Promising outcome of patients with recurrent glioblastoma after Gamma Knife-based hypofractionated radiotherapy.

BACKGROUND: The role of Gamma Knife radiosurgery (GKRS) in recurrent glioblastoma remains unclear. The purpose of this study is to evaluate the effects of GKRS in a group of patients with recurrent glioblastoma, focusing on survival and safety. METHODS: Patients undergoing GKRS for recurrent glioblastoma between September 2014 and April 2019 were included in this study. Relevant clinical and radiosurgical data, including GKRS-related complications, were recorded and analyzed. Overall survival (OS), local progression free survival (LPFS) and prognostic factors for outcome were thoroughly evaluated. RESULTS: Fifty-three patients were analyzed (24 female, 29 male). The median age was 50 years (range, 19-78 years). The median GKRS treatment volume was 35.01 cm3 (range, 2.38-115.57 cm3). Twenty patients (38%) were treated with single fraction GKRS, while 33 (62%) were treated with GKRS-based hypofractionated stereotactic radiotherapy (HSRT). The median prescription dose for single fraction GKRS, 3-fractions HSRT and 5-fractions HSRT were 16 Gy (range, 10-20 Gy), 27 Gy (range, 18-33 Gy) and 25 Gy (range, 25-30 Gy), respectively. The median LPFS and OS times were 8.1 months and 11.4 months after GKRS, respectively. HSRT and Bevacizumab were associated with improved LPFS, while HSRT alone was associated with longer OS. CONCLUSION: Our findings suggested that HRST would likely improve LPFS and OS in definite settings; the addition of Bevacizumab to GKRS was associated with increased rates of local control. No major complications were reported. Further prospective studies are warranted to confirm our findings.

An Investigation into the Relationship of SUR-1TRPM4 Receptor with Peritumoral Edema in High-Grade Glial Tumors.

AIM: To investigate the presence of Sur1-Trpm4 receptors in high-grade glial tumors, and their relationship with edema volumes in preoperative magnetic resonance imaging (MRI) sequences. MATERIAL AND METHODS: MRI sections were extracted from T1-weighted (T1W) and T2-weighted (T2W) sequences and fluidattenuated inversion recovery (FLAIR) images. After that, T1W 3D magnetization-prepared rapid gradient echo (MP-RAGE) sequences were taken with and without contrast medium. Tumor and peritumoral edema volumes were calculated in cubic centimeters. Sur1- Trpm4 receptors were studied by immunohistochemical examination of tissue samples. Relationships between data were analyzed using Spearman's correlation coefficient. RESULTS: In the immunohistochemical examinations, 58% of the samples from patients with high-grade glial tumors were positive for Sur1 and 74% were positive for Trpm4. The volume of tumors was correlated with the volume of peritumoral edema. CONCLUSION: The presence of the Sur1-Trpm4 receptor complex in high-grade glial tumors was confirmed. Further preclinical or clinical studies are required to identify and validate the role of Sur1-Trpm4 in glial tumor subgroups.

Investigation of the effect of carnitine on cerebral vasospasm in experimental subarachnoid hemorrhage model.

