Hulya Ozturk

Nitric Oxide Regulates Expression of Sonic Hedgehog and Hypoxia-Inducible Factor-1α in an Experimental Model of Kidney Ischemia-Reperfusion

This study was designed to determine the effect of L-arginine on hypoxia inducible factor alpha (HIF-1 α) and Sonic hedgehog (Shh) levels considered to be involved in the development of ischemia/reperfusion (I/R) injury. Unilaterally nephrectomized Sprague-Dawley rats were subjected to 60 minutes of left renal ischemia followed by 45 minutes of reperfusion. Group 1 were sham-operated animals; group 2, I-R/Untreated animals; and group 3, I-R/L-Arg-treated animals. Serum creatinine, blood urea nitrogen (BUN), and kidney malondialdehyde (MDA) levels were determined as well as examining the kidneys histologically. The treatment of rats with L-Arg produced a significant reduction in the levels of BUN, creatinine, MDA, and histopathological score compared to renal I/R groups. The Shh expression in the tubulus epithelia were intensely increased in the I-R/L-Arg group when compared to that of the Sham-control and the I-R/untreated groups. Additionally, the HIF-1α expression in the tubulus epithelia and the interstitial spaces were intensely increased in the I-R/L-Arg group. These findings suggest that NO reduces the renal dysfunction associated with I/R of the kidney and may act as a trigger to induce Shh and HIF-1 activity.

N-Acetylcysteine Prevents Deleterious Effects of Ischemia/Reperfusion Injury on Healing of Colonic Anastomosis in Rats

This study was designed to determine the effects of intraperitoneally or orally administered N-acetylcysteine (NAC) on wound healing following resection and anastomosis of a colon segment with ischemia/reperfusion injury. Forty female Spraque-Dawley rats were randomly allocated to one of four groups containing 10 rats each: (1) normal resection plus anastomosis; (2) ischemia/reperfusion plus resection plus anastomosis; (3) ischemia/reperfusion plus resection plus anastomosis plus intraperitoneal NAC; (4) ischemia/reperfusion plus resection plus anastomosis plus oral NAC. Group comparison showed that the anastomosis bursting pressure was significantly higher in group 3 than in the other groups. The mean tissue hydroxyproline concentration in the anastomotic tissue was significantly lower in group 2 than in the other groups. The collagen deposition was significantly increased on day 7 in groups 3 and 4 compared to the other groups. In conclusion, this study demonstrates that NAC significantly prevents the effects of reperfusion injury on colonic anastomoses in a rat model.

Effects of the Nitric Oxide Donor Molsidomine on the Early Stages of Liver Damage in Rats with Bile Duct Ligation: A Biochemical and Immunohistochemical Approach

This study aimed to evaluate the effects of the nitric oxide donor molsidomine on the early stages of liver damage and biochemical changes in rats with bile duct ligation (BDL). Forty prepubertal male Sprague-Dawley rats weighing 125–140 g were studied. Group 1 rats (sham-control, n = 10) were not subjected to any surgical manipulation. Group 2 rats (BDL/untreated, n = 10) were subjected to BDL but no drug was administered. Group 3 rats (BDL/L-NAME, n = 10) received a daily dose of NG-nitro-L-arginine methyl ester (L-NAME) intraperitoneally for 7 days after BDL. Group 4 rats (BDL/molsidomine, n = 10) received a daily dose of molsidomine by gastric tube for 7 days after BDL. After 1 week, biochemical and histological evaluations were performed and the liver hydroxyproline content was measured. Serum bilirubin and liver enzymes were significantly increased in the BDL/untreated, BDL/L-NAME and BDL/molsidomine groups in comparison with the sham-control group 1 week after BDL. However, the liver enzymes were significantly decreased in the BDL/molsidomine group in comparison with the BDL/untreated and BDL/L-NAME groups. In the BDL/L-NAME group, proliferation of portal and periportal biliary ductules with disorganization of the hepatocyte plates, dilated portal spaces and areas of polymorphonuclear leukocyte infiltration, fibrosis and hepatocyte necrosis were observed. In the BDL/molsidomine group, polymorphonuclear leukocyte infiltration, hepatocyte necrosis and fibrosis were rarely seen. The hydroxyproline content in the liver was increased 1 week after obstruction in the BDL/untreated and BDL/L-NAME groups when compared to BDL/molsidomine group. Collagen type-IV expression was not observed in the BDL/molsidomine group in contrast to the BDL/untreated and BDL/L-NAME groups. In conclusion, during 1 week of treatment, the nitric oxide donor molsidomine improved hepatic fibrosis in the hepatic parenchyma and did not affect serum bilirubin values, but positively affected the serum aspartate aminotransferase and alanine aminotransferase values.

