The Effect of Apocynin on Motor and Cognitive Functions in Experimental Alzheimer’s disease.

Scope: We investigated the potential beneficial effect of Apocynin (APO) on motor and cognitive functions in experimental Alzheimer’s disease (AD). Materials and Methods: Experimental AD was induced in rats by intraventricular streptozotocin (STZ) injection. Sham group received artificial cerebrospinal fluid (CSF). Both groups were randomly divided into two subgroups. One of the subgroups received intraperitoneal APO for while the other had normal saline (NS). The animals were evaluated with rotarod, accelerod and Water-Maze tests before and after the treatment. Additionally, biochemical markers of oxidative stress such as malondialdehyde (MDA) and reduced glutathione (GSH) were analyzed from brain specimens. Standard histological evaluation and transmission electron microscopy (TEM) were used to evaluate the neural damage. Results: The difference between STZ+NS in comparison with CSF+NS, CSF+APO and STZ+APO were statistically significant on 30 and 40 rpm on rotarod test. GSH levels, accelerod and Water-Maze test results were not statistically significant between subgroups. However, MDA differences between STZ+NS in comparison with CSF+NS, CSF+APO and STZ+APO were statistically significant. Hemotoxilene eozine staining and TEM results showed apocynins protective effect. Conclusion: These results indicate that APO can provide neuro-protective effect for motor but not for cognitive performance in experimental AD.   Keywords: Alzheimer’s disease, Streptozotocin, Apocynin, Rotarod test, Accelerod test, Water-Maze test</p

The association between different molecular weights of hyaluronic acid and CHAD, HIF-1 alpha, COL2A1 expression in chondrocyte cultures

The aim of the present study was to investigate the effects of three different formulations of hyaluronic acid (HA): Low molecular weight (MW) Sinovial One((R)), medium MW Viscoplus((R)) and high MW Durolane((R)), on chondrocyte proliferation and collagen type II (COL2A1), hypoxia-inducible factor 1 alpha (HIF-1 alpha) and chondroadherin (CHAD) expression in primary chondrocyte cultures. Standard primary chondrocyte cultures were established from osteochondral tissues surgically obtained from 6 patients with gonarthrosis. Cell morphology was evaluated using an inverted light microscope; cell proliferation was determined with a MTT assay and confirmed with acridine orange/propidium iodide staining. Levels of CHAD, COL2A1 and HIF-1 alpha expression were assessed using specific TaqMan gene expression assays. The results demonstrated the positive effect of HA treatment on cell proliferation, which was independent from the MW. COL2A1 expression increased in the medium and high MW HA treated groups. It was observed that HIF-1 alpha expression increased in the high MW treated group alone. CHAD expression increased only in the medium MW HA treated group. Evaluation of gene expression revealed that levels of expression increased as the duration of HA application increased, in the medium and high MW HA treated groups. In terms of increased viability and proliferation, a longer duration of HA application was more effective. Taken together, it may be concluded that the administration of medium and high MW HA may be a successful way of treating diseases affecting chondrocytes in a clinical setting

Lumbar spinal angiolipoma with expanding left neural foramen mimicking lumbar schwannoma; case report and review of the literature

Aim: To describe a patient with lumbar angiolipoma mimicking schwannoma in the posterolateral side of the spinal canal with expansion of the left lumbar foramen and to discuss the clinical, radiologic, and surgical features of these lesions with literature. Methods: Without language restriction in this paper, the electronic databases; The Cochrane Collaboration the Cochrane, The Cochrane Library (Issue 2 of 12, Feb. 2011), ProQuest, US National Library of Medicine, National Institutes of Health (NLM) and PubMed dating from 1966 September to January Week 2 2017, were searched for comparative experimental studies using the terms: “OR”, “AND”. On-line literature searches were conducted using the key words “lumbar angiolipoma”, “schwannoma “, “spinal angiolipoma”, “spinal cord”, and “spinal canal”. We compared this research with our patient. Results: Bilateral L2 total laminectomy, excision of the tumors and bilateral L2-L3 transpedicular stabilization were performed, and complaints improved prominently. Pathological examination was reported as angiolipoma. Conclusion: The research shows that a probable diagnosis in such tumor cases could be made by sufficient pre-op scanning before surgical operations and although angiolipoma has been rarely seen in lumbar posterolateral space, it can be seen in lumbar region and mimic schwannoma as producing symptoms and signs of spinal cord and nerve root compression. © 2017 Akyuva et al

Effects of etanercept, a tumor necrosis factor receptor fusion protein, on primary cell cultures prepared from intact human intervertebral disc tissue

