[Show abstract][Hide abstract] ABSTRACT: Citicoline has been shown to have beneficial effects in a variety of CNS injury models. The aim of this study was to test the effects of citicoline on nerve regeneration and scarring in a rat model of peripheral nerve surgery.
Seventy adult Sprague-Dawley rats underwent a surgical procedure involving right sciatic nerve section and epineural suturing. Rats were assigned to the control or experiment groups to receive a topical application of 0.4 mL of saline or 0.4 mL (100 micromol/L) of citicoline, respectively. Macroscopic, histological, functional, and electromyographic assessments of nerves were performed 4 to 12 weeks after surgery.
In the control versus citicoline-treated rats, SFI was -90 +/- 1 versus -84 +/- 1 (P < .001), -76 +/- 4 versus -61 +/- 3 (P < .001), and -66 +/- 2 versus -46 +/- 3 (P < .001) at 4, 8, and 12 weeks after surgery, respectively. At 12 weeks after surgery, axon count and diameter were 16400 +/- 600 number/mm(2) and 5.47 +/- 0.25 microm versus 22250 +/- 660 number/mm(2) (P < .001) and 6.65 +/- 0.28 microm (P < .01) in the control and citicoline-treated groups, respectively. In citicoline-treated rats, histomorphological axonal organization score at the repair site was (3.4 +/- 0.1) significantly better than that in controls (2.6 +/- 0.3) (P < .001). Peripheral nerve regeneration evaluated by EMG at 12 weeks after surgery showed significantly better results in the citicoline group (P < .05). Nerves treated with citicoline demonstrated reduced scarring at the repair site (P < .001).
Our results demonstrate that citicoline promotes regeneration of peripheral nerves subjected to immediate section suturing type surgery and reduces postoperative scarring.
Full-text · Article · Dec 2007 · Surgical Neurology
[Show abstract][Hide abstract] ABSTRACT: Gastrointestinal stromal tumors (GIST) are mesenchymal tumors originating from the gastrointestinal canal wall. Although a number of studies are performed concerning prognostic factors, no indicators of recurrence or metastasis could be established. In this study we assessed the prognostic value of MIB-1 proliferative index (PI) in GIST, and whether there was a relationship to any other clinicopathological findings.
In the study 37 patients with GIST diagnosis were included. The cases were classified as low, intermediate, and high risk groups according to tumor size and mitotic activity. The average PI of 10% in high risk group was set as the cut-off value.
Of all the cases, those with a MIB-1 PI over the cut-off value had a significantly shorter survival (Log-rank test, p < 0.05). Likewise cases with small bowel tumors with a MIB-1 PI over the cut-off value had a significantly shorter survival (Log-rank test, p < 0.05). A statistically significant negative correlation was found between presence of necrosis and survival using McPearson correlation test (p < 0.01).
MIB-1 PI and presence of necrosis are possible indicators of prognosis especially in GIST cases of the small bowel.
No preview · Article · Apr 2007 · Hepato-gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Studies performed recently have determined that aldosterone has not only a major role in electrolyte and water balance and K excretion, but it also modulates myofibroblast growth in the heart and blood vessels and causes fibrosis. This study investigated the effects of aldosterone blockers in rats with anti-thy 1.1 nephritis, both on proliferation and fibrosis, by comparing it to an angiotensin receptor inhibitor valsartan. Rats with anti-thy 1.1 nephritis were randomly allocated to one of the three following groups of treatment: the control group (group 1); those treated with the aldosterone receptor blocker spironolactone (group 2); and those treated with the ATRB valsartan (group 3). On day 7, the parameters of glomerular fibrosis [transforming growth factor beta, TGF staining areas %], proliferation (Ki-67), and renal damage scores were determined. The TGF-beta and Ki-67 levels of control group were significantly more than the other two groups (p<0.01). The TGF staining areas percentages were significantly decreased compared to control group. The artery, glomerular, and renal injury scores evaluated between the groups were found to be significantly decreased compared to control group. In line with previous studies, this study found that in anti-thy 1.1 mesangioproliferative glomerulonephritis, aldosterone blockage affected proliferation and fibrosis.
[Show abstract][Hide abstract] ABSTRACT: The aim of this experimental study was to evaluate the effects of end-to-side coaptation of the proximal end of a severed nerve to the same intact nerve, in addition to traditional end-to-side coaptation of the distal end, with an aim to use the intact nerve as a nerve conduit in a rat model and to compare the functional and histologic results of this modality to those obtained after nerve grafting and traditional end-to-side nerve coaptation. In group A, a peroneal nerve defect measuring 1 cm was created in the left hind limb, and a nerve graft 1 cm long was used to bridge the defect. In group B, only the distal stump of the peroneal nerve was coapted to the intact tibial nerve. In group C, both ends of the peroneal nerve defect were coapted to the intact tibial nerve in an end-to-side fashion 1.5 cm apart from each other, and in group D, the peroneal nerve defect was left unrepaired. Group E was consisted of nonoperated peroneal nerves that were used to obtain normative data. Although significantly higher myelinated axon densities were observed in groups B and C compared with group A and group E, total number of the myelinated axons was significantly higher only in group C. Peroneal functional index assessments demonstrated that nerve recovery in the peroneal nerve was similar in groups A and C, and both were better than those observed in groups B and D. Collectively, these results suggest that end-to-side coaptation of both ends of a severed nerve to an intact nerve, in case of a nerve defect in this length, may serve as an alternative for nerve grafting.
