Nail Ersoz

Efficacy of hyperbaric oxygen therapy and medical ozone therapy in experimental acute necrotizing pancreatitis.

Objectives: Our aims were to evaluate the efficacy of ozone therapy (OT) in an experimental rat model of acute necrotizing pancreatitis (ANP) and to compare its effects with hyperbaric oxygen (HBO) therapy in this entity. Methods: Forty Sprague-Dawley rats were divided into sham-operated, ANP, ANP + HBO, and ANP + OT groups. Acute necrotizing pancreatitis was induced by infusing 1-mL/kg 3% sodium taurocholate into the common biliopancreatic duct. Hyperbaric oxygen was administered twice daily at a 2.8-atm pressure for 90 minutes. Ozone therapy was set as daily intraperitoneal injections of 0.7-mg/kg ozone/oxygen gas mixture. Hyperbaric oxygen and OT were continued for 3 days after the induction of ANP. The surviving animals were killed at the fourth day, and their pancreases were harvested for biochemical, microbiological, and histopathologic analyses. Results: Serum amylase/lipase and neopterin levels and tissue oxidative stress parameters were similar to shams values in both the ANP + HBO and the ANP + OT groups. Histopathologic injury scores were significantly lower in the treatments groups than in the ANP group. When compared with the ANP group, the number of infected rats was significantly lesser in the ANP + HBO and the ANP + OT groups. Conclusions: Hyperbaric oxygen and OT reduce the severity and the mortality in the experimental rat model of ANP, and a greater benefit was received for OT comparing with HBO.

Erdosteine and Ebselen As Useful Agents in Intestinal Ischemia/ Reperfusion Injury

BACKGROUND Reactive oxygen and nitrogen species generated during reperfusion of the tissue are characteristic of ischemia/reperfusion (I/R) injury. The purpose of the present study was to investigate whether erdosteine and ebselen, molecules with antioxidant properties and peroxynitrite scavenging capability, respectively, can reduce oxidative stress and histological damage in the rat small bowel subjected to mesenteric I/R injury. MATERIALS AND METHODS Forty Sprague-Dawley rats were divided into five groups equally: sham, I/R, I/R plus erdosteine, I/R plus ebselen, and I/R plus erdosteine and ebselen. Intestinal ischemia for 45 min and reperfusion for 3 d were carried out. Ileal specimens were obtained to determine the tissue levels of malondialdehide (MDA), protein carbonyl content (PCC), superoxide dismutase (SOD), glutathione peroxidase (GPx), nitrite/nitrate (NO(x)) level and histological changes. RESULTS Intestinal I/R resulted in increased tissue MDA, PCC, and NO(x) levels and decreased SOD and GPx activities. Both erdosteine and ebselen alone significantly decreased MDA, PCC, and NO(x) levels and increased antioxidant enzymes activities, but all values were different from control. These changes almost returned to control values in the group treated with erdostein and ebselen. Histopathologically, the intestinal injury in rats treated with erdosteine and ebselen as well as combination were less than I/R group. CONCLUSIONS Both erdosteine and ebselen were able to attenuate I/R injury of the intestine via inhibition of lipid peroxidation and protein oxidation, maintenance of antioxidant, and free radical scavenger properties. Nevertheless, combination treatment showed more promising results, suggesting that scavenging peroxynitrite nearby antioxidant activity is important in preventing intestinal I/R injury.

Comparison of the Efficacy of Melatonin and 1400W on Renal Ischemia/Reperfusion Injury: A Role for Inhibiting iNOS

Introduction. We investigated the roles of melatonin (a powerful antioxidant, iNOS inhibitor, and a scavenger of peroxynitrite) and 1400W (a strong and selective inhibitor of inducible nitric oxide) on renal dysfunction and injury induced by ischemia/reperfusion (I/R) of rat kidney, since oxidative and nitrosative injury are believed to be the major causes. Materials and methods. Thirty-two male Sprague-Dawley rats were divided into four groups of sham-operated, I/R, I/R + Melatonin and I/R + 1400W. Rats were given either melatonin (10 mg/kg) or 1400W (10 mg/kg) in the I/R + Melatonin and I/R + 1400W groups respectively at 6 h prior to ischemia and at the beginning of reperfusion via intraperitoneal route. I/R injury was induced by 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood were obtained for histopathologic and biochemical evaluation. Results. Melatonin and 1400W had an ameliorative effect on both oxidative and nitrosative stress in the kidneys against renal I/R injury in rats. In addition, melatonin significantly reduced elevated nitro-oxidative stress product, restored decreased antioxidant enzymes and attenuated histological alterations when compared with 1400W. Conclusions. Both Melatonin and 1400W were efficient in ameliorating experimental I/R injury of the kidneys. Moreover, melatonin was more effective than 1400W possibly through inhibiting iNOS as well as scavenging free oxygen radicals and peroxynitrite.

