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Comparison of ELISA and HPLC-MS methods for the determination of exenatide in biological and biotechnology-based formulation matrices

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Journal of Pharmaceutical Analysis 2019年第3期9卷 143-155页

作者： A.R. Pinho A. Fortuna A. Falcao A.C. Santos R. Seia C. Estevens F. Veiga A.J. Ribeiro Laboratory of Pharmaceutical Technology Faculty of Pharmacy University of Coimbra Polo das Ci^encias da Saúde Azinhaga de Santa Comba 3000-548 Coimbra Portugal Laboratory of pharmacology Faculty of Pharmacy University of Coimbra Polo das Ci^encias da Saúde Azinhaga de Santa Comba 3000-548 Coimbra Portugal CNC e Centre for Neuroscience and Cell Biology University of Coimbra 3004-517 Coimbra Portugal REQUIMTE/LAQV Group of Pharmaceutical Technology Faculty of Pharmacy University of Coimbra Polo das Ci^encias da Saúde Azinhaga de Santa Comba 3000-548 Coimbra Portugal Laboratory of physiology IBILI Faculty of Medicine University of Coimbra Polo das Ci^enicas da Saúde Azinhaga de Sante Comba 300-548 Coimbra Portugal Pharmaceutical Development TECNIMEDE S. A. Quinta da Cerca Caixaria 2565-187 Dois Portos Portugal I3S Instituto de Investiga鐍ao e Inova鐍ao em Sa鷇e Group Genetics of Cognitive Dysfunction IBMC e Instituto de Biologia Molecular e Celular Rua do Campo Alegre 823 4150-180 Porto Portugal

The development of biotechnology-based active pharmaceutical ingredients, such as GLP-1 analogs, brought changes in type 2 diabetes treatment options. For better therapeutic efficiency, these active pharmaceutical ingredients require appropriate administration, without the development of adverse effects or toxicity. Therefore, it is required to develop several quantification methods for GLP-1 analogs products, in order to achieve the therapeutic goals, among which ELISA and HPLC arise. These methods are developed, optimized and validated in order to determine GLP-1 analogs, not only in final formulation of the active pharmaceutical ingredient, but also during preclinical and clinical trials assessment. This review highlights the role of ELISA and HPLC methods that have been used during the assessment for GLP-1 analogs, especially for exenatide.

关键词： Type 2 diabetes Exenatide Therapeutic drug monitoring ELISA HPLC

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Ciliary parathyroid hormone signaling activates transforming growth factor-βto maintain intervertebral disc homeostasis during aging

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Bone Research 2018年第3期6卷 252-265页

作者： Liwei Zheng Yong Cao Shuangfei Ni Huabin Qi Zemin Ling Xin Xu Xuenong Zou Tianding Wu Ruoxian Deng Bo Hu Bo Gao Hao Chen Yusheng Li Jianxi Zhu Francis Tintani Shadpour Demehri Amit Jain Khaled M.Kebaish Shenghui Liao Cheryle A.Séguin Janet L.Crane Mei Wan Hongbin Lu Paul D.Sponseller Lee H.RileyIII Xuedong Zhou Jianzhong Hu Xu Cao Department of Orthopedic Surgery Johns Hopkins University School of MedicineRoss BuildingRoom 229720 Rutland AveBaltimoreMDUSA State Key Laboratory of Oral Diseases West China Hospital of StomatologySichuan UniversityChengduChina Department of Spine Surgery Xiangya HospitalCentral South UniversityChangshaChina Center of Bone Metabolism and Repair(CBMR) Trauma CenterInstitute of Surgery ResearchDaping HospitalThird Military Medical UniversityChongqingChina Guangdong Provincial Key Laboratory of Orthopedics and Traumatology Department of Spinal SurgeryThe First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina Department of Pediatrics Johns Hopkins University School of MedicineRoss BuildingRoom 229720 Rutland AveBaltimoreMDUSA The Russell H.Morgan Department of Radiology and Radiological Science Johns Hopkins University School of MedicineRoss BuildingRoom 229720 Rutland AveBaltimoreMDUSA Faculty of Computer Science College of Information Science and EngineeringXiangya HospitalCentral South UniversityChangshaChina Department of physiology and pharmacology Schulich School of Medicine and DentistryUniversity of Western OntarioLondonONCanada Department of Sports Medicine Xiangya HospitalCentral South UniversityChangshaChina

