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Transdermal delivery of 4-aminopyridine accelerates motor functional recovery and improves nerve morphology following sciatic nerve crush injury in mice

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Neural Regeneration Research 2020年第1期15卷 136-144页

作者： Andrew RClark Chia George Hsu m A Hassan Talukder mark Noble john CElfar Center for Orthopaedic Research and Translational Science Penn State Hershey College of MedicineMilton S.Hershey Medical CenterHersheyPAUSA Department of Orthopaedics The University of Rochester Medical CenterRochesterNYUSA Department of medicine Aab Cardiovascular Research InstituteUniversity of Rochester School of Medicine and DentistryRochesterNYUSA Department of Biomedical Genetics The University of Rochester Medical CenterRochesterNYUSA

Oral 4-aminopyridine(4-AP)is clinically used for symptomatic relief in multiple sclerosis and we recently demonstrated that systemic 4-AP had previously unknown clinically-relevant effects after traumatic peripheral nerve injury including the promotion of re-myelination,improvement of nerve conductivity,and acceleration of functional *** hypothesized that,instead of oral or injection administration,transdermal 4-AP(TD-4-AP)could also improve functional recovery after traumatic peripheral nerve *** with surgical traumatic peripheral nerve injury received TD-4AP or vehicle alone and were examined for skin permeability,pharmacokinetics,functional,electrophysiological,and nerve morphological properties.4-AP showed linear pharmacokinetics and the maximum plasma 4-AP concentrations were proportional to TD-4-AP *** a single dose of TD-4-AP administration demonstrated rapid transient improvement in motor function,chronic TD-4-AP treatment significantly improved motor function and nerve conduction and these effects were associated with fewer degenerating axons and thicker myelin sheaths than those from vehicle *** findings provide direct evidence for the potential transdermal applicability of 4-AP and demonstrate that 4-AP delivered through the skin can enhance in-vivo functional recovery and nerve conduction while decreasing axonal *** animal experiments were approved by the University Committee on Animal Research(UCAR)at the University of Rochester(UCAR-2009-019)on march 31,2017.

关键词： 4-aminopyridine electron microscopy functional recovery nerve conduction velocity peripheral nerve injury pharmacokinetics transdermal administration

GDNF to the rescue:GDNF delivery effects on motor neurons and nerves,and muscle re-innervation after peripheral nerve injuries

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Neural Regeneration Research 2022年第4期17卷 748-753页

作者： Alberto F.Cintrón-Colón Gabriel Almeida-Alves Juliana m.VanGyseghem john m.Spitsbergen Biological Sciences Department Western Michigan UniversityKalamazooMIUSA

Peripheral nerve injuries commonly occur due to trauma,like a traffic *** nerves get severed,causing motor neuron death and potential muscle *** current golden standard to treat peripheral nerve lesions,especially lesions with large(≥3 cm)nerve gaps,is the use of a nerve autograft or reimplantation in cases where nerve root avulsions *** not tended early,degeneration of motor neurons and loss of axon regeneration can occur,leading to loss of *** surgical procedures exist,patients often do not fully recover,and quality of life *** nerves have limited regeneration,and it is usually mediated by Schwann cells and neurotrophic factors,like glial cell line-derived neurotrophic factor,as seen in Wallerian *** cell line-derived neurotrophic factor is a neurotrophic factor known to promote motor neuron survival and neurite *** cell line-derived neurotrophic factor is upregulated in different forms of nerve injuries like axotomy,sciatic nerve crush,and compression,thus creating great interest to explore this protein as a potential treatment for peripheral nerve *** glial cell line-derived neurotrophic factor has shown positive effects in regeneration and functional recovery when applied in experimental models of peripheral nerve *** this review,we discuss the mechanism of repair provided by Schwann cells and upregulation of glial cell line-derived neurotrophic factor,the latest findings on the effects of glial cell line-derived neurotrophic factor in different types of peripheral nerve injuries,delivery systems,and complementary treatments(electrical muscle stimulation and exercise).Understanding and overcoming the challenges of proper timing and glial cell line-derived neurotrophic factor delivery is paramount to creating novel treatments to tend to peripheral nerve injuries to improve patients'quality of life.

