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Iohexol plasma and urinary concentrations in cirrhotic patients:A pilot study

World Journal of Hepatology 2022年第8期14卷 1621-1632页

作者： Paul Carrier Alexandre Destere Baptiste Giguet Marilyne Debette-Gratien Marie Essig Caroline Monchaud Jean-Baptiste Woillard Véronique Loustaud-Ratti Department of Liver Disease Limoges University Hospital CenterU1248INSERMF-87000LimogesFrance Department of Pharmacology Toxicology and Centre of PharmacovigilanceLimoges University Hospital CenterU1248INSERMF-87000LimogesFrance

BACKGROUND Renal failure is an independent prognostic factor for survival in patients with *** to calculate serum creatinine significantly overestimate the glomerular filtration rate(GFR).Plasma clearance of direct biomarkers has been used to improve the accuracy of evaluations of GFR in this population,but no study has simultaneously measured plasma and urinary clearance,which is the gold *** To study calculated plasma and urinary concentrations of iohexol,based on the kinetics of samples collected over 24 h from cirrhotic patients with three different grades of *** One dose of iohexol(5 mL)was injected intravenously and plasma concentrations were measured 11 times over 24 h in nine cirrhotic *** urinary concentration of iohexol was also measured,in urine collected at 4,8,12 and 24 *** The plasma and urinary curves of iohexol were similar;however,incomplete urinary excretion was detected at 24 *** the estimated GFR limits of our population(>30 and<120 mL/min/1.73 m^(2)),the median measured GFR(m GFR)was 63.7 mL/min/1.73 m^(2)(range:41.3–111.3 mL/min/1.73 m^(2)),which was an accurate reflection of the actual ***-based formulas for estimatingGFR showed significant bias and imprecision,while the Brochner–Mortensen(BM)equation accurately estimated the m GFR(r=0.93).CONCLUSION Plasma clearance of iohexol seems useful for determining GFR regardless of the ascites *** will secondly devise a pharmacokinetics model requiring fewer samples andvalidate the BM equation.

关键词： Cirrhosis Glomerular filtration Rate Iohexol Pharmacokinetics Brochner-Mortensen

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Molecular Insight into the Therapeutic Promise of Xuebijing Injection against Coronavirus Disease 2019

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World Journal of Traditional Chinese Medicine 2020年第2期6卷 203-215页

作者： Dan Zhang Jin-Tao Lv Bing Zhang Ri-Na Sa Bing-Bing Ma Xiao-Meng Zhang Zhi-Jian Lin Department of Clinical Chinese Pharmacy School of Chinese Materia MedicaBeijing University of Chinese MedicineBeijing 100029China Center for pharmacovigilance and Rational Use of Chinese Medicine Beijing University of Chinese MedicineBeijing Department of Pharmacy Gansu Provincial HospitalLanzhouChina

Background:The potential human-to-human transmission of the coronavirus pneumonia(coronavirus disease 2019[COVID-19])has caused an outbreak of acute respiratory *** injection is recommended as first-line treatment for the severe and critical patients with *** aim of present study is to interpret the pharmacological mechanisms and molecular connections of Xuebijing injection against COVID-19 by utilizing the approaches of network pharmacology and molecular *** and Methods:Active ingredients of Xuebijing injection were collected by Traditional Chinese Medicine Systems Pharmacology(TCMSP)database,and putative therapeutic targets were screened from TCMSP,Swiss Target Prediction,and STITCH ***,the protein–protein interactions,topological analysis,and pathway enrichment were established to distinguish the hub targets and pathways by employing STRING database,Cytoscape software,DAVID database,*** addition,the potential interaction and binding activity of candidate ingredients in Xuebijing injection with core targets were revealed by molecular docking simulation(Auto Dock software).Results:A total of 115 bioactive components in Xuebijing injection were collected,and416 targets including AKT1,TP53,VEGFA,ALB,TNF and so on were responsible for treating *** analysis revealed that matching core targets were closely associated with the inhibition of cytokine storm for its clinical beneficial effects in severe *** results of enrichment analysis indicated that PI3 K-Akt signaling pathway,human T-cell leukemia virus type 1 infection,mitogen-activated protein kinase signaling pathway,tuberculosis,focal adhesion,TNF signaling pathway,and small-cell lung cancer were represented pathways of Xuebijing injection against COVID-19 in terms of lung inflammation,virus infection,and lung ***,the active ingredients of Xuebijing injection exerted superior binding activities with 3 CLpro and ang