The vasospasm, which develops after subarachnoid hemorrhage (SAH), is an unenlightened table in terms of etiology and results. It is usually associated with decreased perfusion, which is associated with decreased blood flow distal to the affected artery and can be demonstrated radiologically. Acetyl-L-carnitine (ALCAR) can be found in brain tissue and easily crosses the blood-brain barrier. Therefore, in this study, we aimed to investigate the therapeutic efficacy of ALCAR, which is an effective antioxidant amine, on vasospasm development after experimental SAH. In our study, 35 adults male Wistar RATs weighing between 235-250 g were used. These RATs were divided into five groups with n = 7. Group 1 Control group, Group 2 SAH + SF (carrier solution), Group 3 SAH + ALCAR 50 mg\kg intraperitoneally, Group 4 SAH + ALCAR 100 mg\kg intraperitoneally and Group 5 SAH. Subarachnoid hemorrhage was induced by giving autologous arterial blood to the cisterna magna of the animals in groups 2, 3, 4, and 5. At 0.-12.- 24.- 36.- 48.- 60. and 72. h, Group 2 was injected with SF, Group 3 with intraperitoneally ALCAR 50 mg\kg, and Group 4 with intraperitoneally ALCAR 100 mg\kg, respectively. Following perfusion and fixation, the animals were subjected to a wide craniectomy, and the brain, cerebellum, and brain stems were removed globally. Then, sections were taken from the basilar arteries of all animals and photographed at 40X magnification. Basilar artery lumen cross-sectional areas, basilar artery areas, and wall thicknesses were measured from these sections. The basilar artery lumen cross-sectional area was found to be significantly larger in the groups in which SAH was formed and ALCAR 50 mg\kg and ALCAR 100 mg\kg were given compared to the group with only SAH and SAH + SF (p = 0.0408). Basilar artery wall thickness increased in all groups except the control group (p < 0.05). In light of all these findings, it was concluded in our study that Carnitine was effective in the resolution of vasospasm in the experimental SAH model.

Effects of Methylprednisolone in the Treatment of Spinal Cord Injuries by Evaluation of microRNA-21: An Experimental Study.

BACKGROUND AND STUDY AIMS: Spinal cord injury (SCI) is one of the most complicated pathologies that affect active young males. miR-21 primarily regulates several cellular processes. We aimed to elucidate the regulatory role of miR-21 and test methylprednisolone as a disease-modifying agent on experimental SCI tissues. METHODS: A total of 36 8- to 10-week-old adult female Sprague-Dawley rats weighing 250 to 300 g were used. Animals were randomly divided into six groups. Except for groups 1 and 4, the spinal trauma model was applied to all animal groups using the clipping method. In groups 3 and 6, methylprednisolone was given. For real-time polymerase chain reaction (PCR) investigations, rats in groups 1, 2, and 3 were reoperated on after the first postoperative day, whereas those in groups 4, 5, and 6 were reoperated on after postoperative day 7 and spinal cord samples from the laminectomy area were removed for gene expression analysis. Relative gene expression of miR-21, Gfap, Vim, Stat3, Faslg, Pten, Bax, Bcl2, Cox2, and Il6 were determined with quantitative reverse transcription (qRT) PCR. RESULTS: In group 3, the miR-21 expression significantly increased compared with groups 1 and 2. When compared with group 3, a decrease in miR-21 expression was observed in group 6 (p < 0.05). When compared with group 4, group 6 had lower levels of Gfap, Pten, Stat3, and Bax (p < 0.05). CONCLUSIONS: miR-21 supports the beneficial aspects of the body's healing mechanisms following SCI. In the acute phase, the use of methylprednisolone increases miR-21 expression in the early period of trauma. Methylprednisolone increases some astrogliosis and inflammation biomarkers' levels; however, it did not affect the apoptotic biomarkers.

Secukinumab Ameliorates Oxidative Damage Induced by Cerebral Ischemia-Reperfusion in Rats.

AIM: To investigate the histological and biochemical neuroprotective effects of secukinumab (SEC) on cerebral ischemia-reperfusion (IR) injury in Sprague-Dawley male rats. MATERIAL AND METHODS: A total of 28 Sprague-Dawley male rats were randomly and equally divided into the following four groups: Sham, SEC, IR, and IR+SEC groups. Bilateral common carotid arteries were simultaneously separated and blocked for 15 minutes using two vascular mini clips in the IR and IR+SEC groups. The surgical procedure was similarly repeated in the Sham and SEC groups, but the carotid arteries were not clipped. Secukinumab was administered intraperitoneally to the SEC and IR+SEC groups once a week after the surgical procedure. Rat brain tissues were collected for biochemical analysis and histopathological examination 14 days after surgery. RESULTS: Cerebral IR caused abnormal changes in oxidative stress parameters by increasing the malondialdehyde (MDA) level and by decreasing the glutathione (GSH), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) levels. IR also induced histopathological alterations, such as vascular congestion, hemorrhage, and cell infiltration in the rat brain tissues. Secukinumab treatment significantly decreased the MDA levels and increased the GPx, GSH, CAT, and SOD levels. In addition, secukinumab partially prevented histopathological alterations in the brain tissues. The percentage of immunohistochemically Caspase-3-positive cells was high in the IR group; however, SEC decreased the density of cells stained with Caspase-3. CONCLUSION: IR injury was found to cause oxidative and histopathological changes in rat brain tissues, and secukinumab treatment ameliorated these pathological effects. Therefore, secukinumab may be useful to prevent and treat oxidative stressinduced brain damage in patients with ischemic stroke.

