Metin Tilki

Melatonin Protects Against Oxidative Organ Injury in a Rat Model of Sepsis

PurposeBased on the potent antioxidant effects of melatonin, we investigated the putative protective role of melatonin against sepsis-induced oxidative organ damage in rats.MethodsSepsis was induced by cecal ligation and puncture (CLP) in Wistar albino rats. Animals subjected to CLP and sham-operated control rats were given saline or melatonin 10 mg/kg intraperitoneally 30 min before and 6 h after the operation. The rats were killed 16 h after the operation and the biochemical changes were investigated in the liver, kidney, heart, lung, diaphragm, and brain tissues by examining malondialdehyde (MDA) and glutathione (GSH) levels, and myeloperoxidase (MPO) activity. We also examined the tissues microscopically.ResultsSepsis resulted in a significant decrease in GSH levels and a significant increase in MDA levels and MPO activity (P < 0.05–P < 0.001) showing oxidative damage, which was confirmed by histological examination. Melatonin clearly reversed these oxidant responses and the microscopic damage, demonstrating its protective effects against sepsis-induced oxidative organ injury.ConclusionThe increase in MDA levels and MPO activity and the concomitant decrease in GSH levels demonstrate the role of oxidative mechanisms in sepsis-induced tissue damage. Melatonin, by its free radical scavenging and antioxidant properties, ameliorated oxidative organ injury. Thus, supplementing antiseptic shock treatment with melatonin may be beneficial in the clinical setting.

Octreotide improves reperfusion-induced oxidative injury in acute abdominal hypertension in rats.

Ischemia/reperfusion injury plays an important role in the pathogenesis of abdominal compartment syndrome, which is characterized by increased intra-abdominal pressure. The aim of this study was to investigate whether octreotide, a synthetic somatostatin analogue, improves the reperfusion injury after decompression of acute abdominal hypertension. This study was carried out in Wistar albino rats. With the rats under anesthesia, an arterial catheter was inserted intraperioneally and with the use of an aneroid manometer connected to the catheter, intra-abdominal pressure was kept at 20 mm Hg (ischemia group) for 1 hour. In the ischemia/reperfusion group, pressure applied for 1 hour was decompressed and a 1-hour reperfusion period was allowed. In another ischemia/reperfusion group, octreotide was administered (50 μg/kg intraperitoneally) immediately before the decompression of intra-abdominal pressure. At the end of the experiment, liver and intestinal tissues were taken and malondialdehyde (an index of lipid peroxidation) and glutathione (a key to antioxidant) levels andmyeloperoxidase (an index of tissue neutrophil inflltration) activity were estimated. The results demonstrated that tissue levels of malondialdehyde and myeloperoxidase activity were elevated, whereas glutathione levels were reduced in both the ischemia and ischemia/reperfusion groups. Octreotide treatment reversed these oxidant responses. In conclusion, increased intra-abdominal pressure causes oxidative organ damage and octreotide, by controlling the reperfusion of abdominal organs and inhibiting neutrophil inflltration, could improve the reperfusioninduced oxidative damage. Therefore its therapeutic role as a “reperfusion injury-limiting” agent must be further elucidated in intra-aortic pressure-induced abdominal organ injury.

Protective effect of melatonin against ischemia/reperfusion -induced oxidative remote organ injury in the rat

PurposeOxygen free radicals are considered to be important components involved in the pathophysiological tissue alterations observed during ischemia/reperfusion (I/R). Based on the potent antioxidant effects of melatonin, we investigated the putative protective role of melatonin against I/R-induced oxidative remote organ injury.MethodsWistar albino rats were subjected to 1 h of infrarenal aortic occlusion followed by 1 h of reperfusion to induce I/R damage. Melatonin (10 mg/kg, s.c.) or vehicle was administered twice, 15 min prior to ischemia and immediately before the reperfusion period (I/R + Mel or I/R groups). At the end of the reperfusion periods, the rats were decapitated and hepatic, ileal, and lung tissue samples were removed for biochemical analyses of: malondialdehyde (MDA), an end product of lipid peroxidation; the glutathione (GSH) levels, a key antioxidant; and the myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. The serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured to evaluate the liver function. The wet/dry lung weight ratio was calculated to determine the extent of lung damage.ResultsThe results revealed the occurrence of I/R-induced oxidative organ damage, as evidenced by increases in the MDA and MPO activity, and a decrease in GSH. Furthermore the AST, ALT levels, and the wet/dry lung weight ratio, which all increased due to I/R, were all observed to decrease after melationin treatment.ConclusionSince melatonin administration reversed these oxidant responses, it seems likely that melationin has a protective effect against oxidative organ damage induced by I/R.

