Ayse Polat

Dexamethasone Down-Regulates Endothelial Expression of Intercellular Adhesion Molecule and Impairs the Healing of Bowel Anastomoses

OBJECTIVE To find out the role of endothelial expression of intercellular adhesion molecule-1 (ICAM-1) in the healing of intestinal anastomoses in rats, and to establish the effects of peroperative treatment with corticosteroids. DESIGN Experimental animal study. SETTING University hospital, Turkey. MATERIAL 78 Male Wistar rats. INTERVENTIONS Rats were divided into four groups: Group I, colonic anastomosis only (=18); Group II, colonic anastomosis plus caecal ligation and puncture (=18); Group III, colonic anastomosis plus dexamethasone (=18); and Group IV, colonic anastomosis, plus caecal ligation and puncture, plus dexamethasone (=18). Six animals served as the sham group. The animals underwent bowel transsection and primary anastomosis Infection was produced by caecal ligation and puncture Preoperatively, dexamethasone was given intramuscularly in a dose of 2 mg/kg/day. MAIN OUTCOME MEASURES After 1, 3 and 5 days, anastomotic healing and endothelial expression of ICAM-1 were measured microscopically. RESULTS Anastomotic healing was significantly impaired in dexamethasone-treated animals, and endothelial expression of ICAM-1 was reduced. Endothelial expression of ICAM-1 was no higher in the infected group than in controls. Maximum expression of ICAM-1 on endothelial cells was seen on the first day in each group, and declined on the following days, although the sebsequent reduction in expression was not significant. CONCLUSION Dexamethasone down-regulated expression of ICAM-1, which is important in migration of leucocytes from the circulation to the wound site, and significantly impaired the healing of intestinal anastomoses in rats.

The effect of L-carnitine on the prevention of experimentally induced myringosclerosis in rats

The objective of this study was to investigate the possible effect of L-carnitine on the prevention of experimentally induced myringosclerosis. Twenty Sprague-Dawley rats were bilaterally myringotomized. The rats were divided into two groups randomly: group 1 which were intraperitoneally administered saline and group 2 which were intraperitoneally administered L-carnitine. Blood samples were collected for biochemical evaluation and the tympanic membranes were harvested after 28 days. Histopathological and immunohistochemical evaluation were done under light microscopy. The mean malondialdehyde levels were 3.9+/-0.9 in group 2, and 7.9+/-1.1 in group 1 (P<0.001), nitric oxide levels were 25.6+/-6.4 in group 2 and 30.8+/-8.2 in group 1 (P=0.14) and acetylcholinesterase was 1035+/-60 in group 2 and 678+/-35 in group 1 (P=0.001). Myringosclerosis was more frequent and severe in group 1 than group 2 (P<0.007). Immunoreactivity was seen in 16 of 20 tympanic membranes in group 2 and six of 20 tympanic membranes in group 1 (P=0.005). We conclude that L-carnitine diminishes the occurrence of myringosclerosis in rats after myringotomy possibly by antioxidant activity and decreasing the formation of reactive oxygen species.

Ileal atresia associated with a congenital vascular band anomaly: observations on pathogenesis

We report the case of a newborn, who developed intestinal obstruction soon after birth. Exploratory laparotomy revealed a congenital vascular band anomaly extending from the antimesenteric border of the terminal ileum to the gallbladder in association with ileal atresia. Surgical intervention was performed for correction of the disorder. A review of the embryology and congenital vascular bands is presented together with discussion as to possible etiopathogenesis leading to small bowel atresia.

The effects of carnitine on distally-burned dorsal skin flap: an experimental study in rats

OBJECTIVE In ischemia and burn injuries, there are major alterations threatening tissue survival. Increased energy flow requirements are among the major problems in these disorders. Carnitine is an endogenous cofactor, which has a regulatory action on the energy flow from different oxidative sources. The purpose of this study was to determine the effects of carnitine in an experimental flap model. Biochemically, nitric oxide (NO), malondialdehyde (MDA), and acetylcholinesterase levels, and histopathologically tissue examination under light microscope were studied. METHODS In the rat dorsal skin, a 10 cm x 3 cm flap was marked. The most distal 3 cm x 3 cm of the flap was burned to full-thickness. The dorsal flap was elevated, and sutured back to its original site. Sixteen rats were divided into two groups (a control (1) and a study group (2)), consisting of eight rats in each. While the animals in the control group were just followed, the animals in the study group were administrated carnitine with a dose of 100 mg/kg per day for 7 days. RESULTS At the end of the experiment: the mean surviving areas of the flaps were 15.22 cm(2) (50.73%) in group 1, 20.53 cm(2) (68.43%) in group 2, and the difference was statistically significant (P=0.008). In the analysis of blood samples; the mean levels of NO were 22.63 and 40.78 micromol/l; of MDA were 6.74 and 3.79 ng/ml; and of acetylcholinesterase were 136.14 and 222.85 U/l in groups 1 and 2, respectively. The differences in the levels of NO (P=0.001), MDA (0.027) and acetylcholinesterase (P=0.006) were statistically significant. Histopathological examination revealed a full-thickness muscle necrosis in addition to skin tissue in the control group, while healing tissue was present with marked cellularity including mixed inflammatory cells and fibroblast proliferation with an increased vascularity in the form of capillary budding in the study group. CONCLUSION Carnitine has a positive effect in such a model, particularly in preventing the progressive effect of burn, and limiting the necrosis in the full-thickness burned part.

