Sevda Muftuoglu

The preventive effect of heparin on stricture formation after caustic esophageal burns

BACKGROUND/PURPOSE Preventing thrombus formation after caustic esophageal ingestion has been proposed to have beneficial effects. Therefore, an experimental study was carried out to investigate the effects of heparin on the esophagus after caustic burns. METHODS Caustic esophageal burns were produced in rats by irrigation with 50% NaOH as described by Liu. Rats were divided into four groups as follows: group A, animals with esophageal burns, received placebo and underwent autopsy 48 hours after caustic injury; group B, animals with esophageal burns, received subcutaneous heparin treatment and underwent autopsy 48 hours after caustic injury; group C, animals with esophageal burns, received placebo and underwent autopsy 28 days after caustic injury; group D, animals with esophageal burns, received subcutaneous heparin treatment for 7 days and underwent autopsy 28 days after caustic injury. Histopathologic evaluation was performed in all groups, and collagen content of esophageal sections was analyzed by determination of hydroxyproline levels. RESULTS Submucosal vascular thrombosis was encountered in all group A animals but the submucosal venules and arterioles were patent in most of group B animals. Esophageal strictures did not develop in any of group D animals, although varying degree of esophageal stenoses were encountered in all animals of group C. The circumferences of the burned segment have been narrowed to 3+/-1 mm in group C rats. There was obvious collagen deposition in submucosa, and epithelial regeneration was not complete in group C rats. Submucosa and epithelial integrity seemed normal in group D animals. Hydroxyproline contents in group D were significantly lower compared with group C (P < .05). CONCLUSIONS Heparin has ameliorating effects on stricture formation after caustic esophageal burn. Those effects may occur through possible anticoagulant, antithrombotic, and endothelial protective effects, and modifying effects of heparin on wound healing.

Sildenafil attenuates renal ischemia reperfusion injury by decreasing leukocyte infiltration

The aim of the study was to investigate the effects of sildenafil citrate (SC) on renal ischemia reperfusion (I/R) injury in a rat model. Forty eight male Wistar albino rats were randomly assigned into six groups: sham, ischemia, I/R, SC+sham, SC+ischemia and SC+I/R. In the I/R groups, the right kidney was removed and the artery and vein of the left kidney were clamped for 45 min followed by reperfusion for 1 h. In the SC-treated groups, SC dissolved in saline solution was given as a single dose (1 mg/kg) 60 min before the operation. Renal histology was analyzed by scoring the tubular damage and neutrophil infiltration. Tissue myeloperoxidase activity and lipid peroxidation were analyzed. The histological damage and the neutrophil infiltration induced by I/R were significantly less in the SC+I/R group (p = 0.004 and p = 0.003, respectively). Pretreatment with SC significantly diminished the tissue myeloperoxidase activity, indicating the prevention of the neutrophil sequestration into the kidney in the SC+I/R group (p = 0.004); however, it did not result in any changes in lipid peroxidation. Our results in a rat model of ischemia-reperfusion indicate that pre-ischemic treatment with sildenafil citrate can significantly attenuate ischemia/reperfusion-induced renal injury by decreasing leukocyte infiltration.

Myofibroblasts defined by electron microscopy suggest the dedifferentiation of smooth muscle within the sac walls associated with congenital inguinal hernia

Objective To ascertain the presence of myofibroblasts in sacs associated with inguinal hernia in children, through an ultrastructural evaluation using electron microscopy

Erythropoietin Against Cisplatin-Induced Peripheral Neurotoxicity in Rats

Cisplatin (CDDP) is a potent anticancer drug, and neurotoxicity is one of its most important dose-limiting toxicities. In this study we investigated the role of recombinant human erythropoietin (rhuEPO) for protection against CDDP-induced neurotoxicity. All experiments were conducted on female Wistar-albino rats. Animals were randomly assigned to three groups. Group A received only CDDP, group B received CDDP plus rhuEPO, and group C received only rhuEPO. Electroneurography (ENG) was done in the beginning and at the end of 7 wk, then the rats were sacrificed and the sciatic nerve was removed for histopathological examination.The mean initial latency was 2.7438 ms in group A, 2.4875 ms in group B, and 2.62 ms in group C. After 7 wk of treatment, the latency was 2.4938, 2.6313, and 2.3900 ms, respectively. The difference in latencies was not statistically significant. The amplitude of compound muscle action potential (CMAP) was 12.8125 mV, 14.3875 mV, and 14.5600 mV before the treatment and 8.4875, 12.8250, and, 13.0800 mV after treatment, respectively. Amplitude of CMAP was significantly greater in rhuEPO-treated groups (groups B and C) compared to cisplatin only Group A. The mean area of CMAP was 12.2625, 12.3500, and, 12.2800 mV s before the treatment and 5.7125, 10.6463, and 9.1600 mV s after the treatment, respectively. The area of CMAP was significantly larger in rhuEPO-treated groups. In histopathological studies thick, thin, and total number of nerve fibers were 4053, 5050, and 9103, in group A, 5100, 8231, and 13331, in group B, and 5264, 6010, and 11274, in group C respectively. In the microscopic examination active myelinization process was observed in rhuEPO-treated groups. We concluded that at the given dose and schedule CDDP-induced motor neuropathy and rhuEPO prevented this neuropathy by sparing the number of normal nerve fibers and by protecting the amplitude and area of CMAP. We concluded that rhuEPO may also play a role in active myelinization and it is an active agent in protection against CDDP-induced peripheral neuropathy, warranting further clinical studies.

