatonin-treated diabetic group. Diabetes was induced by STZ injection. Melatonin was administered intraperitoneally at the dose of 10 mg/kg for 5 days. Testicular damage was examined by using hematoxylin and eosin staining and periodic acid-Schiff staining, and apoptosis was determined by terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL). Potential disorders associated with seminiferous tubular sperm formation were evaluated using the Johnsen score. Results: Diabetic rats showed a reduction in seminiferous tubule diameter, increased thickening of the basement membrane in seminiferous tubules and degenerated germ cells. TUNEL-positive cells were significantly more numerous in diabetic rats than in control rats. Melatonin significantly attenuated the diabetes-induced morphological changes and germ cell apoptosis in the diabetic rat testis. The number of polymorphonuclear leukocytes was significantly decreased in group 4 when compared to group 3. Conclusions: These results suggest that intraperitoneal administration of melatonin for 5 days is a potentially beneficial agent to reduce testicular damage in adult diabetic rats, probably by decreasing oxidative stress.

Analysis of the antinociceptive effect of systemic administration of tramadol and dexmedetomidine combination on rat models of acute and neuropathic pain

The aim of the present study was to investigate the possible antinociceptive effect of systemic administration of tramadol and dexmedetomidine either alone or in combination on acute and neuropathic pain models in rats. The antinociceptive effects of intraperitoneal (i.p.) tramadol (5-20 mg/kg) and dexmedetomidine (5-20 microg/kg) and three different combinations of tramadol+dexmedetomidine (5+5, 5+10 and 10+5, mg/kg+microg/kg, respectively) were measured by tail-flick and hot-plate methods in acute pain. The effects on the sciatic nerve ligation-induced neuropathic pain was tested by i.p. administration of tramadol (5 mg/kg), dexmedetomidine (5 microg/kg) and tramadol+dexmedetomidine combination (5+5) using a thermal plantar test. Sedation/motor-incoordination was assessed on rotarod. Tramadol and dexmedetomidine produced dose-related antinociception in tail-flick and hot-plate tests. In both tests, combination of these drugs produced an antinociceptive effect that is greater than that produced by tramadol or dexmedetomidine alone at several time points. In hot-plate test, tramadol+dexmedetomidine combination (5+10) exerted the strongest antinociceptive effect, while tramadol+dexmedetomidine combination (10+5) was significantly most effective in tail-flick test. In the neuropathic pain, the antinociceptive effect exerted by tramadol+dexmedetomidine combination (5+5) was also significantly greater than their applications alone. In rotarod test, tramadol (30 and 40 mg/kg), dexmedetomidine (30 and 40 microg/kg), tramadol+dexmedetomidine combination (10+10, 20+20) produced sedation/motor-incoordination, whereas tramadol (5-20 mg/kg), dexmedetomidine (5-20 microg/kg) and tramadol+dexmedetomidine combination (5+5, 5+10 and 10+5) did not produce any effect on sedation/motor-incoordination. The combination of tramadol and dexmedetomidine was more effective in increasing the pain threshold in acute and neuropathic pain when compared with the administration of either of these drugs alone.

Viability of crushed and diced cartilage grafts wrapped in oxidized regenerated cellulose and esterified hyaluronic acid: an experimental study.

Objectives: The objective of this study was to investigate the viability of diced/crushed cartilage grafts wrapped in esterified hyaluronic acid (HYAFF) and oxidized regenerated cellulose (Surgicel) with respect to macroscopic and microscopic parameters.

Effects of repeated administered ghrelin on chronic constriction injury of the sciatic nerve in rats.