Degenerative disc disease(DDD) is associated with intervertebral disc degeneration of spinal instability. Here, we report that the cilia of nucleus pulposus(NP) cells mediate mechanotransduction to maintain anabolic activity in the discs. We found that mechanical stress promotes transport of parathyroid hormone 1 receptor(PTH1 R) to the cilia and enhances parathyroid hormone(PTH) signaling in NP cells. PTH induces transcription of integrin α_vβ_6 to activate the transforming growth factor(TGF)-β-connective tissue growth factor(CCN2)-matrix proteins signaling cascade. Intermittent injection of PTH(iPTH) effectively attenuates disc degeneration of aged mice by direct signaling through NP cells, specifically improving intervertebral disc height and volume by increasing levels of TGF-β activity, CCN2, and aggrecan. PTH1 R is expressed in both mouse and human NP cells. Importantly,knockout PTH1 R or cilia in the NP cells results in significant disc degeneration and blunts the effect of PTH on attenuation of aged discs. Thus, mechanical stress-induced transport of PTH1 R to the cilia enhances PTH signaling, which helps maintain intervertebral disc homeostasis, particularly during aging, indicating therapeutic potential of iPTH for DDD.

关键词： disc injection integrin cells iPTH effect TGF-β human

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Alcohol-induced hypertension: Mechanism and prevention

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World Journal of Cardiology 2014年第5期6卷 245-252页

作者： Kazim Husain Rais A Ansari Leon Ferder Department of physiology Pharmacology and Toxicology Ponce School of Medicine and Health Sciences Ponce PR 00732 United States Department of Pharmaceutical Sciences College of Pharmacy Nova Southeastern University Fort Lauderdale FL 33314 United States

Epidemiological, preclinical and clinical studies es-tablished the association between high alcohol con-sumption and hypertension. However the mechanism through which alcohol raises blood pressure remains elusive. Several possible mechanisms have been pro-posed such as an imbalance of the central nervous system, impairment of the baroreceptors, enhanced sympathetic activity, stimulation of the renin-angio-tensin-aldosterone system, increased cortisol levels, increased vascular reactivity due to increase in intracel-lular calcium levels, stimulation of the endothelium to release vasoconstrictors and loss of relaxation due to inflammation and oxidative injury of the endothelium leading to inhibition of endothelium-dependent nitric oxide production. Loss of relaxation due to inflamma-tion and oxidative injury of the endothelium by angio-tensin II leading to inhibition of endothelium-dependent nitric oxide production is the major contributors of the alcohol-induced hypertension. For the prevention of alcohol-induced hypertension is to reduce the amount of alcohol intake. Physical conditioning/exercise trainingis one of the most important strategies to prevent/treat chronic alcohol-induced hypertension on physiological basis. The efficacious pharmacologic treatment includes the angiotensin-converting enzyme(ACE) inhibitors or angiotensin Ⅱ type 1 receptor blockers(ARBs) which have antioxidant activity and calcium channel blockers. The most effective prevention and treatment of alcohol-induced hypertension is physical exercise and the use of ACE inhibitors or ARBs in the

关键词： Alcohol Hypertension Mechanisms Prevention/treatment Vascular endothelium

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可卡因在脊髓感觉神经元抑制交感阻滞剂胍乙啶引起的血管舒张

可卡因在脊髓感觉神经元抑制交感阻滞剂胍乙啶引起的血管舒张

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第四届东西方国际疼痛会议、中华医学会疼痛学会第三届年会暨麻醉学组第三届学术会议

作者： K.SHIMAMURA T.L.ANTHONY D.L.KREULEN Research Institute of Hypertension Kinki University Research Institute of Hypertension Kinki University 377-2 Ohno-higashi Osakasayama 589 Japan. Dept of pharmacology and Toxicology University of Arizona Tucson AZ 85724 Department of physiology Michigan State University East Lansing MI 48824-1317.

