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Structure-activity relationship of pyrazol-4-ylpyridine derivatives and identification of a radiofluorinated probe for imaging the muscarinic acetylcholine receptor M4

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Acta Pharmaceutica Sinica B 2023年第1期13卷 213-226页

作者： Ahmed haider Xiaoyun Deng Olivia Mastromihalis Stefanie K.Pfister Troels E.Jeppesen Zhiwei Xiao Vi Pham Shaofa Sun Jian Rong Chunyu Zhao Jiahui Chen Yinlong Li Theresa R.Connors April T.Davenport James B.Daunais Vahid Hosseini Wenqing Ran Arthur Christopoulos Lu Wang Celine Valant Steven H.Liang Department of Radiology Division of Nuclear Medicine and Molecular Imaging Massachusetts General Hospital and Harvard Medical SchoolBostonMA 02114USA Department of Nuclear Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Drug Discovery Biology Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleVIC 3052Australia Neuromedicines Discovery Centre Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleVIC 3052Australia Hubei Collaborative Innovation Centre for Non-power Nuclear Technology College of Nuclear Technology&Chemistry and BiologyHubei University of Science and TechnologyXianning 437100China Department of Neurology Massachusetts General HospitalHarvard Medical SchoolBostonMA 02114USA Department of Physiology and Pharmacology Wake Forest School of MedicineWinston SalemNC 27157USA Terasaki Institute for Biomedical Innovation(TIBI) Los AngelesCA 90024USA Center of Cyclotron and PET Radiopharmaceuticals Department of Nuclear Medicine and PET/CT-MRI Centerthe First Affiliated Hospital of Jinan UniversityGuangzhou 510630China

There is an accumulating body of evidence implicating the muscarinic acetylcholine receptor4(M4)in schizophrenia and dementia with Lewy bodies,however,a clinically validated M4positron emission tomography(PET)radioligand is currently *** such,the aim of this study was to develop a suitable M4PET ligand that allows the non-invasive visualization of M4in the ***-activity relationship studies of pyrazol-4-yl-pyridine derivates led to the discovery of target compound 12—a subtype-selective positive allosteric modulator(PAM).The radiofluorinated analogue,[18F]12,was synthesized in 28±10%radiochemical yield,>37 GBq/μmol and an excellent radiochemical purity>99%.Initial in vitro autoradiograms on rodent brain sections were performed in the absence of carbachol and showed moderate specificity as well as a low selectivity of[18F]12 for the M4-rich ***,in the presence of carbachol,a significant increase in tracer binding was observed in the rat striatum,which was reduced by>60%under blocking conditions,thus indicating that orthosteric ligand interaction is required for efficient binding o f[18F]12 to the allosteric ***,however,the presence of carbachol was not required for high specific binding in the non-human primate(NHP)and human striatum,and did not further improve the specificity and selectivity of[18F]12 in higher *** results pointed towards significant species-differences and paved the way for a preliminary PET study in NHP,where peak brain uptake of[18F]12 was found in the putamen and temporal *** conclusion,we report on the identification and preclinical development of the first radiofluorinated M4PET radioligand with promising *** availability of a clinically validated M4PET radioligand harbors potential to facilitate drug development and provide a useful diagnostic tool for non-invasive imaging.

关键词： Muscarinicacetylcholine receptor Positronemission tomography Neuroimaging Neuropharmacology Neurological disorders

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Assessment of Environmental Changes in the Iraqi Marshes by Index of Biological Integrity

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Journal of Environmental Protection 2012年第7期3卷 681-688页

作者： Azhar A. Al-Saboonchi haider S. Abid Abdul Hameed M. Jawad Alobaidy Bahram K. Maulood Ibrahem M. Abd Department of Biology College of Science for Women University of Baghdad Baghdad IRAQ Department of Fisheries and Marine Resources College of Agriculture University of Basrah Basrah IRAQ Environmental Research Center University of Technology Baghdad IRAQ Nature Iraq Sulaimani IRAQ Twin Rivers Institute American University of Iraq-Sulaimani Sulaimani IRAQ

Preventing water flow through the marshes in southern Iraq was a policy of the previous regime in Iraq during 1990’s. This phenomena lead to tremendous structural changes in ecosystems, however after 2003 rehabilitation policy applied to the area was implementd in order to re-establish marshes ecosystems. In this study, a zooplankton Index of Biotic Integrity (Z-IBI) was measured for the first time in different sites in the Iraqi marshes. The following eight metrics were used: zooplankton ratio, relative abundance of Calanoid, relative abundance of Cyclopoid, relative abundance of Cladocera, relative abundance of Rotifera, biomass of tolerant species, biomass of sensitive species, and ratio of zooplankton biomass to phytoplankton biomass. Results of application of Z-IBI on the Iraqi marshes in this study indicate a slight improvement of water quality in the central marshes and degradation in other parts of the marshes. This work may fill part of the existing research gap in the application of the IBI index in Iraqi inland waters to illustrate the effects of previous deterioration in water quality.

