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The Prevalence of Mycoplasma Hyopneumoniae in Commercial Suckling Pigs in Thailand

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World Journal of Vaccines 2012年第3期2卷 161-163页

作者： Alongkot Boonsoongnern Pichai Jirawattanapong Preeda Lertwatcharasarakul Sakukuna Phatthanakunanan Pariwat Poolperm Supanee Urairong Wichian Navasakuljinda Kitcha Urairong Faculty of Veterinary Medicine Kasetsart University Kamphaengsaen campus Nakonpathom Thailand pfizer animal health (Thailand) Limited Bangkok Thailand

The aim of this study was to determine the prevalence of M. hyopneumoniae infection in suckling pigs. Nasal swabs were collected from 300 suckling pigs originating from five farrow-to-finishing farms. One farm had a confirmed PRDC problem (farm A) and four other farms previously had a PRDC problem (farms B, C, D and E). Thirty (30) lactating sows in parity 1, 2 and 3 were selected from each farm (Ten sows per parity). Two piglets from each sow were randomly sampled for nasal swab at 3 weeks of age. The samples were analyzed by the nested PCR technique. Forty five per cent (27/60) of nasal swabs from farm A were found positive. On the other hand, a total of 2.08 per cent were found positive (5/240) from farm B, C, D and E. The tendency of piglet infection per sow by parity showed that first parity had more prevalence than the second and the third parity (60%, 55%, 20%), respectively. We have found a correction between M. hyopneumoniae early infection in suckling pigs and a confirmed PRDC problem (farm A) as oppose to farms that did not have a PRDC problem. The strategies to prevent M. hyopneumoniae early infection are to maintain good lactation, antibiotic prevention program and early M. hyopneumoniae

关键词： Natural Infection M. Hyopneumoniae Suckling Pig Nested PCR

Critical questions in development of targeted nanoparticle therapeutics

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Regenerative Biomaterials 2016年第2期3卷 143-147页

作者： Richard Korsmeyer Pharmaceutical Sciences Pfizer Worldwide R&DGrotonCT 06340USA

One of the fourteen Grand Challenges for Engineering articulated by the US National Academy of Engineering is‘Engineer Better Medicines’.Although there are many ways that better medicines could be engineered,one of the most promising ideas is to improve our ability to deliver the therapeutic molecule more precisely to the desired target.Most conventional drug delivery methods(oral absorption,intravenous infusion etc.)result in systemic exposure to the therapeutic molecule,which places severe constraints on the types of molecules that can be used.A molecule administered by systemic delivery must be effective at low concentrations in the target tissue,yet safe everywhere else in the body.If drug carriers could be developed to deliver therapeutic molecules selectively to the desired target,it should be possible to greatly improve safety and efficacy of therapy.Nanoparticles(and related nanostructures,such as liposomes,nanoemulsions,micelles and dendrimers)are an attractive drug carrier concept because they can be made from a variety of materials engineered to have properties that allow loading and precise delivery of bound therapeutic molecules.The field of targeted nanoparticles has been extraordinarily active in the academic realm,with thousands of articles published over the last few years.Many of these publications seem to demonstrate very promising results in in vitro studies and even in animal models.In addition,a handful of human clinical trials are in progress.Yet,the biopharmaceutical industry has been relatively slow to make major investments in targeted nanoparticle development programs,despite a clear desire to introduce innovative new therapies to the market.What is the reason for such caution?Some degree of caution is no doubt due to the use of novel materials and the unproven nature of targeted nanoparticle technology,but many other unproven technologies have generated intense interest at various times.We believe that the major barrier to the exploration of nanoparticles is because they are so complex

关键词： nanoparticles targeting biodistribution manufacturing

Phylogenetic analysis of the five internal genes and evolutionary pathways of the Greek H3N8 equine influenza virus

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Natural Science 2012年第11期4卷 839-847页

作者： Maria Bountouri Vasileios Ntafis Eirini Fragkiadaki Theo Kanellos Eftychia Xylouri Department of Anatomy and Physiology of Farm animals Faculty of Animal Science and Aquaculture Agricultural University of Athens Athens Greece Department of Anatomy and Physiology of Farm animals Faculty of Animal Science and Aquaculture Agricultural University of Athens Athens Greece pfizer animal health Biologicals Development Sandwich UK

To amplify the NS, NP, PB1, PB2 and PA internal genes of two equine H3N8 influenza A viruses isolated in Greece in 2003 and 2007 five primer pairs were designed. The derived sequences were analysed from a phylogenetic point of view and compared with the evolutionary patters of the HA and NA proteins. Comparison of nucleotide sequences of the five internal genes of the Greek strains showed high similarity (99.3% - 99.7%) to strains isolated from outbreaks in Europe and Asia during 2002-2008. A total of 11 amino acid substitutions of the surface protein NA and the RNP complex proteins were identified in the Greek strains compared to those of progenitor viruses circulating up to 2003. These substitutions were repeated in Chinese and Mongolian isolates from outbreaks in 2007-2008. Notably NS1 protein did not acquired amino acid substitutions and moreover, a stop codon introduced at position 220 was stably maintained in the Greek strains. Phylogenetic trees of the five internal genes did not show the same separation in clades. Greek strains classified them into the American sublineage (as for the PA) Florida clade II (as for the NP, NS1 and PB1) and among Chinese strains of 2007-2008 outbreaks (as for the PB2). Additionally, evolutionary profiles of these internal proteins, except PB2, indicated a parallel evolution fashion to the HA protein, suggesting the possible occurrence of genetic reassortment between H3N8 viruses of district evolutionary lineages. In conclusion, phylogenetic analysis of the internal genes reported in this study could establish a candidate framework for future scientific communications on the phylogenetic diversity and evolution of the equine influenza viruses.