Chronic constriction injury (CCI) is a peripheral mononeuropathic pain model that is caused by an injury to the peripheral nervous system and refractory to available conventional treatment. Mechanisms involved in neuropathic pain are still unclear. Previous studies reveal that proinflammatory cytokines contribute to CCI-induced peripheral nerve pathology. Ghrelin, a novel identified gastric peptide, has been shown to have antinociceptive activity and also anti-inflammatory properties by decreasing proinflammatory cytokines. Therefore, the aim of the present study was to investigate the effects of ghrelin on the CCI and its relationship with proinflammatory cytokines in rats. Wistar rats underwent sciatic nerve ligation to induce CCI fallowed by repeated ghrelin administrations (50 and 100microg/kg i.p., once daily) for a period of 14 days. Mechanical hyperalgesia was assessed before surgery and at day 14 after CCI. TNF-alpha, IL-1beta and IL-6 were measured in blood and spinal cord. The changes of sciatic nerve was assessed histologically by both light and electron microscopy. Ghrelin attenuated mechanical hyperalgesia, reduced spinal TNF-alpha and IL-1beta levels and enhanced sciatic nerve injury with correlated morphometric recovery. These results indicate that the protective effect by ghrelin in the spinal cord is mediated through the suppression of TNF-alpha and IL-1beta. Thus ghrelin may be a promising peptide in the management of neuropathic pain.

Possible involvement of ghrelin on pain threshold in obesity

Pain threshold (or perception) can increase or decrease according to some factors like gender, depression or individual differences. Also, previous studies showed that pain threshold can change in obesity but, these studies on the effects of obesity on pain threshold have given controversial results. In the obese people who were exposed to pain stimulation to determined pain threshold, an increased pain threshold was observed. Contrarily, in the studies using electrophysiological test had lower pain threshold, which indicates a reverse correlation between degree of overweight and the threshold of the nociceptive reflex. These studies indicate possible interrelationships between the endogenous opioids, nociception and obesity or eating behavior. Nevertheless, its mechanism is still unclear. The endocrine changes that play an important role in obesity can lead an increase or decrease in pain threshold. There are a few researches about these hormonal factors which are related to pain pathways, that they are nociceptive (like leptin) or antinociceptive effect (like ghrelin, orexin A and B). Ghrelin is one of the hormones which is related to obesity. There are studies which prove the relationship between this hormone and the systems that play a role in pain modulation in the brain. However, there is no previous knowledge about the effects of ghrelin on pain threshold in obesity. But, many strong evidence are present to hypothesise that ghrelin may have effects on pain threshold. Obesity and fasting are the two main situations in which ghrelin secretion is mostly modified. Circulating ghrelin levels negatively correlate with BMI, meaning increased ghrelin secretion during fasting, malnutrition, cachexia, and in anorexia nervosa and reduced ghrelin secretion in obesity. Therefore, we have the opinion that ghrelin play an important role in obesity-pain relationship and/or regulate other systems that are related to pain pathway. Based on the above analyses, we propose a hypothesis that the diminution of the susceptibility to pain in lean subjects/animals may be induced by the increase in endogenous ghrelin activity, or increased of the susceptibility to pain in obese subject/animals may be induced by the decrease in endogenous ghrelin activity.

The Effects of Remote Ischemic Preconditioning and N-Acetylcysteine with Remote Ischemic Preconditioning in Rat Hepatic Ischemia Reperfusion Injury Model

Background. Remote ischemic preconditioning (RIP) and pharmacological preconditioning are the effective methods that can be used to prevent ischemia reperfusion (IR) injury. The aim of this study was to evaluate the effects of RIP and N-Acetylcysteine (NAC) with RIP in the rat hepatic IR injury model. Materials and Methods. 28 rats were divided into 4 groups. Group I (sham): only laparotomy was performed. Group II (IR): following 30 minutes of hepatic pedicle occlusion, 4 hours of reperfusion was performed. Group III (RIP + IR): following 3 cycles of RIP, hepatic IR was performed. Group IV (RIP + NAC + IR): following RIP and intraperitoneal administration of NAC (150 mg/kg), hepatic IR was performed. All the rats were sacrificed after blood samples were taken for the measurements of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver was processed for conventional histopathology. Results. The hepatic histopathological injury scores of RIP + IR and RIP + NAC + IR groups were significantly lower than IR group (P = 0.006, P = 0.003, resp.). There were no significant differences in AST and ALT values between the IR, RIP + IR, and RIP + NAC + IR groups. Conclusions. In the present study, it was demonstrated histopathologically that RIP and RIP + NAC decreased hepatic IR injury significantly.