Relation between Severity of Injury and the Early Activation of Interleukins in Multiple-Injured Patients

The aim of this study was to evaluate the relation between severity of injury and the early activation of interleukins in multiple-injured patients. Ninety-nine patients with multiple injuries were included in this prospective study. Plasma levels of interleukin (IL)-1, IL-2, IL-6, IL-8 and TNF-α were measured. Injury Severity Score (ISS), Revised Trauma Score (RTS), Glasgow Coma Score (GCS) and the Acute Physiology and Chronic Health Evaluation II (APACHE-II) were all recorded. Of the 99 patients, 82 were male and 17 were female. The mean age was 26.6 ± 20.7 years. The mortality rate for this series was 17%. Patients who died from trauma exhibited a significant increase for IL-2, IL-6 and IL-8 in comparison with patients who survived. Significant differences for ISS, RTS and GCS were found between survivors and non-survivors. Values in all patients with ISS >16 were increased and these increases were significant for IL-6 and IL-2. These data show that the initial increase of IL-2, IL-6 and IL-8 might predict the patients with a high possibility of mortality and a significant increase of IL-2 and IL-6 in patients with ISS >16 might be used in a new developed trauma score combined with ISS as an indicator for the injury severity.

Interleukin 10 reduces testicular damage in experimental testicular ischemia/reperfusion injury.

OBJECTIVE To evaluate the protective effect of interleukin 10 (IL-10) on biochemical and histopathologic changes in experimental testicular ischemia or reperfusion injury (RI) in rats. METHODS Sprague-Dawley rats were randomly divided into 3 groups, each containing 7 rats; sham-control, I-R/untreated group, and I/R treated with IL-10. The ischemia period was 6 hours, and orchiectomy was performed after 1 hour of detorsion. IL-10 was given intraperitoneally in a period of 10 minutes before reperfusion. In all groups, ipsilateral orchiectomies were performed to make histologic examination and biochemical analysis such as malondialdehyde, glutathione peroxidase, and myeloperoxidase (MPO). RESULTS IL-10 treatment significantly decreased the I-R-induced elevation in testes malondialdehyde levels. In the I-R/IL-10-treated group, testes glutathione peroxidase levels were increased compared with the I-R/untreated group rats. MPO activities were significantly increased in the testes tissues of the I-R/untreated group. However, in the I-R/IL-10-treated group, MPO levels significantly decreased. Histopathologically, in the I-R/untreated group rats, edema, congestion, hemorrhage among seminiferous tubules, and necrosis of the germinal cells were predominant features in sections. The testicular injury score was lower in the IL-10-treated group rats compared with the I-R/untreated group. CONCLUSION IL-10 might play a protective role in reducing reperfusion injury.

Protective effect of montelukast, a cysteinyl leukotriene receptor-1 antagonist, against intestinal ischemia-reperfusion injury in the rat.

Abstract Objective : Ischemia-reperfusion (I-R) injury of the intestine is a significant problem because the initial damage caused by ischemia is exacerbated by reperfusion. In this study, we examined the protective effect of montelukast against I-R-induced intestinal tissue damage. Materials and methods : Eight-week-old male Sprague-Dawley rats were randomly divided into three treatment groups: a sham-operated group, a group receiving I-R, and a group receiving I-R plus montelukast (I-R/M). Tissue samples were evaluated and scored histologically. The blood levels of malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), and cardiotrophin-1 (CT-1) were measured. Results : In the I-R group, the histological score and the levels of serum MDA and MPO were increased compared with those in the control group. In the I-R/M group, the histological score and serum MDA and MPO levels were significantly decreased compared with those in the I-R group. Additionally, compared with the IR group, the I-R/M group had increased serum GSH and CT-1 levels and a decreased intestinal injury score. Ileal sections from the I-R/M group showed minimal alterations, characterized by moderate lifting of the epithelial layer from the lamina propria, and few apoptotic enterocytes were observed compare with the number in the I-R group. Conclusion : The findings of the present study demonstrated that montelukast can protect I-R-induced intestinal damage in rats.

Influence of the Platelet-Activating Factor Receptor Antagonist BB-882 on Intra-Abdominal Adhesion Formation in Rats

Postoperative intra-abdominal adhesion formation is a major clinical problem. We aimed to examine the preventive effect of treatment with the platelet-activating factor (PAF) antagonist (lexipafant, BB-882) on experimentally induced intra-abdominal adhesion formation in rats. Twenty male Sprague-Dawley rats weighing 250 and 290 g were studied. Generation of adhesions in rats by brushing a 1-cm2 area of the cecum and the peritoneum on the right side of the abdominal wall was followed by intra-abdominal administration of saline and 5 mg/kg in a volume of 0.2 ml PAF receptor antagonist BB-882. After 45 days, formation of adhesions was graded and histological evaluation was processed. The severity of adhesions was significantly less in the BB-882 group than in the control group (p < 0.001, p < 0.05). The average adhesion scores in the control and BB-882 groups were 3.2 ± 0.6 and 0.6 ± 0.6, respectively, and the difference between both groups was found to be significant (p < 0.0001). The number of polymorphonuclear leukocytes and fibrotic areas was significantly decreased in the BB-882 group when compared to the control group (p < 0.001, p < 0.002). In conclusion, this study confirms the efficacy of BB-882 in the prevention of postoperative intra-abdominal adhesions in a rat model.

