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Development and Validation of a Liquid Chromatographic Method for the Determination of Leflunomide： Application to in vitro Drug Metal Interactions

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Chinese Journal of Chemistry 2011年第9期29卷 1933-1938页

作者： Sultana, Najma Muhammad, Saeed Arayne Khan, Moona Mehboob Nawaz, Muhammd United biotechnologies Karachi 75290 Pakistan Jinnah Medical and Dental College Karachi Pakistan department of Chemistry College of Science UAE University A1-Ain P.O. Box 17551 UAE

Leflunomide is a leading drug for the treatment of rheumatoid arthritis. The principle aim of this study was to develop and validate an RP-HPLC method for the determination of leflunomide in bulk and pharmaceutical dosage form using diclofenac sodium as an internal standard. For this purpose, chromatography was accomplished on a Purospher Start, C18 （5 μm, 12.5 cm×0.46 cm） column at ambient temperature. Methanol ： water （80 ： 20, V/V） solvent system was selected as mobile phase, the pH of which was adjusted to 3.4 by ortho-phosphoric acid and de- livered at a flow rate of 1.2 mLomin-1. Seperation of leflunomide and diclofenac sodium was carried out on a Purospher Start, C18 equipped with a UV-visible detector at 248 nm. The suitability of the method for the quantita- tive determination of the drugs is proven by validation in accordance with the requirements laid down by the Inter- national Conference on Harmonization （ICH） guidelines. The method was accurate （99.55%--100.03%）, specific, linear （R2〉0.999） and precise （intra-day precision 0.023%--0.93% and inter-day precision 0.26%--0.944%） in the range of 0.5--20 μg·mL^-1. The minimum limit of detection and quantification in pharmaceutical formulation were 0.05 and 0.15 μ***^-1, respectively. Thus the proposed method is simple, accurate, reproducible and suitable for the routine analysis of leflunomide in pharmaceutical formulations and was applied to study in vitro drug-metal interactions.

关键词： leflunomide liquid chromatography analytical method in vitro interaction metal

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Targeting histone lysine-specific demethylase KDM1A/LSD1 to control epithelial-mesenchymal transition program in breast cancers

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Journal of Cancer Metastasis and Treatment 2019年第3期4卷 1-9页

作者： Carmen D.Saccà Francesca Gorini Susanna Ambrosio Stefano Amente Barbara Majello department of Biology University of Naples“Federico II”Naples 80126Italy department of Molecular Medicine and Medical biotechnologies University of Naples“Federico II”Naples 80131Italy

Epithelial-mesenchymal transition (EMT) is a plastic and reversible process, essential for development and tissue homeostasis. Under pathological conditions, EMT causes induction of tumor growth, angiogenesis and metastasis. According to its reversible nature, the EMT program is associated with vast epigenetic changes. Targeting the epigenetic network that controls the EMT pathway in disease progression is a novel promising strategy to fight cancer metastasis. The impact of alterations in histone methylation in cancer has led to the identification of histone methyltransferases and demethylases as promising novel targets for therapy. Specifically, the lysine specific demethylase 1 (LSD1, also known as KDM1A) plays a pivotal role in the regulation of EMT. Here we present an overview of the causative role of LSD1 in the EMT process, summarizing recent findings on its emerging functions in cell migration and invasion in breast cancer.

关键词： Lysine specific demethylase 1 KDM1A epithelial-mesenchymal transition breast cancers metastasis invasion LSD1-complex

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Adverse reactions of Amiodarone

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Journal of Geriatric Cardiology 2019年第7期16卷 552-566页

作者： Ruben ML Colunga Biancatelli Viviana Congedo Leonardo Calvosa Marco Ciacciarelli Alessandro Polidoro Luigi Iuliano UOC of Internal Medicine Sapienza University of Rome and ICOT HospitalLatinaItaly Vascular Biology&Mass Spectrometry Laboratory Department of Medico-Surgical Sciences and BiotechnologiesSapienza University of Rome and ICOT HospitalLatinaItaly

Adverse drug reaction is defined by the World Health Organization as any response to a drug that is noxious and unintended and occurs at a dose normally used in *** people are at elevated risk of adverse drug reactions—because of changes in pharmacodynamics,concurrent use of multiple medications and the related drug ***,adverse drug reactions are significantly underestimated in the elderly population that is also exposed to inappropriate *** is an antiarrhythmic drug used commonly for the treatment of atrial fibrillation and is increasingly prescribed in older *** amiodarone is an efficient drug for rhythm control,it’s a carrier of different adverse reactions,and pro and cons must be carefully evaluated before its use especially in older people.