关键词： IBI Nature Iraq Marshes Aquatic Ecology

Therapeutic angiomyogenesis using human non-viral transduced VEGF<sub>165</sub>-myoblasts

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Open Journal of Regenerative Medicine 2012年第1期1卷 1-9页

作者： Peter K. Law Lei Ye Husnain Kh. haider Ping Lu Danlin M. Law Eugene K. W. Sim Cell Therapy Institute Wuhan China Department of Medicine University of Minnesota Minnesota USA Department of Pathology and Laboratory Medicine College of Medicine University of Cincinnati Cincinnati USA Gleneagles JPMC Cardiac Center Brunei Darussalam

This article reviews the scientific development of angiomyogenesis using VEGF165-myoblasts, a patented biotechnology platform in regenerative medicine associated with Human Myoblast Genome Therapy (HMGT), also known as Myoblast Transfer Therapy (MTT). VEGF165-myoblasts are the leading biologics for angiomyogenesis. This review also compares the safety and efficacy of VEGF165-myoblasts transduced using adenoviral vectors, nanoparticles or liposomes, in anticipation of their application in clinical trials in the near future. VEGF165-myoblasts are differentiated myogenic cells capable of extensive division, natural cell fusion, nucleus transfer, cell therapy and genome therapy. Following transplantation they survive, develop and function to revitalize degenerative myocardium in heart failure and ischemic cardiomyopathy animal studies. VEGF165-myoblasts are second generation products of HMGT/MTT which replenishes live cells and genetically repairs degenerating myofibers in Type II diabetes, muscular dystrophies, aging dysfunction and disfigurement. Myoblasts have also been used to enhance skin and muscle appearance in cosmetology. We envision that VEGF165-myoblasts will provide better outcome than their non-tranduced counterparts. Myoblasts are not stem cells. Their competitive advantages over stem cells are presented.

关键词： Angiomyogenesis Cell Therapy Gene Therapy VEGF165-Myoblasts Muscular Dystrophies Heart Failure Ischemic Cardiomyopathy Type II diabetes Anti-Aging Cosmetics Sexual Impotency Baldness Stem Cells

Therapeutic angiomyogenesis using human non-viral transduced VEGF165-myoblasts

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On the Current and Restoration Conditions of the Southern Iraqi Marshes: Application of the CCME WQI on East Hammar Marsh

Open Journal of Regenerative Medicine 2012年第1期1卷 1-9页

作者： Peter K. Law Lei Ye Husnain Kh. haider Ping Lu Danlin M. Law Eugene K. W. Sim Cell Therapy Institute Division of Life Sciences Huazhong University of Science & Technology Department of Medicine University of Minnesota

This article reviews the scientific development of angiomyogenesis using VEGF 165 -myoblasts, a patented biotechnology platform in regenerative medicine associated with Human Myoblast Genome Therapy (HMGT), also known as Myoblast Transfer Therapy (MTT). VEGF 165 -myoblasts are the leading biologics for angiomyogenesis. This review also compares the safety and efficacy of VEGF 165 -myoblasts transduced using adenoviral vectors, nanoparticles or liposomes, in anticipation of their application in clinical trials in the near future. VEGF 165 -myoblasts are differentiated myogenic cells capable of extensive division, natural cell fusion, nucleus transfer, cell therapy and genome therapy. Following transplantation they survive, develop and function to revitalize degenerative myocardium in heart failure and ischemic cardiomyopathy animal studies. VEGF 165 -myoblasts are second generation products of HMGT/MTT which replenishes live cells and genetically repairs degenerating myofibers in Type II diabetes, muscular dystrophies, aging dysfunction and disfigurement. Myoblasts have also been used to enhance skin and muscle appearance in cosmetology. We envision that VEGF 165 -myoblasts will provide better outcome than their non-tranduced counterparts. Myoblasts are not stem cells. Their competitive advantages over stem cells are presented.

