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nerve agents

Matthew Osmond, Sarah M Bernier, Mina B Pantcheva, Melissa D Krebs
Glaucoma is a disease in which damage to the optic nerve leads to progressive, irreversible vision loss. The intraocular pressure (IOP) is the only modifiable risk factor for glaucoma and its lowering is considered a useful strategy for preventing or slowing down the progression of glaucomatous neuropathy. Elevated intraocular pressure associated with glaucoma is due to increased aqueous humor outflow resistance, primarily through the trabecular meshwork (TM) of the eye. Current in vitro models of the trabecular meshwork are oversimplified and do not capture the organized and complex three-dimensional nature of this tissue that consists primarily of collagen and glycoasaminoglycans...
October 24, 2016: Biotechnology and Bioengineering
Ivan V Smirnov, Andrey V Golovin, Spyros D Chatziefthimiou, Anastasiya V Stepanova, Yingjie Peng, Olga I Zolotareva, Alexey A Belogurov, Inna N Kurkova, Natalie A Ponomarenko, Matthias Wilmanns, G Michael Blackburn, Alexander G Gabibov, Richard A Lerner
In vitro selection of antibodies from large repertoires of immunoglobulin (Ig) combining sites using combinatorial libraries is a powerful tool, with great potential for generating in vivo scavengers for toxins. However, addition of a maturation function is necessary to enable these selected antibodies to more closely mimic the full mammalian immune response. We approached this goal using quantum mechanics/molecular mechanics (QM/MM) calculations to achieve maturation in silico. We preselected A17, an Ig template, from a naïve library for its ability to disarm a toxic pesticide related to organophosphorus nerve agents...
October 2016: Science Advances
Jeffrey L Langston, Todd M Myers
The present experiments determined the intramuscular LD50 of VX in male Göttingen minipigs at two stages of development. In pubertal animals (115days old), the LD50 of VX was indeterminate, but approximated 33.3μg/kg. However, in sexually mature animals (152days old), the LD50 was estimated to be only 17.4μg/kg. Signs of nerve agent toxicity in the Göttingen minipig were similar to those described for other species, with some notable exceptions (such as urticaria and ejaculation). Latencies to the onset of sustained convulsions were inversely related to the administered dose of VX in both ages of minipigs...
October 20, 2016: Toxicology Letters
Trond Myhrer, Pål Aas
The threat of chemical warfare agents like nerve agents requires life saving measures of medical pretreatment combined with treatment after exposure. Pretreatment (pyridostigmine) may cause some side effects in a small number of individuals. A comprehensive research on animals has been performed to clarify effects on behavior. The results from these studies are far from unambiguous, since pyridostigmine may produce adverse effects on behavior in animals in relatively high doses, but not in a consistent way...
October 20, 2016: Neuroscience and Biobehavioral Reviews
Jue Hu, Dan Kai, Hongye Ye, Lingling Tian, Xin Ding, Seeram Ramakrishna, Xian Jun Loh
Nerve tissue engineering (TE) requires biomimetic scaffolds providing essential chemical and topographical cues for nerve regeneration. Poly(glycerol sebacate) (PGS) is a biodegradable and elastic polymer that has gained great interest as a TE scaffolding biomaterial. However, uncured PGS is difficult to be electrospun into nanofibers. PGS would, therefore, require the addition of electrospinning agents. In this study, we modified PGS by using atom transfer radical polymerization (ATRP) to synthesize PGS-based copolymers with methyl methacrylate (MMA)...
January 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
Swarupa Kancherla, William J Kohler, Yolandi van der Merwe, Kevin C Chan
Visual function has been shown to deteriorate prior to the onset of retinopathy in some diabetic patients and experimental animal models. This suggests the involvement of the brain's visual system in the early stages of diabetes. In this study, we tested this hypothesis by examining the integrity of the visual pathway in a diabetic rat model using in vivo multi-modal magnetic resonance imaging (MRI). Ten-week-old Sprague-Dawley rats were divided into an experimental diabetic group by intraperitoneal injection of 65 mg/kg streptozotocin in 0...
2016: PloS One
Tomohiro Yamashita, Shota Yamamoto, Jiaming Zhang, Miho Kometani, Daisuke Tomiyama, Keita Kohno, Hidetoshi Tozaki-Saitoh, Kazuhide Inoue, Makoto Tsuda
P2X4 receptors (P2X4R) are a family of ATP-gated non-selective cation channels. We previously demonstrated that activation of P2X4R in spinal microglia is crucial for neuropathic pain, a highly debilitating chronic pain condition, suggesting that P2X4R is a potential therapeutic target for treating neuropathic pain. Thus, the identification of a compound that has a potent inhibitory effect on P2X4R is an important clinical challenge. In the present study, we screened a chemical library of clinically approved drugs and show for the first time that duloxetine, a serotonin and noradrenaline reuptake inhibitor, has an inhibitory effect on rodent and human P2X4R...