What is the effectiveness of beta-glucan for treatment of acute otitis media? / Qual é a eficácia do beta-glucano no tratamento da otite média aguda?

Abstract Introduction: As a supplement, beta-glucan has various therapeutic healing effects generated by the immune cells. It has been scientifically approved and proven to be a biological defense modifier. The aim of this study was to investigate the effects of beta-glucan on treatments administered in an acute otitis media model Objectives: This study investigated the effect of beta-glucan on the treatment of acute otitis media in an acute otitis media -induced animal model. Efficacy was evaluated both immunologically and histologically. Methods: The study sample comprised 35 adult rats, randomly separated into 5 groups of 7: Group 1 (control), Group 2 (acute otitis media, no treatment), Group 3 (acute otitis media + antibiotic), Group 4 (acute otitis media + beta-glucan) and Group 5 (acute otitis media + beta-glucan + antibiotic). Analyses were made of the histopathology and immunology examination results in respect of thickening of the tympanic membrane, epithelium damage, inflammation, and sclerosis. In all groups the serum levels of TNF-α, IL-4, IL-6 and IL-1β were evaluated. Results: All serum cytokine levels were significantly lower in the beta-glucan and antibiotictreated groups compared to the acute otitis media Group. Significant differences in tympanic membrane thickness, inflammation, epithelium damage, and sclerosis values were observed between the acute otitis media + antibiotic and acute otitis media + beta-glucan Groups. According to these parameters, the values in aute otitis media + antibiotic + beta-glucan Group were markedly lower than those of the other groups. There was a significant difference in the acute otitis media + antibiotic + beta-glucan Groups compared to acute otitis media Group (p < 0.001). Conclusions: Both antibiotic and beta-glucan treatment reduced acute otitis media signs of inflammations in an acute otitis media-induced rat model, decreasing histological damage and cytokine levels. Co-administration of antibiotic and beta-glucan led to a significant reduction in tympanic membrane thickness, inflammation, and epithelium damage. Antibiotic + beta-glucan treatment resulted in a greater decrease in tympanic membrane thickness, inflammation, and epithelium damage than in the other groups. From these results, it can be suggested that beta-glucan, in combination with antibiotics may provide an alternative for the treatment of acute otitis media.

Resumo Introdução: Como suplemento, o beta-glucano apresenta vários efeitos terapêuticos gerados pelas células imunológicas. Cientificamente aprovado, mostrou ser um modificador de defesa biológica. Objetivo: Investigar os efeitos do beta-glucano nos tratamentos administrados em um modelo de otite média aguda induzida em um modeloanimal. A eficácia foi avaliada imunológica e histologicamente. Método: A amostra do estudo foi composta por 35 ratos adultos, divididos aleatoriamente em 5 grupos de 7: grupo 1 (controle), grupo 2 (otite média aguda, sem tratamento), grupo 3 (otite média aguda + antibiótico), grupo 4 (otite média aguda + beta-glucano) e grupo 5 (otite média aguda + beta-glucano + antibiótico). Foram feitas análises dos resultados dos exames histopatológicos e imunológicos em relação ao espessamento da membrana timpânica, dano ao epitélio, inflamação e esclerose. Os níveis séricos de TNF-α, IL-4, IL-6 e IL-β foram avaliados em todos os grupos. Resultados: Todos os níveis séricos de citocinas foram significativamente mais baixos nos grupos tratados com beta-glucano e antibióticos em comparação com o grupo otite média aguda. Diferenças significativas na espessura da membrana timpânica, inflamação, dano do epitélio e esclerose foram observadas entre os grupos otite média aguda + antibiótico e otite média aguda + beta-glucano. De acordo com esses parâmetros, os valores no grupo otite média aguda + antibiótico + beta-glucano foram acentuadamente inferiores aos dos demais grupos. Houve uma diferença significante no grupo otite média aguda + antibiótico + beta-glucano em comparação ao grupo otite média aguda (p < 0,001). Conclusão: Ambos os tratamentos com antibiótico e com beta-glucano reduziram os sinais de inflamação da otite média aguda em um modelo de rato com otite média aguda induzida, diminuíram os danos histológicos e os níveis de citocinas. A administração concomitante de antibiótico e beta-glucano levou a uma redução significativa na espessura da membrana timpânica, inflamação e danos ao epitélio. O tratamento com antibióticos + beta-glucano resultou em maior diminuição na espessura da membrana timpânica, inflamação e danos no epitélio do que nos outros grupos. A partir desses resultados, pode-se sugerir que o beta-glucano, em combinação com antibióticos, pode fornecer uma opção para o tratamento da otite média aguda.

