Immunomodulatory Effect of Toll-Like Receptor-3 Ligand Poly I:C on Cortical Spreading Depression

The release of inflammatory mediators following cortical spreading depression (CSD) is suggested to play a role in pathophysiology of CSD-related neurological disorders. Toll-like receptors (TLR) are master regulators of innate immune function and involved in the activation of inflammatory responses in the brain. TLR3 agonist poly I:C exerts anti-inflammatory effect and prevents cell injury in the brain. The aim of the present study was to examine the effect of systemic administration of poly I:C on the release of cytokines (TNF-α, IFN-γ, IL-4, TGF-β1, and GM-CSF) in the brain and spleen, splenic lymphocyte proliferation, expression of GAD65, GABAAα, GABAAβ as well as Hsp70, and production of dark neurons after induction of repetitive CSD in juvenile rats. Poly I:C significantly attenuated CSD-induced production of TNF-α and IFN-γ in the brain as well as TNF-α and IL-4 in the spleen. Poly I:C did not affect enhancement of splenic lymphocyte proliferation after CSD. Administration of poly I:C increased expression of GABAAα, GABAAβ as well as Hsp70 and decreased expression of GAD65 in the entorhinal cortex compared to CSD-treated tissues. In addition, poly I:C significantly prevented production of CSD-induced dark neurons. The data indicate neuroprotective and anti-inflammatory effects of TLR3 activation on CSD-induced neuroinflammation. Targeting TLR3 may provide a novel strategy for developing new treatments for CSD-related neurological disorders. © 2014, Springer Science+Business Media New York

Immunomodulatory Effect of Toll-Like Receptor-3 Ligand Poly I:C on Cortical Spreading Depression

The release of inflammatory mediators following cortical spreading depression (CSD) is suggested to play a role in pathophysiology of CSD-related neurological disorders. Toll-like receptors (TLR) are master regulators of innate immune function and involved in the activation of inflammatory responses in the brain. TLR3 agonist poly I:C exerts anti-inflammatory effect and prevents cell injury in the brain. The aim of the present study was to examine the effect of systemic administration of poly I:C on the release of cytokines (TNF-α, IFN-γ, IL-4, TGF-β1, and GM-CSF) in the brain and spleen, splenic lymphocyte proliferation, expression of GAD65, GABAAα, GABAAβ as well as Hsp70, and production of dark neurons after induction of repetitive CSD in juvenile rats. Poly I:C significantly attenuated CSD-induced production of TNF-α and IFN-γ in the brain as well as TNF-α and IL-4 in the spleen. Poly I:C did not affect enhancement of splenic lymphocyte proliferation after CSD. Administration of poly I:C increased expression of GABAAα, GABAAβ as well as Hsp70 and decreased expression of GAD65 in the entorhinal cortex compared to CSD-treated tissues. In addition, poly I:C significantly prevented production of CSD-induced dark neurons. The data indicate neuroprotective and anti-inflammatory effects of TLR3 activation on CSD-induced neuroinflammation. Targeting TLR3 may provide a novel strategy for developing new treatments for CSD-related neurological disorders. © 2014, Springer Science+Business Media New York

Molecular detection of Trichostrongylus species through PCR followed by high resolution melt analysis of ITS-2 rDNA sequences

Polymerase chain reaction followed by high resolution melting (PCR-HRM) analysis is a simple, rapid and accurate method for molecular detection of various nematode species. The objective of the present study was, for the first time, to develop a PCR-HRM assay for the detection of various animal Trichostrongylus spp. A pair of primers targeting the ITS-2 rDNA region of the Trichostrongylus spp. was designed for the development of the HRM assay. DNA samples were extracted from 30 adult worms of Trichostrongylus spp., the ITS-2-rDNA region was amplified using PCR, and the resultant products were sequenced and characterized. Afterwards, the PCR-HRM analysis was conducted to detect and discriminate Trichostrongylus spp. Molecular sequence analysis revealed that 24, 4, and 1 of the samples were T. colubriformis, T. vitrinus and T. capricola, respectively. Results from PCR-HRM indicated that complete agreement was relatively found between speciation by HRM analysis and DNA sequencing for the detection of Trichostrongylus species. The PCR-HRM analysis method developed in the present study is fast and low-cost; the method can be comparable with other molecular detection techniques, representing a reliable tool for the identification of various species within the Trichostrongylus genus. © 2020 Elsevier B.V

