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Öğe Effects of antineoplastic agents on the peripheral nerves under a surgical tissue expansion procedure: An experimental study(Wiley, 2006) Oktay, M. Faruk; Aşkar, İbrahim; Yıldırım, Ayşe; Gürlek, Ali; Akkuş, Murat; Topçu, İsmail; Meriç, Faruk; 0000-0001-5708-4813Background. Elongation of peripheral nerve by the use of a tissue expander is helpful to repair nerve defects. This study was designed to investigate the effects of some antineoplastic agents on the peripheral nerves under a surgical tissue expansion procedure. Materials and Methods. Twenty-five Wistar rats were used in this study. Following the exposition of the sciatic nerve and placement of two 10/0-nylon sutures in the epineurium 20 mm apart, a tissue expander was then placed under it. Inflation of the expander was immediately accomplished by the separate percutaneous injections of 6, 6, and 8 ml for every 3 min under general anesthesia. The expander was fully deflated at the end of each 3 min The distance between two sutures was measured 1 h later to measure the rate of elongation. Rats were randomly divided into five groups (according to the administered drugs), each consisting of five rats (10 sciatic nerves). Normal saline (1 ml) in the control group (group 1), cyclophosphamide (15 mg/kg) in the group II, cisplatinum (3 mu g/kg) in the group III, mitomycin-C (0.5 mg/kg) in the group IV and 5-fluorouracil (10 mg/kg) in the group V were injected intravenously. Intravenous injections of drugs were performed via the tail vein 30 min before expansion, 48 and 96 h after removal of expander. The incision was reopened on the third and seventh postoperative days, and five sciatic nerves of each group were exposed and then the pinching test was performed to measure regeneration distance. Electro-neurographic changes were recorded. The expanded portion of the sciatic nerve between two sutures was harvested for histological evaluation. Results. There is no significant difference between the elongation rates of all groups (P < 0.05). Histologic evaluation showed that inflammatory changes, vacuolization, intraneural edema, demyelination, axonal changes in the control group, the cisplatinum group and the mitomycin-C group. These changes were significantly decreased in the cyclophosphamide group and the 5-fluorouracil group. In the cyclophosphamide group and the 5-fluorouracil group, the amplitude of compound action potential (CAP) values were significantly higher and the latency was significantly shorter (P > 0.05). Conclusion. We believed that cyclophosphamide and 5-fluorouracil may be helpful in tissue expansion of peripheral nerves, by decreasing the effects of the ischemia-reperfusion injury on the expanded peripheral nerves.Öğe Effects of some pharmacological agents on the survival of unipedicled venous flaps: An experimental study(Wiley-Blackwell, 2001) Aşkar, İbrahim; Saray, Aydın; Gürlek, Ali; Sevin, Kutlu; Sabuncuoğlu, Bizden TavilClinical and experimental studies have been conducted to improve the survival of venous flaps, As a result of these studies, although various survival mechanisms were raised, none obtained satisfactory information. Venous stasis, and the resultant venous thrombosis, is a factor that decreases the survival of venous flaps. In this study, we evaluated the effects of two antiinflammatory agents, etodolac and etofenamate, on the survival of unipedicled venous flaps. In this study, 35 male New Zealand white rabbits (3,500-4,000 g) (70 ears) were used. Perichondrocutaneous flaps, 3 x 4.5 cm in size, were designed and raised, keeping the central veins intact in the middle of venous flap. Central arteries and nerves were ligated and transected both proximally and distally, to prepare unipedicled venous flaps. A silicone sheet was placed between the cartilage tissue and flap, to prevent blood flow and revascularization beneath. The subjects were divided into seven groups, consisting of five rabbits (10 ears). In the negative control group (group 1), the single vascular pedicle of venous flaps, central veins were ligated and flaps sutured into their own place as the composite graft. In the positive control group (group 11), after venous flaps were prepared, normal saline, 0.2 mL, was given subcutaneously. In the first of five experimental groups (group III), unfractionated heparin (100 U/day) was given subcutaneously. In the second experimental group (group IV), etodolac (5 mg/kg/day) was given subcutaneously, In the third experimental group (group V), etophenamate (5 mg/kg/day) was given orally through a feeding tube. In the fourth experimental group (group VI), parnaparin (5 anti-Xa U/kg/day) was given subcutaneously. In the fifth experimental group (group VII), nadroparin (5 anti-Xa U/kg/day) was given subcutaneously, about 7 days postoperatively. At the eighth postoperative day, surviving areas of venous flaps were measured, and the results were evaluated by Kruskal-Wallis ANOVA and Mal Whitney U-test (P < 0.05). Biopsies were also taken from the flaps for histological evaluation of border of necrotic tissue, Surviving areas of unipedicled venous flaps were larger in experimental groups than those in negative and positive control group (P < 0.05). However, comparison of the experimental groups demonstrated no statistically significant dierence (P > 0.05). We concluded that all pharmacological agents used in the experimental groups succeeded in increasing the survival of unipedicled venous flaps. Survival of the unipedicled venous flap was higher in venous flaps than that of composite graft, clearly showing the importance of the venous pedicle.