关键词： Equine Influenza Internal Genes Evolution Pathways

Hepatotoxicity reports in the FDA adverse event reporting system database:A comparison of drugs that cause injury via mitochondrial or other mechanisms

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Acta Pharmaceutica Sinica B 2021年第12期11卷 3857-3868页

作者： Payal Rana Michael D.Aleo Xuerong Wen Stephen Kogut Drug Safety Research&Development PfizerGrotonCT 06340USA University of Rhode Island College of PharmacyKingstonRI 02881USA

Drug-induced liver injury(DILI) is a leading reason for preclinical safety attrition and postmarket drug withdrawals.Drug-induced mitochondrial toxicity has been shown to play an essential role in various forms of DILI,especially in idiosyncratic liver injury.This study examined liver injury reports submitted to the Food and Drug Administration(FDA) Adverse Event Reporting System(FAERS) for drugs associated with hepatotoxicity via mitochondrial mechanisms compared with non-mitochondrial mechanisms of toxicity.The frequency of hepatotoxicity was determined at a group level and individual drug level.A reporting odds ratio(ROR) was calculated as the measure of effect.Between the two DILI groups,reports for DILI involving mitochondrial mechanisms of toxicity had a 1.43(95% CI 1.42-1.45;P 18:benzbromarone,troglitazone,isoniazid,rifampin) were associated with mitochondrial mechanisms of toxicity.The major demographic influence for DILI risk was also examined.There was a higher mean patient age among reports for drugs that were associated with mitochondrial mechanisms of toxicity [56.1±18.33(SD)] compared to non-mitochondrial mechanisms [48±19.53(SD)](P <0.0001),suggesting that age may play a role in susceptibility to DILI via mitochondrial mechanisms of toxicity.Univariate logistic regression analysis showed that reports of liver injury were 2.2(odds ratio:2.2,95% CI 2.12-2.26) times more likely to be associated with older patient age,as compared with reports involving patients less than 65 years of age.Compared to males,female patients were 37% less likely(odds ratio:0.63,95% CI 0.61-0.64) to be subjects of liver injury report

关键词： Mitochondrial toxicity FAERS database Adverse event reporting Drug-induced liver injury Hepatotoxicity

AMPK promotes the survival of colorectal cancer stem cells

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animal Models and Experimental Medicine 2018年第2期1卷 134-142页

作者： Bing Guo Xin Han Diane Tkach Shu-Guang Huang Dong Zhang pfizer Research Novartis Pharmaceuticals Department of Biomedical Sciences College of Osteopathic Medicine New York Institute of Technology

Background: Colorectal cancer(CRC) is the third most commonly diagnosed cancer in males and the second in females worldwide in 2012. In the past 20 years, strong evidence suggests that cancer stem cells are the main culprit of cancer metastasis,chemotherapy resistance, and relapse.Methods: To further understand the unique biological properties of cancer stem cells and uncover novel molecular targets to eradicate them, we first established a panel of patient-derived xenograft(PDX) tumor models using tumors surgically removed from human colorectal cancer patients. We then isolated CRC cancer stem cells based on their ALDH activity using fluorescent-activated cell sorting(FACS)and characterized their metabolic properties.Results: Interestingly, we found that the CRC cancer stem cells(ie, CRC cells with higher ALDH activity, or ALDH+) express higher level of antioxidant genes and have lower level of reactive oxygen species(ROS) than non-CRC cancer stem cells(ie, CRC cells with lower ALDH activity, or ALDHà). The CRC cancer stem cells also possess more mitochondria mass and show higher mitochondrial activity. More intriguingly,we observed higher AMP-activated protein kinase(AMPK) activities in these CRC cancer stem cells. Inhibition of the AMPK activity using 2 AMPK inhibitors, Compound C and Iodotubercidin, preferentially induces cell death in CRC cancer stem cells.Conclusion: We propose that AMPK inhibitors may help to eradicate the CRC cancer stem cells and prevent the relapse of CRCs.

