Evaluation of the effectiveness of oxytocin and enalapril in the prevention of epidural fibrosis after laminectomy in rats

Omurgaya yönelik uygulanan cerrahi girişimler sonrası epidural fibrozis gelişebilmekte ve bu fibrotik doku ameliyat sonrası yineleyen ağrı, yeni gelişen darlık ve bası bulgularına yol açabilmekte hem de yeniden yapılması gereken cerrahi girişimlerin riskini arttırabilmektedir. Bugüne kadar metilprednizolon dışında epidural fibrozisi engellemeye yönelik maliyet düzeyi ve yan etki profili düşük ve yaygın kullanıma uygun olabilecek bir ilaç/bariyer/yöntem tarif edilememiştir. Ancak son zamanlarda metilprednizolonun yara iyileşmesinde çok ciddi yan etkilere sahip olduğu bildirilmeye başlanmıştır. Bu deneysel çalışmada fibrozis ve yara iyileşmesi üzerine olumlu etkileri gösterilmiş olan oksitosinin ve enalapril maleatın ratlarda oluşturulan laminektomi modelinde epidural fibrozis üzerine olası tedavi edici etkileri incelendi ve bu etkiler metilprednizolon ile karşılaştırıldı. Çalışma 300-350 gram ağırlığında ve erkek cinsiyette 32 adet Wistar Albino rat üzerinden yapıldı ve denekler aşağıdaki gruplara ayrıldı: ? SHAM grubu (sadece cerrahi girişim uygulandı; n=6+2) ? MP grubu (cerrahi girişim uygulandı ve intraperitoneal 10mg/kg/gün dozda metilprednizolon sodyum süksinat 14 gün süreyle uygulandı; n=6+2) ? ELP grubu (cerrahi girişim uygulandı ve intraperitoneal 0.75mg/kg/gün dozda enalapril maleat 14 gün süreyle uygulandı; n=6+2) ? OXT grubu (cerrahi girişim uygulandı ve intraperitoneal160µg/kg/gün dozunda oksitosin 14 gün süreyle verildi; n=6+2) Deneklere sedasyon anestezi altında T9-T10-T11 omurlarına standart laminektomi yapıldı ve ilgili gruplara ilgili farmakolojik ajanlar belirlenen dozlarda ve sürede uygulandı. Gruplarda ölen deneklerin yerine yedekte tutulan denekler yerleştirildi. Altı haftanın sonunda tüm deneklere (toplam 24 rat) sedasyon anestezi altında ötenazi uygulandı ve omurgaları blok halinde çıkarılıp laminektomi alanının ortasından iki kısma bölündü. Proksimal omurga parçası histopatolojik incelemeler için ve distal parçası biyokimyasal incelemeler için kullanıldı. Histopatolojik incelemelerde epidural fibrozisin SHAM grubunda en fazla ve MP, ELP ve OXT gruplarında ise en az düzeylerde olduğu görüldü. Ayrıca Masson-Trikrom boyama sonrası yara yerinde kollajen oluşum düzeylerinin SHAM grubunda en fazla ve diğer gruplarda en az ve benzer düzeyde olduğu saptandı. İmmünohistokimyasal incelemelerde kollajen tip 1 immün reaktivitesinin SHAM grubunda en fazla ve MP, ELP ve OXT gruplarında en az ve birbirlerine benzer olduğu gözlendi. ACTA2 immün reaktivitesinin SHAM ve OXT grubunda en fazla ve MP ve ELP gruplarında en az olduğu bulundu. ELISA analizleri sonunda TNF-?, TGF-?, IL-6 ve CTGF doku düzeylerinin SHAM grubunda en fazla ve MP, ELP ve OXT gruplarında en az olduğu saptandı. İlaveten GSH/GSSG düzeylerinin SHAM grubunda en düşük ve diğer üç grupta en yüksek olduğu görüldü. Ayrıca Kaspaz-3 düzeylerinin SHAM grubunda en yüksek ve sırasıyla OXT, ELP ve MP gruplarında en düşük olduğu bulundu. Western blot analizleri sonunda pAMPK düzeyinin ve mTOR/p-mTOR oranının SHAM grubunda en düşük ve sırası ile MP, ELP ve OXT gruplarında en yüksek olduğu görüldü. Bu sonuçlarla metilprednizolonun olumsuz etkileri göz önünde bulundurulduğunda hem enalapril maleatın hem de oksitosinin epidural fibrozis oluşumunu azaltmada/engellemede etkili olabileceği ve herhangi bir olumsuz yan etkiye sahip olmadığı için tercih edilebilecekleri sonucuna varıldı. Ayrıca her ne kadar enalapril maleat oksitosine göre daha güçlü antienflamatuar, antioksidan, antiapoptotik ve otofaji ile ilişkili