关键词： Amiodarone Atrial fibrillation Drug-adverse reaction Drug toxicity

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Higher volume growth rate is associated with development of worrisome features in patients with branch duct-intraductal papillary mucinous neoplasms

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World Journal of Clinical Cases 2022年第17期10卷 5667-5679页

作者： Tommaso Innocenti Ginevra Danti Erica Nicola Lynch Gabriele Dragoni Matteo Gottin Filippo Fedeli Daniele Palatresi Maria Rosa Biagini Stefano Milani Vittorio Miele Andrea Galli Gastroenterology Research Unit Department of Experimental and Clinical Biomedical Sciences"Mario Serio"University of FlorenceFlorence 50134Italy Emergency Radiology Unit Department of ServicesCareggi University HospitalFlorence 50134Italy department of Medical biotechnologies University of SienaSiena 53100Italy

BACKGROUND Branch duct-intraductal papillary mucinous neoplasms(BD-IPMNs)are the most common pancreatic cystic tumours and have a low risk of malignant *** guidelines only evaluate cyst diameter as an important risk factor but it is not always easy to measure,especially when comparing different *** the other side,cyst volume is a new parameter with low interobserver variability and is highly reproducible over *** To assess both diameter and volume growth rate of BD-IPMNs and evaluate their correlation with the development of malignant *** Computed tomography scans and magnetic resonance imaging exams were retrospectively *** diameter was measured on three planes,while the volume was calculated by segmentation:The volume of the entire cyst was determined by manually drawing a region of interest along the edge of the neoplasm on each consecutive slice covering the whole lesion;therefore,a threedimensional volume of interest was finally obtained with the calculated value expressed in cm^(3).Changes in size over time were *** development of worrisome features was *** We evaluated exams of 98 patients across a 40.5-mo median follow-up *** patients developed worrisome *** at baseline were significantly larger in patients who developed worrisome features(diameters P=0.0035,P=0.00652,P=0.00424;volume P=0.00222).Volume growth rate was significantly higher in patients who developed worrisome features(1.12 cm^(3)/year vs 0 cm^(3)/year,P=0.0001);diameter growth rate was higher as well,but the difference did not always reach statistical *** but not diameter growth rate in the first year of follow-up was higher in patients who developed worrisome features(0.46 cm^(3)/year vs 0 cm^(3)/year,P=0.00634).CONCLUSION The measurement of baseline volume and its variation over time is a reliable tool for the follow-up of *** measurement could be a better tool than

关键词： Intraductal papillary mucinous neoplasms Cyst Volume Growth Worrisome features Malignancies

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Restoring the plant productivity of heavy metal-contaminated soil using phosphate sludge,marble waste,and beneficial microorganisms

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Journal of Environmental Sciences 2021年第1期33卷 210-221页

作者： Anas Raklami Abdel-ilah Tahiri Noura Bechtaoui ElGharmali Abdelhay Eloisa Pajuelo Marouane Baslam Abdelilah Meddich Khalid Oufdou Laboratory of Microbial biotechnologies Agrosciencesand Enuironment(BioMAgE)Faculty of Sciences SemlaliaCadi Ayyad UniversityMarrakechMorocco Laboratory of Agri-Food Biotechnologiesand Valorization of Plant Bioresources(Agrobioval)Faculty of Sciences SemlaliaCadi Ayyad UniversityMarrakechMorocco Laboratory of Water Biodiversity and Global ChangeFaculty of Sciences SemlaliaCadi Ayyad UniversityMarrakechMorocco department of Microbiology and Parasitology University of Seville41080 SevilleSpain Laboratory of Biochemistry Faculty of AgricultureNiigata UniversityNiigata 950-2181Japan department of Life and Food Sciences Graduate School of Science and TechnologyNigata UniversityNiigata 950-2181Japan

