Periferik sinir kesisinde topikal uygulanan sitidin, kolin ve sitikolin'in aksonal rejenerasyon ve epinöral skar dokusu üzerine etkilerinin erken ve geç primer sütür modelleriyle araştırılması
The analysis of the effects of topically administered cytidine, choline and citicoline on axonal regeneration and epineural scar formation in early and late suturing models of rat peripheral nerve section
Yazar: ERHAN ARSLAN
Danışman: DOÇ.DR. AHMET BEKAR
Uludağ Üniversitesi / Tıp Fakültesi / Nöroşirürji Ana Bilim Dalı
Derece: Tıpta Uzmanlık, 2006
Konu: Nöroşirürji = Neurosurgery

Özet:
SUMMARYTHE ANALYSIS OF THE EFFECTS OF TOPICALLY ADMINISTEREDCYTIDINE, CHOLINE AND CITICOLINE ON AXONAL REGENERATIONAND EPINEURAL SCAR FORMATION IN EARLY AND LATE SUTURINGMODELS OF RAT PERIPHERAL NERVE SECTIONPeripheral nerve injuries seldom results in complete recovery offunctions and many factors interfere with regeneration. In the present studywe investigated the effects of topically administered CDP-choline (citicoline),cytidine, choline and cytidine plus choline on perineural scar formation,axonal regeneration and functional recovery in early (day1) and late (day 3)suturing models of rat sciatic nerve section.One hundred twenty five, Spraque-Dawley female rats weighting 200-300 gr were used in this study. Right sciatic nerve was sectioned with amicroscissor. Rats in the early suturing groups underwent immediate suturingof their nerves with 8/0 prolene just after nerve section rats, in the latesuturing group 3 days later they underwent the same suturing procedure.Rats in the early suturıng groups; control (KG1) (n=10), CDP-Choline (CDP-KoG1) (n=10), cytidine (SiG1) (n=15), choline (KoG1) (n=10), cytidine pluscholine (Si-KoG1) (n=10) received 4 dzm saline, 100 microM CDP-Choline,100 microM cytidine, 100 microM choline, 100 microM cytidine plus cholinerespectively. Rats in the late suturing groups control (KG2) (n=15), CDP-Choline (CDP-KoG2) (n=15), cytidine (SiG2) (n=15), choline (KoG2) (n=15),cytidine plus choline (Si-KoG2) (n=15) received the same treatment as earlysuturing groups 3 days after nevre sectioning.12 weeks after surgery all rats were sacrificed with high doseTiopental sodium. A thick connective tissue surrounding the suture site wasseen in saline and choline treated rats in the early and late suturing groupson macroscopical examination. Scar formation index values were significantlylower in the early suturing groups: Si-KoG1 (p<0,001), CDP-KoG1 (p<0,01)iiiand SiG1 (p<0,05). No significant difference was found between five groupsin the late suturing groups (p>0,05).Results of histomorphological evaluation revealed larger axondiameter [Si-KoG (day 1; p<0.001, day 3; p<0.01), CDP-KoG (day 1; p<0.01,day 3; p<0.01)], axon count [ Si-koG1 (day 1; p<0.001, day 3; p<0.001),CDP-KoG1 (day 1; p<0.001, day 3; p<0.001)], and axonal organizationscores [ Si-KoG1 (day 1; p<0.001, day 3; p<0.01), CDP-KoG1 (day 1;p<0.001, day 3; p<0.01)] in both the early and late suturing of Si-KoG andCDP-KoG groups than control groups. In the cytidine group there was nosignificant difference in tems of axon numbers, but axon diameters weresignificantly larger (SiG1, p<0.01) (SiG2, p<0.05) compared to control group.Also there was not any significant difference in terms of axon fiber diameterwithin groups in early and late suturing groups (p>0,05).Functional recovery as assessed by sciatic function index (SFI) wasbetter in all groups than the control group especially at the 4th postoperativeweek. [(Si-KoG1; p<0.01), (CDP-KoG1; p<0.05), (SiG1; p<0.05) (Si-KoG2;p<0.01), (CDP-KoG2; p<0.05), (SiG2, p<0.05)]The results of this study suggests that topical application of CDP-choline and cytidine plus choline is effective in preventing scar tissueformation especially on the day of surgery while application of cytidine pluscholine improves functional recovery by potentializing axonal regenerationwhen given in day 1 and 3 (p<0.05). In Conclusion presence of cytidine andcholine in the miliev seems to be necessary for the prevention of scarformation and also for molecular mechanism after primary sutureanastomosis of sectioned peripheral nerves.Key Words: Peripheral nerve, citicoline, choline, cytidineiv

Abstract:
SUMMARYSERUM VASCULAR ENDOTHELIAL GROWTH FACTOR LEVELS INPATİENTS WİTH PRİMARY LUNG CANCER and CORRELATİONBETWEEN SERUM VEGF LEVELS and SERUM NEURON-SPECİFİCENOLASE CYFRA21-1 CARCİNOEMBRYONİC ANTİGEN CA125 andLACTATE DEHYDROGENASELung cancer is the most common cancer and the leading cause ofcancer mortality worlwide. The prognosis for the majority of patients remainspoor. Despite therapeutic efforts, fewer than 10 per cent of patients can becured and enjoy long-term survival. Current studies have focused on patientprognosis by identifying biologic markers and moleculer-targeted therapies.After solid tumors reach a volume of 1-2 mm3, their further outgrowthis strictly dependent on angiogenesis. Angiogenesis plays an important rolein the growth, progresion and metastasis of solid tumors. Angiogenesis isformation of new blood vessels from the pre-existing vascular bed. Amongangiogenic factors, vascular endothelial growth factor (VEGF) is know to be apowerful endothelial cell-spesific mitogen involved in tumorneovascularization. VEGF plays a key role in the development ofneovascularization.In the present study, to assess the clinical significance of VEGF inpatients with lung cancer.Malign group consisted of forty patients, control group consisted oftwenty five patients. Using a ELİSA method, the concentration of VEGF wasmeasured in serum spesimens. Serum levels of neuron-specific enolase(NSE), CYFRA21-1, carcinoembryonic antigen (CEA) ve CA125 wereevaluted by chemiluminescent analysis, serum levels of lactateivdehydrogenase (LDH) were evaluted by enzymatic spectrophotometricanalysis in malign group.In malign group, we found higher serum VEGF levels compared to thecontrols group and these high levels were shown to be statistically significant.There were no associations between serum levels and gender, histologicaltypes, stage and distant metastasis. The cut-off level was 249.8 pg/ml. Thesensitivity and specificity using this threshold were %70 and %76 in patientswith lung cancer. There were no correlation between serum VEGF levels andserum NSE, CYFRA21-1, CEA, CA125 and LDH levels.Conclusion; the study showed that serum concentration of VEGF wasinsreased in lung cancer. VEGF seems to play a key role in angiogenesis.Thus, inhibition of VEGF offers an especially attractive target forantiangiogenic therapy in lung cancer.Key Words: Angiogenesis, VEGF, lung cancer.v