关键词： Coronavirus disease 2019 molecular docking network pharmacology therapeutic mechanism Xuebijing injection

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Redox-sensitive micelles for targeted intracellular delivery and combination chemotherapy of paclitaxel and all-trans-retinoid acid

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Asian Journal of Pharmaceutical Sciences 2019年第5期14卷 531-542页

作者： Lingfei Han Lejian Hu Fulei Liu XinWang Xiaoxian Huang Bowen Liu Feng Feng Wenyuan Liu Wei Qu Department of Natural Medicinal Chemistry China Pharmaceutical UniversityNanjing 210009China Department of Pharmaceutical Analysis China Pharmaceutical UniversityNanjing 210009China Jiangsu Food and Pharmaceutical Science College Huaian223003China Key Laboratory of Drug Quality Control and pharmacovigilance Ministry of EducationChina PharmaceuticalUniversityNanjing210009China

The application of paclitaxel(PTX) in clinic has been restricted due to its poor *** traditional nano-medicines have been developed to improve this defect,while they are still lack of tumor targeting ability and rapid drug release. In this work,an amphiphilic polymeric micelle of hyaluronic acid(HA) – all-trans-retinoid acid(ATRA) with a disulfide bond,was developed successfully for the co-delivery of PTX and ATRA. The combination chemotherapy of PTX and ATRA can strengthen the anti-tumor activity. Along with selfassembling to micelles in water,the delivery system displayed satisfying drug loading capacities for both PTX(32.62% ± 1.39%) and ATRA,due to directly using ATRA as the hydrophobic group. Rapid drug release properties of the PTX-loaded redox-sensitive micelles(HA-SS-ATRA) in vitro were confirmed under reducing condition containing GSH. Besides,HA-CD44 mediated endocytosis promoted the uptake of HA-SS-ATRA micelles by B16 F10 cells. Due to these properties,cytotoxicity assay verified that PTX-loaded HA-SS-ATRA micelles showed concentration-dependent cytotoxicity and displayed obvious combination therapy of PTX and ATRA. Importantly,HA-SS-ATRA micelles could remarkably prolong plasma circulation time after intravenously administration. Therefore,redox-sensitive HASS-ATRA micelles could be utilized and explored as a promising drug delivery system for cancer combination chemotherapy.

关键词： Redox-sensitive Hyaluronic acid All-trans-retinoid acid Tumor targeting Combination chemotherapy

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DT-13, a saponin of dwarf lilyturf tuber, exhibits anti-cancer activity by down-regulating C-C chemokine receptor type 5 and vascular endothelial growth factor in MDA-MB-435 cells

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Chinese Journal of Natural Medicines 2014年第1期12卷 24-29页

作者： ZHAO Ren-Ping LIN Sen-Sen YUAN Sheng-Tao YU Bo-Yang BAI Xian-Shu SUN Li ZHANG Lu-Yong Jiangsu Center for Drug Screening China Pharmaceutical University Jiangsu Center for Pharmacodynamics Research and Evaluation China Pharmaceutical University Department of Complex Prescription of Traditional Chinese Medicine School of Chinese Material Medicine China Pharmaceutical University Department of Molecular Physiology University of Saarland Key Laboratory of Drug Quality Control and pharmacovigilance China Pharmaceutical University Ministry of Education

AIM： To investigate the anticancer activity of DT-13 under normoxia and determine the underlying mechanisms of action. METHODS： MDA-MB-435 cell proliferation, migration, and adhesion were performed to assess the anticancer activity of DT-13, a saponin from Ophiopogonjaponicus, in vitro. In addition, the effects of DT-13 on tumor growth and metastasis in vivo were evaluated by orthotopic implantation of MDA-MB-435 cells into nude mice; mRNA levels of vascular endothelial growth factor （VEGF）, C-C chemokine receptor type 5 （CCR5） and hypoxia-inducible factor 1a （HIF-1a） were evaluated by real-time quantitative PCR; and CCR5 protein levels were detected by Western blot assay. RESULTS： At 0.01 to 1 umol·L -1, DT-13 inhibited MDA-MB-435 cell proliferation, migration, and adhesion significantly in vitro. DT-13 reduced VEGF and CCR5 mRNAs, and decreased CCR5 protein expression by down-regulating HIF-1 a. In addition, DT-13 inhibited MDA-MB-435 cell lung metastasis, and restricted tumor growth slightly in vivo. CONCLUSION： DT-13 inhibited MDA-MB-435 cell proliferation, adhesion, and migration in vitro, and lung metastasis in vivo by reducing VEGF, CCR5, and HIF-la expression.