Pharmacologic characterization of contractile serotonergic receptors in human isolated mesenteric artery.

The 5-hydroxytryptamine (5-HT) receptors mediating contraction in human isolated mesenteric arteries were characterized. Endothelium-denuded human isolated mesenteric arteries were used. 5-HT induced concentration-dependent contractions in mesenteric arteries (Emax, 127.37 ± 7.61% of 80 m M KCl maximal contraction; pD2, 6.73 ± 0.09 [−logEC50]). Sumatriptan, a selective 5-HT1B/1D receptor agonist, induced concentration-dependent contractions in some of the arteries (Emax, 61.82 ± 10.04%; pD2, 6.56 ± 0.21, n = 9) but not in the others (Emax < 5%, n = 13), suggesting that functional 5-HT1B/1D receptors exist in some but not in all mesenteric arteries. GR127935 (a selective 5-HT1B/1D receptor antagonist, 3 n M) inhibited sumatriptan-induced contractions in arteries in which sumatriptan responses were strong in an insurmountable manner. GR127935 (10 n M) also inhibited 5-HT responses and shifted the concentration–response curve of 5-HT to the right significantly (p < 0.05; pD2s were 6.54 ± 0.18 and 5.93 ± 0.11 in the presence of vehicle and GR127935, respectively). Ketanserin (0.01–1 &mgr;M) competitively antagonized 5-HT responses in human mesenteric arteries: pA2 value was 8.40 ± 0.25 (slope of Schild regression, 1.43 ± 0.18; r2, 0.98). Tropisetron (5-HT3 receptor antagonist) and prazosin (&agr;1-adrenoceptor antagonist) did not affect the contractions induced by 5-HT. These results suggest that 5-HT2A and 5-HT1B/1D receptors, but not 5-HT3 and &agr;1-adrenoceptors, are involved in the 5-HT–induced contractions in human isolated mesenteric arteries. Sumatriptan-induced and 5-HT1B/1D receptor-mediated responses vary greatly among patients.

Comparison of hyperbaric oxygen and medical ozone therapies in a rat model of experimental distal colitis

Abstract Objectives. Previous studies have shown that hyperbaric oxygen (HBO) is effective in reducing the severity of acute distal colitis (ADC). Ozone therapy (OT) reduces inflammation in several pathological conditions. We aimed to compare the effects of HBO therapy and OT in an experimental ADC rat model. Materials and methods. Forty rats were randomly divided into four groups: Sham, ADC, ADC + HBO, and ADC + OT. Rats in the sham group were given isotonic saline. In the remaining groups, ADC was created by intracolonic administration of 4% acetic acid. No treatment was given to the ADC group. The rats in the ADC + HBO and ADC + OT groups were given HBO and ozone treatments, respectively. The administration of acetic acid caused an inflammatory response in all animals. Distal colons and blood samples were obtained. Results. The histopathological score was significantly higher in the ADC group compared to the other groups. The histopathological scores in the ADC + HBO and ADC + OT groups were significantly lower compared to the ADC group (both p < 0.001). The most pronounced therapeutic effect was observed in the ADC + OT group. Malondialdehyde and neopterin levels and superoxide dismutase and glutathione peroxidase activities in the ADC group were significantly higher compared to the other groups (p < 0.001). Conclusion. Our data showed that the therapeutic effect of OT is more pronounced than that of HBO therapy. Its possible effect is by means of decreasing inflammation, edema, and oxidative stress. These findings also suggest that it is possible to improve the outcome of ADC by using ozone therapy as an adjuvant therapy.

Pentraxin 3 as a potential biomarker of acetaminophen-induced liver injury.

OBJECTIVE Overdose of acetaminophen (APAP) can lead to severe liver injury in humans and experimental animals. Pentraxin-3 (PTX-3) is produced and released by several cell types. In this study, we aimed to evaluate whether PTX-3 is a potential biomarker in the identification of APAP-induced liver injury. MATERIALS AND METHODS Thirty adult male Wistar rats were randomly divided into three groups: control, APAP-1 and APAP-2 groups. APAP-1 (1 g/kg) and APAP-2 (2 g/kg) group rats were given APAP by gastric tube. Liver tissues and blood samples were obtained for biochemical and histopathological analysis. Biochemical parameters, plasma and liver PTX-3 levels and degree of liver necrosis were measured in all groups. RESULTS APAP treatments caused necrosis in liver and accompanied by elevated liver PTX-3 levels after 48 h. In APAP-1 and APAP-2 groups when compared with control group (7.5±3.3 ng/mg protein), mean liver PTX-3 concentrations were 14.1±3.0 (p=0.032) and 28.5±8.2 (p<0.001) ng/mg protein, respectively. All rats (100%) in the APAP-2 group had the degree 3 liver necrosis. However 10%, 40% and 50% of rats had the degree 1, the degree 2 and the degree 3 liver necrosis in the APAP-1 group, respectively. The degrees of liver necrosis of the APAP-1 and APAP-2 groups were higher than the group of control (p<0.001 and p<0.001, respectively). CONCLUSIONS PTX-3 may have a role in the APAP-induced liver injury in the rats. The elevated liver PTX-3 in the APAP-induced hepatic necrosis might be a marker of acute histological liver damage. Further prospective studies are necessary to clarify the prognostic value of liver PTX-3 for prediction of histological hepatic necrosis in the APAP-induced liver injury.

