Tıp Fakültesi / Faculty of Medicine
Permanent URI for this collectionhttps://hdl.handle.net/11727/1403
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Item Inhibition of the Notch Pathway Promotes Flap Survival by Inducing Functional Neoangiogenesis(2015) Abbas, Ozan Luay; Borman, Huseyin; Terzi, Yunus K.; Terzi, Aysen; Bayraktar, Nilufer; Ozkan, Burak; Yazici, Ayse C.; 0000-0002-7886-3688; 0000-0003-3093-8369; 0000-0002-1225-1320; 0000-0002-3132-242X; 0000-0001-5612-9696; 25180956; Y-8758-2018; AAI-5063-2020; F-7546-2013; AAS-6810-2021; B-4372-2018Objective The Notch pathway seems to function as an antiangiogenic factor, negatively regulating the sprouting effect of vascular endothelial growth factor (VEGF). This function is well defined in embryonic and tumor vasculature. However, little is known about its function in ischemia-induced angiogenesis. In the first part of this study, we investigated the role of Notch in reparative angiogenesis after ischemia. In the second part, we hypothesized that anti-Notch therapy will result in increased angiogenic sprouting. We analyzed the effect of Notch inhibition in the induction of angiogenic sprouting. Methods In the first part, we investigated the effect of ischemia on the Notch ligand delta-like ligand 4 (DLL4). Twenty rats were divided equally into 2 groups. In the surgery group, dorsal skin flap was used as model of ischemia. In the control group, no surgical procedure was performed. DLL4 and VEGF gene expressions were assessed. Immunohistochemical staining was used for detection of DLL4 in tissue materials. Plasma levels of VEGF and DLL4 were measured. In the second part, we investigated the effect of Notch inhibition using a gamma-secretase inhibitor (GSI) on inducing neoangiogenesis. Twenty rats were assigned to 2 equal groups. In all animals, dorsal skin flap was raised and sutured back into its bed. Animals in the GSI-treated group received GSI intravenously after surgery for 3 days. Saline was administered in the control group. Necrotic area measurements, microangiography, and histologic evaluations were performed to compare groups. Results In the first part, VEGF and DLL expressions increased in ischemic tissues (P < 0.01). Immunohistochemical analysis revealed that DLL4 expression was upregulated in capillary endothelial cells after ischemia. Plasma levels for VEGF and DLL4 were higher in the animals that underwent surgery (P < 0.01). In the second part, GSI treatment resulted in higher flap survival rates (P < 0.05). Microscopic analysis exhibited increase in the number of microvascular structures after GSI treatment (P < 0.05). Microangiographic evaluation showed that neovascularization increased in the GSI-applied flaps. Conclusions We present an evidence for the importance of the Notch pathway in the regulation of ischemia-induced angiogenesis. Notch inhibition promotes flap survival by creating a neovasculature that has an increase in vascular density.Item Evaluation of The Effect of Lipid Emulsıon Therapy on The Rat Model in Organophosphate Intoxication and Tissue Pathologies(2014) Celikel, Elif; Arslan, Engin Deniz; Yilmaz, Fevzi; Turhan, Turan; Unal, Muge Tecder; Turhan, Turan; Turhan, Nesrin; Kavalci, Cemil; Karakilic, M. Evvah; Altunkaynak, Hande Ozge; Unal, Muge Tecder; Demir, Ali; AAH-5151-2020Introduction and objective: Organophosphates are frequently used for agricultural spraying in an uncontrolled manner in our country. Humans are usually inadvertently exposed to these chemicals via respiratory, transdermal, or tranconjunctival routes whereas they may also be used for suicidal purposes: Having a high morbidity and mortality, this intoxication causes a high emergency department admission rate (1). Previous studies on lipid therapy in cardiac arrest associated with intoxication of lipophilic agents such as antidepressants, anticonvulsants, antihypertensives, and local anesthetics have reported a 55% increase in survival with these therapies (2). We also studied lipid