Melatonin ameliorates oxidative organ damage induced by acute intra‐abdominal compartment syndrome in rats

Abstract: Acutely increased intra‐abdominal pressure (IAP) can lead to multiple organ failure. As blood flow to intra‐abdominal organs is reduced by high venous resistance, ischemia‐reperfusion (I/R) injury plays an important role in the pathogenesis of abdominal compartment syndrome (ACS) following IAP. Melatonin, a secretory product of the pineal gland, is known to have free radical scavenging and antioxidative properties in several oxidative processes. The objective of this study was to examine the potential protective properties of melatonin on the oxidative organ damage in a rat model of ACS. Under ketamine anesthesia, an arterial catheter was inserted intraperioneally (i.p.) and using an aneroid manometer connected to the catheter, IAP was kept at 20 mmHg (ischemia group; I) for 1 hr. In the ischemia/reperfusion (I/R) group, pressure applied for an hour was decompressed and a 1‐hr reperfusion period was allowed. In another IR group, melatonin was administered (10 mg/kg, i.p.) immediately before the decompression of IAP. The results demonstrate that tissue levels of malondialdehyde (MDA) and myeloperoxidase activity (MPO; index of tissue neutrophil infiltration) were elevated, while glutathione (GSH; a key to antioxidant) levels were reduced in both I and I/R groups (P < 0.05–0.001). Melatonin treatment in I/R rats reversed these changes (P < 0.01–0.001). Moreover, melatonin given to the I/R group reduced the elevations in serum aspartate aminotransferase, alanine aminotransferase and blood urea nitrogen levels and abolished the increase in serum creatinine levels. Our results indicate that melatonin, because of antioxidant and free radical scavenging properties, ameliorates reperfusion‐induced oxidative organ damage. In conclusion, the results of the present study suggest that the therapeutic value of melatonin as a ‘reperfusion injury‐limiting’ agent must be considered in ACS.

Abolition of anti-adhesiogenic effect of heparin by protamine sulfate

OBJECTIVE Intraabdominal adhesion is a frequently encountered condition after surgery and can end up in important complications. The objective of this study is to test whether the antiadhesiogenic effect of heparin could be antagonized by administration of protamine in a rat model. MATERIAL AND METHODS A laparotomy with caecal abrasion model was used in 40 Wistar rats. Single dose of 1 cc saline was injected subcutaneously (SC) in one group (control); 50 IU/kg heparin was injected SC in Group 2; 50 IU/kg protamine SC given to Group 3; 50 IU/kg heparin and 50 IU/kg protamine was given SC to Group 4 for 3 consecutive days. Each group consisted of 10 rats. All rats were sacrificed one week later for macroscopic and microscopic examination and they were scored for adhesion using Mazuji adhesion scale. RESULTS There was significant difference in the heparin group with respect to Mazuji adhesion score, histopathological score (fibrosis, inflammation and vascular proliferation) and S-100 staining (P < 0.05). Additionally, the inflammation was more severe in the mucosa and submucosa compared to serosa in the heparin group (P < 0.01). With respect to fibrosis and vascular proliferation, apart from submucosal fibrosis, heparin group was statistically superior to the control group by means of each layer (P < 0.01). CONCLUSION It seems that heparin is effective preventing adhesion in this rat model. Abolition of heparins antiadhesiogenic effect by protamine administration is likely exerted via its antithrombine activity. Clinical application of our findings in intraabdominal surgery warrants further investigation.

The clinicopathologic characteristics and prognostic factors of gastroesophageal junction tumors according to Siewert classification