Targeting Glioblastoma: The Current State of Different Therapeutic Approaches.

BACKGROUND: Glioma is the primary cancer of the central nervous system in adults. Among gliomas, glioblastoma is the most deadly and aggressive form, with an average life span of 1 to 2 years. Despite implementing the rigorous standard care involving maximal surgical removal followed by concomitant radiation and chemotherapy, the patient prognosis remains poor. Due to the infiltrative nature of glioblastoma, chemo- and radio-resistance behavior of these tumors and lack of potent chemotherapeutic drugs, treatment of glioblastoma is still a big challenge. OBJECTIVE: The goal of the present review is to shed some light on the present state of novel strategies, including molecular therapies, immunotherapies, nanotechnology and combination therapies for patients with glioblastoma. METHODS: Peer-reviewed literature was retrieved via Embase, Ovid, PubMed and Google Scholar till the year 2020. CONCLUSION: Insufficient effect of chemotherapies for glioblastoma is more likely because of different drug resistance mechanisms and intrinsically complex pathological characteristics. Therefore, more advancement in various therapeutic approaches such as antitumor immune response, targeting growth regulatory and drug resistance pathways, enhancing drug delivery and drug carrier systems are required in order to establish an effective treatment approach for patients with glioblastoma.

What is the effectiveness of beta-glucan for treatment of acute otitis media?

INTRODUCTION: As a supplement, beta-glucan has various therapeutic healing effects generated by the immune cells. It has been scientifically approved and proven to be a biological defense modifier. The aim of this study was to investigate the effects of beta-glucan on treatments administered in an acute otitis media model OBJECTIVES: This study investigated the effect of beta-glucan on the treatment of acute otitis media in an acute otitis media -induced animal model. Efficacy was evaluated both immunologically and histologically. METHODS: The study sample comprised 35 adult rats, randomly separated into 5 groups of 7: Group 1 (control), Group 2 (acute otitis media, no treatment), Group 3 (acute otitis media+antibiotic), Group 4 (acute otitis media+beta-glucan) and Group 5 (acute otitis media+beta-glucan+antibiotic). Analyses were made of the histopathology and immunology examination results in respect of thickening of the tympanic membrane, epithelium damage, inflammation, and sclerosis. In all groups the serum levels of TNF-α, IL-4, IL-6 and IL-1ß were evaluated. RESULTS: All serum cytokine levels were significantly lower in the beta-glucan and antibiotic-treated groups compared to the acute otitis media Group. Significant differences in tympanic membrane thickness, inflammation, epithelium damage, and sclerosis values were observed between the acute otitis media+antibiotic and acute otitis media+beta-glucan Groups. According to these parameters, the values in aute otitis media+antibiotic+beta-glucan Group were markedly lower than those of the other groups. There was a significant difference in the acute otitis media+antibiotic+beta-glucan Groups compared to acute otitis media Group (p < 0.001). CONCLUSIONS: Both antibiotic and beta-glucan treatment reduced acute otitis media signs of inflammations in an acute otitis media-induced rat model, decreasing histological damage and cytokine levels. Co-administration of antibiotic and beta-glucan led to a significant reduction in tympanic membrane thickness, inflammation, and epithelium damage. Antibiotic+beta-glucan treatment resulted in a greater decrease in tympanic membrane thickness, inflammation, and epithelium damage than in the other groups. From these results, it can be suggested that beta-glucan, in combination with antibiotics may provide an alternative for the treatment of acute otitis media.

