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https://www.readbyqxmd.com/read/27904474/poly-adp-ribose-polymerase-inhibition-reveals-a-potential-mechanism-to-promote-neuroprotection-and-treat-neuropathic-pain
#1
REVIEW
Prashanth Komirishetty, Aparna Areti, Ranadeep Gogoi, Ramakrishna Sistla, Ashutosh Kumar
Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that limit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially peroxynitrite after the nerve injury. They provoke oxidative DNA damage and consequent over-activation of the poly(ADP-ribose) polymerase (PARP) upregulates pro-inflammatory pathways, causing bioenergetic crisis and neuronal death...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27900576/time-course-behavioral-safety-and-protective-efficacy-of-centrally-active-reversible-acetylcholinesterase-inhibitors-in-cynomolgus-macaques
#2
Lindsey R Hamilton, Steven C Schachter, Todd M Myers
Galantamine hydrobromide and (-)huperzine A, centrally active reversible acetylcholinesterase inhibitors, are potentially superior to the current standard, pyridostigmine bromide, as a pretreatment for organophosphorus chemical warfare nerve agent intoxication. Galantamine, huperzine, and pyridostigmine were compared for time course of acetylcholinesterase inhibition in 12 cynomolgus macaques. Although both galantamine and huperzine shared a similar time course profile for acetylcholinesterase inhibition, huperzine was 88 times more potent than galantamine...
November 30, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27899695/consistent-sex-dependent-effects-of-pkm%C3%AE-gene-ablation-and-pharmacological-inhibition-on-the-maintenance-of-referred-pain
#3
Hibatulnaseer Nasir, Hicham Mahboubi, Sandeep Gyawali, Stephanie Ding, Aiste Mickeviciute, J Vaigunda Ragavendran, André Laferrière, Ursula Stochaj, Terence J Coderre
BACKGROUND: Persistently active PKMζ has been implicated in maintaining spinal nociceptive sensitization that underlies pain hypersensitivity. However, evidence for PKMζ in the maintenance of pain hypersensitivity comes exclusively from short-term studies in males using pharmacological agents of questionable selectivity. The present study examines the contribution of PKMζ to long-lasting allodynia associated with neuropathic, inflammatory, or referred visceral and muscle pain in males and females using pharmacological inhibition or genetic ablation...
2016: Molecular Pain
https://www.readbyqxmd.com/read/27899298/mechanisms-and-time-course-of-menthol-induced-cutaneous-vasodilation
#4
Daniel H Craighead, Nathaniel B McCartney, James H Tumlinson, Lacy M Alexander
Menthol is a vasoactive compound that is widely used in topical analgesic agents. Menthol induces cutaneous vasodilation, however the underlying mechanisms are unknown. Determining the rates of appearance and clearance of menthol in the skin is important for optimizing topical treatment formulation and dosing. The purpose of this study was to determine the mechanisms contributing to menthol-mediated cutaneous vasodilation and to establish a time course for menthol appearance/clearance in the skin. Ten young (23±1years, 5 males 5 females) subjects participated in two protocols...
November 26, 2016: Microvascular Research
https://www.readbyqxmd.com/read/27897119/glaucoma-hot-topics-in-pharmacology
#5
Shiama I Balendra, Parth Arvind Shah, Mishank Jain, Andrzej Grzybowski, Francesca M Cordeiro
BACKGROUND: Glaucoma comprises a group of neurodegenerative diseases resulting in retinal ganglion cell death within the optic nerve head. It is projected to affect almost 80 million people worldwide by 2020. The condition's asymptomatic nature translates to over half of glaucoma sufferers being unaware of their condition. By the time of diagnosis, irreversible blindness is likely to have occurred. Prime areas of glaucoma research therefore include identification and optimization of risk factors for the disease, accurate and early diagnostic tools and novel therapeutic methods...
November 29, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27896434/towards-a-functional-pathology-of-hereditary-neuropathies
#6
REVIEW
Joachim Weis, Kristl G Claeys, Andreas Roos, Hamid Azzedine, Istvan Katona, J Michael Schröder, Jan Senderek
A growing number of hereditary neuropathies have been assigned to causative gene defects in recent years. The study of human nerve biopsy samples has contributed substantially to the discovery of many of these neuropathy genes. Genotype-phenotype correlations based on peripheral nerve pathology have provided a comprehensive picture of the consequences of these mutations. Intriguingly, several gene defects lead to distinguishable lesion patterns that can be studied in nerve biopsies. These characteristic features include the loss of certain nerve fiber populations and a large spectrum of distinct structural changes of axons, Schwann cells and other components of peripheral nerves...
