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Leyla Cinel

Publications and source records attributed to Leyla Cinel.

35 records · Page 2Linked to original sources
PubMed2003

The protective effect of N-acetylcysteine on apoptotic lung injury in cecal ligation and puncture-induced sepsis model.

Apoptotic loss of parenchymal cells may lead to organ dysfunctions in critically ill patients with septic states. As an antioxidant, the protective effects of N-acetylcysteine (NAC) are documented in many experimental and clinical studies. In this experimental study, we investigated the role of chronically used NAC in septic lung injury on a cecal ligation and puncture (CLP) model. To evaluate this, 30 male Wistar rats were randomly divided into four groups as sham (n = 7), CLP (n = 8), sham + NAC (n = 7) and CLP + NAC (n = 8) groups. NAC was administered 150 mg kg(-1) day through intramuscular route beginning 6 h after the operations and lasting for a period of 1 week. One week later, histopathology and epithelial apoptosis were assessed by hematoxylin-eosin and immunohistochemically by M30 and caspase 3 staining to demonstrate septic lung injury. Additionally, lung tissue myeloperoxidase (MPO) activity, malondialdehyde (MDA), and nitrite/nitrate levels were measured. The MPO activity and MDA levels in lung homogenates were found to be increased in CLP group and the administration of NAC prevented their increase significantly (P < 0.05). However, there were no significant differences among the groups regarding nitrite/nitrate levels. The number of apoptotic cells was significantly lower in CLP+NAC group than CLP group, and this finding was supported by M30 and caspase 3 expression in lung (P < 0.05). Lung histopathology was also protected by NAC in CLP-induced sepsis. In conclusion, the chronic use of NAC inhibited MPO activity and lipid peroxidation, which resulted in reduction of apoptosis in lung in this CLP model. Because lung tissue nitrite/nitrate levels did not change significantly, organs other than the lungs may be responsible for producing the increased nitric oxide during sepsis. The chronic use of NAC needs further investigation for its possible antiapoptotic potential in septic states besides its documented antioxidant and antiinflammatory effects.

Acetylcysteine↗
PubMed2003

Ischemic preconditioning reduces intestinal epithelial apoptosis in rats.

Recent experimental studies have described protective effect of ischemic preconditioning (IPC) on ischemia-reperfusion (I/R) injury of the intestine. We hypothesize that to reach a new point of view on the effect of IPC in intestinal barrier function, the relationship between I/R-induced mucosal injury and apoptosis must first be clarified. The present study was undertaken to investigate the role of IPC on intestinal apoptosis and probable contributions of bcl-2 expression to this process. We also investigated the effect of intestinal IPC on ileal malondyaldihyde levels. Forty-four male Wistar rats were randomized into four groups each consisting of 11 rats: sham-operated control, I/R group (30 min of superior mesenteric artery occlusion), IPC-I/R group (10 min of temporary artery occlusion prior before an ischemic insult of 30 min), and IPC alone group (10 min of preconditioning). Twenty-four hours later, ileum samples were obtained. Ileal malondyaldihyde levels were increased in the I/R group (31.9 +/- 18.8 vs. 106.8 +/- 39.8) but not in the IPC alone and IPC-I/R groups (38.1 +/- 13.6 and 44.7 +/- 12.7; P < 0.01). The number of apoptotic cells was significantly lower in IPC-I/R group than that of I/R group, and these findings were further supported by DNA laddering and M30 findings. Diminished bcl-2 expression observed in the ileal specimens of I/R group was prevented by IPC. Our results indicate that IPC may provide a protective effect on ileal epithelium and that this effect is probably the result of a significant increase in the expression of bcl-2 after the insult. The reversal of apoptosis by IPC might help preserving the vitality of intestinal structures that have a critical function, cessation of which often leads to multiorgan dysfunction syndrome.

Animals↗
PubMed2003

Effect of ornithine on the ileal histology, nitric oxide production and lipid peroxidation in LPS-induced endotoxemia.