辣椒辣素敏性感觉神经在豚鼠肠系膜动脉介导了非内皮依赖性血管舒张。预先给予胍乙啶(30μM,30min)可以增强这种舒张。我们研究了胍乙啶对感觉神经的各种作用。除去内皮的肠系膜动脉先被化学性切除交感神经(胍乙啶30μM,30min),后用美速... 详细信息

辣椒辣素敏性感觉神经在豚鼠肠系膜动脉介导了非内皮依赖性血管舒张。预先给予胍乙啶(30μM,30min)可以增强这种舒张。我们研究了胍乙啶对感觉神经的各种作用。除去内皮的肠系膜动脉先被化学性切除交感神经(胍乙啶30μM,30min),后用美速胺(二

关键词：胍乙啶感觉神经元阻滞剂可卡因

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FERROPORTIN1/HEPHAESTIN SYSTEM AND IRON EXPORT FROM CELLS IN THE HEART

FERROPORTIN1/HEPHAESTIN SYSTEM AND IRON EXPORT FROM CELLS IN...

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中国生理学会、中国神经科学会2005年神经内分泌免疫学术研讨会

作者： KP HO Laboratory of Brain Iron Metabolism Department of Applied Biology & Chemical Technology and National Key Laboratory of Chinese Medicine and Molecular pharmacology (Shenzhen) Hong Kong Polytechnic University Hong Kong

Iron is an essential trace element in humans. As in all cells, heart cells require iron for many aspects of their physiology. On the other hand, excess iron in the heart can be potentially harmful via the generation of reactive oxygen species. The vast amount of literatures show that iron-mediated injury plays an important role in the development of a number of heart disorders. Studies on heart iron are therefore crucial for understanding cause of excessive heart iron. Heart cells have the ability to accumulate transferrin-bound iron via transferrin receptor and

关键词： FERROPORTIN1/HEPHAESTIN SYSTEM AND IRON EXPORT FROM CELLS IN THE HEART

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In vitro Antibacterial Efficacy of Bidens pilosa, Ageratum conyzoidesand Ocimum suaveExtracts against HIV/AIDS Patients’ Oral Bacteria in South-Western Uganda

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pharmacology & Pharmacy 2017年第9期8卷 306-323页

作者： Joseph Obiezu Chukwujekwu Ezeonwumelu Muhammad Ntale Steve Okwudili Ogbonnia Ezera Agwu Julius Kihdze Tanayen Keneth Iceland Kasozi Chukwudi Onyeka Okonkwo Anthonia Shodunke Ambrose Amamchukwu Akunne Onokiojare Ephraim Dafiewhare Jennifer Chibuogwu Ebosie Frederick Byarugaba Department of Pharmacy Faculty of MedicineMbarara University of Science and TechnologyMbararaUganda Department of Clinical and Biopharmacy School of PharmacyKampala International University Western CampusIshakaUganda Kampala International University Complementary and Alternative Medicine Research(KIUCAMRES)Group IshakaUganda Department of Chemistry Makerere UniversityKampalaUganda Department of Pharmacognosy Faculty of PharmacyUniversity of LagosLagosNigeria Department of Microbiology Faculty of Biomedical SciencesKampala International University Western CampusIshakaUganda Department of pharmacology and Therapeutics Faculty of MedicineMbarara University of Science and TechnologyMbararaUganda Department of physiology Faculty of Biomedical SciencesKampala International University Western CampusIshakaUganda Department of Human physiology Faculty of Basic Medical SciencesCollege of MedicineNnewi CampusNnamdi Azikiwe UniversityNnewiNigeria Department of Public Health Faculty of Applied SciencesBishop Stuart UniversityMbararaUganda Department of Microbiology Faculty of MedicineMbarara University of Science and TechnologyMbararaUganda Department of Medical Microbiology and Immunology University of KabaleKabaleUganda

The objective of the study was to determine the antibacterial efficacy of Bidens pilosa Aqueous (BPA), Bidens pilosa Ethanolic (BPE), Ageratum conyzoides Aqueous (ACA), Ageratum conyzoides Ethanolic (ACE), Ocimum suave Aqueous (OSA) and Ocimum suave Ethanolic (OSE) extracts on HIV/AIDS patients’ oral bacteria. Healthy green leaves of the plants were collected in Ishaka Uganda, processed and portions separately extracted with hot distilled water and cold ethanol. The susceptibility, MIC and MBC of each extract were determined using standard protocols. The bacteria had significant (p Bidens pilosa, Ageratum conyzoides and Ocimum suave on oral lesions of HIV/AIDS patients made by traditional healers and local people in South-Western Uganda. We recommend a detailed study of structural identities and activities of the active antibacterial principle(s) in these plants for possible new drug entities and verification of the interactive effects of the principle(s) with ARVs and cotrimoxazole used daily by HIV/AIDS patients.