No preview · Article · Oct 2005 · Annals of Plastic Surgery
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to analyze 37 patients with malignant primary gastrointestinal stromal tumors and to compare the findings and their therapeutic implications with those previously reported. The medical records of 37 patients who were diagnosed and operated on between January 1996 and December 2002 were retrospectively reviewed. The patients' age, tumor size, type of surgery, histologic type, mitotic counts, presence of necrosis, Ki-67 proliferative index, National Institutes of Health 2001 consensus classification, immunohistochemical staining, and recurrence were examined to analyze factors affecting survival. Overall actuarial survival for all patients was 46%. When analyzed by type of resection, the complete resection group (R0 resection) had a mean overall survival of 48.2 +/- 6.18 months compared with the patients with incomplete resection (R1-R2) who survived a mean of 10.8 +/- 3.2 months (P=0.00). Univariate analysis showed development of recurrence (P=0.00), tumor size of 8 cm or greater (P=0.05), Ki-67 proliferative index greater than 0.82 (P=0.0448), desmin staining (P=0.0076), age younger than 49 years (P=0.0009), and incomplete resection (P=0.00) to be significantly correlated with a poor survival. In multivariate analysis, desmin staining (P=0.031), tumor size (P=0.033), age (P=0.01), recurrence (P=0.038), and R0 resection (P=0.02) were significant independent prognostic factors. We recommend that more careful preoperative and more frequent postoperative follow-up examinations be performed for patients with large tumors, age of younger than 49 years, and Ki-67 proliferative index greater than 0.82.
No preview · Article · Apr 2005 · Journal of Gastrointestinal Surgery
[Show abstract][Hide abstract] ABSTRACT: Methods
We investigated cyclin D1 expression in proliferative endometrium, endometrial hyperplasia and endometrioid adenocarcinoma, and examined the correlation of cyclin D1 expression with Ki67 as a cell proliferation associated marker. Immunohistochemical expression of cyclin D1 and Ki67 were studied in 30 cases with endometrial carcinoma, 14 cases with atypical hyperplasia, 15 cases with simple hyperplasia and 30 cases with proliferative endometrium.
One out of 30 patients (3.3%) with proliferative endometrium, 1 out of 14 patients (7.1%) with atypical hyperplasia, and 8 out of 30 patients (26.6%) with endometrial carcinoma were found to have immunoreactivity to cyclin D1. All cases of simple hyperplasia had negative staining for cyclin D1. A positive immunoreaction for Ki67 was obtained in all cases. Statistically significant difference was found in cyclin D1 immunoreactivity between both proliferative endometrium and adenocarcinoma, and simple hyperplasia and adenocarcinoma (p<0.05). In patients with adenocarcinoma, cyclin D1 immunoreactive cases had higher mean Ki67 values compared with the non-immunoreactive ones (p<0.05). Ki67 and cyclin D1 immunoreactivity had no impact on overall survival. Univariate analysis revealed a significant relationship between survival and grade and stage (p<0.01). Cyclin D1 expression was not correlated with age, depth of myometrial invasion, lymphovascular space involvement, grade, lymph node metastasis and stage.
Cyclin D1 expression in endometrial carcinoma is higher than proliferative endometrium and simple hyperplasia. These findings support that cyclin D1 may play a role in endometrial carcinogenesis.
No preview · Article · Jan 2005 · Archives of Gynecology and Obstetrics
[Show abstract][Hide abstract] ABSTRACT: After the chondrogenic potential of free grafts of perichondrium was shown in several experimental studies, perichondrium has been used to reconstruct cartilage tissue in various clinical situations. This study investigates the effects of human amniotic fluid on neochondrogenesis from free perichondrial grafts in a rabbit model. Since this fluid contains high concentrations of hyaluronic acid, hyaluronic acid-stimulating activator, growth factors, and extracellular matrix precursors during the second trimester, it may have a stimulating effect on neochondrogenesis. Perichondrial grafts, measuring 20 x 20 mm2 were obtained from the ears of 144 New Zealand young rabbits and were sutured over the paravertebral muscles. The rabbits were randomly divided into three groups with 48 rabbits per group. In group 1, 0.3 ml human amniotic fluid, and in group 2, 0.3 ml saline were injected underneath the perichondrial grafts. Group 3 formed the control group in which no treatment was given. Histologically, neochondrogenesis was evaluated in terms of cellular form and graft thickness at 2, 4, 6, and 8 weeks after surgery. In group 1, the mature cartilage was generated quickly and the cartilage plate in this group was significantly thick and extensive when compared with groups 2 and 3 at 8 weeks ( p<0.05 ANOVA). In conclusion, our study shows that human amniotic fluid enhances neochondrogenesis from free perichondrial grafts. The rich content of hyaluronic acid and growth factors possibly participate in this result.