关键词： electrical muscle stimulation exercise glial cell line-derived neurotrophic factor glial cell line-derived neurotrophic factor delivery motor neuron nerve gap neurotrophic factor peripheral nerve injury Schwann cells skeletal muscle atrophy

Development of 3-actoxymethoxycarbonyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl as an electron paramagnetic resonance imaging reagent for in vivo mapping brain oxygen distribution and infarction in ischemic brain

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生物物理学报 2009年第S1期25卷 101-101页

作者： Gerald m.rosen Department of Pharmaceutical Sciences School of Pharmacy University of Maryland

measurement of oxygen concentration and distribution in brain is essential to understanding the pathophysiology of stroke. Although brain oxygen level is critical for brain tissue survival,

关键词： Development of 3-actoxymethoxycarbonyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl as an electron paramagnetic resonance imaging reagent for in vivo mapping brain oxygen distribution and infarction in ischemic brain

Systemic IL-27 administration prevents abscess formation and osteolysis via local neutrophil recruitment and activation

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Bone Research 2022年第4期10卷 826-837页

作者： Yugo morita motoo Saito Javier Rangel-moreno Anthony m.Franchini john R.Owen john C.martinez john L.Daiss Karen L.de mesy Bentley Stephen L.Kates Edward m.Schwarz Gowrishankar muthukrishnan Center for musculoskeletal Research University of Rochester Medical CenterRochesterNYUSA Division of Allergy Immunology and RheumatologyDepartment of MedicineUniversity of Rochester Medical CenterRochesterNYUSA Department of Environmental medicine University of Rochester School of Medicine and DentistryRochesterNYUSA Department of Orthopedic Surgery Virginia Commonwealth UniversityRichmondVAUSA Department of Orthopedics University of Rochester Medical CenterRochesterNYUSA Department of Pathology and Laboratory medicine University of Rochester Medical CenterRochesterNYUSA

Interleukin-27 is a pleiotropic cytokine whose functions during bacterial infections remain controversial,and its role in patients with *** osteomyelitis is *** address this knowledge gap,we completed a clinical study and observed elevated serum IL-27 levels(20-fold higher,Pmpared with healthy ***,IL-27 serum levels were 60-fold higher in patients immediately following septic death than in uninfected patients(Pmyelitis in WT and IL-27Rα^(−/−)mice with and without exogenous IL27 induction by intramuscular injection of rAAV-IL-27p28 or rAAV-GFP,*** found that IL-27 was induced at the surgical site within 1 day of *** infection of bone and was expressed by m0,m1 and m2 macrophages and osteoblasts but not by ***,exogenous IL-27p28(~2 ng·mL^(−1) in serum)delivery ameliorated soft tissue abscesses and periimplant bone loss during infection,accompanied by enhanced local IL-27 expression,significant accumulation of RORγt^(+)neutrophils at the infection site,a decrease in RANK^(+) cells,and compromised osteoclast *** effects were not observed in IL-27Rα^(−/−)mice compared with WT mice,suggesting that IL-27 is dispensable for immunity but mediates redundant immune and bone cell functions during *** vitro studies and bulk RNA-seq of infected tibiae showed that IL-27 increased nos1,nos2,il17α,il17f,and rorc expression but did not directly stimulate ***,these results identify a novel phenomenon of IL-27 expression by osteoblasts immediately following *** infection of bone and suggest a protective role of systemic IL-27 in osteomyelitis.

关键词： abscess protective immunity

Coal rib response during bench mining: A case study

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International Journal of mining Science and Technology 2018年第1期28卷 107-113页

作者： morgan m.Sears john Rusnak mark Van Dyke Gamal Rashed Khaled mohamed michael Sloan Ground Control Branch NIOSH Pittsburgh Mining Research Division

In 2016, room-and-pillar mining provided nearly 40% of underground coal production in the United *** the past decade, rib falls have resulted in 12 fatalities, representing 28% of the ground fall fatalities in *** coal *** of these 12 fatalities(75%) have occurred in room-andpillar *** objective of this research is to study the geomechanics of bench room-and-pillar mining and the associated response of high pillar ribs at overburden depths greater than 300 *** paper provides a definition of the bench technique, the pillar response due to loading, observational data for a case history, a calibrated numerical model of the observed rib response, and application of this calibrated model to a second site.

