Melatonin and Selenium Suppress Docetaxel-Induced TRPV1 Activation, Neuropathic Pain and Oxidative Neurotoxicity in Mice.

Docetaxel (DT) has been reported to positive therapeutic actions in the treatment of glioblastoma, breast tumors, and prostate cancers. However, it can also induce peripheral neuropathic pain and neurotoxicity as adverse effects. Expression level of TRPV1 cation channel is high in dorsal root ganglion (DRG), and its activation via capsaicin and reactive oxygen species (ROS) mediates peripheral neuropathic pain in mice. As cancer is known to increase the levels of ROS, the protective roles of melatonin (MT) and selenium (Se) were evaluated on the TRPV1-mediated neurotoxicity and pain in the DT-treated mice. Mice and TRPV1 expressing SH-SY5Y cells were equally divided into control, MT, Se, DT, DT+MT, and DT+Se groups. In the results of pain tests in the mice, we observed a decrease in DT-mediated mechanical and heat neuropathic pain by MT and Se. The results of plate reader assay and laser confocal microscopy image analyses indicated a protective role of MT and Se on the DT-induced increase of mitochondrial ROS, cytosolic ROS, apoptosis, lipid peroxidation, intracellular free Zn2+, Ca2+, and caspase-3 and -9 levels in the DRG and SH-SY5Y cells. MT and Se modulated DT-induced decreases of total antioxidant status, reduced glutathione and glutathione peroxidase in the DRG. However, the effects of DT were not observed in the non-TRPV1 expressing SH-SY5Y cells. Hence, MT and Se mediated protective effects against DT-induced adverse peripheral oxidative neurotoxicity and peripheral pain. These effects may be attributed to potent antioxidant properties of MT and Se.

Solitary Plasmacytoma of the Frontal Bone.

Extramedullary plasmacytoma and solitary plasmacytoma are localized neoplasms. Solitary plasmacytoma of bone consists about 4% of malignant plasma cell tumors. A plasmacytoma involving the frontal bone is unusual, and a limited number of cases have been reported. We present a rare case of a solitary plasmacytoma of the frontal bone manifesting as a forehead lump.

Pregabalin reduces oxaliplatin-induced oxidative neurotoxicity through modulation of TRPV1 channels in DBTRG neuronal cell line.

As a member of the platinum drug group, oxaliplatin (OXAL) is used to treat brain tumors, although its use is limited through excessive calcium ion (Ca) influx and reactive oxygen species (ROS) production in neurons. The Ca permeable transient receptor potential vanilloid 1 (TRPV1) channel is activated by ROS, and its activity might be reduced by the antioxidant property of pregabalin (PREGAB). This study aimed to investigate the protective action of PREGAB against OXAL-induced oxidative neurotoxicity in human glioblastoma (DBTRG) cells. The DBTRG cells were divided into four treatment groups: control, PREGAB (500 µM for 1 h), OXAL (25 µM for 24 h), and PREGAB + OXAL. In the laser confocal microscope and plate reader analyses, apoptosis, mitochondrial membrane depolarization (JC-1), cell death (propidium iodide/Hoechst rate), and ROS-level production increased by activating TRPV1 in the cells using the OXAL treatment, although the cell viability values decreased. However, these values were recovered in the PREGAB + OXAL group using PREGAB and TRPV1 inhibitor (capsazepine) treatments. In the patch-clamp analyses, OXAL-induced TRPV1 channel activation in the OXAL group also decreased in the PREGAB + OXAL group using the PREGAB and capsazepine treatments. In conclusion, the apoptosis and oxidant actions of OXAL were increased by activation of the TRPV1 channel, but this effect was diminished by the PREGAB treatment. PREGAB treatment has the potential to be an effective strategy in the treatment of OXAL-induced oxidative neurotoxicity.

Does a Vertebra Fracture Cause a Tumor? A Dorsolumbar Paraspinal Desmoid Tumor: Case Report

Extraabdominal desmoid tumors are uncommon soft-tissue tumors. The etiology of the tumor is still unclear. Injury is one of the etiological factors of soft-tissue tumors. A 41-year-old female patient who had a traumatic vertebral body fracture on the thoracic spine was treated conservatively. Two and a half years later, she presented a painful, palpable swelling on the thoracolumbar region. In the present report, was discuss the patient, who underwent a surgery to remove the desmoid tumor (aggressive fibromatosis), within the context of the current literature. The literature on desmoid tumor caused by a trauma is rare. This is the first case that demonstrates an extraabdominal desmoid tumor following a spinal fracture. The swelling on the region of the trauma must be examined carefully and desmoid tumor must be kept in mind as a possible diagnosis.