emulsion therapy (LET) in poisoning with organophosphates that are lipophilic. Materials and method: This study used 30 male Wistar-albino rats of 12 months of age weighting 288 to 428 gr. The animals were randomly grouped into 5 groups: Group 1 Was the control group; Group 2 organophosphate+serum physiologic (SF) group; Group 3 organophosphate+LET group; Group 4 arganophosphate + Atropin(A)+ Pralidoxime (PAM) group; and Group 5 organophosphate+LET+A+PAM group. After an 8-hour clinical observation period the rats were sacrificed and Wad pseudocholitiesterase, cholesterol; and triglyceride levels were studied. Renal, hepatic, splenic, and cerebral tissues were sampled to be examined under light microscope. Results : There were significant differences between the groups with respect to cholesterol, triglyceride, but not pseudocholine-sterase level Dizziness was the first observed clinical symptom, followed by hindleg paralysis, foreleg paralysis, and general paralysis. After general paralysis salivation was usually observed together with gasping breathing. Rats with the above clinical course were sacrificed. The clinical picture progressed rapidly after foreleg paralysis. The toxic clinical course was observed in 100% of rats in Group 2 (organophosphate + SF) and Group 3 (Organophosphate +LET) and its mortality rate was high. No significant difference was observed between both groups with respect to time to symptom onset. This may be interpreted as that LET treatment alone was not effective. Conclusion: In the present study we did not observe any beneficial effect of LE treatment alone on mortality of organophosphate intoxication. According to our results, however, it may be beneficial when used in conjunction to Classical therapy. Considering its relatively low side effect profile and pros and cons, we believe that it can be used as a supportive therapy in organophosphate poisoning.Item Effects of Ciprofloxacin on Fetal Rat Liver During Pregnancy and Protective Effects of Quercetin(2017) Dogan, Z.; Elbe, H.; Taslidere, E.; Soysal, H.; Cetin, A.; Demirtas, S.; 0000-0001-7131-2317; 0000-0003-1723-2556; 28836867; V-5131-2018; ABI-8046-2020; AAL-4660-2020Urinary tract infections are common in pregnant women and ciprofloxacin frequently is used as a broad spectrum antibiotic. It has been suggested that ciprofloxacin causes liver damage in fetuses. Quercetin is a flavonoid with antioxidant properties. We investigated the efficacy of quercetin treatment for preventing fetal liver damage caused by ciprofloxacin. Pregnant rats were divided into four groups: untreated control group (C), 20 mg/kg quercetin for 21 days group (Q), 20 mg/kg twice/day ciprofloxacin for 10 days group (CP), and 20 mg/kg, ciprofloxacin + quercetin for 21 days group (CP + Q). Fetal livers were removed on day 21 of gestation to measure antioxidants and for histological observation. Malondialdehyde (MDA) and glutathione (GSH) levels, and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were measured in tissue samples. GSH-Px, SOD and CAT activities were significantly lower in the CP group compared to group C. A significant increase in MDA was observed in the CP group compared to group C. There was no significant difference in GSH levels in any group. MDA levels were lower and CAT, SOD and GSH-Px enzyme activities were higher in the CP + Q group compared to group CP. Liver samples of the CP group exhibited central vein dilation, portal vein congestion, pyknotic nuclei and cytoplasmic vacuolization in some hepatocytes. Histological changes were less prominent in the rats treated with quercetin. Use of ciprofloxacin during pregnancy caused oxidative damage in fetal liver tissue. Oxidative stress was ameliorated by quercetin. Quercetin supports the antioxidant defense mechanism and it is beneficial for treating fetal liver damage caused by ciprofloxacin.Item Erythropoietin May Attenuate Lung Inflammation in A Rat Model of Meconium Aspiration Syndrome(2016) Turhan, Ali