Comparison of histopathologic findings of initial and recurrent lumbar disc herniation.

OBJECTIVE: Recurrent lumbar disc hernia (RLDH) is a common and challenging complication after an initial discectomy. This study aimed to investigate the relationship between the histopathologic outcomes of the initial and recurrent disc tissues. METHODS: This study investigated 70 patients who underwent a microdiscectomy and subsequently developed same-level same-side lumbar disc herniation (LDH) recurrence. The clinic, western blot, and immunohistochemical evaluations of patients with initial LDH and RLDH were conducted and statistically analyzed. RESULTS: The effect of inflammation and apoptosis in the degenerative changes of intervertebral disc hernia and increased histopathologic findings in RLDH was demonstrated. The degeneration of the hernia disc tissue is a major pathological process, which is characterized by cellular apoptosis, inflammation, and reduced synthesis of extracellular matrix. Currently, there is no clinical therapy targeting the reversal of disc degeneration. CONCLUSIONS: This, therefore, stay away from factors that increase inflammation in the intervention of intervertebral disc hernia, applying to reduce inflammation the medicines, could allow reducing disc collagen degeneration, and more successful outcomes. These findings might shed some new lights on the mechanism of disc degeneration and provide new strategies for the treatments of initial and recurrent LDH.

Antitumor activity of irinotecan with ellagic acid in C6 glioma cells.

OBJECTIVE: Irinotecan-based combination chemotherapies in malignant gliomas need to be examined. The aim of this study was to investigate the synergetic effect of ellagic acid, a natural polyphenolic antioxidant compound, with irinotecan, an inhibitor of topoisomerase I enzyme, on the growth, cadherin switch, and angiogenic processes of a glioma cell line. METHODS: A combination of 100 µM ellagic acid and 100 µM irinotecan was applied to rat C6 glioma cells for 24th, 48th, and 72nd h. The cell proliferation was evaluated by 5-bromo-2'-deoxyuridine immunocytochemistry. The expression levels of vascular endothelial growth factor, E-cadherin, and N-cadherin were measured using real-time polymerase chain reaction and their immunoreactivities using immunocytochemistry. RESULTS: The treatment of irinotecan with combining ellagic acid enhanced antitumor activity and the synergistic effect of these reduced the cell proliferation of C6 glioma by inhibiting the cadherin switch and promoting the antiangiogenic processes. CONCLUSIONS: Further research is required to prove a negative relationship between C6 glial cell proliferation and irinotecan with ellagic acid application. Our preliminary data suggest that even with the extremely short-term application, irinotecan with ellagic acid may affect glioma cells at the level of gene and protein expression.

Antitumor activity of irinotecan with ellagic acid in C6 glioma cells

SUMMARY OBJECTIVE: Irinotecan-based combination chemotherapies in malignant gliomas need to be examined. The aim of this study was to investigate the synergetic effect of ellagic acid, a natural polyphenolic antioxidant compound, with irinotecan, an inhibitor of topoisomerase I enzyme, on the growth, cadherin switch, and angiogenic processes of a glioma cell line. METHODS: A combination of 100 μM ellagic acid and 100 μM irinotecan was applied to rat C6 glioma cells for 24th, 48th, and 72nd h. The cell proliferation was evaluated by 5-bromo-2′-deoxyuridine immunocytochemistry. The expression levels of vascular endothelial growth factor, E-cadherin, and N-cadherin were measured using real-time polymerase chain reaction and their immunoreactivities using immunocytochemistry. RESULTS: The treatment of irinotecan with combining ellagic acid enhanced antitumor activity and the synergistic effect of these reduced the cell proliferation of C6 glioma by inhibiting the cadherin switch and promoting the antiangiogenic processes. CONCLUSIONS: Further research is required to prove a negative relationship between C6 glial cell proliferation and irinotecan with ellagic acid application. Our preliminary data suggest that even with the extremely short-term application, irinotecan with ellagic acid may affect glioma cells at the level of gene and protein expression.

Assessment relationship between the femoral artery vasospasm and dorsal root ganglion cell degeneration in spinal subarachnoid hemorrhage: an experimental study.