The Role of Rac1 on Carbachol‐induced Contractile Activity in Detrusor Smooth Muscle from Streptozotocin‐induced Diabetic Rats

This study was designed to determine the role of the small GTPase Rac1 on carbachol‐induced contractile activity in detrusor smooth muscle using small inhibitor NSC 23766 in diabetic rats. Rac1 expression in bladder tissue was also evaluated. In the streptozotocin (STZ)‐induced diabetic rat model, three study groups were composed of control, diabetic and insulin‐treated diabetic subjects. The detrusor muscle strips were suspended in organ baths at the end of 8–12 weeks after STZ injection. Carbachol (CCh) (10−9–10−4 M) concentration–response curves were obtained both in the absence and in the presence of Rac1 inhibitor NSC 23766 (0.1, 1 and 10 μM). Diabetes‐related histopathological changes and Rac1 expressions were assessed by haematoxylin and eosin staining and immunohistochemical staining, respectively. CCh caused dose‐dependent contractile responses in all the study groups. Rac1 inhibitor NSC 23766 inhibited CCh‐induced contractile responses in all groups, but this inhibition seen in both diabetes groups was greater than in the control group. Histological examination revealed an increased bladder wall thickness both in the diabetes and in the insulin‐treated diabetes groups compared to the control group. In immunohistochemical staining, expression of Rac1 was observed to be increased in all layers of bladder in both diabetic groups compared to the control group. In the diabetic bladders, increased expression of Rac1 and considerable inhibition of CCh‐induced responses in the presence of NSC 23766 compared to those of the control group may indicate a specific role of Rac1 in diabetes‐related bladder dysfunction, especially associated with cholinergic mediated detrusor overactivity.