The aim of the present study was to investigate the effects of etanercept (ETA), a tumor necrosis factor (TNF) inhibitor, on human cell cultures prepared from intact intervertebral disc tissue. ETA is used as a treatment for cases of rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis and ankylosing spondylitis accompanied by moderate or severe joint pain. ETA was applied to primary cell cultures [annulus fibrosus and nucleus pulposus (NP) from intact intervertebral disc tissue]. Cell cultures without ETA treatment served as the control group. Morphological and quantitative molecular analyses of the two groups were performed. The number of viable cells and cell proliferation decreased in the ETA-treated cultures as compared with those in the control group. Furthermore, in the treatment group, the chondroadherin gene, an NP-specific marker, was not expressed after 24 h. By contrast, the cartilage oligo matrix protein was expressed 24, 48 and 72 h post-ETA treatment, while its expression was significantly lower than that in the control group. In addition, the expression of interleukin-1 beta, as well as matrix metallopeptidase-7 and -19, was markedly decreased. Overall, the cell proliferation and gene expression in the ETA-treated cells were significantly different from those in the control group (P<0.05). These results suggest that the treatment duration and dosage of TNF inhibitors, which are used to suppress active inflammation, should be considered in the clinical setting. These biological agents may delay the healing of intervertebral disc tissue damage by slowing cell proliferation and altering gene expression via anabolic and catabolic pathways

Kyphoplasty in the early oncologic diagnosis and treatment of vertebral fractures: A clinical study

Aim: To elucidate the characteristics of kyphoplasty in correlation with spinal metastasis. Material and Methods: Data of patients treated by kyphoplasty between January 2017 and December 2019 were reviewed retrospectively. Preoperative prophylactic antibiotics and low-molecular-weight heparin injections were performed. Postoperative follow-up was conducted at least 24 hours after the procedure. All patients were treated under sedoanalgesia. Bone biopsies were collected from all patients. Results: One hundred ninety-nine vertebra fractures were treated in 130 patients. The mean age of the patients was 65.27 ± 8.79 years (18–90 years) and 66 patients were male (50.7%). Forty-five patients had osteoporosis, six patients showed malignancy, and osteomyelitis was found in three patients, while the others’ presentations were secondary to trauma. Most commonly, the L1 (n=59), Th12 (n=45), and L2 (n=34) levels were found to develop vertebral fractures. Forty patients had multiple levels of vertebral fracture, with a higher rate of osteoporosis (n=24; 60%). Three patients showed undiagnosed oncologic disease with an initial diagnosis of acute fracture following minor trauma, while the primary oncologic diagnosis was established by bone biopsy taken during the routine procedure in each procedure (e.g., plasmacytoma, lymphoma, adenocarcinoma of the lung). None of the patients developed an infection due to kyphoplasty, permanent neuromotor deficit, or mortality. The mean postoperative hospital length of stay was 1.6 days. Conclusion: Bone biopsy should be performed to diagnose early spinal metastases. Although an accurate bone biopsy may not be obtained from some patients, particularly from those with osteoporosis, performing bone biopsy during the procedure does not cause time loss or any other complications and protects the surgeon from possible medicolegal problems

Lumbar Disc Herniation Might Spontaneously Regress, While Neuropathic Pain Might Start: Retrospective Clinical Study

Lumbar disc herniation (LDH) is a common cause of low back pain and radicular pain. The aim of our study was to evaluate the regression of LDH in patients who are considered to require surgical treatment but prefer conservative treatment. Patients who presented between January 2018 and June 2020 and who did not accept the recommended surgical treatment following a diagnosis of LDH based on clinical and radiological findings were retrospectively reviewed. All 12 of the patients included in the study showed spontaneous regression of LDH during outpatient clinical follow-up. Our study included 12 patients (seven male and five female). The mean age was 46.5 (the youngest was 30 years old; the oldest was 70 years old). Regression was observed at the L2-L3 level in two patients (10%), at the L4-L5 level in four patients (40%), and at the L5-S1 level in six patients (50%). On the follow-up examination of all patients, the severity of their pain was evaluated with the Visual Analogue Scale, and all patients described a reduction in pain (min: 2, max: 8). Ten patients described radicular pain at the initial examination, eight patients received physical therapy and rehabilitation treatment before the follow-up examination, and nine patients described neuropathic pain at the follow-up examination. Spontaneous regression of LDH is rare. While conservative treatments provided partial improvement in the complaints of these patients, conservative treatments usually cannot prevent the development of neuropathic pain

Phase i study on the safety and preliminary efficacy of allogeneic mesenchymal stem cells in hypoxic-ischemic encephalopathy