2016: PloS One
Sheng-Jie Shiue, Chi-Hsu Wang, Tao-Yeuan Wang, Yi-Chun Chen, Jen-Kun Cheng
OBJECTIVE: T-type channel (TCC) CaV3.2 plays a pivotal role in pain transmission. In this study, we examined the effects of intrathecal TCC blockers on CaV3.2 expression in a L5/6 spinal nerve ligation (SNL) pain model. The neurotoxicity of TCC blockers were also evaluated. METHODS: Male Sprague-Dawley rats (200-250 g) were used for right L5/6 SNL to induce neuropathic pain. Intrathecal infusion of saline or TCC blockers [mibefradil (0.7 μg/h) or ethosuximide (60 μg/h)] was started after surgery for 7 days...
October 17, 2016: Acta Anaesthesiologica Taiwanica: Official Journal of the Taiwan Society of Anesthesiologists
Marina Hovakimyan, Oliver Stachs, Olmiere Céline, Rudolf F Guthoff
PURPOSE: Corneal collagen cross-linking (CXL) is associated with massive cellular damage, the long-term clinical consequences of which have still to be elucidated. In this study, we seek to determine whether matrix-based regenerating agent (RGTA) therapy has a positive influence on stromal regeneration after CXL. METHODS: Twelve New Zealand white rabbits were randomly divided into 2 groups of 6. CXL of the right cornea was performed in both groups, followed by topical corneal application of one drop of vehicle or one drop of RGTA...
October 14, 2016: Cornea
Michael J Murray, Heidi DeBlock, Brian Erstad, Anthony Gray, Judi Jacobi, Che Jordan, William McGee, Claire McManus, Maureen Meade, Sean Nix, Andrew Patterson, M Karen Sands, Richard Pino, Ann Tescher, Richard Arbour, Bram Rochwerg, Catherine Friederich Murray, Sangeeta Mehta
OBJECTIVE: To update the 2002 version of "Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient." DESIGN: A Task Force comprising 17 members of the Society of Critical Medicine with particular expertise in the use of neuromuscular-blocking agents; a Grading of Recommendations Assessment, Development, and Evaluation expert; and a medical writer met via teleconference and three face-to-face meetings and communicated via e-mail to examine the evidence and develop these practice guidelines...
November 2016: Critical Care Medicine
Lluís Pascual, Sameh El Sayed, Ramón Martínez-Máñez, Ana M Costero, Salvador Gil, Pablo Gaviña, Félix Sancenón
Mesoporous silica nanoparticles loaded with rhodamine B and capped with acetylcholinesterase are able to be selectively opened and deliver their cargo in the presence of nerve agent simulant diisopropyl fluorophosphate (DFP).
October 18, 2016: Organic Letters
F Sakakibara, K Takahama, M Nanri, E Sasaki
Patients with spinal cord injury (SCI) usually develop lower urinary tract dysfunctions, including detrusor overactivity which is also known to be a risk factor for upper urinary tract dysfunction. Antimuscarinic agents, such as propiverine, have been used clinically for the treatment of detrusor overactivity. Also, propiverine has been known to possess antagonistic activity against L-type Ca(2+) channels and transient receptor potential vanilloid subtype 1 (TRPV1), in addition to activity against muscarinic receptors...
September 2016: Drug Research
Rafael da Costa Monsanto, Aline Gomes Bittencourt, Natal José Bobato Neto, Silvia Carolina Almeida Beilke, Fabio Tadeu Moura Lorenzetti, Raquel Salomone
Introduction Ramsay Hunt syndrome is the second most common cause of facial palsy. Early and correct treatment should be performed to avoid complications, such as permanent facial nerve dysfunction. Objective The objective of this study is to review the prognosis of the facial palsy on Ramsay Hunt syndrome, considering the different treatments proposed in the literature. Data Synthesis We read the abstract of 78 studies; we selected 31 studies and read them in full. We selected 19 studies for appraisal...
October 2016: International Archives of Otorhinolaryngology
Yahya Baltu, Hakan Uzun, Guzin Yesim Özgenel
BACKGROUND: The postoperative development of epineural and extraneural scar tissue adversely affects peripheral nerve surgery outcomes. Although several surgical methods, pharmacological agents, and chemical materials have been used to prevent epineural scar formation in both clinical and experimental models, the results are still unsatisfactory. The purpose of this study was to investigate the efficacy of buccal mucosa graft (BMG) wrapping on epineural scarring in an adult rat model...