关键词： AMP-activated protein kinase cancer metabolism colorectal cancer stem cells patient-derived xenograft

Chemistry-led investigations into the mode of action of NAMPT activators,resulting in the discovery of non-pyridyl class NAMPT activators

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Acta Pharmaceutica Sinica B 2023年第2期13卷 709-721页

作者： Siyuan Tang Miguel Garzon Sanz Oliver Smith Andreas Krämer Daniel Egbase Paul W.Caton Stefan Knapp Sam Butterworth Division of Pharmacy and Optometry School of Health SciencesManchester Academic Health Sciences CentreUniversity of ManchesterManchester M139PLUK Structural Genomics Consortium(SGC) 60438 Frankfurt Am MainGermany Buchmann Institute for Life Sciences(BMLS) 60438 Frankfurt Am MainGermany Institut für Pharmazeutische Chemie Goethe University60438 Frankfurt Am MainGermany Frankfurt Cancer Institute(FCI) 60596 Frankfurt Am MainGermany Department of Diabetes School of Cardiovascular and Metabolic Medicine&SciencesFaculty of Life Sciences&MedicineKing's College LondonLondon SE11ULUK

The cofactor nicotinamide adenine dinucleotide(NAD+)plays a key role in a wide range of physiological processes and maintaining or enhancing NAD+levels is an established approach to enhancing healthy aging.Recently,several classes of nicotinamide phosphoribosyl transferase(NAMPT)activators have been shown to increase NAD+levels in vitro and in vivo and to demonstrate beneficial effects in animal models.The best validated of these compounds are structurally related to known urea-type NAMPT inhibitors,however the basis for the switch from inhibitory activity to activation is not well understood.Here we report an evaluation of the structure activity relationships of NAMPT activators by designing,synthesising and testing compounds from other NAMPT ligand chemotypes and mimetics of putative phosphoribosylated adducts of known activators.The results of these studies led us to hypothesise that these activators act via a through-water interaction in the NAMPT active site,resulting in the design of the first known urea-class NAMPT activator that does not utilise a pyridine-like warhead,which shows similar or greater activity as a NAMPT activator in biochemical and cellular assays relative to known analogues.

关键词： Nicotinamide phosphoribosyl transferase activator healthy aging Drug discovery Bioisosteres Medicinal chemistry

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利用技术推动孵化场的现代化

国外畜牧学（猪与禽） 2014年第3期34卷 29-31页

作者：王晶晶 Tarsicio Villalobos pfizer家禽保健公司

卵内接种作为一种能够让1日龄雏鸡及早获得免疫力的有效方法已被人们广泛接受。尤其在美国，大多数大型专业化孵化场已采用这种技术。在美国以外的地区，卵内接种也被一些较小规模的孵化场采用。然而，孵化场的基本条件对使这种技术得... 详细信息

卵内接种作为一种能够让1日龄雏鸡及早获得免疫力的有效方法已被人们广泛接受。尤其在美国，大多数大型专业化孵化场已采用这种技术。在美国以外的地区，卵内接种也被一些较小规模的孵化场采用。然而，孵化场的基本条件对使这种技术得到有效利用非常重要。

关键词：有效利用孵化场技术现代化 1日龄雏鸡免疫力专业化小规模

Innovative Approaches in Safety Assessment of New Therapeutics:Global Perspectives

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Innovative Approaches in Safety Assessment of New Therapeuti...

Ninety-day administration of dl-3-n-butylphthalide for acute ischemic stroke： a randomized, double-blind trial

中国毒理学会第五次全国学术大会

作者： Tim Anderson pfizer Inc.

＜正＞Pharmaceutical research and development（R＆D） is a long,stepwise,resource-risky,market-competitive process.The purpose of non-clinical safety assessment is to establish the safety profile of new therapeutic ca...

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Chinese Medical Journal 2013年第18期126卷 3405-3410页

作者： CUI Li-ying ZHUYi-cheng GAO Shan WANG Jian-ming PENG Bing NI Jun ZHOU Li-xin HE Jia MA Xiu-qiang Department of Neurology Peking Union Medical College Hospital Chinese Academy of Medical Science & Peking Union Medical College Beijing 100730 China Department of health Statistics Second Military Medical University Shanghai 200433 China

Background DI-3-n-butylphthalide （NBP）, first isolated from the seeds of celery, showed efficacy in animal models of stroke. This study was a clinical trial to assess the efficacy and safety of NBP with a continuous dose regimen among patients with acute ischemic stroke. Methods A randomized, double-blind, double-dummy trial enrolled 573 patients within 48 hours of onset of ischemic stroke in China. Patients were randomly assigned to receive a 14-day infusion of NBP followed by an NBP capsule, a 14- day infusion of NBP followed by aspirin, or a 14-day infusion of ozagrel followed by aspirin. The efficacy measures were Barthel index score and the modified Rankin scale （mRS） at day 90. Differences among the three groups on mRS were compared using X2 test of proportions （with two-sided e=0.05） and Logistic regression analysis was conducted to take the baseline National Institutes of health Stroke Scale （NIHSS） score into consideration. Results Among the 535 subjects included in the efficacy analysis, 90-day treatment with NBP was associated with a significantly favorable outcome than 14-day treatment with ozagrel as measured by mRS （P 〈0.001）. No significant difference was found among the three groups on Barthel index at day 90. The rate of adverse events was similar among the three groups. Conclusions The 90-day treatment with NBP could improve outcomes at the third month after stroke. The NBP treatment （both intravenous and oral） is safe （ChiCTR-TRC-09000483）.

关键词： ischemic stroke medical treatment dl-3-n-butylphthalide