关键词： DT- 13 Saponin Ophiopogonjaponicus Anticancer activity CCR5 VEGF HIF- 1 a

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Organic anion transporter 1 and 3 contribute to traditional Chinese medicine-induced nephrotoxicity

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Chinese Journal of Natural Medicines 2020年第3期18卷 196-205页

作者： SHEN Qing-Qing WANG Jing-Jing ROY Debmalya SUN Li-Xin JIANG Zhen-Zhou ZHANG Lu-Yong HUANG Xin Jiangsu Key Laboratory of Drug Screening China Pharmaceutical UniversityNanjing 210009China Jiangsu Center for Pharmacodynamics Research and Evaluation China Pharmaceutical UniversityNanjing 210009China Key Laboratory of Drug Quality Control and pharmacovigilance Ministry of EducationChina Pharmaceutical UniversityNanjing 210009China Center for Drug Screening and Pharmacodynamics Evaluation School of PharmacyGuangdong Pharmaceutical UniversityGuangzhou 510006China

With the internationally growing popularity of traditional Chinese medicine(TCM), TCM-induced nephropathy has attracted public attention. Minimizing this toxicity is an important issue for future research. Typical nephrotoxic TCM drugs such as Aristolochic acid, Tripterygium wilfordii Hook. f, Rheum officinale Baill, and cinnabar mainly damage renal proximal tubules or cause interstitial nephritis. Transporters in renal proximal tubule are believed to be critical in the disposition of xenobiotics. In this review, we provide information on the alteration of renal transporters by nephrotoxic TCMs, which may be helpful for understanding the nephrotoxic mechanism of TCMs and reducing adverse effects. Studies have proven that when administering nephrotoxic TCMs, the expression or function of renal transporters is altered, especially organic anion transporter 1 and 3. The alteration of these transporters may enhance the accumulation of toxic drugs or the dysfunction of endogenous toxins and subsequently sensitize the kidney to ***-related drug combination and clinical biomarkers supervision to avoid the risk of future toxicity are proposed.

关键词： Traditional Chinese medicine Nephrotoxicity Renal tubular epithelial cell Organic anion transporter Aristolochic acid Tripterygium wilfordii Hook.f. Rheum officinale Baill

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The role of neutrophils in triptolide-induced liver injury

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Chinese Journal of Natural Medicines 2018年第9期16卷 653-664页

作者： WANG Xin-Zhi ZHANG Shen-Ye XU Yao ZHANG Lu-Yong JIANG Zhen-Zhou Jiangsu Key Laboratory of Drug Screening Jiangsu Center for Pharmacodynamics Research and Evaluation China Pharmaceutical University Nanjing 210009 China Faculty of Health and Medical Science University of Copenhagen Copenhagen Denmark Key Laboratory of Drug Quality Control and pharmacovigilance China Pharmaceutical University Ministry of Education Nanjing 210009 China Jiangsu Key Laboratory of Traditional Chinese Medicine Evaluation and Translational Research Nanjing 210009 China

Triptolide(TP) induces severe liver injury, but its hepatotoxicity mechanisms are still unclear. Inflammatory responses may be involved in the pathophysiology. Neutrophils are the first-line immune effectors for sterile and non-sterile inflammatory responses. Thus, the aim of the present study was to investigate the neutrophilic inflammatory response in TP-induced liver injury in C57 BL/6 mice. Our results showed that neutrophils were recruited and accumulated in the liver, which was parallel to or slightly after the development of liver injury. Neutrophils induced release of myeloperoxidase and up-regulation of CD11 b, which caused cytotoxicity and hepatocyte death. Hepatic expressions of CXL1, TNF-α, IL-6, and MCP1 were increased significantly to regulate neutrophils recruitment and activation. Up-regulation of toll like receptors 4 and 9 also facilitated neutrophils infiltration. Moreover, neutrophils depletion using an anti-Gr1 antibody showed mild protection against TP overdose. These results indicated that neutrophils accumulation might be the secondary response, not the cause of TP-induced liver injury. In conclusion, the inflammatory response including neutrophil infiltration may play a role in TP-induced hepatotoxicity, but may not be severe enough to cause additional liver injury.