Effect of ornithine which is known to inhibit L-arginine uptake via cationic amino acid transport system has been tested, and compared to aminoguanidine, an iNOS inhibitor in lypopolysaccharide (LPS)-induced endotoxemia in rats. Serum nitrite/nitrate and malondialdehyde (MDA) level have been measured, and ileal histology has also been examined. Endotoxin increased serum nitrite/nitrate and MDA levels from 15.7+/- 2.4 micromol/ml and 2.1 +/-0.2 nmol/ml to 23.1 +/- 1.0 micromol/ml and 5.2+/- 0.3 nmol/ml (both P<0.05), respectively. In addition, LPS caused ileal degeneration. L-ornithine (500 mg/kg) did not improve septic manifestations, i.e., serum nitrite/nitrate and MDA levels did not differ from those in endotoxemia. Neither does it have an improving action on ileal histology. However, higher dose of L-ornithine (2,500 mg/kg) lowered the increased level of nitrite/nitrate and MDA by LPS. Moreover, it restored ileal histology from grade 3 (median) to 0 (median) (P<0.05). On the other hand, aminoguanidine (100 mg/kg) normalized serum nitrite/nitrate and MDA levels but not ileal histology in endotoxemic rats. In conclusion, high dose of L-ornithine could improve endotoxemic parameters in LPS-treated rats.

Animals↗
PubMed2002

The inhibitory effect of topical N-acetylcysteine application on myringosclerosis in perforated rat tympanic membrane.

OBJECTIVE: Myringosclerosis often occurs in patients in whom ventilation tube insertion and tympanoplasty procedures are performed. Recent studies have revealed a relationship between the development of myringosclerosis and oxygen-derived free radicals, and some investigations have demonstrated that free radical scavengers prevent the development of myringosclerosis. N-acetylcysteine is a well-known anti-oxidant and anti-inflammatory agent. In this study, we aimed to investigate the preventive effect of N-acetylcysteine on myringosclerosis in myringotomized rat tympanic membranes. METHODS: Twenty Sprague-Dawley rats were bilaterally myringotomized and divided into four groups. Group 1 received no treatment, group 2 was treated with topical saline solution in Spongostan, group 3 received topical 0.6 mg N-acetylcysteine in Spongostan and group 4 received 1.2 mg N-acetylcysteine in Spongostan daily for 12 days. Tympanic membranes were examined by otomicroscopy on day 12. Then, the membranes were harvested and evaluated histologically by light microscopy. RESULTS: The tympanic membranes of groups 1 and 2 (saline and non-treated) showed extensive occurrence of myringosclerosis, whereas groups 3 and 4 (treated with N-acetylcysteine) showed lesser occurrence of myringosclerosis in otomicroscopic evaluation (P<0.01). Under light microscopic examination, lamina propria of pars tensa was found thicker in groups 3 and 4 when compared with groups 1 and 2. There was no significant difference between groups 3 and 4 (P: 0.30). CONCLUSIONS: Topically applied N-acetylcysteine was found to be effective in the prevention of sclerotic lesions in myringotomized rat tympanic membranes.

Acetylcysteine↗
PubMed2002

Poly(Adp-ribose) synthetase inhibition prevents lipopolysaccharide-induced peroxynitrite mediated damage in diaphragm.