Fluid resuscitation in the treatment of uncontrolled hemorrhagic shock

ZusammenfassungGRUNDLAGEN: Der Effekt von Volumenersatz auf Hämodynamik und Überleben nach Milzverletzung in Ratten wurde untersucht. METHODIK: Hämorrhagischer Schock wurde bei 70 Ratten durch Milzverletzung induziert. Volumenersatztherapie: Gruppe 1 (n = 10) sham-operiert; Gruppe 2 (n = 10) MMV war nicht therapiert und nach 45 Minuten die Splenektomie durchgeführt; Gruppe 3 (n = 10) MMV, nach 45 Minuten mit 7,5 ml/kg/h NaCl (HTS-7,5) therapiert und nach 45 Minuten die Splenektomie durchgeführt; Gruppe 4 (n = 10) MMV, mit 35 ml/kg/h Ringer Lactat (RL-35) Lösung therapiert und die Splenektomie durchgeführt; Gruppe 5 (n = 10) MMV, mit 70 ml/kg/h Ringer Lactat (RL-70) Lösung therapiert und die Splenektomie durchgeführt; Gruppe 6 (n = 10), MMV, mit 35 ml/kg/h von 0,9 % NaCl (NaCl-35) und die Splenektomie durchgeführt; und Gruppe 7 (n = 10) MMV, mit 70 ml/kg/h von 0,9 % NaCl (NaCl-70) und die Splenektomie durchgeführt. ERGEBNISSE: Niedrig- und Hoch-Volumen Ringer Lactat (RL-35, RL-70) Infusion steigert MMV, die Pulsfrequenz und den Hämatokrit-Spiegel vs. zur unbehandelten Gruppe (p < 0,001), jedoch die beste Wirkung brachte RL-35. TBL mit RL-35 (22 % des Blut-Volumens) war geringer vs. RL-70 und den anderen Gruppen (p < 0,01). Die Überlebenszeit war am besten mit RL-35 und RL-70 für 60 min und 120 min (p < 0,05). SCHLUSSFOLGERUNGEN: Kontinuierliche Infusion von RL-35 und RL-70 für 60 und 120 min erbrachte die besten Ergebnisse in diesem Ratten-Modell der Milzverletzung.SummaryBACKGROUND: We evaluated the effect of continuous fluid resuscitation on the hemodynamic response and survival following massive splenic injury (MSI) in rats. METHODS: Uncontrolled hemorrhagic shock was produced in 70 rats by sharp transaction. The animals were randomized into 7 groups: group 1 (n = 10), sham-operated; group 2 (n = 10), MSI was untreated and splenectomy was performed after 45 min; group 3 (n = 10), MSI treated after 15 min with 7.5 ml/kg/h of 7.5% NaCl (HTS-7.5) and splenectomy after 45 min; group 4 (n = 10), MSI treated with 35 mL/kg/h Ringers lactate (RL) solution (RL-35) and splenectomy; group 5 (n = 10), MSI treated with 70 mL/kg/h RL (RL-70) and splenectomy; group 6 (n = 10), MSI treated with 35 mL/kg/h of 0.9% NaCl (NaCl-35) and splenectomy; and group 7 (n = 10), MSI treated with 70 mL/kg/h of 0.9% NaCl (NaCl-70) and splenectomy. RESULTS: Small and high volume ringer lactate (RL-35, RL-70) infusion increased MAP, pulse rate, and hematocrit level compared to untreated group (p < 0.001); however, best response was inquired by RL-35. TBL with RL-35 (22% of blood volume) was less than RL-70 and other groups (p < 0.01). High rate of early mortality (33.4% at 30 min) with HTS infusion was noticed. TBL was moderately increased in NaCl-70 (32% of blood volume) compared to NaCl-35 (30% of blood volume). Survival time was better with RL-35 and RL-70 at 60 min and 120 min, respectively, compared to other groups (p < 0.05). CONCLUSIONS: In conclusion, continuous infusion of HTS, RL-70, NaCl-35 and NaCl-70 following massive splenic injury in uncontrolled hemorrhagic shock resulted in a significant increase in intra-abdominal bleeding compared to lower dose RL-35 and greatest survival time was noticed with RL-35 and RL-70 at 60 and 120 min, respectively.

797 THE ANTINOCICEPTIVE EFFECT OF TRAMADOL PLUS DEXMEDETOMIDINE COMBINATION ON ACUTE AND NEUROPATHIC PAIN IN THE RAT MODELS

Background: Pulse Mode Radiofrequency lesioning of suprascapular nerve is a novel; non-ablative technique has been shown to be effective in pain control and improved shoulder joint movements [1]. Objective: To establish patients perception to Pulse radiofrequency lesioning and to determine its efficacy in reducing pain resistant to conventional drug therapy. Methodology: Thirteen patients who were treated with Pulse Radiofrequency lesioning of the suprascapular nerve for chronic shoulder pain were sent a questionnaire evaluating the efficiency of the treatment received. Ten patients returned their completed forms to clinical audit department for analysis. Summary of findings: The majority of patients (8/10) had the treatment once and two patients had received treatment three times. Fifty percent of patients (5/10) reported either no change in the level of pain or that the pain had became worse since treatment. Fifty percent of patients (5/10) indicated that the duration of the effects of the treatment lasted less than six months. Eighty percent of the patients did not reduce their pain relief medication since the treatment. Sixty percent of patients recorded that they would consider further treatments with Pulse Radiofrequency while thirty percent recorded that they would not consider further treatments. Conclusions: The efficacy of Pulse Radiofrequency lesioning was found to be equivocal in this small sample of patients. Further large sample size study is needed before conclusions can be drawn on its effectiveness.