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Novel small molecule retrograde transport blocker confers post-exposure protection against ricin intoxication

Acta Pharmaceutica Sinica B 2020年第3期10卷 498-511页

作者： Xu Zhao Haixia Li Jia Li Kunlu Liu Bo Wang Yuxia Wang Xingzhou Li Wu Zhong National Engineering Research Center for the Emergency Drug Beijing Institute of Pharmacology and ToxicologyBeijing 100850China State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijing 100850China

Ricin is a highly toxic type 2 ribosome-inactivating protein(RIP)which is extracted from the seeds of castor *** is considered a potential bioterror agent and no effective antidote for ricin exists so *** this study,by structural modification of a retrograde transport blocker Retro-2cyc1,a series of novel compounds were *** primary screen revealed that compound 27 has an improved antiricin activity compare to positive *** vitro pre-exposure evaluation in Madin-Darby Canine Kidney(MDCK)cells demonstrated that 27 is a powerful anti-ricin compound with an EC50 of 41.05 nmol/L against one LC(lethal concentration,5.56 ng/mL)of *** studies surprisingly indicated that 27 confers post-exposure activity against ricin *** in vivo study showed that 1 h post-exposure administration of 27 can improve the survival rate as well as delay the death of ricin-intoxicated mice.A drug combination of 27 with monoclonal antibody mAb4 C13 rescued mice from one LD(lethal dose)ricin challenge and the survival rate of tested animals is 100%.These results represent,for the first time,indication that small molecule retrograde transport blocker confers both in vitro and in vivo post-exposure protection against ricin and therefore provides a promising candidate for the development of anti-ricin medicines.

关键词： Ricin toxin Ribosome-inactivating proteins Retrograde transport post-exposure antidote Ricin antibody

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post-exposure Prophylaxis against HBV and HIV Infection in Health Care Workers

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Advances in Infectious Diseases 2013年第3期3卷 193-199页

作者： Azar Hadadi Mojgan Karbakhsh Mehrnaz Rasoolinejad Mahboobeh Haji Abdolbaghi Nahid Hadadi Shirin Afhami Negin Esmaeelpour-Bazzaz Internal Medicine Ward Sina Hospital Tehran University of Medical Sciences Tehran Iran

Healthcare Workers (HCWs) are constantly at risk of exposure to viral infections such as hepatitis B virus (HBV), human immune deficiency virus (HIV) and hepatitis C virus (HCV). We aim at demonstrating the results of a three-year period of a surveillance program in Iran with the prospective follow-up of HCWs exposed to blood-borne viruses. HCWs who had experienced an occupational exposure to HBV, HCV or HIV from September 2005 to 2008 were enrolled in the study. Age, gender, route of exposure, type of fluid, type of virus, job, department, working shift, work experience, wearing gloves when exposed, history of HBV vaccination and the serum level of anti HBs antibody were recorded for all participants through an individual interview. Serum samples were taken from both HCWs and the sources of exposure and were tested by enzyme linked immunosorbent assay (ELISA). The data were gathered through questionnaires completed by a nurse under the supervision of a specialist of infectious diseases. In this study, 100 HCWs who were occupationally exposed to HIV, HCV or HBV were included. Most exposures had occurred among nurses (35%), followed by residents (29%), interns (18%), housekeepers (7%), the lab staff (6%), and specialists (5%). Most of the exposures had occurred in emergency (21%) and surgical (20%) wards. The most common route of exposure was percutaneous injuries (77%) and the most common cases had contacted with needles and angiocaths (71.1%) during injection or opening vein routes (21%). Establishing a surveillance system for registering the occurrence of occupational hazardous exposures, performing prophylactic measures and following up the exposed is a necessity in hospitals so that the number of exposures and occupational diseases among the HCWs can be decreased.