November 28, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27890860/renal-denervation-by-ct-guided-periarterial-injection-of-hyperosmolar-saline-vincristine-paclitaxel-and-guanethidine-in-a-pig-model
#7
Patrick Freyhardt, Ricardo Donners, Alex Riemert, Jörg Schnorr, Nicola Stolzenburg, Jan Leo Rinnenthal, Ulrich Bernhardt, Bernd Hamm, Rolf W Günther, Florian Streitparth
AIMS: To evaluate feasibility, safety and efficacy of renal sympathetic denervation with CT- guided periarterial injection of potentially neurolytic agents in pigs. METHODS AND RESULTS: Unilateral injection of formulations containing either 5 M hyperosmolar saline, vincristine, paclitaxel or guanethidine around the renal artery was performed in 24 normotensive pigs with 6 animals per group. Needle placement and injections were performed under CT-fluoroscopy guidance...
November 29, 2016: EuroIntervention
https://www.readbyqxmd.com/read/27879566/the-effect-of-an-acid-sensing-ion-channels-asics-inhibitor-on-pain-related-behavior-by-nucleus-pulposus-applied-on-the-nerve-root-in-rats
#8
Yoshihiro Kobayashi, Miho Sekiguchi, Shin-Ichi Konno
STUDY DESIGN: Controlled, interventional, animal study. OBJECTIVE: To examine the effect of an inhibitor of acid-sensing ion channel 3 (ASIC3) on pain-related behavior induced by application of the nucleus pulposus (NP) onto the dorsal root ganglion (DRG) in rats. SUMMARY OF BACKGROUND DATA: ASIC3 is associated with acidosis pain in inflamed or ischemic tissues and is expressed in sensory neurons and NP cells. The ASIC3 inhibitor, APETx2, increases the mechanical threshold of pain in models of knee osteoarthritis or postoperative pain...
November 22, 2016: Spine
https://www.readbyqxmd.com/read/27878135/control-of-the-heart-rate-of-rat-embryos-during-the-organogenic-period
#9
Helen E Ritchie, Carolina Ragnerstam, Elin Gustafsson, Johanna M Jonsson, William S Webster
The aim of this study was to gain insight into whether the first trimester embryo could control its own heart rate (HR) in response to hypoxia. The gestational day 13 rat embryo is a good model for the human embryo at 5-6 weeks gestation, as the heart is comparable in development and, like the human embryo, has no functional autonomic nerve supply at this stage. Utilizing a whole-embryo culture technique, we examined the effects of different pharmacological agents on HR under normoxic (95% oxygen) and hypoxic (20% oxygen) conditions...
2016: Hypoxia
https://www.readbyqxmd.com/read/27863166/validating-metal-organic-framework-nanoparticles-for-their-nanosafety-in-diverse-biomedical-applications
#10
Stefan Wuttke, Andreas Zimpel, Thomas Bein, Simone Braig, Katharina Stoiber, Angelika Vollmar, Dominik Müller, Kirsten Haastert-Talini, Jörn Schaeske, Meike Stiesch, Gesa Zahn, Alexander Mohmeyer, Peter Behrens, Oliver Eickelberg, Deniz A Bölükbas, Silke Meiners
Metal-organic frameworks (MOFs) are promising platforms for the synthesis of nanoparticles for diverse medical applications. Their fundamental design principles allow for significant control of the framework architecture and pore chemistry, enabling directed functionalization for nanomedical applications. However, before applying novel nanomaterials to patients, it is imperative to understand their potential health risks. In this study, the nanosafety of different MOF nanoparticles is analyzed comprehensively for diverse medical applications...