STUDY DESIGN: Animal proof of principle study. OBJECTIVES: To investigate neurodegeneration in rabbit L4-dorsal root ganglion (DRG) cells by creating experimental spinal subarachnoid hemorrhage (SAH), we aimed to show the neuronal pathway between L4-DRG and femoral artery. SETTING: Ataturk University, Medical Faculty, Animal Laboratory, Erzurum, Turkey. METHODS: This study was designed on 20 rabbits, which were randomly divided into three groups: Spinal SAH (n = 8), SHAM (n = 6), and control (n = 6) groups. Animals were followed for 20 days and then killed. Vasospasm index values of the femoral artery and neuron density of L4-DRG were analyzed. RESULTS: The number of degenerated neurons in DRG was higher in the spinal SAH than the control and SHAM groups (p < 0.001). But, the difference between the control group and the SHAM group was not significant. Normal neuron densities were significantly lower in the spine SAH group compared to the SHAM and the control groups. There was a statistically significant increase in vasospasm index values of the spinal SAH group compared to the other two groups (p < 0.001). CONCLUSIONS: Decreased volume of the femoral artery lumen was showed in animals with spinal SAH compared with control and SHAM groups. Increased degeneration of the L4 dorsal root ganglion in animals with spinal SAH was also demonstrated. Our findings might shed light on the planning of future experimental studies and evaluating the clinical relevance of such studies.

Evaluation of the association between biochemical and immunohistochemical score of caspase-9 and TNFα, and the grading of lumbar disc herniation.

OBJECTIVE: The aim of our study is to investigate the influence of caspase-9 and tumour necrosis factor alpha (TNFα) in the grade of lumbar disc herniation. We determined the strength of different predictors such as age, gender, disc grading, caspase-9 and TNFα. METHODS: We retrospectively reviewed 84 patients who had discectomies. Histological and biochemical evaluations of disc specimens were performed. All patients were scanned by the magnetic resonance imaging (MRI) scanner before the operation. Masson's trichrome stain, biochemical analysis and immunohistochemical staining were performed to measure the expression levels of caspase-9 and TNFα. The results were evaluated statistically. RESULTS: This study included 84 patients (mean age: 41.59 ± 12.21 years; range: 19-76): 60 men (age 40.47 ± 12.63 years) and 24 women (44.42 ± 10.81 years). No statistically significant age difference was found between the genders (p = 0.182). MRI scans showed 16 patients had protrusion, 44 had extrusion and 24 had sequestration of discs. There was a statistically significant negative correlation between the grading of lumbar disc herniations and age (p < 0.001, r = -0.509). Histological and biochemical analyses of disc materials were done. Inflammation, collagen fibre deterioration, apoptotic process, TNFα and caspase-9 were seen to increase with increasing disc grading (p < 0.01). CONCLUSIONS: Biochemical and immunohistochemical score of caspase-9 and TNFα indicate the grading of lumbar disc herniation. As the grading of disc herniation increases, inflammation of cells and collagen fibre disruption increase and accelerate the apoptotic process. Apoptosis in disc nucleus pulposus cells may reduce disc herniation.

Pediatric Spinal Traumas.

INTRODUCTION: Although childhood trauma is a major cause of morbidity and mortality, the incidence of spinal trauma is significantly lower in children than in adults. Existing studies on pediatric spinal trauma (PST) largely concern cervical trauma because of its frequency of incidence. We aimed to obtain more information by examining all types of spinal trauma, and evaluating factors such as age, trauma type, injury type, and American Spinal Injury Association score and comparing them with data from the literature. METHODS: We retrospectively reviewed 30 pediatric trauma patients with spinal pathology confirmed by spinal imaging. RESULTS: The mean age was 166.4 months. Mean age for each mechanism of injury was: 142.7 months for a simple fall, 149.0 months for injury involving a foreign object, 163.5 months for a fall from a height, and 181.6 months for traffic accidents. There was no statistically significant difference in mean age for different mechanisms of injury (p = 0.372). The levels of the spinal injuries were: lumbar 53.3% (16), thoracic 26.6% (8), and cervical 20.0% (6). Mean age for each level of spinal injury was 113.3 months for the cervical area, 172.2 months for the thoracic area, and 183.3 months for the lumbar area. Mean age was found to be statistically significant (p = 0.000). DISCUSSION: PST is uncommon and the type of trauma and the spinal level affected varies with age. Cervical trauma predominates at younger ages, but adult-like traumas begin to occur with increasing age. It should be considered that the risk of developing neurological deficits is higher in pediatric patients than in adults, and the risk of multisystem injury is also high.