Although the precise mechanism by which sepsis causes impairment of respiratory muscle contractility has not been fully elucidated, oxygen-derived free radicals are thought to play an important role. In our experimental study, the effects of poly(ADP-ribose) synthetase (PARS) inhibition on the diaphragmatic Ca(2+)-ATPase, malondialdehyde (MDA), and 3-nitrotyrosine (3-NT) levels and additionally histopathology of the diaphragm in lipopolysaccharide (LPS)-induced endotoxemia are investigated.Thirty-two male Wistar rats, weighing between 180-200 g were randomly divided into four groups. The first group (control; n=8) received saline solution and the second (LPS group; n=8) 10 mgkg(-1) LPS i.p. 3-Aminobenzamide (3-AB) as a PARS inhibitor; was given to the third group (C+3-AB, n=8) 20 min before administration of saline solution while the fourth group (LPS+3-AB, n=8) received 3-AB 20 min before LPS injection. Six hours later, under ketamin/xylasine anesthesia diapraghmatic specimens were obtained and the rats were decapitated. Diaphragmatic specimens were divided into four parts, three for biochemical analyses and one for histopathologic assessment. In the LPS group, tissue Ca(2+)-ATPase levels were found to be decreased and tissue MDA and 3-NT levels were found to be increased (P<0.05). In the LPS+3-AB group, 3-AB pretreatment inhibited the increase in MDA and 3-NT levels and Ca(2+)-ATPase activity remained similar to those in the control group (P<0.05). Histopathologic examination of diaphragm showed edema between muscle fibers only in LPS group. PARS inhibition with 3-AB prevented not only lipid peroxidation but also the decrease of Ca(2+)-ATPase activity in endotoxemia. These results highlights the importance of nitric oxide (NO)-peroxynitrite (ONOO(-))-PARS pathway in preventing free radical mediated injury. PARS inhibitors should further be investigated as a new thearapetic alternative in sepsis treatment.

Animals↗
PubMed2002

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.

Animals↗
PubMed2002

Selenium pretreatment prevents bacterial translocation in rat intestinal ischemia/reperfusion model.

Protective role of selenium against free radical damage was first demonstrated in the heart and this effect was further questioned in other systems. In the present study, the effects of exogenously administered selenium on intestinal fine morphology, lipid peroxidation, and bacterial translocation (BT) in experimental intestinal ischemia/reperfusion (I/R) model were examined. Thirty-two male Wistar rats weighing 250-300 g were randomized into four groups. Sham group (n=8) underwent laparotomy only. In the I/R group (n=8), laparotomy was performed and the superior mesenteric artery was occluded using an atraumatic microvascular clamp for 30 min. In corresponding selenium-treated groups (n=8 each), sodium selenate was given 0.2 mg kg(-1)day(-1) intraperitoneally (i.p.) for 3 consecutive days, prior to surgery for either laparotomy only or with I/R. Twenty-four hours later, tissue samples from liver, spleen, and mesenteric lymph nodes were obtained under sterile conditions for microbiological analysis and further evaluation of I/R-induced intestinal injury. Ileum samples were fixed in 10% formaldehyde for histopathological evaluation. In the I/R group, the incidence of bacteria-isolated mesenteric lymph nodes, spleen, and liver was significantly higher than other groups (P<0.05). Selenium supplementation prevented I/R-induced BT and significantly reduced the I/R-induced intestinal injury (P<0.05). Tissue MDA levels from the ileum specimens of selenium-treated rats were significantly lower than that of the I/R group (P<0.05). Our results provide evidence that the relationship between BT and lipid peroxidation in intestinal tissue is crucial. Selenium pretreatment reduces lipid peroxidation which contributes to the maintenance of intestinal mucosal integrity.

Animals↗
PubMed2002

The effects of antithrombin-III on inducible nitric oxide synthesis in experimental obstructive jaundice. An immunohistochemical study.

