Mustafa Kerem

Beta-glucan attenuates inflammatory cytokine release and prevents acute lung injury in an experimental model of sepsis.

Sepsis is one of the most important risk factors in acute respiratory distress syndrome (ARDS). &bgr;-Glucan is a potent reticuloendothelial modulating agent, the immunobiological activity of which is mediated in part by an increase in the number and function of macrophages. In this study, we investigated the putative protective role of &bgr;-glucan against sepsis-induced lung injury. Sepsis was induced by cecal ligation and puncture (CLP) in Wistar rats. The control group received saline, and the treatment groups received &bgr;-glucan or &bgr;-glucan + &bgr;-1,3-D-glucanase. Five hours thereafter, plasma tumor necrosis factor (TNF) &agr;, interleukin (IL) 1&bgr;, and IL-6 levels were determined. Presence of lung injury was determined via lung tissue myeloperoxidase (MPO) activity, intercellular adhesion molecule (ICAM) 1 levels, and histopathological examination at 18 h after CLP. In a separate set of experiments, survival was monitored for 7 days after CLP. &bgr;-Glucan treatment led to a significant increase in survival rate (63% in glucan-treated rats vs 38% in saline-treated rats). Administration of the &bgr;-glucan inhibitor abrogated &bgr;-glucans survival benefit (50%). After CLP, plasma TNF-&agr;, IL-1&bgr;, and IL-6 concentrations were increased in control animals. When &bgr;-glucan was administered, it completely blocked the elevation of TNF-&agr;, IL-1&bgr;, and IL-6. Administration of &bgr;-1,3-D-glucanase suppressed glucan-induced decrease in cytokines. Animals treated with &bgr;-glucan showed a significant reduction in lung injury score, a marked decrease in ICAM-1 expression, and a significant decrease in MPO levels. In contrast, &bgr;-1,3-D-glucanase caused a significantly increased MPO and ICAM-1 levels in the lung. These data reveal that &bgr;-glucan treatment improved the course of CLP-induced peritonitis and attenuated the lung injury. Administration of &bgr;-glucanase inhibited the &bgr;-glucan activity and resulted in enhanced lung injury.

Hepatic Energy Metabolism and the Differential Protective Effects of Sevoflurane and Isoflurane Anesthesia in a Rat Hepatic Ischemia-Reperfusion Injury Model

BACKGROUND: We investigated the effects of isoflurane and sevoflurane in a warm liver ischemia-reperfusion (IR) model on cytokines, hepatic tissue blood flow (HTBF), energy content, and liver structure. METHODS: Seventy-two Wistar rats were randomly assigned into 1 of 3 groups: Control group, no volatile anesthetics; sevoflurane group, 2% sevoflurane; isoflurane group, 1.5% isoflurane. Thirty minutes after the start of volatile anesthetics, rats were subjected to 45 min hepatic ischemia and 2 and 4 h of reperfusion. Rats were killed at the end of ischemia, 2 and 4 h of reperfusion. Aspartate aminotransferase and alanine aminotransferase, HTBF, malondialdehyde, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, energy charge, and histologic examination were used to evaluate the extent of liver injury. RESULTS: Serum alanine aminotransferase and aspartate aminotransferase levels were similar in control and isoflurane groups while there was a significant decrease in the sevoflurane group in the postischemic period (P < 0.01). HTBF was remarkably better in the sevoflurane group than in the isoflurane group and worse in the control group. Tissue malondialdehyde levels were significantly low in the sevoflurane group compared with the isoflurane group at 2 h of reperfusion (P < 0.05) and reached its maximum value in the postischemic period in the control group. After ischemia, 2 and 4 h of reperfusion, tumor necrosis factor-α and interleukin-1β values were lowest in the sevoflurane group and highest in the control group but it was not statistically significant (P > 0.05). In the sevoflurane group, hepatic adenosine triphosphate and energy charge were significantly high at all measurement times. At the postischemic period, energy charge was lower compared with the sevoflurane and isoflurane groups. The degree of hepatocyte injury was small in the sevoflurane group. CONCLUSIONS: Clinically relevant concentrations of sevoflurane given before, during, and after hepatic ischemia protected the liver against IR injury, whereas the effects of isoflurane on hepatic IR injury were not notable.

L-alanin-L-glutamine supplementation improves the outcome after colorectal surgery for cancer.

