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

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

Application of Starch Foams Containing Plant Essential Oils to Prevent Mold Growth and Improve Shelf Life of Packaged Bread

In the recent years, considerable attention has been allocated in the area of using natural preservatives in foods, especially vegetable oils.  Starch foams prepared from high amylose starch are useful for encapsulation of substances such as chemicals, liquids or solids, including flavor compounds, pharmaceuticals and essential oils. The foams have the ability to trap the active material and subsequently release the activity. Cinnamon oil is absorbed to foam starch microparticles and acts as an antimicrobial agent. This study was designed and implemented to evaluate the use of starch foam containing vegetable oil to prevent mold growth and improve packaged bread shelf life. For this purpose, first cinnamon essential oil was extracted with water by distillation method then, 250 groups of bread were prepared within polypropylene plastic bags. Various amounts of cinnamon essential oil (500, 750, 1000and1500ppm) with 1 g of starch foam powder inside sterilized filter paper were added to these packages.The obtained results of multi-way and intergroup repeated tests indicated that there was a significant difference (P &lt;0/05) between the control groups and various groups containing cinnamon essential oil in terms of microbial load. In the groups containing essential oils, less increase was showed in microbial load and with increasing concentrations of cinnamon essential oil, mold and yeast growth rate decreased. It concluded that by using starch foam containing cinnamon essential oil in bulky bread packing at ambient temperature (25°C), the spoilage process of bulky bread can be postponed 3 to 6 days, and it can be used as an appropriate natural and antifungal preservative in packaging of bread

Functional brain changes after alternative pharmacological interventions in posttraumatic stress disorder: A systematic review of clinical trials

Abstract Background Posttraumatic stress disorder (PTSD) is a complex and heterogeneous mental health condition that can develop after exposure to a traumatic event. Clinical trials have used alternative pharmacological agents to treat PTSD, but their associated neural correlates remain unclear. The present systematic review aims to summarize the changes in brain function associated with the use of these alternative pharmacological agents in PTSD. Methods Clinical trials using functional magnetic resonance imaging, either at rest or during the performance of tasks, were included if they compared the effects of alternative pharmacological agents between PTSD patients and either trauma‐exposed controls or never‐exposed healthy controls. Results Sixteen studies were included, of which 11 used intranasal oxytocin, 2 used hydrocortisone, and 3 used delta‐9‐tetrahydrocannabinol (THC). Oxytocin administration was associated with the normalization of functional connectivity between the ventromedial prefrontal cortex and amygdala as well as enhanced the function of brain regions specifically involved in emotion processing (e.g., amygdala), working memory (e.g., dorsolateral prefrontal cortex), and reward (e.g., putamen). Hydrocortisone did not influence brain function at rest or during the performance of an autobiographical memory task, whereas THC was associated with the reduction of the amygdala and increased medial prefrontal cortex activation. Conclusions This systematic review identified preliminary evidence for normalizing brain function after the use of alternative pharmacological agents. Importantly, sex‐specific differences were noted, in particular when using oxytocin, that will require further investigation

Photobiomodulation therapy improves the growth factor and cytokine secretory profile in human type 2 diabetic fibroblasts

Impaired wound healing is a common complication of diabetes mellitus (DM) and the underlying mechanism of this impairment is still unclear. Fibroblast, as the main reconstructing cell, secretes some critical growth factors and cytokine contributing to wound healing. It is well known that DM alters the behavior of these cells and photobiomodulation therapy (PBMT) compensates some impairments in diabetic fibroblasts. Therefore, the aim of the present study was to demonstrate the impact of diabetes and the role of PBMT through low level laser irradiation on secretory profile of human diabetic fibroblasts. Primary human dermal fibroblasts from normal (HDFs) and diabetic (DHDFs) donors were harvested. For PBMT, the DHDFs were irradiated with a Helium-Neon laser at 632.8 nm wavelength and energy density of 0.5 J/cm2, as laser treated group (LT-DHDFs). Next, some cellular behaviors and secretory profiling array for 60 growth factors/cytokines were investigated in LT-DHDFs and then compared with those of controls. The data showed that the PBMT could compensate such impairments occurred in DHDFs in terms of viability, proliferation, and migration. Furthermore, considering our novel findings, out of those 20 growth factors/cytokines involved in cell proliferation, immune system regulation, and cell-cell communication pathways, which significantly decreased in DHDF as compared with HDFs, the PBMT could compensate seven in LT-DHDFs as compared with DHDFs. The seven growth factor/cytokines, which are mainly involved in cell-cell communication, positive regulation of cell proliferation, and chemokine mediated pathway included BDNF, Eotaxin-3, FGF6, FGF7, Fractalkine, fit-3ligand, and GCP-2. Therefore, it is suggested that scrutinizing these differentially secreted molecules and the impaired pathways in DHDFs, in combination with those compensated in LT-DHDFs, could raise our knowledge to manage diabetic ulcer through a feasible and cost effective intervention, specifically PBMT. © 2020 Elsevier B.V

Effects of epidural injection of glucocorticoid and its combination with bupivacaine in palliating chronic low back pain due to discopathy

Chronic low back pain is defined as consistent or pendulous pain over 3 months. Epidural steroid injections (ESI) are common in treatment of chronic back pain. The present study was aimed to investigate the effects of epidural injection of glucocorticoid and bupivacaine compared to glucocorticoid alone in relieving chronic back pain due to discopathy. A randomized clinical trial was performed in the Shohada Medical Educational Center, Tabriz, Iran. Patients with chronic back pain who were candidates for epidural drug injection were recruited. They were divided into two groups of steroids or steroid and bupivacaine. Pain intensity, Oswestry Disability Index (ODI), Straight Leg Rising (SLR) test as well as clinical variables were evaluated before treatment and 3th month thereafter. Overall, 17 males and 23 females with a mean age ± SD of 47.54 ± 12.11 years were enrolled in two equal groups. No significant difference was observed between two groups in terms of gender and body mass index. In both groups, a significant relationship was observed for ODI (p =0.001), pain intensity (p =0.001), and SLR test (p=0.001) before and after treatment. However, the corresponding association was not observed for ODI, pain intensity and SLR test (p>0.05). Epidural steroid injections either alone or combined with Bupivacaine with no priority are effectively relief chronic low back pain due to discopathy