Sonochemical synthesis of ErVO4/MnWO4 heterostructures: Application as a novel nanostructured surface for electrochemical determination of tyrosine in biological samples

Present strategy introduces a novel method established for the synthesis of spherical shape ErVO4/MnWO4 heterostructures by a sonochemical method. This heterostructures with optima morphology can be synthesized by changing power and time ultrasound irradiation without any capping agent. BET analysis revealed that ErVO4/MnWO4 prepared in the presence of ultrasonic procedure has 75 times specific surface area as much as that of those was produced in the absence of ultrasonic rays. A variety of analyses (i.e., BET, XRD, TEM, EDS, FT-IR, and SEM) were applied for characterization of the ErVO4/MnWO4. Next, a selective and sensitive nanostructured sensor based on ErVO4/MnWO4 nanocomposite modified carbon paste electrode (ErVO4/MnWO4/CPE) was constructed for electrochemical detection of tyrosine (Tyr). The electrochemical characterizations were performed using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). Compared with the unmodified CPE, the oxidation peak current was significantly enhanced for Tyr. The impact of effective parameters on voltammetric response of Tyr was analyzed with design of experiments (DOE) and response surface methodology (RSM). Under the optimized conditions, the oxidation peak current of Tyr was linear over a range of 0.08�400.0 μM with a detection limit of 7.7 nM. Finally, the usage of the proposed method was confirmed by the recovery tests of Tyr in biological samples. © 201

Adeno-associated virus as a gene therapy vector: strategies to neutralize the neutralizing antibodies

Adeno-associated virus (AAV)-derived vectors are currently the most common type of viral vectors used in gene therapy clinical trials. The presence of neutralizing antibodies (NAbs) against wild-type AAVs in the host body is one of the limitations for the successful use of AAV vectors. AAV capsid manipulation, by which recombinant vectors lose their ability to interact with NAbs, can help overcome this obstacle. Various methods can be used for this purpose, including directed evolution as well as conjugation of certain chemical groups to AAV epitopes. The present review concisely explains the use of AAV vectors in the clinic for gene therapy of some diseases, their limitations, and solutions to these limitations. © 2019, Springer Nature Switzerland AG

Potential drugs used in the antibody–drug conjugate (ADC) architecture for cancer therapy

Cytotoxic small-molecule drugs have a major influence on the fate of antibody–drug conjugates (ADCs). An ideal cytotoxic agent should be highly potent, remain stable while linked to ADCs, kill the targeted tumor cell upon internalization and release from the ADCs, and maintain its activity in multidrug-resistant tumor cells. Lessons learned from successful and failed experiences in ADC development resulted in remarkable progress in the discovery and development of novel highly potent small molecules. A better understanding of such small-molecule drugs is important for development of effective ADCs. The present review discusses requirements making a payload appropriate for antitumor ADCs and focuses on the main characteristics of commonly-used cytotoxic payloads that showed acceptable results in clinical trials. In addition, the present study represents emerging trends and recent advances of payloads used in ADCs currently under clinical trials. © 2019 Wiley Periodicals, Inc

Solitary osteochondroma of the twelfth rib with intraspinal extension and cord compression in a middle-aged patient

<p>Abstract</p> <p>Background</p> <p>Osteochondroma is a disease of growing bone and thus typically presents in younger patients. It has rarely been described in middle-aged and elderly patients. Data on the occurrence of osteochondroma show that the reported incidence of costal osteochondroma is very low. Moreover, costal osteochondroma arising at the costovertebral junction with neural foraminal extension and spinal cord compression is extremely rare.</p> <p>Case presentation</p> <p>This study reports the case of a 58-year-old patient with a solitary osteochondroma of the 12th rib with intraspinal extension and spinal cord compression. The clinical history, plain radiographs, computed tomography (CT), magnetic resonance imaging, and pathologic findings of the reported patient have been reviewed. The relevant medical literature has also been reviewed. The patient was treated with surgery for complete tumour excision to avoid tumour recurrence. After surgery, the patient's symptoms improved. An additional CT scan obtained at 1 year after surgery did not show any evidence of recurrence.</p> <p>Conclusions</p> <p>This patient is the oldest patient reported to have this rare form of costal osteochondroma. The age of the patient and the erosion of the adjacent bones raised clinical suspicion of malignancy; therefore, surgical management involved complete tumour excision with thoracolumbar fixation and fusion.</p