November 15, 2016: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/27863093/potential-effect-of-mechano-growth-factor-e-domain-peptide-on-axonal-guidance-growth-in-primary-cultured-cortical-neurons-of-rats
#11
Meili Liu, Xufeng Niu, Gang Zhou, Zhengtai Jia, Ping Li, Yubo Fan
Establishing appropriate synaptic connections and plasticity is a critical need in neuronal regeneration and development. Mechano growth factor (MGF) and its C-terminal E-domain peptide with 24 amino acids, MGF-Ct24E, are potential neuroprotective agents. Our preliminary study indicates that Netrin-1 can guide axonal growth and its expression is sensitive to MGF, but how MGF regulates the expression of Netrin-1 and its receptor DCC is still unclear. Here, we investigate the effect of MGF-Ct24E on the expression of Netrin-1 and DCC in primary cultured cortical neurons in vitro and the adult rat brain in vivo...
November 15, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27861125/4-aminopyridine-promotes-functional-recovery-and-remyelination-in-acute-peripheral-nerve-injury
#12
Kuang-Ching Tseng, Haiyan Li, Andrew Clark, Leigh Sundem, Michael Zuscik, Mark Noble, John Elfar
Traumatic peripheral nerve damage is a major medical problem without effective treatment options. In repurposing studies on 4-aminopyridine (4-AP), a potassium channel blocker that provides symptomatic relief in some chronic neurological afflictions, we discovered this agent offers significant promise as a small molecule regenerative agent for acute traumatic nerve injury. We found, in a mouse model of sciatic crush injury, that sustained early 4-AP administration increased the speed and extent of behavioral recovery too rapidly to be explained by axonal regeneration...
November 14, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27859240/the-neuroprotective-effect-of-latanoprost-acts-via-klotho-mediated-suppression-of-calpain-activation-after-optic-nerve-transection
#13
Kotaro Yamamoto, Kota Sato, Masayoshi Yukita, Masayuki Yasuda, Kazuko Omodaka, Morin Ryu, Kosuke Fujita, Koji M Nishiguchi, Shigeki Machida, Toru Nakazawa
Latanoprost was first developed for use in glaucoma therapy as an ocular hypotensive agent targeting the prostaglandin F2α (FP) receptor. Subsequently, latanoprost showed a neuroprotective effect, an additional pharmacological action. However, although it is well known that latanoprost exerts an ocular hypotensive effect via the FP receptor, it is not known whether this is also true of its neuroprotective effect. Klotho was firstly identified as the gene linked to the suppression of ageing phenotype: the defect of klotho gene in mice results ageing phenotype such as hypokinesis, arteriosclerosis and short lifespan...
November 15, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27858099/-percutaneous-embolization-and-ultrasound-scissors-for-removal-of-a-carotid-body-tumor
#14
I I Venara-Vulpe, B Morisod, G B Morand, J-B Zerlauth, C Simon
Paragangliomas are highly vascularized usually benign neoplasms originating from the sympathoadrenal and parasympathetic paraganglia of the autonomic nervous system. When resectable, the management of these tumors consists of surgical ablation preceded by transarterial embolization. The aim of this article is to describe a novel treatment strategy combining intralesional percutaneous embolization with dissection using ultrasound scissors. The case of a 74-year-old women presenting with a Shamblin type III carotid body paraganglioma is presented...
December 2016: HNO
https://www.readbyqxmd.com/read/27854511/a-negative-feedback-loop-between-autophagy-and-immune-responses-in-mycobacterium-leprae-infection
#15
Yuelong Ma, Li Zhang, Jie Lu, Tiejun Shui, Jia Chen, Jun Yang, Joanna Yuan, Yeqiang Liu, Degang Yang
The obligate intracellular bacterium Mycobacterium leprae is the causative agent of leprosy and primarily infects macrophages, leading to irreversible nerve damage and deformities. So far, the underlying reasons allowing M. leprae to persist and propagate in macrophages, despite the presence of cellular immunity, are still a mystery. Here, we investigated the role of autophagy, a cellular process that degrades cytosolic materials and intracellular pathogens, in M. leprae infection. We found that live M. leprae infection of macrophages resulted in significantly elevated autophagy level...