Haydar; Atici, Aytug; Muslu, Necati; Polat, Ayse; Sungur, Mehmet Ali; 27266360Background: Inflammation is believed to play a key role in the pathophysiology of meconium aspiration syndrome (MAS). Purpose of the Study: The objective was to determine whether the recombinant human Erythropoietin (rhEPO) pretreatment could attenuate meconium-induced inflammation. Materials and Methods: In this study, 24 ventilated adult male rats were studied to examine the effects of recombinant human EPO (rhEPO) onmeconium-induced inflammation. Seventeen rats were instilled with human meconium (1.5 mL/kg, 65 mg/mL) intratracheally and ventilated for 3 hours. rhEPO (1000 U/kg) (n = 9) or saline (n = 8) was given to the animals. Seven rats that were ventilated and not instilled with meconium served as a sham-controlled group. Analysis of the blood gases, interleukin (IL)-1 beta, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha in blood and bronchoalveolar lavage (BAL) fluid samples, and lung tissue myeloperoxidase levels were performed. Results: Intrapulmonary instillation of meconium resulted in the increase of TNF-alpha (p = 0.005 and p < 0.001, respectively) and IL-8 concentrations (p < 0.001 and p < 0.001, respectively) in BAL fluid in the EPO + meconium and saline + meconium groups compared with the sham-controlled group. rhEPO pretreatment prevented the increase of BAL fluid IL-1 beta, IL-6, and IL-8 levels (p < 0.001, p = 0.021, and p = 0.005, respectively), and serum IL-6 levels (p = 0.036). Conclusion: rhEPO pretreatment is associated with improved BAL fluid and serum cytokine levels. Pretreatment with rhEPO might reduce the risk of developing of meconium-induced derangements.Item Impact of radial extracorporeal shock wave therapy in post-laminectomy epidural fibrosis in a rat model(2021) Haberal, Bahtiyar; Simsek, Ekin Kaya; Akpinar, Koray; Simsek, Duygu Turkbey; Sahinturk, Fikret; https://orcid.org/0000-0002-1668-6997; https://orcid.org/0000-0003-3438-1633; https://orcid.org/0000-0002-0471-3177; 33463432; W-9080-2019; AAV-8821-2021; AAI-7972-2021Objectives: This study aims to investigate the effect of radial extracorporeal shock wave therapy (rESWT) treatment in the prevention of epidural fibrosis after laminectomy in rats. Materials and methods: Eighteen 16-month-old male Sprague-Dawley rats weighing 300 g were used in this experimental study between November 2019 and February 2020. The rats were randomly divided into two groups as the control group (L3-L4 total laminectomy without any treatment) and the study group (L3-L4 total laminectomy plus rESWT). The rats were sacrificed at the postoperative sixth week and the lumbar spine was excised en bloc, fixed, and decalcified. Sections were stained with hematoxylin-eosin to evaluate epidural fibrosis, acute inflammation, chronic inflammation, and vascular proliferation. Results: The median value and standard deviations were obtained based on histological examinations. Accordingly, epidural fibrosis decreased significantly in the study group compared to the control group. There was no statistically significant difference between the groups in terms of acute and chronic inflammation response and vascular proliferation. Conclusion: The rESWT application immediately after surgery is effective in preventing epidural fibrosis after laminectomy in rats.Item Relaxant effect of diallyl sulfide on nonpregnant rat uterus: Involvement of voltage-dependent calcium channels(2020) Efe, Oguzhan E.; Lux, K. Michael; Emre Aydingoz, Selda; Tuncer, Meral; 0000-0002-3243-7843; 0000-0003-3360-5092; 0000-0001-7823-7620; 32830389; W-7908-2019; AAD-9901-2021; ABA-4291-2020Aim We aimed to determine the effect and mechanism of action of diallyl sulfide (DAS), an active component of sulfur-containing foods such as garlic on rat uterine activity. Methods Isometric tension changes in longitudinal uterine strips obtained from 20 female Sprague-Dawley rats (250-300 g) in estrus stage of estrous cycle were studied in isolated organ baths containing