Red and White Thrombus Characteristics in Patients Undergoing Carotid Endarterectomy.

OBJECTIVE: The study aimed to compare the characteristics of red and white thrombi in patients undergoing carotid endarterectomy. MATERIAL AND METHODS: The study was conducted in 81 patients with ischemic stroke who underwent carotid endarterectomy for carotid artery stenosis. Carotid plaques were graded by two pathologists. Thrombus materials were divided into two groups: white and red. The parameters of assessment were plaque rupture, lipid core, fibrous cap thickness, inflammation, intraplaque hemorrhage, calcification, necrotic core, and neovascularization. Normally distributed data were evaluated using Mann-Whitney U and Chi-squared tests. RESULTS: The ratio of white and red thrombus was 19.8% and 80.2%, respectively. Lipid core, plaque rupture, necrotic core, neovascularization, intraplaque hemorrhage, obstruction, and inflammation were observed more in red thrombus, which were statistically significant. Calcification and fibrous cap thickness were not statistically significant in the two groups. Moreover, intimal smooth muscle cells were present in all thrombus types. CONCLUSION: In our study, we found that red thrombi had more unstable characteristics than white thrombi. Thus, the risk for ischemic cerebrovascular events is more in red thrombi. However, this finding cannot be generalized due to the small number of patients in this study. Therefore, studies involving more patients are needed.

Neuroprotective effects of the new Na channel blocker rs100642 in global ischemic brain injury.

INTRODUCTION: RS100642, a mexiletine analogue, is a novel sodium channel blocker with neuroprotective and antioxidant activities. The protectivity of RS100642, which has been shown against focal cerebral ischemia, was investigated in global cerebral ischemia in this study. MATERIAL AND METHODS: Global cerebral ischemia was induced for five minutes in adult male Wistar Albino rats via the 4-vessel occlusion method. Intravenous administration of 1 mg/kg RS100642 following reperfusion for 30 min (RS100642 group) was compared with a sham treatment group (ischemia group) and nonischemized group (control) histologically based on morphology and caspase-3 immunohistochemistry, and biochemically based both on measurement of oxidative stress including malondialdehyde (MDA) levels, superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities and on assessment of apoptosis including caspase-3 and -8 activities and tumor necrosis factor α (TNF-α) levels at the end of 6 h. RESULTS: While the RS100642 group had significantly lower MDA levels and higher SOD activities than the sham treatment group (p < 0.05), GPx and CAT activities of the RS100642 and sham treatment groups were similar (p > 0.05) and significantly lower than those of the controls (p < 0.05). Necrosis and caspase-3 activity and immunoreactivity in the RS100642 group were significantly lower than those in the sham treatment group (p < 0.05), while there was no significant difference between groups regarding caspase-8 and TNF-α (p > 0.05). CONCLUSIONS: Na+ channel blockade by RS100642 has remarkable neuroprotective effects following global brain ischemia/reperfusion damage. Further research is required to determine the optimum dose and time of administration.