Öğe Etofenamat'ın random paternli sıçan dorsal deri flebi yaşayabilirliği üzerine etkisi(2000) Aşkar, İbrahim; Gürlek, Ali; Sabuncuoğlu, Bizden T.; Sevin, KutluDeri defektlerinin rekonstrüksiyonu için birçok deri flebi geliştirilmiştir. Distal flep nekrozu, özellikle uzun deri flepleri kaldırılırken, önemli bir problem olarak karşımıza çıkmaktadır. Bu nedenle, distal flep nekrozunu önlemek ve flep yaşayabilirliğini artırmak için birçok deneysel ve klinik çalışma yapılmıştır. Bu deneysel çalışmada, anti-inflamatuar ajan olan etofenamatın deri flebi yaşayabilirliği üzerindeki etkisi araştırıldı. Sprague-Dawley cinsi sıçanlarda, 3x10 cm boyutlarında pannikulus karnozus içeren kaudal tabanlı random paternli dorsal deri flebi kaldırılıp, yerine iade edildi. Kontrol grubuna herhangi bir farmakolojik ajan verilmezken, deney grubuna postoperatif dönemde yedi gün boyunca etofenamat 10 mg/kg/gün, im olarak verildi. Yedinci günde deri fleplerinin yaşayan alanları ölçüldü ve sonuçlar "Student's t-test" ile değerlendirildi. Yaşayabilen flep oranları etofenamat grubunda %83.27 ve kontrol grubunda %65.70 olarak bulundu. Etofenamatın flep yaşayabilirliğini, kontrol grubuna oranla, istatistiksel olarak anlamlı bir şekilde arttırdığı bulundu (p<0.05). Yedinci günde nekroz-canlı doku hattından biyopsi alındı ve histopatolojik değerlendirme yapıldı. Histopatolojik değerlendirmede, nekroz-canlı doku sınırında, her iki grupta da flep ile flep yatağı arasında damarlanmada artış görülürken, deney grubunda kontrol grubuna oranla daha az inflamatuar hücre infiltrasyonu izlendi.Öğe Protective effects of some antineoplastic agents on ischemia-reperfusion injury in epigastric island skin flaps(Wiley-Liss, 2006) Aşkar, İbrahim; Oktay, Mehmet Faruk; Gürlek, Ali; Baç, BilselNeutrophil depletion has a beneficial effect on ischemic myocardium and skeletal muscle upon reperfusion. Antineoplastic agents reduce blood neutrophils effectively, and lead to neutrophil depletion. The purpose of this study was to investigate the effects of four antineoplastic agents in low doses (cyclophosphamide, cisplatinum, mitomycin-C, and 5-fluorouracil) on ischemia-reperfusion injury, using an epigastric island skin-flap model in rats. Fifty male Sprague-Dawley rats, weighing 250-300 g, were randomly divided into five groups, each consisting of 10 rats: control, cyclophosphamide, cisplatinum, mitomycin-C, and 5-fluorouracil groups. Epigastric island skin flaps (measuring 3.5 x 4 cm) were raised and subjected to 10 h of in situ ischemia, followed by 7-day reperfusion and evaluation. Treatment with antineoplastic agents (cyclophosphamide, cisplatinum, mitomycin-C, and 5-fluorouracil) was used to introduce neutropenia. Complete blood counts, cutaneous bleeding time, and skin-flap survival were evaluated. Additionally, levels of malonyldialdehyde (MDA), nitric oxide (NO), glutathione (GSH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were measured from extracted skin tissue. Numbers of leukocytes and platelets were decreased in all experimental groups. However, neutropenia and thrombocytopenia were not seen. Cutaneous bleeding activity was prolonged in all experimental groups, but not above the normal value. MDA and NO levels were found to be lower in all four antineoplastic agent groups than in the control group, while GSH, GSH-Px, and SOD enzyme activities were significantly higher (P < 0.05). However, MDA and NO levels were significantly decreased in the cyclophosphamide and 5-fluorouracil groups, as compared to the cisplatinum and mitomycin-C groups (P < 0.01). Also, GSH, GSH-Px, and SOD enzyme activities were significantly increased in the cyclophosphamide and 5-fluorouracil groups, compared to the other two antineoplastic agent groups (P < 0.01). We conclude that antineoplastic agents have beneficial effects on ishemia-reperfusion injuries when their doses are carefully adjusted, by decreasing the number of leukocytes and platelets, and altering the activity of free oxygen radicals. (c) 2006 Wiley-Liss, Inc.Öğe Salutary effects of radiopaque contrast media on the survival of random-pattern skin flaps in the rat(Wiley, 2004) Aşkar, İbrahim; Bozkurt, Mehmet; Oktay, Mehmet Faruk; Gürlek, Ali; Keleş, CelalettinThe radiopaque contrast medium diatrizoate, has a vasodilator effect so that it is used in sudden-deafness secondary ischemic injury. However, ischemic problems are encountered, especially when longer flaps are elevated. A longer flap also has ischemic and relatively ischemic tissue, and may obtain some benefit from contrast media. Forty male Sprague-Dawley rats, weighing about 350-400 g, were used, and randomly divided into four groups (n = 10 rats each group): group 1 was the control, group 2 the diatrizoate, group 3 the iopamidol, and group 4 the iothalamate group. A rectangular 3 x 10 cm caudally based dorsal skin flap was elevated, and sutured back to its original place. In the control group, no pharmacologic agent was administered. Sodium-meglumine-diatrizoate 10 mg/kg/day was administered parenterally in the first experimental group (diatrizoate group); iopamidol 10 mg/kg/day in the second experimental group (iopamidol group); and iothalamate sodium 10 mg/kg/day in the third experimental group (iothalamate group) for 7 postoperative days. On postoperative day 7, all flaps were photographed, and the area of flap survival was measured by using a polar planimeter. The results were statistically evaluated with the Kruskal-Wallis test and Mann-Whitney U-test (P = 0.05). The mean flap survival ranged from 79% in the iopamidol group to 83% in the diatrizoate group, and was significantly greater in all experimental groups (P < 0.05) compared to the control group (59%). There was no significant difference between experimental groups (P < 0.05). We believe that radiopaque contrast media have a beneficial effect in improving skin flap viability when distal flap necrosis is a potential complication of longer flaps.