Krebs-Henseleit solution. Results Diallyl sulfide (10(-8)-10(-6) M) caused a concentration-dependent relaxation on KCl (60 mM)-induced contractions and inhibited spontaneous peristaltic activity of uterine strips (P < 0.05). None of the following antagonists significantly changed the inhibitory effect of DAS on both KCl-precontracted uterine strips and spontaneous peristaltic activity of the uterus (P > 0.05): nitric oxide synthase inhibitor L-NAME (10(-4) M), hydrogen sulfide-producing enzymes cystation beta synthase and cystation gamma-lyase inhibitors, aminooxyacetic acid (10(-4) M) and propargylglycine (10(-3) M) and nonselective cyclooxygenase inhibitor indomethacin (10(-4) M). However, in calcium-free Krebs solution containing high KCl (30 mM), DAS significantly inhibited CaCl2(10(-5)-10(-2) M)-induced uterine contractions in a concentration-dependent manner (P < 0.05). Conclusion Diallyl sulfide has a relaxing effect on KCl-contracted rat uterus strips and an inhibitory effect on spontaneous uterine activity, possibly by decreasing the calcium influx into the cytoplasm of uterine smooth muscle cells.Item Effects of Algan Hemostatic Agent on bleeding time in a rat tail hemorrhage model(2020) Totuk, Ozgan Melike Gedar; Guzel, Sevket Ergun; Ekici, Husamettin; Kumandas, Ali; Aydingoz, Selda Emre; Yilmaz, Enis Cagatay; Kirdan, Taylan; Midi, Ahmet; 0000-0001-7823-7620; 33107963; ABA-4291-2020BACKGROUND: Algan Hemostatic Agent (AHA) is a multi-herbal extract containing a standardized amount of Achillea millefolium, Juglans regia, Lycopodium clavatum, Rubus caesius or Rubis fruciosus, Viscum album, and Vitis vinifera, each of which is effective in hemostasis. In this study, we aimed to investigate the effects of AHA on bleeding time in a rat tail hemorrhage model. METHODS: Forty-eight Sprague Dawley rats (5-7 weeks old, 180-210 g) were randomly and equally allocated to six groups as follows: heparin plus saline (heparinized control), heparin plus AHA-soaked sponge, heparin plus liquid form of AHA, saline (non-heparinized control), AHA-soaked sponge and liquid form of AHA. Heparin (640 IU/kg) was administered intraperitoneally three times a day for three days in heparinized groups. For the bleeding model, the tail of rats was transected. According to the study group, either saline- or AHA-soaked sponge or liquid form of AHA was applied over the hemorrhage area. In AHA- or saline-soaked sponge groups, once the bleeding time had started, it was checked every 10 seconds. If the bleeding did not stop after 40 seconds, it was accepted as a failure. In liquid AHA group, the duration of bleeding was measured using a chronometer and defined as the time (seconds) from wounding until the bleeding stopped. RESULTS: Bleeding time in the heparinized and non-heparinized control groups was over 40 seconds. After applying the sponge form of AHA on the wound area, bleeding time was significantly shortened to less than 20 seconds in both heparinized and non-heparinized rats (p<0.001 for both). The liquid form of AHA stopped bleeding in 5.0 +/- 1.2 seconds and 8.0 +/- 1.3 seconds in heparinized and non-heparinized groups, respectively. CONCLUSION: AHA is a highly effective topical hemostatic agent in a rat tail hemorrhage model, thus may provide for a unique clinically effective option for control of bleeding during surgical operations or other emergencies.Item The effect of N-acetyl cysteine on biofilm layers in an experimental model of chronic otitis media(2020) Callioglu, Elif Ersoy; Bercin, Sami; Basdemir, Gulcin; Kiris, Muzaffer; Tatar, Ilkan; Tuzuner, Arzu; Oguzhan, Tolga; Muderris, Tuba; Sargon, Mustafa Fevzi; Korkmaz, Mehmet Hakan; 33558775Objective. The aim of this study was to investigate the efficacy of N-acetylcysteine (NAC) on biofilm layers and on the course of disease in chronic otitis media. Methods. Twenty-five rats that were induced with chronic otitis media (COM) were separated into three groups. In Group 1 (N = 18), 0.2% ciprofloxacin + 0.1% dexamethasone