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Development of an HPLC–UV assay method for the simultaneous quantification of nine antiretroviral agents in the plasma of HIV-infected patients

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Journal of Pharmaceutical Analysis 2016年第6期6卷 396-403页

作者： Nitin Charbe Sara Baldelli Valeria Cozzi Simone Castoldi Dario Cattaneo Emilio Clementi Unit of clinical pharmacology Department of Biomedical and Clinical Sciences L. Sacco University Hospital Università di Milano 20157 Milan Italy clinical pharmacology Unit CNR Institute of Neuroscience Department of Biomedical and Clinical Sciences L. Sacco University Hospital Università di Milano 20157 Milan Italy Scientific Institute IRCCS Eugenio Medea Bosisio Parini Italy

A new method using high-performance liquid chromatography coupled with ultra violet detection(HPLC–UV)was developed and validated for the simultaneous quantification of atazanavir,dolutegravir,darunavir,efavirenz,etravirine lopinavir,raltegravir,rilpivirine and tipranavir in human *** the first time we reported here the development and validation of an HPLC–UV assay to quantify the frequently administered 9antiretroviral compounds including dolutegravir and rilpivirine.A simple solid phase extraction procedure was applied to 500 μL aliquots of *** chromatographic separation of the drugs and internal standard(quinoxaline) was achieved with a gradient of acetonitrile and sodium acetate buffer on a C_(18) reverse-phase analytical column with a 25 min analytical run *** curves were optimised according to the therapeutic range of drug concentrations in patients,and the coefficient of determination(r^2) was higher than0.99 for all *** intraday and interday precisions(RSD) for all compounds were less than 15.0%,and the mean accuracy(% deviation from nominal concentration) was also found to be less than 15.0%.Extraction recovery range was between 80% and 120% for all drugs *** solid phase extraction and HPLC–UV method enable a specific,sensitive,and reliable simultaneous determination of nine antiretroviral agents in *** extraction efficiency and low limit of HPLC–UV quantification make this method suitable for use in clinical trials and therapeutic drug monitoring.

关键词： HPLC–UV Antiretrovirals Bioanalytical method validation

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PD-1 inhibitors monotherapy in hepatocellular carcinoma: Meta-analysis and systematic review

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Hepatobiliary & Pancreatic Diseases International 2019年第6期18卷 505-510页

作者： Ioannis A.Voutsadakis Algoma District Cancer Program Sault Area Hospital section of Internal Medicine Division of Clinical Sciences Northern Ontario School of Medicine

Background:Immunity plays a major role in carcinogenesis and this is the case also for hepatocellular carcinomas(HCC).Checkpoint inhibitors,novel drugs that enhance the immune system’s ability to attack cancers,have been successfully introduced for the therapy of various malignancies including *** important target of these drugs is the PD-L1/PD-1 ligand/receptor pair and several clinically available inhibitors of this pair *** sources:A search of the literature until April 20,2019 was performed in the MEDLINE/PubMed database,the Embase database and the Cochrane Central Register of Controlled *** clinical studies describing treatment with PD-L1/PD-1 inhibitors as monotherapy in HCC patients were *** characteristics with relevance for treatment efficacy,such as liver function,disease extend and previous treatment,were extracted from identified *** and survival outcomes were the primary focus of the *** estimates of response rates and survival were calculated using a random or fixed effect model,depending on *** common adverse effects were also recorded and ***:Three studies(two on nivolumab and one on pembrolizumab)with a total of 400 patients were included in the *** summary response rate(RR)was 17.3%[95%confidence interval(CI):13.2%–21.4%].The summary disease control rate(DCR)was 56.6%(95%CI:44.7%–68.5%).Summary progression free survival(PFS)was 3.5 months(95%CI:2.8–4.2 months).Summary overall survival(OS)was 10.4 months(95%CI:3.5–17.2 months).Adverse effect rate was low and also consistent with the adverse effect profile of PD-L1/PD-1 inhibitors in other disease ***:Pembrolizumab and nivolumab are the only checkpoint inhibitors with data in *** of their effectiveness discloses rates not dissimilar to other systemic therapies available for this *** interest also are the observed long responses in a sub-set of ***