The absence of bile in the gastrointestinal tract stimulates bacterial overgrowth and bacterial translocation. In the response to endotoxin and LPS-induced endotoxemia which may be prevented by antithrombin-III (AT-III); endothelial cells; and various cells release cytokines, nitric oxide (NO) and other mediators. The purpose of this study was to examine blood NO levels and renal inducible NO synthase (iNOS) expression and determine whether AT-III has an inhibiting effect on renal injury and iNOS expression in obstructive jaundice (OJ). Forty rats were randomized into four groups: group A (Sham), group B (Sham+AT-III, 250 IU kg(-1)), group C (OJ), group D (OJ+AT-III, 250 IU kg(-1)). All animals were sacrificed on the 10th day and blood samples were taken for bilirubin and NO level determination. In addition, iNOS expression of the renal tissues was evaluated immunohistochemically. Blood NO levels were found to be 32.99 micromol l(-1) in group A, 32.26 micromol l(-1) in group B, 46.33 micromol l(-1) in group C, and 34.71 micromol l(-1) in group D. The intensity of iNOS staining in the OJ+AT-III group was less than the intensity of iNOS staining in the OJ group in the renal tissue. This study shows that OJ causes increased production of NO in blood and increased iNOS expression in the kidney. AT-III inhibits iNOS expression and reduces the level of blood NO. Thus, our findings indicate that under conditions of OJ, AT-III limits renal cellular injury by inhibiting LPS-induced iNOS expression.

Animals↗
PubMed2002

Immunohistological analysis of mast cell numbers in the intratumoral and peritumoral regions of prostate carcinoma compared to benign prostatic hyperplasia.

Recently, some studies reported the presence of mast cells in various malignancies and their role in tumor growth. The aim of the study was to determine the utility of mast cell numbers in evaluating benign and malignant prostate lesions, and to ascertain whether there are variations in the numbers of mast cells with the Gleason grade. The relationship between mast cell numbers and patient age was also investigated. Retrospectively, 104 prostate specimens were examined for the presence of mast cells. The study group consisted of 57 benign prostatic hyperplasias and 47 prostate carcinomas. The paraffin sections were stained with anti-human mast cell tryptase immunohistologically. The numbers of positively staining cells in five high-power fields were counted, and their mean was calculated. There was no relationship found between mast cell numbers and age statistically. The mean mast cell numbers of the intratumoral region were significantly different from those of the peritumoral region (p = 0.0001). While the difference between benign hyperplasia and the intratumoral region was found to be significant (p = 0.0001), no difference between hyperplasia and the peritumoral region was noted (p = 0.762). There was no statistical difference between Gleason score groups (p = 0.452), and there was no interaction between score groups and intraperitumoral regions (p = 0.355).

Adenocarcinoma↗
PubMed2002

Intestinal ischemic preconditioning protects the intestine and reduces bacterial translocation.

Ischemic preconditioning (IPC) was first demonstrated in the heart, but this protective effect has been also recently described in the intestine. The aim of this study was to determine the effects of intestinal ischemic preconditioning on the morphology of intestine and bacterial translocation. Twenty-four male Wistar rats weighting 250 to 300 g were randomized into three groups. A control group of rats (n = 8) were subjected laparotomy. In an ischemic group (n = 8), laparotomy was performed and the superior mesenteric artery was occluded by an atraumatic clamp for 30 min. In the preconditioned group (n = 8), before the ischemia-reperfusion (I/R) period (as in ischemic group), rats were subjected to an initial 10 min of intestinal ischemia and 10 min of reperfusion. Twenty-four hours later, to evaluate whether the I/R induced intestinal injury and bacterial translocation (BT), tissue and blood samples were collected, and liver, spleen, and mesenteric lymph node specimens were obtained under sterile conditions for microbiological analysis. Samples of ileum were removed for both biochemical and histopathological evaluation. In the I/R group, the incidence of bacteria-isolated mesenteric lymph nodes, spleen, liver, and blood was significantly higher than other groups (P < 0.05). IPC prevented I/R-induced BT and it significantly reduced the I/R-induced intestinal injury (P < 0.05). Increased inducible nitric oxide (NO) synthase (iNOS) expression observed on the ileal specimens of the I/R group was found to be prevented by IPC. Our data suggest IPC as a key factor that reduces BT and iNOS activation in intestinal I/R. This is the first study showing that intestinal IPC blocks the cascade of events that causes BT and intestinal injury that may lead to sepsis.