sodium phosphate + 0.5 mg/ml NAC solution was locally injected to the right ear of the rats; in Group 2, (N=18) 0.2% ciprofloxacin + 0.1% dexamethasone sodium phosphate was locally injected to the left ear of the rats. No treatment was applied to either ear of rats in Group 3 (N = 5). Histopathological and scanning electron microscope (SEM) evaluations were performed in all groups. Results. SEM revealed biofilm formation in all COM induced groups. No significant difference was seen between groups 1 and 2 in terms of suppuration levels, fibrosis, inner ear involvement, infection staging and biofilm formation (p > 0.05). Conclusions. In this study, while histopathological and SEM evaluation revealed no effect of 0.5 mg/ml NAC on the biofilm layer in COM-induced rats, further studies with NAC at different concentrations are still needed on different types of experimental animals.Item Prostaglandin F receptor expression in intrauterine tissues of pregnant rats(2014) Anadol, Elvan; Kanca, Halit; Yar, Atiye Seda; Helvacioglu, Fatma; Menevse, Sevda; Calguner, Engin; Erdogan, DenizIn this investigation, we studied the expression and localization of rat prostaglandin F (FP) receptor in uterine tissues of rats on gestational Days 10, 15, 18, 20, 21, 21.5 and postpartal Days 1 and 3 using Western blotting analysis, real-time PCR, and immunohistochemistry. A high level of immunoreactivity was observed on gestational Days 20, 21, and 21.5 with the most significant signals found on Day 20. FP receptor protein was expressed starting on gestational Day 15, and a fluctuating unsteady increase was observed until delivery. Uterine FP receptor mRNA levels were low between Days 10 and 18 of gestation (p < 0.05). The transcript level increased significantly on Day 20 and peaked on Day 21.5 just before labor (p < 0.05). There was a positive correlation between FP receptor mRNA expression and serum estradiol levels (rs = 0.78; p < 0.01) along with serum estradiol/progesterone ratios (rs = 0.79; p < 0.01). In summary, we observed an increase FP receptor expression in rat uterus with advancing gestation, a marked elevation of expression at term, and a concominant decrease during the postpartum period. These findings indicate a role for uterine FP receptors in the mediation of uterine contractility at term.Item Protective effects of growth hormone on bacterial translocation and intestinal damage in rats with partial intestinal obstruction(2014) Kaymakci, A.; Guven, S.; Ciftci, I.; Akillioglu, I.; Aktan, M.; Eker, H.H.; Sutcu, A.; Abasiyanik, A.; 25077360Objective: One of the reasons of bacterial translocation (BT) is the complete or partial intestinal obstructions (PIO) of the gastrointestinal system. In this study, we aimed to investigate the effects of recombinant human Growth Hormone (rhGH) on BT in rats with partial intestinal obstruction (PIO). Material and methods: The rats were randomly divided into the 4 groups: Group I: Sham-operated (SO) (n = 12), Group II control PIO (n = 12), Group III: PIO with rhGH treatment for 5 days (n = 12), Group IV: PIO with rhGH treatment 5 days before PIO and 5 days after PIO (a total of 10 days) (n = 12). In the groups III and IV, the effects of 5 and 10 days administered rhGH were examined. Results: The level of serum and of intestinal fluid IgA was significantly higher in the Group IV compared to the Group I, Group II and Group III. In the Group IV, the number of small intestinal goblet and colonic goblet cells, and the lengths of intestinal mucosal villi and crypt depths were statistically significantly higher than in Groups II and III. The rate of bacterial translocation was higher in the Group II: 100 % in MLNs, 41.6 % in blood culture and 50.8 % in the liver cultures, it was significantly higher compared to the other groups (p < 0.01). Conclusions: The study results demonstrated that administration of rhGH to the rats with PIO for at least 10 days decreased bacterial translocation (Fig. 3, Ref. 25). Text in PDF www.elis.sk.