关键词： Hepatocellular carcinoma Immune checkpoint inhibitors Nivolumab Pembrolizumab Meta-analysis

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Brain natriuretic peptide and optimal management of heart failure

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2005年第9期6卷 877-884页

作者：李楠王建安 Division of clinical pharmacology and Cardiology Sir Run Run Shaw Hospital School of Medicine Zhejiang University Hangzhou 310016 China

Aside from the important role of brain natriuretic peptide (BNP) in diagnosis, and differential diagnosis of heart failure, this biological peptide has proved to be an independent surrogate marker of rehospitalization and death of the fatal disease. Several randomized clinical trials demonstrated that drugs such as beta blocker, angiotensin converting enzyme inhibitor, spiro- nolactone and amiodarone have beneficial effects in decreasing circulating BNP level during the management of chronic heart failure. The optimization of clinical decision-making appeals for a representative surrogate marker for heart failure prognosis. The serial point-of-care assessments of BNP concentration provide a therapeutic goal of clinical multi-therapy and an objective guid- ance for optimal treatment of heart failure. Nevertheless new questions and problems in this area remain to be clarified. On the basis of current research advances, this article gives an overview of BNP peptide and its property and role in the management of heart failure.

关键词： Brain natriuretic peptide (BNP) Heart failure Drug therapy

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Geraniol alleviates cyclophosphamide-induced cardiotoxicity in mice

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Asian Pacific Journal of Tropical Biomedicine 2024年第10期14卷 427-435页

作者： Shahid Karim Rasheed A.Shaik Department of clinical pharmacology Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia Department of pharmacology and Toxicology Faculty of PharmacyKing Abdulaziz UniversityJeddahSaudi Arabia

Objective:To explore the effect of geraniol on cyclophosphamide-induced ***:Mice were divided into five groups:the control group,the cyclophosphamide group(200 mg/kg cyclophosphamide,*** day 7),the group treated with geraniol 100 and 200 mg/kg from day 1 to day 14,along with a single dose of cyclophosphamide on day 7,and the geraniol alone group(200 mg/kg geraniol from day 1 to day 14).At the end of the study,animals were sacrificed,and blood and heart were collected and analyzed for biochemical,histopathological,and immunohistochemical ***:Treatment with 200 mg/kg geraniol significantly reduced the levels of cardiac injury markers,malondialdehyde,and inflammatory and apoptotic markers,while increasing antioxidant activities in mice with cyclophosphamide-induced ***,it remarkably alleviated histopathological aberrations in cardiac ***:Geraniol attenuates cyclophosphamide-induced cardiotoxicity via antioxidant,anti-inflammatory,and antiapoptotic effects.

关键词： Geraniol Cardiotoxicity Natural product Cyclophosphamide Inflammation Apoptosis

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GRK2 inhibits Flt-1^(+)macrophage infiltration and its proangiogenic properties in rheumatoid arthritis

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Acta Pharmaceutica Sinica B 2024年第1期14卷 241-255页

作者： Xuezhi Yang Yingjie Zhao Qi Wei Xuemin Zhu Luping Wang Wankang Zhang Xiaoyi Liu Jiajie Kuai Fengling Wang Wei Wei Institute of clinical pharmacology Anhui Medical UniversityKey Laboratory of Anti-Inflammatory and Immune MedicineAnhui Collaborative Innovation Center of Anti-Inflammatory and Immune MedicineMinistry of EducationHefei 230032China Department of clinical pharmacology the Second Affiliated Hospital of Anhui Medical UniversityHefei 230601China

Rheumatoid arthritis(RA)is an autoimmune disease with a complex ***-derived macrophages(MDMs)infiltration are associated with RA *** have reported the deletion of G-protein-coupled receptor kinase 2(GRK2)reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor ***,as more GRK2-interacting proteins were discovered,the GRK2 interactome mechanisms in RA have been ***,in the collagen-induced arthritis mouse model,we performed genetic GRK2 deletion using GRK2^(f/f)Lyz2-Cre^(+/−)*** inflammation and M1 polarization were improved in GRK2^(f/f)Lyz2-Cre^(+/−)*** experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptorγ(PPARγ)as a new GRK2-interacting *** further confirmed that fms-related tyrosine kinase 1(Flt-1),which promoted macrophage migration to induce angiogenesis,was inhibited by GRK2-PPARγ***,excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγligand-binding domain and enhanced Flt-1 ***,the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology,Flt-1^(+)macrophages induced-synovial inflammation,and ***,we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular *** GRK2 activity is a viable strategy to inhibit MDMs infiltration,affording a distinct way to control joint inflammation and angiogenesis of RA.