The Correlation of Meralgia Paresthetica and Spinal Surgery in Prone Position.

AIM: To investigate the incidence, risk factors, and recovery of patients with meralgia paresthetica (MP) following posterior spine surgery. MATERIAL AND METHODS: Patients who underwent posterior spine surgeries in prone position at the authors’ clinics were included in this study. Patients with preoperative MP were excluded. RESULTS: Among the 560 patients who underwent spine surgery in prone position, 117 (21%) had impaired sensation along the anterolateral aspect of the thigh. One hundred three of them were treated with conservative treatment, whereas 14 underwent surgery for MP. CONCLUSION: Conservative treatment is the first option for MP. Patients who do not recover with conservative treatment may undergo surgical treatment.

Evaluation of the Neuroprotective Role of Boric Acid in Preventing Traumatic Brain Injury-Mediated Oxidative Stress.

AIM: Oxidative stress(OS) and lipid peroxidation(LP) occur in a cell due to irreversible damage resulting from incidents such as traumatic brain injury(TBI). The aim of our study was to investigate the possible neuroprotective effect of boric acid (BA) by examining the changes in catalase (CAT) activity and levels of CAT and malondialdehyde (MDA) in brain tissues from rats with closed head trauma. MATERIAL AND METHODS: The study consisted of three groups: control ,TBI and TBI + BA. Animals in the control and TBI groups received saline ,while animals in the TBI + BA group received BA through daily oral gavage, for 14 days prior to TBI was performed using the modified Marmarou impact acceleration model . After 24 hours,animals were euthanized and brain tissue obtained to measure the levels of MDA and to assess the activity of CAT. RESULTS: MDA levels and CAT activity were significantly higher in the TBI group versus the control group. However, they were significantly lower in the TBI + BA group compared to TBI alone. Similarly, edema and necrotic neurons were observed in the TBI group, but not in the control or TBI + BA groups. CONCLUSION: Based on biochemical and histopathological evidence, we determined that TBI induced LP and OS were inhibited by pre-treatment with BA.

Mitochondrial oxidative stress-induced brain and hippocampus apoptosis decrease through modulation of caspase activity, Ca2+ influx and inflammatory cytokine molecular pathways in the docetaxel-treated mice by melatonin and selenium treatments.

Docetaxel (DOCE) is widely used to treat several types of glioblastoma. Adverse effects DOCE seriously limit its clinical use in several tissues. Its side effects on brain cortex and hippocampus have not been clarified yet. Limited data indicated a protective effect of melatonin (MLT) and selenium (SELEN) on DOCE-induced apoptosis, Ca2+ influx and mitochondrial reactive oxygen species (ROS) in several tissues except brain and hippocampus. The purpose of this study is to discover the protective effect of MLT and SELEN on DOCE-induced brain and hippocampus oxidative toxicity in mice. MLT and SELEN pretreatments significantly ameliorated acute DOCE-induced mitochondrial ROS production in the hippocampus and brain tissues by reducing levels of lipid peroxidation, intracellular ROS production and mitochondrial membrane depolarization, while increasing levels of total antioxidant status, glutathione, glutathione peroxidase, MLT, α-tocopherol, γ-tocopherol, vitamin A, vitamin C and ß-carotene in the tissues. Furthermore, MLT and SELEN pretreatments increased cell viability and TRPM2 channel activation in the hippocampus and brain followed by decreased activations of TNF-α, IL-1ß, IL-6, and caspase -3 and - 9, suggesting a suppression of calcium ion influx, apoptosis and inflammation responses. However, modulator role of SELEN on the values in the tissues is more significant than in the MLT treatment. MLT and SELEN prevent DOCE-induced hippocampus and brain injury by inhibiting mitochondrial ROS and cellular apoptosis through regulating caspase -3 and - 9 activation signaling pathways. MLT and SELEN may serve as potential therapeutic targets against DOCE-induced toxicity in the hippocampus and brain.

Selenium Enhances the Apoptotic Efficacy of Docetaxel Through Activation of TRPM2 Channel in DBTRG Glioblastoma Cells.