The association between neopterin and acetaminophen-induced nephrotoxicity

Introduction: In large dosages, acetaminophen (APAP) produces acute kidney necrosis in most mammalian species. High neopterin levels have been accepted as strong indicators for the clinical severity of some diseases. In this study, we aimed to evaluate whether neopterin is a biomarker in the identification of APAP-induced nephrotoxicity. Materials and Methods: Thirty adult male Wistar rats were randomly divided into three groups: control, APAP-1, and APAP-2 groups. APAP-1 and APAP-2 group rats were given a single dose of 1 and 2 g/kg body weight of APAP by gastric tube, respectively. Kidney tissues and blood samples were obtained for biochemical and histopathological analyses. Biochemical parameters, serum and kidney neopterin levels, and the grade of tubular injury were compared in the control, APAP-1, and APAP-2 group animals. Results: APAP treatments caused tubular necrosis in the kidney and increase in serum creatinine concentrations accompanied by elevated serum and kidney neopterin levels. In the rats of groups APAP-1 and APAP-2 when compared with that of the control group (109.1 pmol/mg protein), median kidney neopterin concentrations were 162.1 (p = 0.089) and 222.2 (p < 0.001) pmol/mg protein, respectively. The grade of tubular injury of the APAP-1 and APAP-2 groups was higher than the group of control (both p < 0.001). Conclusions: Serum and kidney neopterin levels could be sensible alternative to evaluate the risk to have nephrotoxicity because of APAP overdose. The elevated serum and kidney neopterin in the APAP-induced tubular necrosis might be a marker of acute histological kidney injury.

Melatonin prevents peritoneal adhesions in rats

Background and Aim:  Intra‐abdominal adhesions are important postoperative complications following abdominal surgery. The adhesions that develop form the basis of more advanced pathology such as intestinal obstruction or infertility. Melatonin is secreted from the pineal gland in a circadian pattern; this molecule has potent antioxidant characteristics and has beneficial effects in many models of inflammation. The aim of this study was to evaluate the effects of melatonin on peritoneal adhesions created in rats.

A Rare Complication after Thyroidectomy: Perforation of the Oesophagus: a Case Report

Abstract Perforation of the cervical oesophagus after thyroidectomy is an exceptionally rare complication. Total thyroidectomies, particularly for recurrent cases might possess an increased risk. Although rare, it has high mortality and morbidity. A patient that developed oesophagus perforation after a total thyroidectomy in a peripheral hospital for recurrent nodular goitre was treated and followed-up in our clinic. This well-documented case is discussed in conjunction with the information presented in the literature.

Efficacy of melatonin, mercaptoethylguanidine and 1400W in doxorubicin- and trastuzumab-induced cardiotoxicity.

Abstract:  Doxorubicin (DOX) and Trastuzumab (TRAST) are effective agents for the treatment of many neoplastic diseases. Cardiotoxicity is a major side effect of these drugs and limit their use. In this study, the possible protective effects of melatonin (MEL), mercaptoethylguanidine (MEG), or N‐(3‐(aminomethyl) benzyl) acetamidine (1400W) against the cardiotoxicity of DOX and TRAST were tested. Male Sprague‐Dawley rats received an injection of DOX (20 mg/kg) alone or in combination with TRAST (10 mg/kg) to induce cardiotoxicity; daily treatments with MEL (10 mg/kg × 2), MEG (10 mg/kg × 2), or 1400W (10 mg/kg × 2) were begun 36 hr before and continued for 72 hr after DOX and TRAST administration. Oxidant/antioxidant indices of the cardiac tissue, namely, malondialdehyde, superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px), as well as serum levels of creatine phosphokinase (CK‐MB) were measured. Additionally, the injury scores were evaluated histopathologically. Malondialdehyde levels were significantly higher, while SOD and GSH‐Px activities were significantly reduced in rats with DOX‐ or DOX+TRAST‐induced cardiotoxicity compared to normal values. All three treatment agents significantly reversed oxidative stress markers. Serum CK‐MB levels were significantly increased after treatment with DOX and DOX+TRAST; these changes were also reversed by each of the treatments and resulted in near normal levels. Both the DOX‐ and DOX+TRAST‐treated rats presented similar histopathologic injuries; in the animals treated with the protective agents, histologic protection of the cardiac tissue was apparent. These results suggested that MEL, MEG, as well as 1400W are effective in preventing DOX‐ or DOX+TRAST‐induced cardiotoxicity.