olarak daha güçlü rejeneratif etkinliğe sahip olsa da oksitosinin moral üzerine olan olumlu etkileri nedeni ile hipertansiyonu olmayan hastalarda tercih edilebileceği düşünüldü. Ancak hipertansiyonu olan ve enalapril kullanım kontrendikasyonu bulunmayan hastalarda enalapril maleatın öncelikle tercih edilebileceği savunuldu.Epidural fibrosis that may develop after surgical interventions can cause recurrent pain, new stenosis, and neural compression findings after surgery, and increase the risk of surgical interventions that need to be performed again. To date, no drug/barrier/method has been described, other than methylprednisolone, to prevent epidural fibrosis with a low-cost level and side-effect profile and suitable for widespread use. However, it has been reported that methylprednisolone has serious side effects on wound healing. In this study, the possible therapeutic effects of oxytocin and enalapril maleate on epidural fibrosis in the laminectomy model in rats were examined and these effects were compared with methylprednisolone. Thirty-two male Wistar Albino rats weighing 300-350 grams were divided into the following groups: - SHAM group (surgical intervention was performed; n=6+2) - MP group (surgical intervention was performed and methylprednisolone succinate at a dose of 10mg/kg/day was administered intraperitoneally for 14 days; n=6+2) - ELP group (surgical intervention was performed and 0.75mg/kg/day enalapril maleate was administered intraperitoneally for 14 days; n=6+2) - OXT group (surgical intervention was performed and 160µg/kg/day oxytocin was administered intraperitoneally for 14 days; n=6+2) Under sedation anesthesia, standard laminectomy was performed on T9-T10-T11 segments of the subjects, and pharmacological agents were administered to the relevant groups at the determined doses and time. Subjects who were kept in reserve were placed in the place of the subjects who died in the groups. Six weeks later, all subjects (24 rats) were euthanized under sedation anesthesia. The proximal part of the laminectomized spine sections was used for histopathological examinations and the distal part for biochemical analyses. Histopathological examinations revealed that epidural fibrosis and collagen formation levels were higher in the SHAM group, and lower in the MP, ELP, and OXT groups. Immunohistochemical examinations showed that collagen type 1 immunoreactivity was higher in the SHAM group and lower and similar in the MP, ELP, and OXT groups. ACTA2 immunoreactivity was higher in the SHAM and OXT groups and the lower in MP and ELP groups. The ELISA results showed that TNF-?, TGF1?, IL-6, CTGF, GSH/GSSG and Caspase-3 tissue levels were higher in the SHAM group and lower in the MP, ELP, and OXT groups, respectively. The western blot analysis determined that pAMPK tisue levels and mTOR/p-mTOR values were lower in the SHAM group and higher in MP, ELP and OXT groups, respectively. Considering these results and the negative effects of methylprednisolone, it was concluded that both enalapril maleate and oxytocin can be effective in reducing/preventing epidural fibrosis formation and they can be preferred because they do not have any side effects. In addition, although enalapril maleate has stronger antiinflammatory, antioxidant, antiapoptotic, and autophagy-associated regenerative activities than oxytocin, it was thought that oxytocin could be preferred in patients without hypertension due to its positive effects on cognition and morale. However, it was argued that enalapril maleate could be preferred primarily in patients with hypertension and no contraindications for enalapril maleate use