The Relationship between Serum Level of Osteoprotegerin and Post-laminectomy Epidural Fibrosis in Rabbit

Abstract: Background & Aims: Epidural fibrosis (EF) is part of natural physiological tissue response to laminctomy and it may be an important cause of failed back surgery syndrome (FBSS). There is still no effective medical or surgical therapy for EF. Osteoprotegerin (OPG) is a soluble member of the tumor necrosis factor receptor family that might play a role in postoperative EF. The objective of this study was to evaluate the relationship between serum OPG level and EF after laminectomy. Methods: Sixty rabbits were employed and divided randomly into two groups. Group A contained 20 rabbits as controls and group B contained 40 rabbits that underwent bilateral laminecyomy at L4 and L5 lumbar levels under an approved surgical protocol. Serum sample was obtained after 8 weeks from all rabbits and then the animals in group B were killed in accordance with the guidelines for euthanasia. The spine segment from L3 to L6 was removed en bloc. The amount of scar tissue at the laminectomy defect was scored on an ordinal score from 0 to 3 with a scoring system similar to that of He et al. According to the amount of scar the rabbits in group B, were divided into two groups: B1 with low fibrosis (grade 0, 1) and B2 with high fibrosis (grade 2, 3). The serum OPG level of groups A, B1 and B2 were determined using ELISA method. The one way ANOVA was used to assess significant difference among groups. Results: Serum OPG level ranged from 0-4 Pmol/l_with a median of 1.5 Pmol/l in group A, 0-6 Pmol/l with a median of 2.42 Pmol/l n group B1 and 0-6 Pmol/l with a median of 2.15 Pmol/l in group B2. There was not any significant difference in OPG levels among these 3 groups. Conclusion: This study showed no relation between OPG level and existence of postlaminectomy EF after 8 weeks. Keywords: Osteoprotegerin, Fibrosis, Epidural space, Laminectom

Congenital Absence of the Posterior Element of C1, C2, and C3 Along with Bilateral Absence of C4 Pedicles: Case Report and Review of the Literature

Background: Abnormalities of the posterior arch of vertebrae are rare conditions that may incidentally be found on neck radiographs. We report a case and present a comprehensive review of the literature. Case Description: A 10-year-old boy presented with intermittent paresthesia in the lower extremities, mild neck pain, and episodes of drop attacks following neck flexion. Radiologic investigations depicted a complete absence of the posterior element of C1, C2, and C3 along with bilateral absence of C4 pedicles. Conclusions: The diagnosis of posterior arch abnormalities is of high-level of importance because of resultant neurologic defects. To the best of our knowledge, no case of this type has been reported in literature thus far. © 2017 Elsevier Inc

The effect of Gel Foam on post laminectomy epidural fibrosis in rabbits

&quot;nBackground: Epidural fibrosis (EF) is a part of normal physiological tissue response to laminectomy and it may be an important cause of failed back surgery syndrome (FBSS). The objective of this study was to evaluate the effect of using gel foam after laminectomy on reduction of epidural fibrosis. &quot;nMethods: In this prospective study forty five rabbits were recruited. The cases undergone bilateral laminectomy at the L4 and L5 lumbar levels under an approved surgical protocol. After eight weeks the rabbits were sacrificed and the spinal segments from L3 to L6 were removed en bloc. The amount of scar tissue at the laminectomy defect was scored. The fibroblast and inflammatory cell counts were also compared between two groups. &quot;nResults: In this study 55% of group A rabbits were placed in grade 0 or I, grade II fibrosis could be detected in the remaining 45%. In group B these amounts were 73.7% and 26.3% respectively, which no significant statistical difference could be detected between two arms (p=0.189). Comparing the quantity of fibroblasts 40% of group A rabbits were recognized as grade I and the other 60% as grade II and grade I fibrosis was discovered in 42.1% of group B rabbits, while other 57.9% suffered from grade II fibrosis, again no significant statistical difference could be attributed between two arms (p=0.576). Also comparing inflammatory cell counts detected in the specimens no significant statistical difference could be detected either (p=0.465). &quot;nConclusion: According to this study using gel foam during the laminectomy surgery in rabbits has no obvious effect in reducing post laminectomy epidural fibrosis after eight weeks of follow-up