The rate of mitosis of cancer cells is significantly higher than normal primary cells with increased metabolic needs, which in turn enhances the generation of reactive oxygen species (ROS) production. Higher ROS production is known to increase cancer cell dependence on ROS scavenging systems to counteract the increased ROS. Therapeutic options which selectively modulate the levels of intracellular ROS in cancers are likely candidates for drug discovery. Docetaxel (DTX) has demonstrated antitumor activity in preclinical and clinical studies. It is thought that DTX induces cell death through excessive ROS production and increased Ca2+ entry. The Ca2+ permeable TRPM2 channel is activated by ROS. Selenium (Se) has been previously used to stimulate apoptosis for the treatment of glioblastoma cells resistant to DTX. However, the potential mechanism(s) of the additive effect of DTX on TRPM2 channels in cancer cells remains unclear. The aim of this study was to evaluate the effect of combination therapy of DTX and Se on activation of TRPM2 in DBTRG glioblastoma cells. DBTRG cells were divided into four treatment groups: control, DTX (10 nM for 10 h), Se (1 µM for 10 h), and DTX+Se. Our study showed that apoptosis (Annexin V and propidium iodide), mitochondrial membrane depolarization (JC1), and ROS production levels were increased in DBTRG cells following treatment with Se and DTX respectively. Cell number and viability, and the levels of apoptosis, JC1, ROS, and [Ca2+]i, induced by DTX, were further increased following addition of Se. We also observed an additive increase in the activation of the NAD-dependent DNA repair enzyme poly (ADP-ribose) polymerase-1 (PARP-1) activity, which was accompanied by a decline in its essential substrate NAD+. As well, the Se- and DTX-induced increases in intracellular Ca2+ florescence intensity were decreased following treatment with the TRPM2 antagonist N-(p-amylcinnamoyl) anthranilic acid (ACA). Therefore, combination therapy with Se and DTX may represent an effective strategy for the treatment of glioblastoma cells and may be associated with TRPM2-mediated increases in oxidative stress and [Ca2+]i.

Surgical options for meralgia paresthetica: long-term outcomes in 13 cases.

BACKGROUND: Meralgia paresthetica is an entrapment neuropathy of the lateral femoral cutaneous nerve that may cause paresthesias, pain, and sensory loss of the anterior and lateral thigh. Treatment is primarily medical. Surgery is an option for patients who do not respond to medical treatments. METHODS: Patients whose symptoms did not improve after medical and conservative treatment for at least 3 months were included in this study. These patients underwent neurolysis and decompression surgery and had a mean postoperative follow-up of 38 months. Their pain levels were assessed by the VAS scoring system. RESULTS: In 8 (61.5%) patients, the symptoms completely resolved within the first 3 months. In 5 (38.5%) patients, the complaints persisted partially and the recovery was observed after 12 months. In patients having a metabolic etiology, the duration of recovery was up to 12 months. CONCLUSION: The long term results of surgery are good though only partial improvemnts in reported pain were seen in the early postoperative period, especially in patients with a metabolic etiology.

Bone Turnover in Vertebral Fractures: Does it Effect the Decision of Surgery?

BACKGROUND AND AIM: Instrumentation is commonly used in spinal surgery to stabilize the fracture. In the present study, we aimed to compare the early and late changes seen in bone production and degradation products in patients with traumatic spinal fracture who had been treated surgically or conservatively. MATERIALS AND METHODS: Forty-three patients were admitted to the Neurosurgery Department with thoracolumbar or lumbar fracture in this prospective study. Patients were divided into two groups of surgically treated (n = 23) and nonsurgically/conservatively treated (n = 20) patients. The early and late changes seen in bone production and degradation products were compared in patients with traumatic spinal fracture who had been treated surgically or conservatively. RESULTS: In conservatively treated patients, although osteocalcin level was slightly increased and deoxypiridinoline (DPD)/creatinine was slightly decreased after the treatment, the difference was not statistically significant (P = 0.08 and P = 0.539, respectively). There is no significant difference between admission time, posttreatment late period osteocalcin level, and DPD/creatinine ratio between the two group of patients (P = 0.215 and P = 0.236, respectively). CONCLUSION: We suggest that the healing and fusion processes in fractured vertebrae not only followed by the radiological examination but also by noninvasive biochemical changes seen in the serum levels of bone formation and resorption markers.