Assisted natural remediation(ANR)has been highlighted as a promising,less expensive,and environmentally friendly solution to remediate soil contaminated with heavy *** tested the effects of three amendments(10%compost,C;5 or 15%phosphate sludge,PS5 and PS15;and 5 or 15%marble waste,MW5 and MW15)in combination with microorganism inoculation(rhizobacteria consortium alone,mycorrhizae alone,and the two incombination)on alfalfa in contaminated *** concentrations of Zn,Cu,and Pb were measured,along with proline and malondialdehyde *** microbiological and physicochemical properties of the mining soil were *** of the amendments allowed germination and promoted *** with the rhizobacteria consortium and/or mycorrhizae stimulated plant *** and MW stimulated the production of *** of alfalfa with the rhizobacteria-mycorrhizae mixture and the application of MW allowed the safe cultivation of the legume,as shown by the low concentrations of metals in plant *** and Pb concentrations were below the limits recommended for animal grazing and accumulated essentially in *** analyses showed the positive effect of the amendments on the soil physicochemical *** treatments increased soil p H(around 7),total organic carbon,and assimilable phosphorus ***,an important decrease in soluble heavy metals concentrations was ***,our findings revealed that the applied treatments reduced the risk of metal-polluted soils limiting plant *** ANR has great potential for success in the restoration of polymetallic and acidic mining soils using the interaction between alfalfa,microorganisms,and organomineral amendments.

关键词： Bioaugmentation Bioremediation Mine soil Heavy metals Immobilization Rhizostabilization Root microbiome Wastes added-value

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Elucidating the pathological mechanisms of neurodegeneration in the lethal serpinopathy FENIB

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Neural Regeneration Research 2022年第8期17卷 1733-1734页

作者： Elena Miranda Giovanna Galliciotti department of Biology and biotechnologies‘Charles Darwin’and Pasteur Institute-Cenci Bo-lognetti Foundation Sapienza University of RomeRomeItaly Institute of Neuropathology University Medical Center Hamburg-EppendorfHamburgGermany

The term serpinopathies was introduced to describe a family of diseases caused by point mutations in serine protease inhibitors,or *** inhibit their cognate protease by an irreversible suicide mechanism starting with the attack of the active site serine on the reactive center loop of the inhibitor,followed by formation of a covalent complex between both proteins,insertion of the reactive center loop of the serpin into its own beta-sheet A,and culminating in distortion of the active site of the serine protease and thus irreversible *** inhibitory mechanism,reminiscent of the movement of a mousetrap,requires a structural flexibility that proves to be unfavorable when the folding of the serpin is altered by mutations responsible for conformational rearrangements,allowing an intermolecular domain exchange characterized by the insertion of the C-terminal domain of a molecule into a second one,thus forming a *** of this insertion reaction leads to the formation of serpin polymers that accumulate within the endoplasmic reticulum(ER)of the cell and consequently reduces the secretion of the wild-type serpin(Greene et al.,2016).

关键词： insertion irreversible starting

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A rare case of omental extra-gastrointestinal stromal tumor showing two coexisting mutations on exon 14 of the PDGFRA gene

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Gastroenterology Report 2021年第4期9卷 377-379,I0003页

作者： Gianluca Caruso Luca Pacini Angelo Iossa Claudio Di Cristofano Daniela Bastianelli Gianfranco Silecchia Maria Mele Vincenzo Petrozza Antonella Calogero Elena De Falco Pathology Unit ICOT HospitalSapienza University of RomeLatinaItaly Clinical Pathology Unit ICOT HospitalSapienza University of RomeLatinaItaly Division of General Surgery and Bariatric Centre of Excellence Department of Medical-Surgical Sciences and BiotechnologiesSapienza University of RomeRomeItaly department of Medical-Surgical Sciences and biotechnologies Faculty of Pharmacy and MedicineSapienza UniversityLatinaItaly Laboratory of Clinical Pathology ICOT HospitalLatinaItaly Mediterranea Cardiocentro NaplesItaly

Introduction Gastrointestinal stromal tumors(GISTs)are neoplasms arising from mesenchymal cells localized into the muscularis propria of the gastrointestinal(GI)tract[1];5%of GISTs are extra-GISTs(EGISTs),as they differently originate from adipose tissue adjacent to the GI tract(omentum and mesentery)or from the pancreas[2].So far,both GISTs and EGISTs have been managed indistinctively by combining surgery,histopathological distinctive features,imaging,and molecular ***.