The anti-oxidant and anti-apoptotic activities of selenium in the prevention of myringosclerosis in rats

The possible effect of selenium on the prevention or reduction in occurrence of myringosclerosis was investigated. Fifteen rats were myringotomized bilaterally and separated into two groups. Nine rats were treated with selenium in the study group. Six rats were administered physiological serum and formed the control group. The occurrence of myringosclerotic lesions and anti-apoptotic activity in the tympanic membranes of the two groups were compared otomicroscopically and histopathologically. The sclerosis was occasional in three, moderate in five and severe in three tympanic membranes in the control group. On the other hand sclerosis was observed in only two of 18 specimens in the study group and sclerosis was seen only occasionally in these two sections. Although Bcl-2 staining, which indicates apoptosis, was not statistically different between the groups, it was observed that apoptosis was slightly more apparent in the study group (eight of 18 tympanic membranes versus two of 12 tympanic membranes in the control group). In conclusion, the formation of myringosclerosis following myringtomoy in rats can be reduced by intraperitoneal selenium administration.

The effects of corticosteroids and vitamin A on the healing of tracheal anastomoses

OBJECTIVE This study investigates the deleterious effects of corticosteroids on tracheal anastomotic healing and the ability of vitamin A to reverse these effects in a rat model. METHODS Forty-two adult Wistar rats were randomly divided into five groups. The animals underwent tracheal transection and primary anastomoses. The groups were assigned as follows: Group I, sham (N=6); Group II, control (N=6); Group III, dexamethasone, 0.1 mg/kg/day intramuscularly (N=10); Group IV, dexamethasone 0.1 mg/kg/day intramuscularly+vitamin A 10000 IU/kg/day by gavages (N=10); and Group V, vitamin A 10000 IU/kg/day by gavages for a week (N=10). After 7 days, anastomotic healing was assessed by measurement of bursting pressure, hydroxyproline content and subsequent histological grading using the modified Ehrlich/Hunt scale. RESULTS Bursting pressures and hydroxyproline contents were as follows: Group I: 977+/-8 mmHg and 11.80+/-0.3 microg/mg (mean+/-standard error of the mean); Group II: 890+/-55 mmHg and 9.93+/-0.6 microg/mg; Group III: 555+/-26 mmHg and 11.90+/-1.3 microg/mg; Group IV: 873+/-73 mmHg and 10.24+/-2.2 microg/mg; Group V: 905+/-45 mmHg and 7.51+/-0.8 microg/mg, respectively. Bursting pressure of Group III was found to be significantly lower when compared to other groups (P<0.0001). However, statistical significance was not found among the study groups for the hydroxyproline content. Except for inflammatory cell infiltration, histological parameters including epithelial regeneration, fibroblast proliferation, collagen content, and angiogenesis demonstrated significant differences among the groups. CONCLUSION The present study demonstrates that dexamethasone significantly impairs the healing of tracheal anastomoses in rats and postoperative administration of vitamin A appreciably reverses this inhibitory effect. Patients receiving corticosteroids may benefit from vitamin A when undergoing prolonged intubation and laryngotracheal reconstruction.