Objective  To investigate the effect of l‐alanine‐l‐glutamine (Gln) on postoperative complication rate and duration of hospitalization in patients operated for colorectal cancer.

Comparison of free jejunal graft with gastric pull-up reconstruction after resection of hypopharyngeal and cervical esophageal carcinoma

The purpose of this study is to evaluate the operative outcomes of a gastric pull-up and free jejunal graft reconstruction after resection of hypopharyngeal and cervical esophageal carcinoma. Records of all patients who underwent esophageal resection for carcinoma of the hypopharynx and cervical esophagus were reviewed. Reconstruction after esophagectomy was performed using the gastric pull-up (n = 38) or free jejunal graft (n = 14) techniques. The hypopharynx was the most common primary tumor site for the free jejunal graft group, whereas the gastric pull-up group had lesions more frequently in the cervical esophagus (P < 0.05). Both operative time and blood loss in the gastric pull-up group were significantly longer and excessive than those of the free jejunal graft group (P < 0.05). The graft survival rate was 95% (32/34) in the gastric pull-up group and 93% (13/14) for the free jejunal transfer group. The overall leakage rate was 1.9% (1/52). Three patients died (6%) in the postoperative period. There was no significant difference with regard to operative morbidity and mortality between the gastric pull-up group and free jejunal graft group. In conclusion, both free jejunal graft and gastric pull-up are safe and effective methods for the immediate restoration of alimentary continuity.

Peroxisome proliferators-activated alpha agonist treatment ameliorates hepatic damage in rats with obstructive jaundice: an experimental study

BackgroundPeroxisome proliferators-activated receptor alpha (PPARα) activation modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of short-term administration of fenofibrate, a PPARα agonist, on proinflammatory cytokines, apoptosis, and hepatocellular damage in cholestasis.MethodsForty male Wistar rats were randomly divided into four groups: I = sham operated, II = bile duct ligation (BDL), III = BDL + vehicle (gum Arabic), IV = BDL + fenofibrate (100 mg/kg/day). All rats were sacrificed on 7th day after obtaining blood samples and liver tissue. Total bilirubin, aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), gamma-glutamyl transferase, (GGT), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1 β), and total bile acid (TBA) in serum, and liver damage scores; portal inflammation, necrosis, bile duct number, in liver tissue were evaluated. Apoptosis in liver was also assessed by immunohistochemical staining.ResultsFenofibrate administration significantly reduced serum total bilirubin, AST, ALT, ALP, and GGT, TNF-α, IL-1 β levels, and TBA (P < 0.01). Hepatic portal inflammation, hepatic necrosis, number of the bile ducts and apoptosis in rats with BDL were more prominent than the sham-operated animals (P < 0.01). PPARα induction improved all histopathologic parameters (P < 0.01), except for the number of the bile duct, which was markedly increased by fenofibrate therapy (P < 0.01).ConclusionShort-term administration of fenofibrate to the BDL rats exerts beneficial effects on hepatocellular damage and apoptosis.

Effect of timing of glutamine-enriched enteral nutrition on intestinal damage caused by irradiation.

Intestinal mucosal damage and bacterial translocation are clinical problems that may be caused by the use of ionizing radiation. Glutamine (Gln) support reduces the mucosal barrier in several ways. This study was undertaken to investigate the effect of timing of Gln-enriched enteral nutrition (EN) on bacterial translocation and mucosal damage due to radiotherapy (RT). A rat model of whole body irradiation was designed in which a single dose of 485 cGy was given. A total of 50 rats were randomly assigned to the following 5 groups, each of which comprised 10 rats: (1) balanced rat chow given for 8 days without RT (group 1); (2) balanced rat chow given 4 days before and 4 days after RT (group 2); (3) Gln-enriched EN given 4 days before RT (group 3); (4) Gln-enriched EN given 4 days after RT (group 4); and (5) Gln-enriched EN given 4 days before and 4 days after RT (group 5). Mesenteric lymph node and ileum samples were removed for evaluation of bacterial translocation (BT) and histopathologic investigation, respectively. BT and intestinal mucosal injury scores in all rats that received RT were higher than in rats without RT. No difference was seen in parameters between groups 3 and 4 (P>.05, P>.016, respectively); BT and intestinal mucosal injury scores of group 5 were significantly lower than those of groups 3 and 4 (P<.05, P<.016, respectively). Meanwhile, the BT and mesenteric injury scores of group 5 were significantly lower than those of group 2 (P<.05, P<.016, respectively). As a result, intestinal injury due to RT was significantly decreased by Gln-enriched EN support given before and after whole body RT.