关键词： GRK2 Monocyte-derived macrophages Rheumatoid arthritis PPARg Flt-1

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Fat:A matter of disturbance for the immune system

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World Journal of Gastroenterology 2010年第38期16卷 476-4772页

作者： Alessandro Federico Elena D’Aiuto Francesco Borriello Giusi Barra Antonietta Gerarda Gravina Marco Romano Raffaele De Palma section of Gastroenterology Department of Clinical and Experimental MedicineSecond University of Naples section of clinical Immunology Department of Clinical and Experimental Medicine Second University of Naples

Obesity is increasingly being recognized as a risk factor for a number of benign and malignant gastrointestinal conditions. However, literature on the underlying pathophysiological mechanisms is sparse and ambiguous. There is compelling evidence that both overnutrition and undernutrition negatively interfere with the immune system. Overnutrition has been found to increase susceptibility to the development of inflammatory diseases, autoimmune diseases and cancer. In the regulation of immune and in? ammatory processes, white adipose tissue plays a critical role, not only as an energy store but also as an important endocrine organ. The obese state is characterised by a low-grade systemic in? ammation, mainly as a result of increased adipocytes as well as fat resident-and recruited-macrophage activity. In the past few years, various products of adipose tissue including adipokines and cytokines have been characterised and a number of pathways linking adipose tissue metabolism with the immune system have been identified. Activation of the innate immune system plays a major role in hepatic steatosis. Non-alcoholic fatty liver disease includes a wide spectrum of diseases, from pure steatosis to non-alcoholic steato-hepatitis in the absence of signif icant alcohol consumption. Although steatosis is considered a non-progressive disease, non-alcoholic steatohepatitis may deteriorate in advanced chronic liver diseases, cirrhosis, and hepatocellular carcinoma. An important parallel between obesityrelated pathology of adipose tissue and liver pertains to the emerging role of macrophages, and growing evidence suggests that Kupffer cells critically contribute to progression of non-alcoholic fatty liver disease. Moreover, a close link between specif ic immune activation and atherosclerosis has been well established, suggesting that fat can directly trigger immune responses. This review discusses the role of fat as "a matter of disturbance for the immune system" with a focus on hepat

关键词： Adipocytokine Adipose tissue Fat Immune system Kupffer cell Natural killer Steatosis

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Portopulmonary hypertension and hepatopulmonary syndrome

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World Journal of Gastroenterology 2014年第25期20卷 8072-8081页

作者： Florence Aldenkortt Marc Aldenkortt Laurence Caviezel Jean Luc Waeber Anne Weber Eduardo Schiffer Division of Anesthesiology Department of AnesthesiologyClinical Pharmacology and Intensive CareGeneva University Hospitals1211 GenevaSwitzerland

Portopulmonary hypertension (POPH) and hepatopulmonary syndrome (HPS) are two frequent complications of liver disease, with prevalence among liver transplant candidates of 6% and 10%, respectively. Both conditions result from a lack of hepatic clearance of vasoactive substances produced in the splanchnic territory. Subsequently, these substances cause mainly pulmonary vascular remodeling and some degree of vasoconstriction in POPH with resulting elevated pulmonary pressure and right ventricular dysfunction. In HPS the vasoactive mediators cause intrapulmonary shunts with hypoxemia. Medical treatment is disappointing overall. Whereas liver transplantation (LT) results in the disappearance of HPS within six to twelve months, its effect on POPH is highly unpredictable. Modern strategies in managing HPS and POPH rely on a thorough screening and grading of the disease’s severity, in order to tailor the appropriate therapy and select only the patients who will benefit from LT. The anesthesiologist plays a central role in managing these high-risk patients. Indeed, the important hemodynamic and respiratory modifications of the perioperative period must be avoided through continuation of the preoperatively initiated drugs, appropriate intraoperative monitoring and proper hemodynamic and respiratory therapies.

