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Connexin therapeutics:blocking connexin hemichannel pores is distinct from blocking pannexin channels or gap junctions

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Neural Regeneration Research 2021年第3期16卷 482-488页

作者： Monica L.Acosta Mohd N.Mat Nor Cindy X.Guo Odunayo O.Mugisho Frazer P.Coutinho ilva d.rupenthal Colin R.Green School of Optometry and Vision Science University of AucklandAucklandNew Zealand Faculty of Medicine Universiti Sultan Zainal AbidinTerengganuMalaysia department of Ophthalmology University of AucklandAucklandNew Zealand Buchanan Ocular Therapeutics Unit Department of OphthalmologyAucklandNew Zealand New Zealand National Eye Centre University of AucklandAucklandNew Zealand Centre for Brain Research Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand Brain Research New Zealand–Rangahau Roro Aotearoa AucklandNew Zealand

Compounds that block the function of connexin and pannexin protein channels have been suggested to be valuable therapeutics for a range of *** of these compounds are now in clinical trials,but for many of them,the literature is inconclusive about the molecular effect on the tissue,despite evidence of functional *** the different channel types has distinct physiological and pathological implications and this review describes current knowledge of connexin and pannexin protein channels,their function as channels and possible mechanisms of the channel block effect for the latest therapeutic *** summarize the evidence implicating pannexins and connexins in disease,considering their homeostatic versus pathological roles,their contribution to excesive ATP release linked to disease onset and progression.

关键词： connexin gap junction gap19 hemichannel pannexin retina tonabersat

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development of a novel stability indicating RP-HPLC method for quantification of Connexin43 mimetic peptide and determination of its degradation kinetics in biological fluids

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Journal of Pharmaceutical Analysis 2017年第6期7卷 365-373页

作者： Rohit Bisht ilva d. rupenthal Sreevalsan Sreebhavan Jagdish K. Jaiswal Buchanan Ocular Therapeutics Unit(BOTU) Department of OphthalmologyNew Zealand National Eye CentreFaculty of Medical and Health SciencesUniversity of AucklandAuckland 1142New Zealand Auckland Cancer Society Research Centre Faculty of Medical and Health SciencesUniversity of AucklandAuckland 1142New Zealand

Connexin43 mimetic peptide （Cx43MP） has been intensively investigated for its therapeutic effect in the management of inflammatory eye conditions, spinal cord injury, wound healing and iscbemia-induced brain damage. Here, we report on a validated stability-indicating reversed-phase high performance liquid chromatography （RP-HPLC） method for the quantification of Cx43MP under stress conditions. These included exposure to acid/base, light, oxidation and high temperature. In addition, the degradation kinetics of the peptide were evaluated in bovine vitreous and drug-free human plasma at 37℃. detection of Cx43MP was carried out at 214 nm with a retention time of 7.5 min. The method showed excellent linearity over the concentration range of 0.9-250μg/mL （R2a0.998）, and the limits of detection （LOd） and quantification （LOQ） were found to be 0.90 and 2.98 μg/mL, respectively. The accuracy of the method determined by the mean percentage recovery at 7.8, 62.5 and 250μg/mL was 96.79%, 98.25% and 99.06% with a RSd of〈 2.2%. Accelerated stability studies revealed that Cx43MP was more sensitive to basic conditions and completely degraded within 24 h at 37℃（0% recovery） and within 12 h at 80℃ （0.34% recovery）. Cx43MP was found to be more stable in bovine vitreous （t1/2 slow= 171.8 min） compared to human plasma （t1/2slow = 39.3 min） at 37℃ according to the two phase degradation kinetic model. These findings are important for further pre-clinical development of Cx43MP.

关键词： RP-HPLC determination biological fluids

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Research and development of the back-end electronics for the two-dimensional improved resistive plate chambers in CMS upgrade

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Radiation detection Technology and Methods 2021年第2期5卷 181-191页