Delayed Energy Protection of Ischemic Preconditioning on Hepatic Ischemia/Reperfusion Injury in Rats

Background: Hepatic ischemia/reperfusion (IR) injuries associated with hepatic resections are unresolved problems in the clinical practice. The aim of this study is to elucidate the effect of ischemic preconditioning (IPC) on the energy charge (EC) and related mechanisms at the late phase of hepatic IR injury. Methods: 30 Wistar rats were randomly divided into sham, IR and IPC groups. The model of partial hepatic IR was used. The rats were subjected to 60 min hepatic ischemia, pretreated by IPC (10/15 min) or not. After 24 h of reperfusion, serum alanine aminotransferase (ALT), nitrite/nitrate (NOx), malondialdehyde (MDA), hepatic tissue arginase activity, adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and EC of the liver were measured. Results: Liver injury reduced by IPC is measured by liver tissue arginase activity and serum ALT. Tissue NOx levels in rats pretreated with IPC were significantly higher than levels in the IR group (p < 0.001). Tissue levels of MDA in the liver of the IPC group were found to be significantly lower than the levels in the IR group (p < 0.001). ATP and EC levels 24 h after hepatic ischemia in rats pretreated with IPC were higher than the levels in the IR (p < 0.05). All groups had similar ADP and AMP levels in the liver tissues. The IPC procedure significantly reduced the hepatic necrosis (p < 0.001). Conclusion: The results of this study demonstrated that pretreatment with IPC improved tissue ATP, EC, and hepatic necrosis at late stages of ischemia reperfusion injury of the liver. Increased nitric oxide, reduced MDA and arginase activity seemed to play a regulatory role in this delayed protective effect of IPC.

Ischemic preconditioning improves liver regeneration by sustaining energy metabolism after partial hepatectomy under ischemia in rats.

Abstract: Background: The protective effect of ischemic preconditioning (IPC) has been reported on improvement of survival, reduction of liver necrosis and enhancement of the regenerative capacity of hepatocytes after partial hepatectomy. This study was undertaken to confirm that IPC has a significant impact on regeneration of hepatocytes after partial hepatectomy in ischemically damaged liver. In addition, we sought to examine the role of adenine nucleotides in this process.

Effects of two conventional preoperative radiation schedules on anastomotic healing in the rat colon.

Background: Preoperative radiotherapy (RT) is an increasingly popular form of adjunct therapy for rectal cancer; however, little is known about its effects on matrix metalloproteinase (MMP) expression in colonic anastomotic healing. Methods: Wistar rats were irradiated to a total dose of 25 or 40 Gy. Four days after the end of RT, an end-to-end colorectal anastomosis was performed. Animals were sacrificed at 1, 3, and 7 days after the anastomosis. A control group was studied similarly, but was not irradiated. Results: No significant differences were found in peritonitis rate and anastomotic complications. The average bursting pressure and breaking strength were only reduced significantly in the rats irradiated with 40 Gy. However, the concentration and the content of hydroxyproline in anastomotic tissues were unchanged. In irradiated rats, MMP-2 and MMP-9 were significantly increased at 40 Gy, but not at 25 Gy. On the other hand, 25-Gy irradiation induced a smaller increase in the levels of the tissue inhibitors of metalloproteinase-1 compared with the controls. Conclusion: Anastomotic strength is adversely affected by high-dose fractionated preoperative RT. In contrast, preoperative RT at 25 Gy in five fractions over 5 days is safe with regard to the maintenance of wound strength in colorectal anastomosis.

Wegener's granulomatosis with massive gastrointestinal hemorrhage due to jejunal and colonic involvement: report of a case.

Wegener’s granulomatosis (WG) is a systemic necrotizing vasculitis of unknown etiology characterized mainly by the involvement of the upper airways, lungs, and kidneys. Although most organ systems can be involved, gastrointestinal involvement in WG is notably uncommon. We herein present the case of a WG patient who developed two massive gastrointestinal hemorrhages treated respectively by surgery and angiographic embolization of the bleeding artery. The present case indicates that gastrointestinal manifestations might thus be considered in the natural history of WG.