关键词： Deep cover Bench mining Thick seam Retreat mining Rib response Rib support

THE NEED FOR ALTERNATIVE ASSAYS TO BACTERIAL GROWTH INHIBITION FOR THE CONTROL OF ANTITUmOUR ANTIBIOTICS

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中国抗生素杂志 1984年第6期9卷 504-506+500页

作者： john m. C. Gutteridge Division of Antibiotics and Chemistry London National Institute for Biological Standards and Control

Antitumour Antibiotics Antibacterial activity,in mose cases,led to the discovery and isolationof antitumour antibiotics although,becauseof their high toxicity,they areseldom considered for clinical treatmentof *** propertieshave,however,continued to beused as the basis for their standardisationand *** use of inhibitionof microbial growth by these drugs forthese purposes offers several advantagesof which relative simplicity,thepossibility of some level of automatonand the attainment of a high degreeof precision,are *** obviousquestion that must arise from such

关键词： BLm DNA THE NEED FOR ALTERNATIVE ASSAYS TO BACTERIAL GROWTH INHIBITION FOR THE CONTROL OF ANTITUmOUR ANTIBIOTICS

Evidence of proteins, chromosomes and chemical markers of DNA in exceptionally preserved dinosaur cartilage

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National Science Review 2020年第4期7卷 815-822页

作者： Alida m.Bailleul Wenxia Zheng john R.Horner Brian K.Hall Casey m.Holliday mary H.Schweitzer Key Laboratory of Vertebrate Evolution and Human Origins Institute of Vertebrate Paleontology and Paleoanthropology Chinese Academy of Sciences CAS Center for Excellence in Life and Paleoenvironment Department of Biological Sciences North Carolina State University Department of Geology University of Lund Honors Program Chapman University Department of Pathology and Anatomical Sciences University of Missouri North Carolina museum of Natural Sciences Department of Biology Dalhousie University

A histological ground-section from a duck-billed dinosaur nestling(Hypacrosaurus stebingeri) revealed microstructures morphologically consistent with nuclei and chromosomes in cells within calcified *** hypothesized that this exceptional cellular preservation extended to the molecular level and had molecular features in common with extant avian cartilage. Histochemical and immunological evidence supports in situ preservation of extracellular matrix components found in extant cartilage, including glycosaminoglycans and collagen type II. Furthermore, isolated Hypacrosaurus chondrocytes react positively with two DNA intercalating stains. Specific DNA staining is only observed inside the isolated cells, suggesting endogenous nuclear material survived fossilization. Our data support the hypothesis that calcified cartilage is preserved at the molecular level in this mesozoic material, and suggest that remnants of once-living chondrocytes, including their DNA, may preserve for millions of years.

关键词： cartilage dinosaur nuclei chromosomes collagen Ⅱ DNA markers

LIQUID CRYSTAL BASED ROTATING ORTHOGONAL POLARIZATION ImAGING SYSTEm

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Journal of Innovative Optical Health Sciences 2009年第3期2卷 245-251页

作者： QUN ZHU IAN m.STOCKFORD john A.CROWE STEPHEN P.mORGAN School of Electrical and Electronic Engineering University of Nottingham University Park NottinghamUK NG72RD

Rotating orthogonal polarization imaging provides images of the polarization properties of scattering media which are free from surface *** the technique has been demonstrated using manually rotated Glan–Thompson polarizers to control and analyze the polarization state of the light entering and emerging from the *** paper describes a system that performs these functions using liquid crystal *** system is tested using a polarizing target embedded within a scattering medium and is compared with monte Carlo *** results compare well with those obtained with manual rotation of *** liquid crystal based approach has advantages over the previous system in terms of ease of use,speed,and repeatability and is therefore an important step towards taking the technique into routine clinical use.

关键词： Liquid crystal polarization orthogonal surface reflection scattering tissue.

Digital capture of fingerprints in a disaster victim identification setting:a review and case study

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Forensic Sciences Research 2019年第4期4卷 293-302页

作者： Bryan T.johnson john A.J.m.Riemen Federal Bureau of Investigation QuanticoVAUSA Dutch National Police ZoetermeerThe Netherlands

Identification of victims following a mass fatality is conducted by collecting and analysing a series of scientific identifiers and contextual information of each ***,there has been a paradigm shift demanding that this complex identification process be accelerated to meet the needs of the surviving families,politicians and even the *** fingerprint identification is a fast and efficient means of victim identification,and through the use of new advances in technology,the digital capture of fingerprints in a disaster victim identification(DVI)setting will play a strong *** paper provides an overview of current technology and explains how this technology can adapt to current DVI *** malaysian Airlines Flight 17(mH17)incident is a recent example of a DVI event that utilized new digital fingerprint capture technology and further demonstrates why such technology is warranted in future mass fatality operations.

关键词： Forensic sciences disaster victim identification postmortem fingerprints digital fingerprint capture INTERPOL DVI ridgeology