Animals↗
PubMedDate not supplied

Effect of caffeic acid phenethyl ester on treatment of experimentally induced methicillin-resistant Staphylococcus epidermidis endophthalmitis in a rabbit model.

This study investigated the anti-inflammatory effects of caffeic acid phenethyl ester (CAPE), a natural bee-produced compound, and compared it with corticosteroids in the treatment of experimentally induced methicillin-resistant Staphylococcus epidermidis (MRSE) endophthalmitis in addition to intravitreal antibiotics. An experimental endophthalmitis model was produced in 24 New Zealand albino rabbits by unilateral intravitreal injection of 0.1 ml of 4.7 x 10(4) colony-forming units (CFU) methicillin-resistant S. epidermidis. The animals were then divided randomly into three treatment groups and a control group, group 1 (six rabbits), received only intravitreal vancomycin (1.0 mg/0.1 ml); group 2 (six rabbits), received both intravitreal vancomycin (1.0 mg/0.1 ml) and intravitreal dexamethasone (400 microg/0.1 ml) and group 3 (six rabbits), received both intravitreal vancomycin (1.0 mg/0.1 ml) and subtenon CAPE (10 mg/0.3 ml) after 24 h post-infection. No treatment was given to the control group. Treatment efficacy was assessed by clinical examination, vitreous culture and histopathology. There were no statististically significant differences between clinical scores of all groups in examinations at 24 and 48 h post-infection (p = 0.915 and p = 0.067 respectively), but in examinations at 72 h post-infection and after 7 days post-infection, although the clinical scores of treatment groups were not significantly different from each other, they were significantly lower than the control group (p < 0.05). The culture results of all groups were sterile. As a result, CAPE was found to be as effective as dexamethasone in reducing inflammation in the treatment of experimental MRSE endophthalmitis when used with antibiotics. More studies are needed to determine the optimal administration route and effective dosage of this compound.

Analysis of Variance↗
PubMedDate not supplied

Bcl-2, iNOS, p53 and PCNA expression in normal, disordered proliferative, hyperplastic and malignant endometrium.

We attempted to determine Bcl-2, inducible nitric oxide synthase (iNOS), p53 and proliferating cell nuclear antigen (PCNA) expression, and the relationships between them, in endometrioid adenocarcinomas and precursor lesions. Expression of Bcl-2, iNOS, p53 and PCNA were investigated immunohistochemically in 91 samples from benign (proliferative (pEM), secretory (sEM), disordered proliferative (dEM), inactive/atrophic (aEM), hyperplastic endometrium) and malignant endometrial tissue. Staining scores for Bcl-2 in the dEM, endometrial hyperplasia (EMH) and endometrioid cancer (ECA) groups were higher than in the pEM group (P = 0.004; P = 0.036 and P = 0.020, respectively). A significant difference in proliferating cell nuclear antigen staining was found between simple and complex EMH samples (P = 0.000). An inverse relationship was found between iNOS and p53 in the hyperplasia group (r = -0.533, P = 0.019). While a significant difference was found in p53 staining in ECA between the pEM, dEM and EMH groups, no such difference was found in iNOS staining. In addition, there was no direct relationship between iNOS and p53 in the ECA group. It was concluded that the interaction between iNOS, p53 and Bcl-2 in proliferative processes in the development of type 1 endometrioid adenocarcinomas is different from that in tumors originating in other organs.

Adenocarcinoma↗
PubMedDate not supplied

Massive pleural effusion in an 18-year-old girl with Ewing sarcoma.