Possible predictive markers in surgical decision making in patients with degenerative or isthmic lumbar spondylolisthesis

Background: Although age, comorbidity, duration and severity of symptoms, slippage degree, and flexion-extension slipping stability during X-ray imaging are effective in making a surgical decision in patients with spondylolisthesis, these factors are rarely based on definitive evidence. The aim of this study was to determine the efficacy of clinical, radiological and biochemical findings in surgical decision making in these patients. Materials and Methods: Patients’ data including age, gender, degree and type (i.e. degenerative or isthmic) of the spondylolisthesis, urinary incontinence, neurogenic claudication were recorded. Radiological imaging studies (lumbar dynamic X-ray, computed tomography, magnetic resonance imaging), serum glucose, C-reactive protein and erythrocyte sedimentation rate values of the patients obtained during hospital admissions were evaluated. Results: Forty patients were followed conservatively and 12 patients were treated surgically. Degenerative spondylolisthesis was seen in 22 patients. Nine patients had neurogenic urinary incontinence and 19 patients had neurogenic claudication. When the patients were divided into two groups with and without surgical treatment, the presence of the pars defect, slipping distance in a neutral position and slipping distance in flexion position was significantly different between groups. A positive correlation was found between pars defect and surgical treatment. Likelihood ratio test results revealed that the presence of pars defect, neurogenic claudication and neurogenic urinary incontinence could be the best parameters in decision making the surgical treatment. Conclusion: The presence of pars defect, neurogenic claudication and urinary incontinence could be the best parameters that may help the surgeon to make the surgical treatment decision

Analysis of biochemical laboratory values to determine etiology and prognosis in patients with subarachnoid hemorrhage: a clinical study

KISA, Ucler/0000-0002-8131-6810; BAKAR, BULENT/0000-0002-6236-7647WOS: 000459561000008PubMed: 30417744Objectives: The aim of this study was to establish prognostic and predictive markers in patients with subarachnoid hemorrhage (SAH) using simple laboratory methods. Methods: A retrospective examination was made of patients with SAH diagnosed secondary to isolated head trauma, isolated anterior communicating artery aneurysm rupture, and angiography-negative SAH. Age, gender, Glasgow Coma Scale (GCS) scores, and Fisher's grade scores, Glasgow Outcome Scale (GOS) scores, leukocyte count, neutrophil count, lymphocyte count, platelet count, neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio results (PLR) were evaluated. Results: NLR and PLR values, which were similar in patients with spontaneous SAH, were significantly high in patients with traumatic SAH. NLR and PLR values could be 80% sensitive and 75% specific for distinguishing traumatic SAH from spontaneous SAH. Eosinophil count was lower in patients with angiography-negative SAH and patients with aneurysmal SAH than in patients with traumatic SAH. Initially measured GCS score, Fisher's grade score, eosinophil, neutrophil and lymphocyte counts could be prognostic in all patients with SAH. Moreover, it was concluded that the initially measured number of eosinophils might be directly related to patient prognosis. The eosinophil count was generally found to be high in traumatic SAM patients and it was observed that this parameter could be predictive for these patients. Lymphocyte count and NLR values could be prognostic markers in patients with angiography-negative SAH. Conclusion: NLR, PLR and eosinophil count values could be predictive for etiological factors (traumatic SAH or spontaneous SAH) of patients who were admitted unconscious to the emergency room with SAH detected on radiological imaging

Analysis of radiological measurement parameters that can predict the type of treatment to be applied in odontoid fractures: Clinical research

Introduction: Although various conservative and surgical treatment methods have been proposed, treatment options for patients with odontoid fractures remain controversial. This study was conducted to determine some demographic and radiological measurement parameters that can predict treatment options in patients with odontoid fractures. Materials and Methods: The patients were separated into the surgery (−) group (n = 9) and the surgery (+) group (n = 10). Patient data were recorded of age, gender, type of odontoid fracture, morphological measurement results obtained from computed tomography images, treatment regimens, duration of stay in the hospital, and mortality rate. In the operating room, a halo-vest corset or Philadelphia-type cervical collar was applied to the surgery (−) patients after the reduction of the fracture under fluoroscopy. Anterior odontoid lag screw fixation was performed on surgery (+) patients. Results: The amount of displacement of the fractured odontoid, the distance between the C1 vertebra and the odontoid process, the angle between the posterior wall of the odontoid process and the posterior wall of the clivus, the slip angle, and the anterior to posterior width of the spinal canal were not different between the groups. No difference was determined between the groups in respect of the amount of lateral displacement of the odontoid process in the spinal canal in the axial plane and the angle of the fractured odontoid process with the C2 vertebral body. Conclusion: This preliminary study showed that the demographic data and radiological measurement parameters analyzed in the present study could not be used as predictive markers either in decision-making for treatment modality or mortality risk