Endoglin (CD 105) expression in human lymphoid organs and placenta

Endoglin (CD 105) is a cell surface antigen widely expressed on vascular endothelium, syncytiotrophoblast, some tissue macrophages, certain culture cells (including early leukemic B-lineage) and some endothelial cell lines. Though its relation to the transforming growth factor-beta (TGF-beta) receptor system is well documented, its function and detailed pattern of expression still remain to be clarified. We examined the differential tissue distribution of endoglin in human lymphoid organs and placenta with several anti-CD 105 monoclonal antibodies (mAbs) using an indirect immunoperoxidase technique, and performed semi-quantitative measurements using an image-analyzing system for comparison. Arterial, venous and capillary endothelia in these organs were reactive with anti-CD 105 mAbs at varying intensities. Interestingly, a distinctly stronger staining pattern was observed in the high endothelial venules (HEVs) which may indicate a special role for endoglin in lymphocyte trafficking. Syncytiotrophoblast expressed endoglin strongly on their apical cell membrane. Extravillous trophoblasts at certain locations selectively expressed endoglin on their cell membranes, suggesting a special role for this surface antigen during trophoblast differentiation.

Effect of Trimetazidine on Retinal Ischemia/Reperfusion Injury in Rats

Purpose: To investigate the effect of trimetazidine (TMZ), an antioxidant agent, on the ischemia/reperfusion (I/R) injury in rat retina histopathologically. Methods: The retinal I/R model was carried out by the 4-vessel occlusion method on Wistar albino rats. Twenty-one rats were divided into 7 groups, each comprising 3 rats. The animals in groups 1, 2 and 3 underwent 30 min of ischemia + 4 h of reperfusion and were treated by the administration of saline, TMZ before reperfusion and TMZ before ischemia, respectively. The animals in groups 4, 5 and 6 underwent 90 min of ischemia + 4 h of reperfusion and were treated in the same way as those in groups 1, 2 and 3, respectively. The 7th group was sham operated. Results: Thirty and 90 min of ischemia followed by 4 h of reperfusion induced retinal injury in the rat retina. Histopathologically, the inner plexiform and inner nuclear layers were the most affected parts. TMZ was able to reduce almost all retinal I/R damage when administered before ischemia. A cytoprotective effect of TMZ was partly observed in those animals which were treated before reperfusion. Conclusion: TMZ seemed to have a protective effect against retinal I/R injury in rats.

Protection against cisplatin-induced nephrotoxicity by recombinant human erythropoietin.

Cisplatin (CDDP) is a potent nephrotoxin, and nephrotoxicity is its most important dose-limiting toxicity. In this study, we aimed to investigate the role of recombinant human erythropoietin (rhEPO) in the protection of cisplatin-induced nephrotoxicity and compare its efficacy with the cell-protective agent amifostine. All experiments were conducted on female Wistar albino rats. Animals were randomly assigned to four groups, each including six rats. Group A received only CDDP, group B received CDDP plus rhEPO, group C received CDDP plus amifostine, and group D received only rhEPO. At the end of 7 wk, hemoglobin (Hgb), hematocrite (Htc), blood urea nitrogen (BUN), and creatinine (Cr) levels were determined and kidneys of the rats were removed. The weights of the kidneys were measured and sent for histopathological examination. Proximal tubules from four areas of the kidney (outer cortex, inner cortex, the medullary ray, and outer stripe of outer medulla [OSOM]) were evaluated. There were statistically significant differences among the groups in terms of tubular scores, including overall renal tubular score, cortex, inner cortex, OSOM, and medullary ray tubular scores, and Htc levels. Group A rats had the worse tubular scores in all categories when compared to group D rats. When the results of groups B and C were compared, there were no differences in terms of BUN, Cr levels, and tubular scores, but the Htc level was significantly higher in group B. Group B rats had better overall and OSOM tubular scores when compared to group A. Group C also had better overall and OSOM tubular scores compared to group A. The present study showed for the first time that rhEPO plays an important role in the prevention of cisplatin-induced nephrotoxicity and it is as effective as amifostine.