关键词： Angiomyogenesis Cell Therapy Gene Therapy VEGF 165 -Myoblasts Muscular Dystrophies Heart Failure Ischemic Cardiomyopathy Type II diabetes Anti-Aging Cosmetics Sexual Impotency Baldness Stem Cells

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Journal of Environmental Protection 2011年第3期2卷 316-322页

作者： Azhar Al-Saboonchi Abdul-Razak M. Mohamed Abdul Hameed M. Jawad Alobaidy haider S. Abid Bahram K. Maulood 不详

Water quality of the East Hammar marsh after restoration was assessed by using the Canadian Council of Ministers of the Environment Water Quality Index (CCME WQI).The model was applied in two approaches based on the historical data and the CCME aquatic life guidelines as objectives. Variables included in the index calculation were Water Temperature, Dissolved Oxygen, Salinity, pH value, Total Nitrogen, Ammonia, Nitrate, Phosphorus and Sodium. The CCME WQI analysis in both approaches reflected that water quality of the East Hammar marsh is rated as poor based on 2005-2006 data, meaning that the conditions of the marsh are often depart from natural or desirable levels particularly in respect to sodium and nitrogenous compounds;it simply has not recovered yet. The results reflect that the marsh area is still far from the current guideline criteria and, too far from restoration.

关键词： WQI Iraqi Marshes Restoration Nature Iraq

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凤眼莲吸收水中化学物质的机理及其利用

世界环境 1986年第3期 8-11页

作者： S.Z.haider 谷立维 Department of Chemistry University of Dhaka Dhaka 2 BANGLADESH

引言当我们考虑处理自然界的生物循环问题时,通常要对水体中有毒的有机和无机金属化合物的平衡状况进行观测。凤眼莲(俗称水葫芦——译注)奇特的快速增殖现象,以及它吸收

关键词：凤眼莲金属离子阳离子 pH 凤眼蓝水生花卉正离子植物膜化学物质

Evaluation of Charcot Neuroarthropathy in Diabetic Foot Disease Patients at Tertiary Hospital

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Surgical Science 2016年第6期7卷 250-257页

作者： Ahmed M. A. Kensarah Nisar haider Zaidi Abdulhaleem Noorwali Hager Aref Ahmed Mohammed Makki Afaf Ghunaim Wail Tashkandi Sara Mohammad Beayari Adel Johari Department of Surgery Faculty of Medicine King Abdulaziz University Hospital King Abdulaziz University Jeddah Saudi Arabia

Purpose: To evaluate Charcot neuroarthropathy in diabetic foot patients at tertiary hospital. Methods and Material: It is a retrospective study from 2005 to 2015 of Charcot foot patients in diabetic patients admitted in King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Sixty-four patients were admitted as diabetic foot disease and were studied by reviewing patients records of demography, pain, discharge, duration of disease, duration and types of diabetes IDDM [Insulin Dependant Diabetes Mellitus] NIDDM [Non Insulin Dependent Diabetes Mellitus], history of trauma, peripheral vascular disease, obesity, hypertension, co-morbid conditions, previous surgery, involvement of fore foot/midfoot/hindfoot, deformity, ulcer and treatment like casts, offloading devices, pharmacological like biphosphonates, debridement, osteotomy, arthrodesis, exostectomy, and amputation. Results: Majority of patients were males (81.2%). Mean age was 61.75 years. Pain was reported in 25% of patients, numbness in 12.5%, foot deformity in 23.4%, pus discharge in 73.4%, difficulty in walking in 12.5%, and 10.9% had history of trauma. Majority of patients were NIDDM 68.8%, IDDM 31.3%, (62.5% had DM more than 10 years and 36.9% had DM less than 10 years), controlled DM in 21.9% and uncontrolled DM in 73.4%, nephropathy in 46.3%, neuropathy in 59.4%, retinopathy in 40.6%, cardiomyopathy in 48.4% and vasculopathy in 56.3%. Charcot arthropathy was in 28.1% of cases and forefoot was involved in 65.5%, midfoot in 4.7% and hindfoot/ankle in 21.9%. It was forefoot which was mainly involved in Charcot joint disease. It was demonstrated by X-rays which showed subluxation in 40.6%, dislocation in 54.7%, disorganized foot joints in 42.2%, bone resorption in 23.4%, osteomyelitis in 14.1%, fractures in 50%, joint collapse in 39.1% and destruction of articular surfaces in 37.5%. Debridement was done in 25% of cases while 75% of patients underwent some sort of amputation. 14.1% of patients underwent above k