关键词： post-exposure Prophylaxis HBV Infection HIV Infection Health Care Workers

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Causes of delay in offering rabies post-exposure prophylaxis services in Abadeh district of Iran

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Journal of Acute Disease 2020年第1期9卷 20-26页

作者： Ahmad Karimi Behnam Karimi Ahmad Karimifard Nabiollah Taherimotlagh Amin Kasraei Fatemeh Safikhani Fatemeh Majidpour Mohammad Yandarani Department of Communicable Disease Surveillance&Control Abadeh Health CenterShiraz University of Medical SciencesShirazIran Department Rescue Abadeh Red Crescent SocietyFars Red Crescent SocietyShirazIran Departments of Biostatistics and Epidemiology School of Public HealthShahid Sadoughi University of Medical SciencesYazdIran Department of Communicable Disease Surveillance&Control Ahram Health CenterBushehr University of Medical SciencesBushehrIran

Objective:To identify the reasons for delayed reception of post-exposure prophylaxis(PEP).Methods:In this cross-sectional study,a total of 1407 individuals with animal bites who were referred to the Abadeh Rabies Treatment Center were investigated using the census method from January 2012 to December *** patients were divided into two groups based on their delay times to referral and receive PEP:timely referral(less than 48 h after the bite)and delayed referral(equal to or longer than 48 h after the bite).Frequency,Chi-square,and logistic regression tests were ***:.The average delay time was(16.33±11.37)*** level of education(OR:3.87;95%CI:1.19-12.54;P=0.02),active economic age(21-35 and 36-50 years-old,OR:12.81;95%CI:3.16-51.97;P<0.001 and OR:3.83,95%CI:3.83-58.61;P<0.001 respectively),occupation(OR:9.16;95%CI:1.89-44.29;P=0.006),long distance from the rabies treatment center(OR:3.41;95%CI:2.03-5.72;P<0.001),bites by household and domestic animals(OR:12.22;95%CI:2.29-65.18,P=0.003),superficial injuries(OR:4.51;95%CI:1.38-14.73;P=0.01),and residence in rural area(OR:12.74;95%CI:6.58-24.66;P<0.001)had significant correlations with delayed referral of ***:To reduce the delay time,the high-risk groups should be informed about the importance of timely referral via educational ***,rabies treatment services should be rendered at the nearest possible center.

关键词： Rabies Zoonosis post-exposure prophylaxis Rabies vaccines Abadeh

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Epidemiological patterns of animal bites in Abadeh district of central Iran from 2012 to 2018: A cross-sectional study

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Journal of Acute Disease 2019年第6期8卷 265-268页

作者： Ahmad Karimi Behnam Karimi Ahmad Karimifard Nabiollah Taherimotlagh Amin Kasraei Mohammad Yandarani Fatemeh Safikhani Fatemeh Majidpour Department of Communicable Disease Surveillance&Control Abadeh Health CenterShiraz University of Medical SciencesShirazIran Department of Rescue Abadeh Red Crescent SocietyFars Red Crescent SocietyShirazIran Department of Communicable Disease Surveillance&Control Ahram Health CenterBushehr University of Medical SciencesBushehrIran Departments of Biostatistics and Epidemiology School of Public HealthShahid Sadoughi University of Medical SciencesYazdIran

Objectives:To investigate the epidemiology of animal bites and associated factors in Abadeh district(central Iran)from 2012 to ***:In this cross-sectional study,1407 individuals with animal bites who were referred to the Abadeh Rabies Treatment Center were investigated by using the census method from 2012 to *** variables included the victim's demographic information(age,gender,occupation),the type of biting animals(dog,cat,and other animals),the domesticated and wild animals,the time of biting based on year and month,the residence location(urban or rural),the treatment status,and the anatomical location of the ***:The annual incidence rate of animal bites was 189.62 per 100000 *** 83.4%of the victims were *** average age was(33.66±18.97)years and individuals in the age range of 36-50 years were greater at *** of the animal bites were from dogs(77.8%).About two thirds(62.1%)of the bites were from household animals.A total of 57.1%of individuals lived in urban *** victims were engaged in farming and animal *** highest prevalence of animal bites(37.4%)happened in the *** of the patients had any clinical signs of ***:To reduce the incidence of animal bites,high-risk groups including farmers and ranchers should be educated about bite prevention,and it should be ensured that they are managed correctly.

关键词： Animal bite Rabies Zoonosis post-exposure prophylaxis Rabies vaccines Epidemiology Abadeh

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