Effects of Melatonin Administration on Intestinal Adaptive Response After Massive Bowel Resection in Rats

This study evaluates whether melatonin can improve the structure of the small intestine and enhance adaptation in an experimental model of short bowel syndrome. Thirty Sprague–Dawley rats were divided randomly into three experimental groups of 10 animals each. In one group, only laparotomy was performed and these rats served as the sham-control group (G1). The remaining 20 rats underwent 90% small bowel resection (SBR) and formed the two experimental groups: the SBR/untreated group (G2), and the SBR/melatonin-treated group (G3). Rats in the SBR/untreated group received no therapeutic treatment. Rats in the SBR/melatonin-treated group received melatonin intraperitoneally for 3 weeks. The animals were weighed daily. All rats underwent relaparotomy on day 21 of the experiment. Remnant small bowel was excised and evaluated for villus height, total mucosal thickness, and crypt cell mitosis. After the 90% SBR, all animals suffered from diarrhea and weight loss between the first and the sixth postoperative days. The body weight of the SBR/melatonin group showed significant increases at the beginning of postoperative day 10 and day 21 in comparison to that of the SBR/untreated group. The rats treated with melatonin had significantly greater villus height and crypt cell mitosis compared to the sham-control group and the SBR/untreated group. In addition, the mucosal thickness was significantly increased in the SBR/melatonin-treated group compared to the SBR/untreated rats. These observations suggest that melatonin treatment increases villus height, total mucosal thickness, and crypt cell mitosis after massive SBR and it may exert a considerable effect on the mucosal adaptive response in short bowel syndrome in rats.

The outcome of one-stage hypospadias repairs

OBJECTIVE Hypospadias is an increasingly common condition, and many procedures have been described for operative correction. We reviewed our experience of different techniques of one-stage hypospadias repair. MATERIALS AND METHODS We retrospectively reviewed 107 hypospadic boys who were younger than 15 years between January 1986 and June 2003. We included all patients who underwent one-stage hypospadias repair. All patients were evaluated for age, type of hypospadias, associated anomalies, surgical technique, and morbidity rate. The functional and cosmetic results were evaluated at 1 month, 6 months and 1 year postoperatively. Univariate analysis was done to identify those variables that might serve as interdependent predictors of postoperative complications. RESULTS The median age was 7 years (6 months to 13 years). Severe chordee was observed in 15 patients. The majority of cases were anterior hypospadias (53%), while the majority of complications were observed in the middle group (62%). Cosmetic and functional results were satisfactory in the majority of the patients. Complications included 16 fistulae (15%) and 11 meatal stenoses (10%). Some prognostic factors such as age, insertion of a suprapubic cystostomy tube, suture structure, and time of catheter removal did not significantly affect the risk of complication, whereas some other factors such as associated anomalies, severe chordee, middle and posterior hypospadias, and use of a pedicle island flap were significant in their relation to the complication rate. CONCLUSION Such possible risk factors as severe chordee, middle and posterior localized hypospadias, and use of a pedicle island flap may increase the postoperative complication rate. There is no gold-standard technique for hypospadias repair; the procedure of choice should depend on the individual anatomy of the penis. The long-term outcome after puberty has to be awaited.

Esophageal, tracheal and pulmonary parenchymal alterations in experimental esophageal atresia and tracheoesophageal fistula. A histological and morphometric study.

Pulmonary complications are among the most important causes of morbidity and mortality in neonates with esophageal atresia and tracheofistula. We aimed to investigate the possible causes of respiratory complications encountered in esophageal atresia (EA) and tracheoesophageal fistula (TEF) in an experimental model. Sprague-Dawley fetal rats treated with adriamycin were used for the experiment. Time mated pregnant rats were given 1.75 mg/kg of adriamicyn intraperitoneally on days 6–9 of gestation. The fetuses were sacrified on day 21, weighed, and dissected under the surgical microscope. The animals were divided into four groups: (1) control group; (2) saline-injected group; (3) adriamycin-induced EA group, and (4) adriamycin administered but without development of EA. The lungs, esophagus, and trachea were excised and underwent histological examination. The mucosa of distal esophagus was thickened (p < 0.05); the submucosa was thinner (p < 0.05); and the muscular layer was thickened (p < 0.05) in fetuses with EA and TEF. In adriamycin-treated rats, in which EA and TEF developed, tracheal cartilage was loosened and formed into a D or C shape. The cartilage was fragmented into several segments on transverse sections in most fetuses. Alveolar septa were thin in lungs of fetus with EA and TEF (p < 0.05), without any fibrosis or evidence of parenchymal abnormality microscopically. Our findings suggest that respiratory complications may contribute to structural lesions in the trachea and particularly in the distal esophagus but not in the pulmonary parenchyma itself.