关键词： End stage liver disease Hepatopulmonary syndrome Portopulmonary Hypertension Anesthesia

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Non-alcoholic fatty liver disease:Epidemiology,pathophysiology and an update on the therapeutic approaches

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Asian Pacific Journal of Tropical Biomedicine 2022年第3期12卷 99-114页

作者： Rehab F.Abdel-Rahman Department of pharmacology Medical Research and Clinical Studies InstituteNational Research Centre12622-DokkiGizaEgypt

Non-alcoholic fatty liver disease(NAFLD)denotes a spectrum of fatty liver disease in individuals without significant alcohol *** is set to be the most common etiology of serious liver diseases in numerous nations when accompanied by obesity and type 2 *** is further histologically categorized into the non-alcoholic fatty liver(NAFL;steatosis without hepatocellular injury)and non-alcoholic steatohepatitis(NASH)which is characterized by the coexistence of hepatic steatosis and inflammation and is accompanied by hepatocyte injury(ballooning),either with or without *** is considered the benign and reversible stage arising from the excessive accumulation of triglycerides in ***,NASH is a more progressive stage of NAFLD,due to the increased risks of evolving more serious diseases such as cirrhosis,hepatocellular *** concept,however,has been lately challenged by a hypothesis of multiple parallel hits of NAFLD,in which steatosis and NASH are separate entities rather than two points of the NAFLD spectrum,not only from a set of histological patterns but also from a pathophysiological *** current review highlights the epidemiology and pathophysiology of NAFLD,and its progression towards steatohepatitis,with special focus on the novel imminent therapeutic approaches targeting the molecular aspects and the pathogenic pathways involved in the development,and progression of NAFLD.

关键词： Non-alcoholic fatty liver disease Steatosis Insulin sensitizers Glucagon-like peptide-1 analogues Dipeptidyl peptidase-4 inhibitors Farnesoid X receptor agonists

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Erratum to DYRK1A suppression restrains Mcl-1 expression and sensitizes NSCLC cells to Bcl-2 inhibitors

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Cancer Biology & Medicine 2022年第7期19卷 1109-1110页

作者： Yangling Li Dongmei Zhou Shuang Xu Mingjun Rao Zuoyan Zhang Linwen Wu Chong Zhang Nengming Lin Department of clinical pharmacology Hangzhou First People’s HospitalNanjing Medical UniversityHangzhou 310006China Department of clinical pharmacology Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang ProvinceHangzhou First People’s HospitalZhejiang University School of MedicineHangzhou 310006China Institute of pharmacology College of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhou 311402China School of Medicine Zhejiang University City CollegeHangzhou 310015China

In the published paper1,errors appeared in Figure 1D on page *** Figure 1D,an incorrect gel image was shown for Bcl-xL in NCI-H1299 *** 1D has been updated to correct the mistake *** errors do not affect the conclusio... 详细信息

关键词： Figure NSCLC restrain

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Autoantibodies in Alzheimer's disease:potential biomarkers,pathogenic roles,and therapeutic implications

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The Journal of Biomedical Research 2016年第5期30卷 361-372页

作者： Jianming Wu Ling Li Department of Veterinary and Biomedical Sciences University of Minnesota Department of Experimental and clinical pharmacology University of Minnesota

Alzheimer＇s disease （AD） is a prevalent and debilitating neurodegenerative disorder in the elderly. The etiology of AD has not been fully defined and currently there is no cure for this devastating disease. Compelling evidence sug- gests that the immune system plays a critical role in the pathophysiology ofAD. Autoantibodies against a variety of molecules have been associated with AD. The roles of these autoantibodies in AD, however, are not well understood. This review attempts to summarize recent findings on these autoantibodies and explore their potential as diagnostic/ prognostic biomarkers for AD, their roles in the pathogenesis of AD, and their implications in the development of effective immunotherapies for AD.

关键词： Alzheimer's disease autoimmune autoantibody biomarker pathogenesis immunotherapy

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