October 14, 2016: Journal of Plastic Surgery and Hand Surgery
Ruihe Lin, Jingli Cai, Eric W Kostuk, Robert Rosenwasser, Lorraine Iacovitti
BACKGROUND: Dimethyl fumarate (DMF), working via its metabolite monomethylfumarate (MMF), acts as a potent antioxidant and immunomodulator in animal models of neurologic disease and in patients with multiple sclerosis. These properties and their translational potential led us to investigate whether DMF/MMF could also protect at-risk and/or dying neurons in models of ischemic stroke in vitro and in vivo. Although the antioxidant effects have been partially addressed, the benefits of DMF immunomodulation after ischemic stroke still need to be explored...
October 13, 2016: Journal of Neuroinflammation
Manuel P Pereira, Sebastian Mühl, Esther M Pogatzki-Zahn, Konstantin Agelopoulos, Sonja Ständer
In recent years, measurement of the intraepidermal nerve fiber (IENF) density has gained relevance in the diagnostics of chronic pruritus. This method allows the objectification and quantification of a small-fiber neuropathy, which may manifest clinically with pruritus, pain or dysesthetic sensory symptoms, such as burning, stinging and tingling sensations or numbness. Upon suspicion of a small-fiber neuropathy as a cause for chronic pruritus, targeted diagnostic procedures are essential for the early detection of the neuroanatomical changes...
October 11, 2016: Dermatology and Therapy
Rudra Prasad Roy, Kaushik Ghosh, Manas Ghosh, Amitava Acharyya, Ambarish Bhattacharya, Mrinal Pal, Sisir Chakraborty, Nilanjan Sengupta
BACKGROUND: Long-term therapy with metformin was shown to decrease the Vitamin B12 level and manifested as peripheral neuropathy. AIM: The aim of this study is to define the prevalence of Vitamin B12 deficiency in early Type 2 diabetic patients (duration ≤5 years or drug treatment ≤3 years) and the relationship among metformin exposure and levels of cobalamin (Cbl), folic acid, and homocysteine (Hcy) with severity of peripheral neuropathy. METHODOLOGY: This is a cross-sectional study involving randomly selected ninety patients (male 56, female 34) between age groups of 35 and 70 years, comparing those who had received >6 months of metformin (Group A) (n = 35) with those without metformin (Group B) (n = 35) and patients taking metformin with other oral hypoglycemic agent (Group C) (n = 20)...
September 2016: Indian Journal of Endocrinology and Metabolism
David Daewhan Kim, Nabil Sibai
INTRODUCTION: Greater occipital nerve blocks (GONB) have been used for headache but their benefit may be short. Ready et al performed intrathecal injections on rabbits and reported neurologic/histologic changes that required concentrations of at least 8%. Our study tests the hypothesis that the neurolytic effects of GONB with 10% lidocaine can prolong relief. METHODS: After an approval from Henry Ford Hospital Institutional Review Board, a chart review was performed for patients who had GONB with 10% lidocaine...
2016: Journal of Pain Research
Daniel Horák, Milan Beneš, Zuzana Procházková, Miroslava Trchová, Arsenii Borysov, Artem Pastukhov, Konstantin Paliienko, Tatiana Borisova
Changes in cholesterol concentration in the plasma membrane of presynaptic nerve terminals nonspecifically modulate glutamate transport and homeostasis in the central nervous system. Reduction of the cholesterol content in isolated rat brain nerve terminals (synaptosomes) using cholesterol-depleting agents decreases the glutamate uptake and increases the extracellular level of glutamate in nerve terminals. Extraction of cholesterol from the plasma membrane and its further removal from the synaptosomes by external magnetic field can be achieved by means of magnetic nanoparticles with immobilized cholesterol-depleting agent such as O-methyl-β-cyclodextrin (MCD)...
October 4, 2016: Colloids and Surfaces. B, Biointerfaces
Chang-Cai Liu, Gui-Lan Huang, Hai-Ling Xi, Shi-Lei Liu, Jing-Quan Liu, Hui-Lan Yu, Shi-Kun Zhou, Long-Hui Liang, Ling Yuan
This work describes a novel and sensitive non-isotope dilution method for simultaneous quantification of organophosphorus nerve agents (OPNAs) soman (GD) and VX adducts to butyrylcholinesterase (BChE), their aged methylphosphonic acid (MeP) adduct and unadducted BChE in plasma exposed to OPNA. OPNA-BChE adducts were isolated with an off-column procainamide-gel separation (PGS) from plasma, and then digested with pepsin into specific adducted FGES(*)AGAAS nonapeptide (NP) biomarkers. The resulting NPs were detected by UHPLC-MS/MS MRM...
October 3, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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