作者： P.Cao Z-A.Liu J.Zhao H.Kou J.Tao J.Song W.Gong N.Wang A.Samalan M.Tytgat N.Zaganidis G.A.Alves F.Marujo F.Torres.da.S.ilva.de.Araujo E.M.da Costa d.de Jesus damiao H.Nogima A.Santoro S.Fonseca de Souza A.Aleksandrov R.Hadjiiska P.Iaydjiev M.Rodozov M.Shopova G.Sultanov M.Bonchev A.dimitrov L.Litov B.Pavlov P.Petkov A.Petrov S.J.Qian C.Bernal A.Cabrera J.Fraga A.Sarkar S.Elsayed Y.Assran M.El Sawy M.A.Mahmoud Y.Mohammed X.Chen C.Combaret M.Gouzevitch G.Grenier I.Laktineh L.Mirabito K.Shchablo I.Bagaturia d.Lomidze I.Lomidze V.Bhatnagar R.Gupta P.Kumari J.Singh V.Amoozegar B.Boghrati M.Ebraimi R.Ghasemi M.Mohammadi Najafabadi E.Zareian M.Abbrescia R.Aly W.Elmetenawee N.de Filippis A.Gelmi G.Iaselli S.Leszki F.Loddo I.Margjeka G.Pugliese d.Ramos L.Benussi S.Bianco d.Piccolo S.Buontempo A.di Crescenzo F.Fienga G.de Lellis L.Lista S.Meola P.Paolucci A.Braghieri P.Salvini P.Montagna C.Riccardi P.Vitulo B.Francois T.J.Kim J.Park S.Y.Choi B.Hong K.S.Lee J.Goh H.Lee J.Eysermans C.Uribe Estrada I.Pedraza H.Castilla-Valdez A.Sanchez-Hernandez C.A.Mondragon Herrera d.A.Perez Navarro G.A.Ayala Sanchez S.Carrillo E.Vazquez A.Radi A.Ahmad I.Asghar H.Hoorani S.Muhammad M.A.Shah I.Crotty department of Physics and Astronomy Ghent UniversityProeftuinstraat 869000 GhentBelgium Centro Brasileiro Pesquisas Fisicas R.Dr.Xavier Sigaud150-UrcaRio de JaneiroRJ 22290-180Brazil dep.de Fisica Nuclear e Altas Energias Instituto de FisicaUniversidade do Estado do Rio de JaneiroRua Sao Francisco Xavier524BR-Rio de Janeiro 20559-900RJBrazil Bulgarian Academy of Sciences Inst.for Nucl.Res.and Nucl.EnergyTzarigradsko shaussee Boulevard 721784 SofiaBulgaria Faculty of Physics University of Sofia5 James Bourchier Boulevard1164 SofiaBulgaria School of Physics Peking UniversityBeijing 100871China Institute of High Energy Physics UCAS/CAS19(B)Yuquan RoadShijingshan DistrictBeijing 100049China Universidad de Los Andes Apartado Aereo 4976Carrera 1Eno.18A 10BogotaCOColombia Egyptian Network for High Energy Physics Academy of Scientific Research and Technology101 Kasr El-Einy St.CairoEgypt The British University in Egypt(BUE) P.O.Box 43Elsherouk CitySuez Desert RoadCairo 11837Egypt Suez University Elsalam CitySuez-Cairo RoadSuez 43522Egypt department of Physics Faculty of ScienceBeni-Suef UniversityBeni-SuefEgypt Center for High Energy Physics Faculty of ScienceFayoum UniversityEl-Fayoum 63514Egypt Univ Lyon Univ Claude Bernard Lyon 1CNRS/IN2P3IP2I LyonUMR 582269622 VilleurbanneFrance Georgian Technical University 77 Kostava Str.Tbilisi 0175Georgia department of Physics Panjab UniversityChandigarh 160014India School of Particles and Accelerators Institute for Research in Fundamental Sciences(IPM)P.O.Box 19395-5531TehranIran School of Engineering Damghan UniversityDamghan ***Iran INFN Sezione di BariVia Orabona 470126 BariItaly INFN Laboratori Nazionali di Frascati(LNF)Via Enrico Fermi 4000044 FrascatiItaly INFN Sezione di NapoliComplesso Univ.Monte S.AngeloVia Cintia80126 NaplesItaly INFN Sezione di PaviaVia Bassi 6PaviaItaly INFN Sezione di Pavia and University of PaviaVia Bassi 6PaviaItaly Hanyang University 222 Wangsimni-roSageun-dongSeongdong

Purpose To complement and ensure redundancy in the endcap muon system of the Compact Muon Solenoid(CMS)detector and to extend the Resistive Plate Chamber(RPC)system coverage,improved RPCs(iRPCs)with either orthogonal layer strips with one-end electronics or single layer strips with two-end electronics providing more precise time measurement will be installed in the very forward pseudorapidity region of|η|dout system needs to support twodimensional(2d)or two-end *** addition,it must combine detector data with Timing,Trigger and fast Control(TTC)and Slow Control(SC)into one data stream over a bi-directional optical link with a line rate of 4.8 Gb/s between the Front-End Electronics(FEE)and the Back-End Electronics(BEE).To fulfill these requirements,a prototype BEE for the iRPC 2d chamber has been researched and *** A Micro-Telecommunication and Computing Architecture(μTCA)-based processing card was designed in this study to establish a prototype system together with aμTCA *** Giga-Bit Transceiver(GBT)protocol is integrated to provide bi-directional communication between the FEE and BEE.A server is connected with the BEE by a Gigabit Ethernet(GbE)link for SC and a 10-GbE link for data AcQuisition(dAQ).Results The Bit Error Rate(BER)test of the back-end board and a joint test with the iRPC 2d prototype chamber were *** less than 1.331×10−16 was *** timemeasurement with a resolution of 3.05 nswas successfully realized,and detector efficiencies of 97.7%for longitudinal strips and 96.0%for orthogonal strips were *** results demonstrate the correctness and reliability of the prototype *** The BEE prototype satisfies the requirements for the iRPC 2d chamber,and it worked stably and reliably during a long-term joint test run.

关键词： CMS iRPC TTC SC BEE μTCA GBT dAQ

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