关键词： Charcots Diabetes Arthropathy Diabetic Foot Prevalence

Comparison of the reverse bevel versus Franseen type endoscopic ultrasound needle

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World Journal of Gastrointestinal Endoscopy 2020年第9期12卷 266-275页

作者： Chi Wing Chow Syeda Asma haider Krish Ragunath Guruprasad P Aithal Martin W James Jacobo Ortiz-Fernandez-Sordo Aloysious Dominic Aravinthan Suresh Vasan Venkatachalapathy National Institute for Health Research Nottingham Biomedical Research Centre Nottingham University Hospitals National Health Service Trust and University of NottinghamNottingham NG72UHUnited Kingdom Department of Pathology Nottingham University Hospitals National Health Service TrustNottingham NG72UHUnited Kingdom Nottingham Digestive Diseases Centre School of MedicineUniversity of NottinghamNottingham NG72RDUnited Kingdom National Institute for Health Research Nottingham Biomedical Research Centre Nottingham University Hospitals National Health Service Trust and University of NottinghamNottingham NG27UHUnited Kingdom

BACKGROUND Reverse bevel(RB)needle is widely used for endoscopic ultrasound fine needle biopsy(EUS-FNB).A 3-plane symmetrical needle with Franseen geometry(FG)has recently become *** To compare the clinical efficacy of FG to that of RB *** A retrospective cohort study of all adult patients who underwent EUS-FNB for solid and mixed lesions either with 22G RB needle or 22G FG needle between January 2016 and February 2019 was *** cytology slides were reviewed by an independent gastrointestinal cytopathologist blinded to the needle used and the initial cytology *** primary and secondary outcomes were to assess the sample adequacy using Euro-cytology criteria and the number of cell clusters,*** Two hundred and twenty six procedures were included in the *** needle was used in 128 procedures and FG needle in 98 *** baseline characteristics of both groups were *** multivariable analysis,FG needle(P=0.02)and location of the lesion(P<0.01)were independently associated with adequate ***,the use of FG needle(P=0.04)and the size of the lesion(P=0.02)were independently associated with acquisition of increased number of cell *** FG needle is superior to RB needle in acquiring adequate tissue and attaining higher number of cell clusters for solid and mixed lesions.

关键词： Endoscopic ultrasound Fine needle aspiration Fine needle biopsy Reverse bevel Franseen geometry Tissue acquisition

板裂结构岩体边坡弯折变形机制的非连续变形分析

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中外公路 2023年

作者：袁思凡李同录 Mumtaz haider 张常亮李萍黄土高原水循环与地质环境教育部野外科学观测研究站长安大学地质工程与测绘学院

板裂结构岩体边坡弯折变形在水电工程和公路工程边坡中十分常见，成为工程建设和安全运营的隐患之一。现场调查发现，该类岩体弯折破坏多出现在构造应力集中、河流下切强烈和坡度陡的斜坡上，斜坡一般由坚硬的中薄层反倾岩体组成，具有... 详细信息

板裂结构岩体边坡弯折变形在水电工程和公路工程边坡中十分常见，成为工程建设和安全运营的隐患之一。现场调查发现，该类岩体弯折破坏多出现在构造应力集中、河流下切强烈和坡度陡的斜坡上，斜坡一般由坚硬的中薄层反倾岩体组成，具有板裂结构。弯折破坏从宏观上看既不是崩塌，也不是滑坡，而是一种不连续变形，传统用于斜坡稳定性分析的极限平衡法不适合此类斜坡的评价。为此，本文以G108国道在秦岭山区的边坡弯折现象为为例，考虑山体抬升与河谷下切作用，用非连续变形分析(DDA)方法模拟了边坡弯折破坏全过程，分析了其演化形成机制。结果表明，随着河谷下切，岩体在自身重作用下沿片理面层间错动，向河谷方向缓慢倾倒，形成贯通的弯折面以后，转变为滑坡形式破坏。对此类边坡的评价，应采用数值模型模拟其变形破坏的全过程，判断目前所处的状态和发展趋势，以便为加固治理提供依据。

关键词：板裂结构岩体弯折破坏 DDA 河谷侵蚀岩体边坡