Ellagic Acid Enhances Antitumor Efficacy of Temozolomide in an in vitro Glioblastoma Model.

AIM: To observe the effect of combining ellagic acid (EA), a natural phenol present in fruits and vegetables, and temozolomide (TMZ) on the proliferation and expression profile of C6 glioma cell line. MATERIAL AND METHODS: Rat C6 glioma cells were treated with 100-?M EA combined with 100 ?M TMZ for 24, 48, and 72 hours (h). Cell proliferation and p53 and caspase-3 protein levels were evaluated using immunocytochemistry. Multi drug resistance 1 (MDR1), O6-methylguanine-DNA methyltransferase (MGMT), and apoptotic protein (caspase-3 and p53) expressions were assessed using reverse transcription polymerase chain reaction (RT-PCR). RESULTS: EA combined with TMZ conspicuously reduced the cell viability at all incubation times (p < 0.001). EA significantly downregulated MGMT expression regardless of the presence of TMZ even at early hours (p < 0.001). The combination therapy reduced MDR1 expression only on 48 h in comparison with TMZ alone. EA alone upregulated caspase-3 at 48 h but upregulated p53 at 48 and 72 h. The combined therapy enhanced the immunoreactivities of p53 and caspase-3 proteins independent of the treatment durations but not of the genes. CONCLUSION: EA combined with TMZ may have a potential antiproliferative efficacy by inhibiting MGMT expression and activating apoptotic protein, p53 and caspase-3, expression.

Ellagic Acid Enhances the Antitumor Efficacy of Bevacizumab in an In Vitro Glioblastoma Model.

BACKGROUND: The anticarcinogenic effect of ellagic acid (EA), a natural phenol of fruits and vegetables, has been investigated in several types of tumors. The combined effect of EA with bevacizumab (BEV), a common drug used in treatment of recurrent glioma, on glioblastoma has not been reported. This study observed the combined effect of EA with BEV on the expression profile of the C6 glioma cell line. METHODS: Rat C6 glioma cells were treated with EA at 100 µmol/L concentration in combination with BEV at 100 ng/mL concentration for 24, 48, and 72 hours. Cell proliferation was detected by 5-bromo-2'-deoxyuridine immunohistochemistry, and p53 and caspase-3 protein levels were determined by immunohistochemistry and assessed by the H-Score. Expression profiles for P-glycoprotein (MDR1), O6-methylguanine DNA methyltransferase (MGMT), caspase-3, and p53 related proteins were detected by reverse transcriptase polymerase chain reaction after EA treatment with or without BEV. RESULTS: EA combined with BEV conspicuously reduced the cell viability of C6 glioma cells for all incubation times. EA significantly downregulated expression of MGMT regardless of combination with BEV even in the early hours after treatment. Combined EA and BEV reduced MDR1 expression only at 72 hours. EA affected the apoptotic proteins of p53 and caspase-3 at protein level in a time-dependent manner, but not at gene level. CONCLUSIONS: This study suggests successful antiproliferative efficacy of EA combined with BEV, probably through inhibition of MGMT expression and time-dependent inhibition of MDR1. EA combined with BEV may be an alternative treatment for drug-resistant gliomas.

Combining Ellagic Acid with Temozolomide Mediates the Cadherin Switch and Angiogenesis in a Glioblastoma Model.

OBJECTIVE: We aimed to evaluate the combined effect of ellagic acid (EA) and temozolomide (TEM) on the cadherin switch and angiogenesis in the C6 glioma cell line. METHODS: A total of 100 µM EA and 100 µM TEM were applied to rat C6 glioma cells for 24, 48, and 72 hours. Cell proliferation was detected by 5-bromo-2'-deoxyuridine immunohistochemistry. The messenger RNA and protein levels of E-cadherin, N-cadherin, and vascular endothelial growth factor (VEGF) were determined by real-time polymerase chain reaction and their immunohistochemistry, respectively, subsequent to EA treatment combined with TEM. RESULTS: EA in combination with TEM conspicuously reduced the viability of C6 glioma cells at all incubation times (P < 0.001). EA upregulated the expression of E-cadherin at the gene and protein levels in a time-independent manner (P < 0.05 and P < 0.001, respectively). By the presence of TEM, the increase was exaggerated at 24-hour incubation (P < 0.01). Conversely, EA reduced N-cadherin expression and immunoreactivity in a time-independent manner (P < 0.05 and P < 0.001, respectively), and combination with TEM enhanced this effect at the 24th hour (P < 0.001). Combination also downregulated the gene expression (P < 0.001) and immunoreactivity of VEGF only at 72 hours (P < 0.001). CONCLUSIONS: A successful therapeutic efficacy of EA combined with TEM is suggested probably by inhibiting the cadherin switch and angiogenesis.