No preview · Article · Aug 2004 · British Journal of Plastic Surgery
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to investigate the effects of combined application of human amniotic membrane wrapping and hyaluronic acid injection on peripheral nerve scarring in an adult rat model. After circumferential epineurectomies of right sciatic nerves were performed in each of 72 rats, nerves were randomly divided into three groups: (1) nothing was done additional to epineurectomy; (2) the epineurectomized segment was wrapped with human amniotic membrane; and (3) the epineurectomized segment was wrapped with human amniotic membrane and hyaluronic acid was injected inside. The extent of adhesions and perineurial scar thickness was macroscopically and histologically evaluated at 4 and 12 weeks. The least adhesion and perineurial scar tissue were observed in nerves treated with human amniotic membrane wrapping and hyaluronic acid injection. This combination appears to be safe and effective in preventing perineurial scar formation after peripheral nerve surgery in rats.
No preview · Article · Mar 2004 · Journal of Reconstructive Microsurgery
[Show abstract][Hide abstract] ABSTRACT: A thirty-seven-year-old male patient presented with dysphagia and hoarseness six months after complete remission of acute myeloid leukemia (AML-M0), which had been treated with chemotherapy. Physical examination revealed left vocal cord paralysis and involvement of the 9th, 10th, and 12th cranial nerves. Sagittal and axial magnetic resonance scans of the nasopharynx and neck showed a mass in the left retropharyngeal and perivertebral regions, 6x4 cm in size; another mass in the left vallecula, and infiltration of the right preepiglottic tissue by another mass of 2 cm. There was no bone marrow involvement. A diagnosis of granulocytic sarcoma without leukemia relapse was made and the FLAG-Ida regimen was administered, after which partial regression of the masses was observed. However, the patient died due to a pulmonary infection on the 17th day of chemotherapy.
No preview · Article · Jan 2004 · Kulak burun bogaz ihtisas dergisi: KBB = Journal of ear, nose, and throat
[Show abstract][Hide abstract] ABSTRACT: A 76-year-old woman underwent surgery for pelvic mass, during which a 13 x 8-cm right ovarian tumor was discovered. On histopathological examination, she was diagnosed with an endodermal sinus tumor with right tubal metastasis. The patient was treated with four cycles of Bleomycin, Etoposide and Cisplatin. She died of disseminated disease four years later.
No preview · Article · Nov 2003 · Journal of Obstetrics and Gynaecology Research
[Show abstract][Hide abstract] ABSTRACT: New cartilage formation originated from perichondrium has previously been researched in many clinical and experimental studies. 1-6 After these studies, the use of perichondrium for the repair of cartilage defects has been used clinically when enhancing neochondrogenesis has been found to be of great value in decreasing the recovery period. Collagen is the major protein of whole connective tissue, and in vitro positive effects of collagen matrices on neochondrogenesis have also been studied before. 7-9 In this experimental study, in vivo effects of heterologous collagen sponge in perichondrial neochondrogenesis were examined in an animal model, and acceleration and enhancement effects were observed.
Full-text · Article · Jun 2003 · Annals of Plastic Surgery
[Show abstract][Hide abstract] ABSTRACT: Peripheral nerve repair surgery is still replete with challenges. Despite technical improvements in microsurgery, classic methods of nerve repair have failed to provide satisfactory results. The purpose of this study was to investigate the effects of amniotic fluid from humans on peripheral nerve scarring and regeneration in rats.
Forty adult Sprague-Dawley rats were used in this study. After the right sciatic nerve in each rat was transected and repaired using an epineural suture procedure, the nerves were divided into two groups according to the solution applied around the repair site: experimental group, 0.3 ml human amniotic fluid (HAF); and control group, 0.3 ml saline. Macroscopic and histological evaluations of peripheral nerve scarring were performed 4 weeks postsurgery. Nerves treated with HAF demonstrated a significant reduction in the amount of scar tissue surrounding the repair site (p < 0.05). No evidence of a reaction against HAF was noted. Functional nerve regeneration was measured once every 2 weeks by using a sciatic function index until 12 weeks postsurgery. Functional recovery in nerves treated with amniotic fluid occurred significantly faster than that in nerves treated with saline (p < 0.05). Peripheral nerve regeneration was evaluated histomorphologically at 12 weeks postsurgery. Nerves treated with amniotic fluid showed significant improvement with respect to the indices of fiber maturation (p < 0.05).
Preliminary data show that HAF enhances peripheral nerve regeneration. The preventive effect of HAF on epineural scarring and the rich content of neurotrophic and neurite-promoting factors possibly contribute to this result.
No preview · Article · Feb 2003 · Journal of Neurosurgery