Ewing sarcoma is a bone tumour that commonly appears between ages five and 10 in the diaphysis of the long bones and predominantly presents with pain and swelling. The case of an 18-year-old girl who presented with back pain, cough, dyspnea, weakness and fever is described. Chest radiograph showed a homogenous density in the middle and inferior zones of the right hemithorax. Thoracic computed tomography revealed a diffuse pleural effusion and a 6.99 cm x 4.45 cm solid mass composed of lobulated, small cystic lesions and calcifications in the right hemithorax. Biochemical analysis of pleural fluid showed hemorrhagic effusion and exudate. A pleural needle biopsy demonstrated solid uniform tumour cells with narrowed cytoplasm, round nuclei and uncertain nucleoli. All of the tumour cell cytoplasms stained with CD99. The pathological examination supported Ewing sarcoma. Three-phase Tc-99m methylene diphosphonate scintigraphy of the whole body showed pathological tracer uptake in a broad area of the eighth costal bone and in smaller areas of the ninth and 10th costal bones. This case is reported because Ewing sarcoma is a rare cause of pleural effusion in clinical practice among younger adults.

Adolescent↗
PubMedDate not supplied

The efficacy of intravitreal levofloxacin and intravitreal dexamethasone in experimental Staphylococcus epidermidis endophthalmitis.

This study was designed to investigate the efficacy of intravitreal levofloxacin, and intravitreal levofloxacin and dexamethasone combined in Staphylococcus epidermidis endophthalmitis. Albino rabbits (n = 25), infected with an intravitreal inoculum of S. epidermidis (1.0 x 10(5) colony forming units/0.1 ml), were divided into five groups (n = 5). Groups 1 and 2 received treatment 24 h after the inoculation, and groups 3 and 4 48 h after the inoculation. No treatment was given to the control group. Treatment efficacy was assessed by vitreous culture, clinical examination and histopathology. Five days after treatment, groups 1 and 2 had significantly lower clinical scores than the control group (p = 0.004, p = 0.007). The culture results of the treatment groups were sterile. The histopathological scores of the treatment groups were lower than the control group (p = 0.007). Studies on retinal toxicity and dose-response relation are needed to prove the efficacy of levofloxacin in S. epidermidis endophthalmitis.

Animals↗
PubMedDate not supplied

The effect of preventive use of alanyl-glutamine on diaphragm muscle function in cecal ligation and puncture-induced sepsis model.

BACKGROUND: Low muscle glutamine levels during sepsis are associated with reduced protein synthesis and elevated protein breakdown, in particular myofibrillar protein breakdown. Thus, in a cecal ligation and puncture (CLP)-induced sepsis model in the rat, we hypothesized that glutamine pretreatment would protect the diaphragm muscle function. METHODS: Eighty-four male Wistar rats weighing between 180 g and 200 g received standard amino acid solution 1.2 g kg(-1) per day intraperitoneally (IP) or standard amino acid solution 1.2 g kg(-1) per day plus alanyl-glutamine (GLN) 0.25 g kg(-1) per day (IP) during the first 6 days of the experiment. On the seventh day, CLP or sham procedures were applied. The sham and CLP groups were equally divided into 3 subgroups according to the termination of the experiment, which took place at either the 24th hour, 48th hour, or 72nd hour. After the compound muscle action potentials (CMAP) were recorded from the diaphragms of the rats at these selected times, they were decapitated under ketamine/xylazine anesthesia, and diaphragms were harvested for biochemical and histopathological examination. RESULTS: The mean area and amplitude of CMAP were significantly larger in sham+GLN groups when compared with CLP and CLP+GLN groups at all times (p < .05). Diaphragm Ca+2 -ATPase levels were found to be significantly decreased in CLP group at all times compared to sham groups (p < .05). Diaphragm reduced glutathione levels were significantly higher in sham+GLN groups when compared with CLP and CLP+GLN groups at all times (p < .05). In histopathologic assessment, moderate neutrophil infiltration, which was observed in CLP48, was significantly reduced with alanyl-glutamine supplementation in CLP+GLN48 group (p < .05). CONCLUSIONS: This study showed that glutamine pretreatment did not improve diaphragm muscle function, but prevented the biochemical and histopathological changes in diaphragmatic muscle in CLP-induced sepsis. However, further studies are needed to clarify whether a higher dose of glutamine supplementation might protect the diaphragmatic muscle functions.

Action Potentials↗