BACKGROUND Hypoxic-ischemic encephalopathy (HIE) is a leading cause of morbidity and mortality in the adult as well as in the neonate, with limited options for treatment and significant dysfunctionality. AIM To investigate the safety and preliminary efficacy of allogeneic mesenchymal stem cells (MSCs) in HIE patients. METHODS Patients who had HIE for at least 6 mo along with significant dysfunction and disability were included. All patients were given Wharton's jelly-derived MSCs at 1 × 106/kg intrathecally, intravenously, and intramuscularly twice a month for two months. The therapeutic effects and prognostic implications of MSCs were evaluated by multiple follow-ups. Functional independence measure (FIM), modified Ashworth, and Karnofsky scales were used to assess any side effects, neurological and cognitive functions, and overall outcomes. RESULTS The 8 subjects included in the study had a mean age of 33.25 ± 10.18 years. Mean HIE exposure and mean post-HIE durations were 45.63 ± 10.18 and 19.67 ± 29.04 mo, respectively. Mean FIM score was 18.38 ± 1.06, mean modified Ashworth score was 43.5 ± 4.63, and mean Karnofsky score was 20. For the first 24 h, 5 of the patients experienced a subfebrile state, accompanied by mild headaches due to intrathecally administration and muscle pain because of intramuscularly administration. Neurological and functional examinations, laboratory tests, electroencephalography, and magnetic resonance imaging were performed to assess safety of treatment. Mean FIM score increased by 20.88 ± 3.31 in the first month (P = 0.027) and by 31.38 ± 14.69 in 12 mo (P = 0.012). The rate of patients with an FIM score of 126 increased from 14.58% to 16.57% in the first month and 24.90% in 12 mo. CONCLUSION Multiple triple-route Wharton's jelly-derived MSC administrations were found to be safe for HIE patients, indicating neurological and functional improvement. Based on the findings obtained here, further randomized and placebo research could be performed

Effect of Balloon Khphoplasty Treatment for Osteoporotic Vertebral Fracture on Spinal Balance

Introduction: Osteoporotic vertebral fractures and spinal degeneration are common consequences of aging, and co-occurrence of these two pathologies can impair spinal balance leading to development of further deformities. The most common treatment measure for osteoporotic vertebral fractures is percutaneous balloon kyphoplasty which can potentially improve spinal balance along the sagittal and coronal planes. However, there is limited evidence in support of this issue to date. Materials and Methods: This study included 49 patients (27 males, 22 females) who were diagnosed with osteoporotic vertebral fracture. The patients were evaluated preoperatively and one year postoperatively using threedimensional thoracolumbar computed tomography scans. The lumbar lordosis and sacral slope angle were used to assess the sagittal plane, while coronal plane assessment was carried out using Cobb’s angle. The angle values before and after treatment were compared statistically. Results: The mean age of the study participants was 72.16 years (range: 61– 94 years), and 28.6% and 71.4% of the patients exhibited thoracic and lumbar vertebral fractures, respectively. Moreover, 19 patients exhibited spontaneous or minor traumatic vertebral fractures, and 16 patients diagnosed with degenerative scoliosis exhibited a significant improvement in Cobb’s angle after treatment. The comparison of pre-and postoperative mean sacral slope and lumbar lordosis angles showed an increase in both values and these differences, although not statistically significant, in agreement with previous literature. Conclusion: Percutaneous balloon kyphoplasty has become an increasingly popular treatment measure for osteoporotic vertebral fracture due to its ability to effectively correct spinal imbalance in patients. © 2023, Turkish Geriatrics Society. All rights reserved

Resveratrol attenuates hypoxia-induced neuronal cell death, inflammation and mitochondrial oxidative stress by modulation of TRPM2 channel

AbstractHypoxia (HYPX) induced-overload Ca2+ entry results in increase of mitochondrial oxidative stress, inflammation and apoptosis in several neurons. Ca2+ permeable TRPM2 channel was gated by ADP-ribose (ADPR) and reactive oxygen species (ROS), although its activity was modulated in HYPX-exposed neurons by resveratrol (RSV). The aim of this study was to evaluate if a therapy of RSV can modulate the effect of HYPX in the TRPM2 expressing SH-SY5Y neuronal and HEK293 (no expression of TRPM2) cell lines. The SH-SY5Y and HEK293 cells were divided into four groups as control, RSV (50 μM and 24 hours), and HYPX and RSV + HYPX. For induction of HYPX in the cells, CoCl2 (200 μM and 24 hours) incubation was used. HYPX-induced intracellular Ca2+ responses to TRPM2 activation were increased in the SH-SY5Y cells but not in the HEK293 cells from coming H2O2 and ADPR. RSV treatment improved intracellular Ca2+ responses, mitochondrial function, suppressed the generation of cytokine (IL-1β and TNF-α), cytosolic and mitochondrial ROS in the SH-SY5Y cells. Intracellular free Zn2+, apoptosis, cell death, PARP-1, TRPM2 expression, caspase −3 and −9 levels are increased through activating TRPM2 in the SH-SY5Y cells exposed to the HYPX. However, the values were decreased in the cells by RSV and TRPM2 blockers (ACA and 2-APB). In SH-SY5Y neuronal cells exposed to HYPX conditions, the neuroprotective effects of RSV were shown to be exerted via modulation of oxidative stress, inflammation, apoptosis and death through modulation of TRPM2 channel. RSV could be used as an effective agent in the treatment of neurodegeneration exposure to HYPX.</jats:p