关键词：胃肠道外间质瘤 neoplasms muscular

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Cardiac stromal cells on stage:From dull filler to specialized actors

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BIOCELL 2022年第8期46卷 1875-1877页

作者： VITTORIO PICCHIO FRANCESCA PAGANO ISOTTA CHIMENTI department of Medical Surgical Sciences and biotechnologies Sapienza UniversityLatina04100Italy Institute of Biochemistry and Cell Biology National Council of Research(IBBC-CNR)Monterotondo00015Italy Mediterranea Cardiocentro Napoli80122Italy

Cardiac stromal cells have faced through the years a significant evolution in their definitions concerning their phenotypes,markers,and *** are surging to key roles in physiopathology,becoming important targets to be exploited for cardiac *** this perspective,we briefly discuss their role in novel therapeutic strategies for enhancing cardiac repair and regeneration.

关键词： Cardiac fibroblasts Cardiac stroma Cardiac repair Cardiac remodeling

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An isolate alpha-fetoprotein producing gastric cancer liver metastasis emerged in a patient previously affected by radiation induced liver disease

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World Journal of Hepatology 2013年第7期5卷 398-403页

作者： Vincenzo Cardinale Gianmaria De Filippis Alessandro Corsi Augusto La Penna Michele Rossi Carlo Catalano Paolo Bianco Adriano De Santis Domenico Alvaro department of Medico-Surgical Sciences and biotechnologies Sapienza University of Rome department of Radiology Sapienza University of Rome department of Molecular Science Sapienza University of Rome department of Clinical Medicine Sapienza University of Rome department of Radiology Sant'Andrea Hospital Sapienza University of Rome

We report a case of an isolated hepatic neoplasia which originated in a site of the liver previously affected by radiation induced liver disease (RILD) in a patient resected for gastric cancer and referred to us for high serum alpha-fetoprotein (AFP) levels. This case challenged us in distiguishing, even histologically, between primary liver cancer and AFP producing gastric cancer metastasis. Only a panel of immunohis-tochemical markers allowed the definitive diagnosis of liver metastasis of endodermal stem cell-derived and AFP producing gastric cancer. We discuss the criteria for a differential diagnosis, as well as the possible link between RILD and emergence of liver neoplasia.

关键词： Alpha-fetoprotein producing gastric cancer Hepatoid adenocarcinoma Liver metastasization Radiation induced liver disease

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Progressive loss of striatal dopamine terminals in MPTP-induced acute parkinsonism in cynomolgus monkeys using vesicular monoamine transporter type 2 PET imaging([^(18)F]AV-133)

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Neuroscience Bulletin 2014年第3期30卷 409-416页

作者： Yajing Liu Feng Yue Rongping Tang Guoxian Tao Xiaomei Pan Lin Zhu Hank F.Kung Piu Chan department of Neurobiology Xuanwu Hospital of Capital Medical University Key Laboratory of Neurodegenerative Diseases Ministry of Education Xuanwu Hospital of Capital Medical University Beijing Key Laboratory on Parkinson's Disease Wincon Theracells biotechnologies Inc. Key Laboratory of Radiopharmaceuticals Beijing Normal University department of Radiology University of Pennsylvania

The 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine （MPTP）-induced parkinsonism model, particularly in non-human primates, remains the gold-standard for studying the pathogenesis and assessing novel therapies for Parkinson＇s disease. However, whether the loss of dopaminergic neurons in this model is progressive remains controversial, mostly due to the lack of objective in vivo assessment of changes in the integrity of these neurons. In the present study, parkinsonism was induced in cynomolgus monkeys by intravenous administration of MPTP （0.2 mg/kg） for 15 days; stable parkinsonism developed over 90 days, when the symptoms were stable. Noninvasive positron emission tomographic neuroimaging of vesicular monoamine transporter 2 with 9-[18F] fluoropropyl-（＋）-dihydrotetrabenazine （[18F]AV-133） was used before, and 15 and 90 days after the beginning of acute MPTP treatment. The imaging showed evident progressive loss of striatal uptake of [18SF]AV-133. The dopaminergic denervation severity had a significant linear correlation with the clinical rating scores and the bradykinesia subscores. These findings demonstrated that [18F]AV-133 PET imaging is a useful tool to noninvasively evaluate the evolution of monoaminergic terminal loss in a monkey model of MPTP-induced parkinsonism.

关键词： Parkinson's disease non-human primate [18F]AV-133 VMAT2 positron emission tomography

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