November 17, 2016: DNA and Cell Biology
https://www.readbyqxmd.com/read/27854085/co-cccurrence-of-guillain-barre-syndrome-and-primary-sj%C3%A3-gren-syndrome-in-an-elderly-woman
#16
Yu-Kai Lin, Fu-Chi Yang, Feng-Cheng Liu, Jiunn-Tay Lee, Yueh-Feng Sung
PURPOSE: Co-occurrence of Guillain-Barré syndrome (GBS) and other autoimmune diseases is rare. We present the case of a patient with co-occurrence of GBS and primary Sjögren syndrome (pSS). CASE REPORT: An 82-year-old woman presented with acute ascending flaccid paralysis and acute respiratory failure. Nerve conduction studies and cerebrospinal fluid analysis confirmed the diagnosis of GBS of acute inflammatory demyelinating polyradiculoneuropathy subtype. The initial unresponsiveness to plasma exchange therapy raised the suspicion of other potential diseases...
September 15, 2016: Acta Neurologica Taiwanica
https://www.readbyqxmd.com/read/27844147/acute-ivabradine-treatment-reduces-heart-rate-without-increasing-atrial-fibrillation-inducibility-irrespective-of-underlying-vagal-activity-in-dogs
#17
Kazunori Uemura, Masashi Inagaki, Can Zheng, Toru Kawada, Meihua Li, Masafumi Fukumitsu, Masaru Sugimachi
Ivabradine, a bradycardic agent, has been shown to stably reduce patient's heart rate (HR) in the setting of acute cardiac care. However, an association between atrial fibrillation (AF) risk and acute ivabradine treatment remains a controversial clinical issue, and has not been thoroughly investigated. Bradycardia and abnormal atrial refractoriness induced by ivabradine treatment may enhance vulnerability to AF induction, especially when vagal nerve is concurrently activated. We aimed to experimentally investigate the effects of acute ivabradine treatment with/without concurrent vagal activation on AF inducibility...
November 14, 2016: Heart and Vessels
https://www.readbyqxmd.com/read/27834417/inferior-alveolar-nerve-block-for-the-treatment-of-teeth-presenting-with-irreversible-pulpitis-a-systematic-review-of-the-literature-and-meta-analysis
#18
Stefano Corbella, Silvio Taschieri, Francesco Mannocci, Eyal Rosen, Igor Tsesis, Massimo Del Fabbro
OBJECTIVE: The objective of the present systematic review was to evaluate, in patients with irreversible pulpitis affecting mandibular posterior teeth, if premedication with nonsteroidal anti-inflammatory drugs can increase the efficacy of inferior alveolar nerve block (IANB) if compared to placebo administration; if one anesthetic agent is more effective than another; if 1.8 mL injection is more effective than 3.6 mL injection to increase the efficacy of IANB; and if supplementary buccal injection is able to increase the efficacy of IANB as compared to a negative control/placebo group...
November 10, 2016: Quintessence International
https://www.readbyqxmd.com/read/27833160/photothermal-therapy-improves-the-efficacy-of-a-mek-inhibitor-in-neurofibromatosis-type-1-associated-malignant-peripheral-nerve-sheath-tumors
#19
Elizabeth E Sweeney, Rachel A Burga, Chaoyang Li, Yuan Zhu, Rohan Fernandes
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive tumors with low survival rates and the leading cause of death in neurofibromatosis type 1 (NF1) patients under 40 years old. Surgical resection is the standard of care for MPNSTs, but is often incomplete and can generate loss of function, necessitating the development of novel treatment methods for this patient population. Here, we describe a novel combination therapy comprising MEK inhibition and nanoparticle-based photothermal therapy (PTT) for MPNSTs...
November 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27830420/organophosphate-hydrolyzing-enzymes-as-first-line-of-defence-against-nerve-agent-poisoning-perspectives-and-the-road-ahead
#20
REVIEW
A R Satvik Iyengar, Abhay H Pande
Nerve agents (NAs) are extremely neurotoxic synthetic organophosphate (OP) compounds exploited as weapons of mass destruction in terrorist attacks and chemical warfare. Considering the current world scenario, there is a persistent threat of NA-exposure to military personals and civilians. Various prophylactic and post-exposure treatments (such as atropine and oximes) available currently for NA-poisoning are inadequate and unsatisfactory and suffer from severe limitations. Hence, developing safe and effective treatment(s) against NA-poisoning is a critical necessity...
November 9, 2016: Protein Journal
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