Beta-glucan attenuates cerebral ischemia/reperfusion-induced neuronal injury in a C57BL/J6 mouse model

Beta-glucans (ßg), that have many useful effects on human health, are natural polysaccharides. Our aim in this study was to determine useful effect of ßg against oxidative and neuronal damage caused by global cerebral ischemia/reperfusion (IR) in stroke imitated mice via surgical operation. A total of 40 mice divided into four equal groups randomly. The group 1 (sham operated) was kept as control. Bilateral carotid arteries of subjects in group 2 (I/R) and group 4 (I/ R + ßg) were clipped for 15 min, and the mice in group 4 (I/R + ßg) were treated with ßg (50 mg/kg/day), while the mice in group 2 (I/R) were treated with only vehicle for 10 days. The mice of group 3 (ßg) were treated with ßg for 10 days without carotid occlusion. Global cerebral I/R significantly increased oxidative stress and decreased members of anti-oxidant defense system. In addition, I/R caused histopathological damage in the brain tissue. However, ßg treatment ameliorated both oxidative and histopathological effects of I/R. Our present study showed that ßg treatment significantly ameliorated oxidative and histological damage in the brain tissue caused by cerebral I/R. Therefore, ßg treatment can be used as supportive care for ischemic stroke patients

Sudden-onset paraplegia during pregnancy caused by haemorrhage in a spinal cord haemangioblastoma: A case report.

Spinal cord haemangioblastomas are rare central nervous systems tumours, and haemorrhage.It is an uncommon occurance. We report a 28-year-old pregnant patient who presented with paraplegia due to acute haemorrhage of a spinal haemangioblastoma. Magnetic resonance imaging showed extensive syrinx cavities, an intramedullary lesion at the T4-T5 spinal cord level e, and a subarachnoid haemorrhage. Digital subtraction angiography showed the feeding artery and dilated tortuous draining vein within the dural sac. The lesion was deemed a haemangioblastoma. The histopathological examination confirmed the diagnosis. Postoperatively, the paraplegia improved and the patient was able to walk within 2 weeks. Imaging is important for early diagnosis to prevent patients persistent neurological deficits.

Chrysin prevents brain damage caused by global cerebralischemia/reperfusion in a C57BL/J6 mouse model.

BACKGROUND/AIM: The present study investigated the neuroprotective effects of chrysin (CRS) following global cerebral ischemia and reperfusion (I/R) in a C57BL/J6 mouse model. MATERIALS AND METHODS: A total of 40 mice were equally divided into four groups: (1) sham-operated (SH = control), (2) global cerebral I/R (I/R), (3) CRS, and (4) CRS + I/R. In the I/R group, the bilateral carotid arteries were clipped for 15 min and the mice were treated with vehicle (corn oil) for 10 days. In the CRS group, CRS (50 mg/kg) was given for 10 days without carotid occlusion. In the CRS + I/R group bilateral carotid arteries were clipped for 15 min and the mice were also treated with CRS (50 mg/kg) for 10 days. All of the rats were sacrificed under anesthesia on day 10, and neurodegenerative histological changes in the brain and tissue levels of oxidants and antioxidants were evaluated. RESULTS: CRS treatment significantly reversed the oxidative effects of I/R and inhibited the development of neurodegenerative histopathologies. In the CRS + I/R group, the decrease in TBARS levels and increase in GSH levels were similar to those in the SH group. CONCLUSION: Treatment with CRS can positively affect the neural system of mice and it can be used for the treatment of global cerebral I/R.

The evaluation of vertebrobasilar artery system in neuro-Behçet and Behçet disease using magnetic resonance angiography.

The aim of this study is the evaluation of the vertebrobasilar artery system in patients with Behçet's and Neuro-Behçet's disease. For this aim; 20 adults with clinically diagnosed Behcet's disease, 20 adults with Neuro-Behçet's disease, and 19 age- and gender-matched controls were examined by magnetic resonance angiography (MRA). During MRA, diameters of left vertebral artery (LVA), right vertebral artery (RVA), basilar artery (BA), and proximal segment (P1) of posterior cerebral artery between origin and junction with the posterior communicating artery were measured. In all groups, LVA was dominant than RVA (P < 0.05). The diameters of BA and right P1 of Neuro-Behçet's disease were larger than the other groups (P < 0.05). In addition, the diameters of left P1 of Neuro-Behçet's disease were larger but not statistically significant. There is no difference between the groups in terms of gender. Behçet's disease can affect vascular structures; therefore vertebrobasilar artery system should be examined in patients with Behçet's and Neuro-Behçet's disease.