OBJECTIVE The treatment of gastroesophageal junction tumors remains controversial due to confusion on whether they should be considered as primary esophageal or as gastric tumors. The incidence of these tumors with poor prognosis has increased, thus creating scientific interest on gastroesophageal cancers. Esophagogastric cancers are classified according to their location by Siewert, and the treatment of each type varies. We evaluated the prognostic factors and differences in clinicopathologic factors of patients with gastroesophageal junction tumor, who have been treated and followed-up in our clinics. MATERIAL AND METHODS We retrospectively analyzed 187 patients with gastroesophageal junction tumors who have been operated and treated in the Oncology Department between 2005 and 2014. The chi-square test was used to evaluate differences in clinicopathologic factors among Siewert groups I, II and III. Prognostic factors were analyzed by univariate and multivariate analysis. RESULTS The median age of our patients was 62 years, and approximately 70% was male. Nineteen patients (10.2%) had Siewert I tumors, 40 (21.4%) II, and the remaining 128 (64.4%) had Siewert III tumors. Siewert III tumors were at more advanced pathologic and T stages. Preoperative chemoradiotherapy was mostly applied to Siewert group I patients. There was no difference between the 3 groups in terms of recurrence. While the median overall survival and 2-year overall survival rate were 26.6 months and 39.6%, the median disease free survival and disease free survival rates were 16.5 months and 30.1%, respectively. The N stage, pathologic stage, vascular invasion, lymphatic invasion, perineural invasion, surgical margin, and grade were associated with both overall survival and disease free survival, while pathologic stage and presence of recurrence were significant factors for overall survival. The median disease free survival for Siewert III tumors was 20 months, 11.3 month for Siewert I tumors, and 14 months for Siewert II tumors, but the finding was not statistically significant (p=0.08). CONCLUSION Although gastroesophageal junction tumors were grouped according to their location and they exerted different clinicopathologic properties, their prognosis was similar.

Prominent gastroduodenal artery: Endosonographic sign of celiac artery stenosis

Celiac artery (CA) stenosis is a relatively common finding in patients undergoing pancreaticoduodenectomy (PD). In the presence of CA stenosis, arterial blood supply to the celiac territory is usually sustained from the superior mesenteric artery (SMA) through well-developed collaterals. In this paper, the authors report endosonographically identified prominent gastroduodenal artery as the sign of CA stenosis for the first time. Uncovering previously unidentified vascular abnormality, endoscopic ultrasound (EUS) has improved patient management. The patient had uneventful collateral preserving PD.

Capecitabine-cisplatin versus 5-fluorouracil/leucovorin in combination with radiotherapy for adjuvant therapy of lymph node positive locally advanced gastric cancer

Aim of the Study: Although surgery is considered to be curative treatment, recurrence rates are high in gastric cancer. Adjuvant 5-fluorouracil (5-FU) based chemoradiotherapy has been shown to improve the prognosis. We compared tolerability and efficacy of the two different chemotherapy regimens; 5-FU/leucovorin (LV) versus cisplatin with capecitabine (XP) combined with radiotherapy (RT) in the adjuvant therapy of the lymph node positive locally advanced gastric cancer. Materials and Methods: Totally, 104 patients who underwent curative surgery with lymph node resection were evaluated, respectively. Patients were stratified two group based on the adjuvant chemoradiotherapy regimen. Group 1 (n = 46) received XP followed capecitabine with RT (XRT) then XP. Group 2 (n = 58) received 5-FU/LV combined with RT postoperatively. Two groups were compared based on clinicopathological parameters. Factors related with disease-free survival (DFS) and overall survival (OS) were analyzed. Results: Totally, 32 patients had recurrent disease, and there was no difference between two groups. While peritoneal metastasis was more common in XP arm, distant metastasis was commonly seen in 5-FU/LV arm. There was no significant difference between two groups in regard of Grade 3/4 toxicitis; hematologic toxicities were more in 5-FU/LV group than XP arm. In addition, dose modification because of toxicities were more frequent in 5-FU/LV arm (P = 0.003). For all groups, lymph node dissection type was related with DFS, surgical margin and recurrence were important for OS. Conclusion: XP-XRT regimen is well tolerated with lower toxicity compared the standard 5-FU/LV-RT. Although there is no difference with respect to outcome, patients with XP arm without the necessity of intravenous catheter admitted hospital less frequent than bolus5-FU/LV arm.

The Impact of Western Physicians on the Modernization of Turkish Surgery and Medicine, 1827–1936

Efforts of modernizing the Ottoman Empire and society started during the 19th century. Initially reforms have been limited by institutions such as the armed forces, faculty of engineering and medicine. For this reason, a large number of western physicians invited to state to take prestigious positions in its few existing medical schools and other state establishments, in particular help with reforming its higher education. After the establishment of young Turkish Republic, western forms of science, medicine, art and literature penetrated the culture and continued to flourish. This article brings to light the efforts of these surgeons, and physicians and tells about their contributions to surgery and medicine in Turkey.