Evaluation of the Short- and Long-Term Effectiveness of Pulsed Radiofrequency and Conventional Radiofrequency Performed for Medial Branch Block in Patients with Lumbar Facet Joint Pain.

Background: Diagnosis of lumbar facet joint disease is the sum of the combinations consisting of history, physical activity, and diagnostic imaging frequently including computed tomography and magnetic resonance imaging scans. Prevalence of facet-based chronic low back pain is 15-45%. Intra-articular injections with corticosteroid or medial branch block are traditionally used prevalently in the management of chronic low back pain due to lumbar facet joints. However, the evidence levels of these procedures are at either a low or a medium level. Radiofrequency neurolysis of the lumbar medial branch can be used as an alternative in the management of lumbar facet joint pain. There are two types of radiofrequency applications for radiofrequency neurolysis as pulsed radiofrequency and conventional radiofrequency. Materials and Methods: Patients with lumbar facet pain were separated into 2 groups. Group 1 (n=75): patients were given pulsed radiofrequency under fluoroscopy. Group 2 (n=43): patients were given conventional radiofrequency under fluoroscopy. Pre-op and post-op 1st, 3rd, and 6th month and 1st and 2nd year Visual Analogue Scale values of all patients were asked, recorded, and statistically compared. Visual Analogue Scale values of the groups in the same months were compared as well. At the end of the second year, Odom criteria of both groups were recorded and statistically compared. Results: Preoperation Visual Analogue Scale values and postoperation 1st, 3rd, and 6th month and 1st and 2nd year Visual Analogue Scale values were compared in Group 1 and Group 2, and there was a statistically significant difference between preoperation Visual Analogue Scale values and postoperation 1st, 3rd, and 6th month and 1st and 2nd year Visual Analogue Scale values in both groups. However, the number of repetitions of the operation was higher in Group 1. In the comparison of Odom criteria for both groups at the end of the second year, it was observed that the patients in Group 2 were more satisfied with the treatment. Conclusion: Conventional radiofrequency in patients with lumbar facet joint pain for medial branch neurolysis effectively decreases Visual Analogue Scale values in both short and long term. The quality of life and daily activities of patients were better at conventional radiofrequency.

The effects of systemically administered methylprednisolone and recombinant human erythropoietin after acute spinal cord compressive injury in rats.

The study design was to decrease the damage of spinal cord on the experimentally induced acute spinal cord injury in rats. The objective of this study was to evaluate whether recombinant human erythropoietin (rHu-EPO) and methylprednisolone (MPSS) improve neurological function and histopathological changes if systemically administered after traumatic spinal cord injury. This study included 48 rats that underwent experimental SCI. Forty-eight animals were randomly divided into six groups. Animals constituted a moderate compression of 0.6 N that was produced by application of an aneurysm clip at level T3 for 1 min. rHu-EPO (1,000 and 3,000 U (Unit) per kg of body weight i.p.) and MPSS (30 mg/kg) were administered 5 min after injury, and control group was saline treated. (1) Control group (n=8), (2) MPSS group (n=8), (3) rHu-EPO 1,000 U group (n=8), (4) MPSS + rHu-EPO 1,000 U group (n=8), (5) rHu-EPO 3,000 U group (n=8), and (6) MPSS + rHu-EPO 3,000 U group (n=8). The neurological function and histopathology were evaluated at 24 and 72 h. According to the neurological functional test scores significant improvements between the control group and the other groups that had taken medical treatment were observed (P<0.001). Histopathologically severe ischemic findings were observed in the control group. A significant decrease in ischemic damage was detected in MPSS + rHu-EPO 3,000 U group (P<0.001). The most significant neurological functional and histopathological improvements were observed after systemical administration of MPSS + rHu-EPO 3,000 U and rHu-EPO 3,000 U. Furthermore, the MPSS + rHu-EPO 3,000 U group provides the most improved neurological functional and histopathological recovery.