关键词： Triptolide Liver injury Inflammatory response Neutrophil Depletion

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Liver metabolomics study reveals protective function of Phyllanthus urinaria against CCl_4-induced liver injury

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Chinese Journal of Natural Medicines 2017年第7期15卷 525-533页

作者： GUO Qing ZHANG Qian-Qian CHEN Jia-Qing ZHANG Wei QIU Hong-Cong ZHANG Zun-Jian LIU Bu-Ming XU Feng-Guo MOE Key Laboratory of Drug Quality Control and pharmacovigilance China Pharmaceutical University Nanjing 210009 China State key laboratory of natural medicine China Pharmaceutical University Nanjing 210009 China State Key Laboratory for Quality Research in Chinese Medicines Macao University of Science & Technology Avenida Wai Long Taipa Macao China Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards Nanning 530022 China

Phyllanthus Urinaria L.(PUL) is a traditional Chinese medicine used to treat hepatic and renal disorders. However, the mechanism of its hepatoprotective action is not fully understood. In the present study, blood biochemical indexes and liver histopathological changes were used to estimate the extent of hepatic injury. GC/MS and LC/MS-based untargeted metabolomics were used in combination to characterize the potential biomarkers associated with the protective activity of PUL against CCl_4-induced liver injury in rats. PUL treatment could reverse the increase in ALT, AST and ALP induced by CCl_4 and attenuate the pathological changes in rat liver. Significant changes in liver metabolic profiling were observed in PUL-treated group compared with liver injury model group. Seventeen biomarkers related to the hepatoprotective effects of PUL against CCl_4-induced liver injury were screened out using nonparametric test and Pearson's correlation analysis(OPLS-DA). The results suggested that the potential hepatoprotective effects of PUL in attenuating CCl_4-induced hepatotoxicity could be partially attributed to regulating L-carnitine, taurocholic acid, and amino acids metabolism, which may become promising targets for treatment of liver toxicity. In conclusion, this study provides new insights into the mechanism of the hepatoprotection of Phyllanthus Urinaria.

关键词： Metabolomics Hepatic protection Phyllanthus Urinaria Carbon tetrachloride

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Identification of impurities in nafamostat mesylate using HPLC-ITTOF/MS:A series of double-charged ions

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Journal of Pharmaceutical Analysis 2020年第4期10卷 346-350页

作者： Yuxin Zhang Lufan An Lin Zhang Rulin Wang Yuan Tian Zunjian Zhang Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical SchoolNanjing210008PR China Jiangsu D&R Pharmaceutical Corporation Taizhou225312PR China Department of Pharmacy General Hospital Tianjin Medical UniversityTianjin300052PR China Key Laboratory of Drug Quality Control and pharmacovigilance(Ministry of Education) China Pharmaceutical UniversityNanjing210009PR China

Nafamostat mesylate is a serine protease inhibitor used in the treatment of acute *** impurities in nafamostat mesylate,the active pharmaceutical ingredient(API),were profiled via high performance liquid chromatography tandem ion trap coupled with time-of-flight mass spectrometer(HPLC-IT-TOF/MS).The chromatography was performed on an ACE-3 C18 column(200 mm4.6 mm,3 mm)using methanol and 0.1%formic acid in purified water as mobile phase at a flow rate of 1.0 mL/*** ions were detected by IT-TOF/MS with a full-scan mass analysis from m/z 100 to *** total,eleven impurities were detected in nafamostat mesylate *** impurity profile was estimated based on the HPLC-IT-TOF/MS data,including accurate masses,MSn fingerprints of fragmentation pathways and a series of double-charged ***,seven impurities were identified and reported for the first *** results will provide technical support for the quality control and clinical safety of nafamostat mesylate.