THE ROLE OF POLY(ADP-RIBOSE) SYNTHETASE INHIBITION IN PREVENTING ENDOTOXEMIA-INDUCED INTESTINAL EPITHELIAL APOPTOSIS

In this lipopolysaccharide (LPS)-induced endotoxemia model, the effects of 3-aminobenzamide (3-AB), a poly(ADP-ribose) synthetase (PARS) inhibitor, on ileal apoptosis were evaluated by light microscopy and M30 cell death staining. Moreover, the relationship between Bcl-2, iNOS expression, and serum nitrate (NO(3)(-)) levels were investigated. Thirty-two male Wistar rats, weighing 180-220g were randomly divided into four groups. The group I (control; n=8) received saline and group II (sepsis; n=8) received 10 mg kg(-1) LPS intraperitoneally. 3-AB was given to the group IV (S+3-AB; n=8) 20 min before giving LPS and to the group III (C+3-AB; n=8) 20 min before giving saline. Six hours later, blood and ileum samples were taken. Endotoxemic group exhibited significant apoptosis in intestinal epithelial cells and the immunohistochemical examination with M30 was demonstrated that the 3-AB reduced the LPS-induced intestinal apoptosis. Serum NO(3)(-) level was increased in endotoxemic group, whereas the elevation of NO(3)(-) level was prevented in LPS+3-AB group (P<0.05). The increased iNOS expression observed in the LPS group was also prevented by 3-AB. Compared with the endotoxemic group, ileal epithelial columnar cells from LPS+3-AB group had a dense Bcl-2 staining which was almost identical with control. In conclusion, 3-AB decreases LPS-induced apoptosis in ileum by preventing LPS-induced depletion of Bcl-2 and blocking iNOS gene. Modification of Bcl-2 expression by PARS inhibitors should further be investigated as a new therapeutic alternatives in septic states.

Platelet-activating factor antagonist (ABT-491) decreases neuronal apoptosis in neonatal rat model of hypoxic ischemic brain injury

Hypoxic ischemic brain injury (HIBI) is a common cause of neonatal mortality and morbidity. To date, no study has investigated the role of platelet-activating factor (PAF) antagonists on neuronal apoptosis in neonatal rat model of HIBI. In the present study, we evaluated the effect of a highly potent and selective PAF antagonist (ABT-491) on neuronal apoptosis in neonatal rat model of HIBI. Seven-day-old Wistar rat pups were subjected to right common carotid artery ligation and hypoxia (92% nitrogen and 8% oxygen) for 2 h. They were treated with ABT-491 or saline either immediately before or after hypoxia. In sham group animals, neither ligation, nor hypoxia was performed. Neuronal apoptosis was evaluated by the terminal-transferase mediated dUTP biotin nick-end-labeling (TUNEL) and caspase-3 staining methods. Administration of ABT-491 either before or after hypoxia resulted in significant reduction of the numbers of apoptotic cells in both hemispheres, when compared to saline treatment group. The numbers of apoptotic cells in right hemispheres in all groups were significantly higher than that in the left hemispheres. These results suggested that ABT-491, a highly potent and selective PAF antagonist, administration either before or after hypoxia reduces apoptosis and we propose that ABT-491 may be a novel approach in the treatment of HIBI.

Neuroprotective effect of levetiracetam on hypoxic ischemic brain injury in neonatal rats

PurposeHypoxic-ischemic brain injury that occurs in the perinatal period is one of the leading causes of mental retardation, visual and auditory impairment, motor defects, epilepsy, cerebral palsy, and death in neonates. The severity of apoptosis that develops after ischemic hypoxia and reperfusion is an indication of brain injury. Thus, it may be possible to prevent or reduce injury with treatments that can be given before the reperfusion period following hypoxia and ischemia. Levetiracetam is a new-generation antiepileptic drug that has begun to be used in the treatment of epilepsy.MethodsThe present study investigated the effects of levetiracetam on neuronal apoptosis with histopathological and biochemical tests in the early period and behavioral experiments in the late period.ResultsThis study showed histopathologically that levetiracetam reduces the number of apoptotic neurons and has a neuroprotective effect in a neonatal rat model of hypoxic-ischemic brain injury in the early period. On the other hand, we demonstrated that levetiracetam dose dependently improves behavioral performance in the late period.ConclusionsBased on these results, we believe that one mechanism of levetiracetam’s neuroprotective effects is due to increases in glutathione peroxidase and superoxide dismutase enzyme levels. To the best of our knowledge, this study is the first to show the neuroprotective effects of levetiracetam in a neonatal rat model of hypoxic-ischemic brain injury using histopathological, biochemical, and late-period behavioral experiments within the same experimental group.

Does Helicobacter pylori play a role in the development of chronic adenotonsillitis

OBJECTIVE Evaluation of the possible relationship between chronic adenotonsillitis and Helicobacter pylori (HP). PATIENTS AND METHODS The study was performed prospectively on 91 pediatric patients who underwent tonsillectomy, adenoidectomy or adenotonsillectomy due to chronic tonsillitis and/or adenoiditis. The adenotonsillectomy specimens were examined for HP colonization by rapid urease test (RUT) and immunohistochemical evaluation. Before surgery, anti-HP IgG and IgA antibody titers were detected by enzyme linked immunosorbent assay (ELISA) test in venous blood samples of the patients. RESULTS The RUT was positive in only two of the adenoidectomy specimens (2.2%) and in none of the tonsillectomy specimens. A positive result was not detected in any tonsillectomy specimens using immunohistochemical examination. Serum IgG antibody was positive in 21 (23%) patients, IgA antibody was detected in 7 (7.69%) patients and both tests were positive only in 3 (3.29%) patients. CONCLUSION The results of this study suggested that HP would not colonize in tonsil tissue of patients with chronic tonsillitis.