The effects of iloprost, a prostacyclin analogue, in experimental ischaemia/reperfusion injury in rat ovaries

Ovarian torsion is a surgical emergency affecting not only the ipsilateral ovary but also contralateral ovary. Although the conventional treatment is salpingo-oophorectomy, recent studies advocate detorsion. We hypothesized that iloprost, an analogue of prostacyclin with cytoprotective properties, may prevent the harmful effects of ischaemia-reperfusion injury in bilateral ovaries after unilateral ovarian torsion-detorsion in rat. In this study, 24 female Wistar-albino female rats were divided into four groups. Ovarian torsion was produced by applying vascular clamps to right ovaries. In Group I, bilateral oophorectomy was performed. In group II, bilateral oophorectomy was performed after a unilateral torsion period of 4h. In group III, bilateral ovaries were removed, following unilateral torsion-detorsion periods each lasted for 4h. Saline was injected i.p. 30 min before detorsion. In group IV, same experimental protocol, which was conducted in group III, was repeated. Iloprost was injected i.p. 30 min before detorsion instead of saline in group IV. Tissue levels of malondialdehyde (MDA) and nitric oxide (NO), which are the indicators for oxidative stress were determined and histopathological evaluation was performed in bilateral ovaries in all groups. The MDA and NO levels for ipsilateral ovaries of four groups were compared and no significant difference was found (p>0.05). The same comparison were done for the contralateral sides and no difference was seen either (p>0.05). In histological examination, iloprost produced improvement in I/R-induced alterations in ipsilateral and contralateral ovaries. In conclusion, these results showed that iloprost has beneficial effect on the histological appearances in both the ipsilateral and contralateral rat ovaries after unilateral torsion-detorsion.

The effects of Gemcitabine and Vinorelbine on inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) distribution of MCF-7 breast cancer cells.

Gemcitabine, which induces S-phase arrest, and Vinorelbine, which arrests microtubule organization, are two agents that have demonstrate preferred anti-tumor activity. Nitric oxide acts in diverse functions including anti-tumor and anti-pathogenic activities. In this study, we aimed to examine the distribution of immunoreactivities of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in cells of the MCF-7 breast cancer cell line in response to treatment with Gemcitabine (G), Vinorelbine (V) and combination of Gemcitabine and Vinorelbine (G+V). The distributions of iNOS and eNOS were determined by using indirect immunoperoxidase or immunofluorescence methods and ELISA. Cells incubated with G, V and G+V for 24, 48 and 72h were immunolabelled with anti-eNOS and anti-iNOS primary antibodies. Apoptosis was determined by TUNEL assay. A significant increase of eNOS immunolabelling on MCF-7 cells treated with G and G+V was observed. Apoptotic cells were also detected in G, V and G+V treated MCF-7 cells. The immunolabelling of iNOS was detected in all groups but this immunoreactivity was not different among the groups. In conclusion, while G treatment, induced S-phase arrest, triggered the NOS pathway after treatment of MCF-7 cells, V treatment, arrested microtubule organization and did not change the NOS pathway. Detection of increased eNOS immunolabelling and apoptosis after G treatment of MCF-7 cells could be important to the treatment of human breast cancer.

Ultrastructural analysis of the chorda tympani nerve in chronic suppurative otitis media.

Objective: To compare ultrastructure of the chorda tympani nerve by light and electron microscopy in patients with otosclerosis and chronic suppurative otitis media. Study Design: Comparative prospective study. Setting: Tertiary care, referral medical center. Patients: The tympanic segments of chorda tympani nerves were collected for ultrastructural investigation in 20 cases with chronic suppurative otitis media and 10 cases with otosclerosis that underwent middle ear surgery. Results: Histopathologic examinations of the suppurative group showed that unmyelinated fibers were almost totally lost and replaced by collagen fibers. The thickness of the myelin sheaths was very slender, whereas some of them were atrophic. A substantial increase was encountered in the endoneural collagen substance and connective tissue, whereas inflammatory elements and edema were present occasionally. Degenerative alterations of the myelinated fibers mainly occurred in the form of adaxonal vacuoles. There was disorganization and separation of parallel lamellae of Schmidt-Lanterman clefts. Conclusion: The chorda tympani nerve should be preserved in otologic surgery. However, inadvertent dissection of the chorda tympani nerve in chronic suppurative otitis media surgery will not possibly cause a postoperative disturbance in light of ultrastructural changes that occur in the nerve.