关键词： Nafamostat mesylate Impurity Structure identification Double-charged ion

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The Adverse Event Profile in Patients Treated with Transferon<sup>TM</sup>(Dialyzable Leukocyte Extracts): A Preliminary Report

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Pharmacology & Pharmacy 2015年第2期6卷 65-74页

作者： Toni Homberg Violeta Sáenz Jorge Galicia-Carreón Iván Lara Edgar Cervantes-Trujano Maria C. Andaluz Erika Vera Oscar Pineda Julio Ayala-Balboa Alejandro Estrada-García Sergio Estrada-Parra Mayra Pérez-Tapia Maria C. Jiménez-Martínez Clinical Trials Branch and Clinical Immunology Service Unit of External Services and Clinical Research (USEIC) National School of Biological Sciences National Polytechnic Institute Mexico City Mexico unit of pharmacovigilance Unit of External Services and Clinical Research (USEIC) National School of Biological Sciences National Polytechnic Institute Mexico City Mexico Department of Immunology National School of Biological Sciences National Polytechnic Institute Mexico City Mexico unit of R&D in Bioprocesses (UDIBI) National School of Biological Sciences National Poly-technic Institute Mexico City Mexico Department of Biochemistry Faculty of Medicine National Autonomous University of Mexico Mexico City Mexico

Background: Dialyzable leukocyte extracts (DLE) are heterogeneous mixtures of peptides less than 10 kDa in size that are used as immunomodulatory adjuvants in immune-mediated diseases. TransferonTM is DLE manufactured by National Polytechnic Institute (IPN), and is registered by Mexican health-regulatory authorities as an immunomodulatory drug and commercialized nationally. The proposed mechanism of action of TransferonTM is induction of a Th1 immunoregulatory response. Despite that it is widely used, to date there are no reports of adverse events related to the clinical safety of human DLE or TransferonTM. Objective: To assess the safety of TransferonTM in a large group of patients exposed to DLE as adjuvant treatment. Methods: We included in this study 3844 patients from our Clinical Immunology Service at the unit of External Services and Clinical Research (USEIC), IPN. Analysis was performed from January 2014 to November 2014, searching for clinical adverse events in patients with immune-mediated diseases and treated with TransferonTM as an adjuvant. Results: In this work we observed clinical nonserious adverse events (AE) in 1.9% of patients treated with TransferonTM (MD 1.9, IQR 1.7 - 2.0). AE were 2.8 times more frequently observed in female than in male patients. The most common AE were headache in 15.7%, followed by rash in 11.4%, increased disease-related symptomatology in 10%, rhinorrhea in 7.1%, cough in 5.7%, and fatigue in 5.7% of patients with AE. 63% of adverse event presentation occurred from day 1 to day 4 of treatment with TransferonTM, and mean time resolution of adverse events was 14 days. In 23 cases, the therapy was stopped because of adverse events and no serious adverse events were observed in this study. Conclusion: TransferonTM induced low frequency of nonserious adverse events during adjuvant treatment. Further monitoring is advisable for different age and disease groups of patients.

关键词： Dialyzable Leukocyte Extracts Adverse Events Monitoring Drug Safety Adjuvant Therapy Immunoregulation Guidelines Transfer Factor pharmacovigilance

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Exploration of pH-sensitive rhodamine-based probe reversible binging Cu（Ⅱ） for double channel detecting biothiols

Exploration of pH-sensitive rhodamine-based probe reversible...

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中国化学会第29届学术年会

作者： Xiao-juan Li Jin-Long Chen Department of Pharmaceutical Analysis China Pharmaceutical University Key Laboratory of Drug Quality Control and pharmacovigilance China Pharmaceutical UniversityMinistry of Education

a pH-sensitive rhodamine-based probederivatives（RhM）was synthesized and explored as a fluorescence Off-On assay using Cu2+/RhM complex as a novel chemosensor for double channel detecting *** new small probe could bound to Cu2+reversibly and selectively under pH 3.0 to 7.0,which caused reversible change in the fluorescence intensity quenching and UV-visible absorbance *** was pH-sensitive which shows the highest fluorescence and absorbance response toward Cu2+ion under a pH 4.3 ***,biothiols such as GSH,Cys,Hcy could react with Cu2+/RhM complex resulting to release RhM reversibly over common amino acids,thereby enhancing the fluorescence and decreasing the absorbance.

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