关键词： Antibacterial Efficacy Bidens Pilosa Ageratum Conyzoides Ocimum Suave Oral Bacteria HIV/AIDS Uganda

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The Antihypertensive Effect of Hydro-methanolic Extract of Tulbaghia acutiloba *** L-NAME induced Hypertensive Rats

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Clinical Complementary Medicine and pharmacology 2023年第3期3卷 50-59页

作者： Isaiah Arhin Kogi Moodley Himansu Baijnath Usri H.Ibrahim Irene Mackraj Discipline of Human physiology School of Laboratory Medicine and Medical SciencesCollege of Health SciencesUniversity of KwaZulu-NatalDurban 4000South Africa Ward Herbarium School of Life SciencesUniversity of KwaZulu-NatalDurban 4000South Africa

Background:Traditional use of Tulbaghia acutiloba(TA)in South Africa includes treating various illnesses,such as infectious diseases and ***,the effect of this indigenous plant on renal and haematological parameters(as indicators of antihypertensive efficacy)has not been investigated ***:This study aimed to evaluate the change of renal and haematological parameters after treatment with the hydro-methanolic extract of the leaf of Tulbaghia acutiloba *** L-NAME-induced hypertensive ***:Male albino Wistar rats received an oral dose of 50 mg·kg^(-1)body weight(bw)of N𝜔-Nitro-L-arginine methyl ester hydrochloride(L-NAME)daily for 5 *** groups(7 animals in each group)were identified to receive different treatments as concurrent daily doses of(40,60 and 80 mg·kg^(-1)bw),ramipril(10 mg·kg^(-1)bw)(positive control)and water(hypertension model).Mean arterial blood pressure was measured weekly using the tail-cuffmethod.A 24-hour urine sample was collected for each rat *** day 36,the rats were euthanized,and blood samples were collected for the determination of renal function and haematological *** mRNA gene expression was performed for NF-kB,Ho1 and ***:The treatment of the hypertensive rats with TA resulted in a significant reduction in the mean arterial blood pressure,with a pronounced effect observed in the 80 mg·kg^(-1)dose of TA compared to the positive *** TA-treated group showed increased creatinine clearance(Ccr),urine volume and a reduction in serum crea-tinine,proteinuria and urine protein-creatinine ratio(UPr/UCr).TA treatment also decreased lipid peroxidation in renal tissues and erythrocytes while increasing SOD,CAT,GSH and NO ***,red cell distribu-tion width(RDW),white blood cells(WBC),neutrophil to lymphocyte ratio(NLR),lymphocyte to monocyte ratio(LMR),platelet and mean platelet volume(MPV)were significantly reduced in the TA and ramipril treated groups with the maxim

关键词： Tulbaghia acutiloba Renal function Haematological parameters Hypertension Antioxidant

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Contribution of oxidative stress to pulmonary arterial hypertension

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World Journal of Cardiology 2010年第10期2卷 316-324页

作者： Vincent G DeMarco Adam T Whaley-Connell James R Sowers Javad Habibi Kevin C Dellsperger Department of Internal Medicine University of Missouri School of Medicine Diabetes and Cardiovascular Laboratory University of Missouri School of Medicine Department of Medical pharmacology and physiology University of Missouri School of Medicine Harry S Truman Veterans Affair Medical Center

Recent data implicate oxidative stress as a mediator of pulmonary hypertension (PH) and of the associated pathological changes to the pulmonary vasculature and right ventricle (RV). Increases in reactive oxygen species (ROS), altered redox state, and elevated oxidant stress have been demonstrated in the lungs and RV of several animal models of PH, including chronic hypoxia, monocrotaline toxicity, caveolin-1 knock-out mouse, and the transgenic Ren2 rat which overexpresses the mouse renin gene. Generation of ROS in these models is derived mostly from the activities of the nicotinamide adenine dinucleotide phosphate oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide synthase. As disease progresses circulating monocytes and bone marrow-derived monocytic progenitor cells are attracted to and accumulate in the pulmonary vasculature. Once established, these inflammatory cells generate ROS and secrete mitogenic and fibrogenic cytokines that induce cell proliferation and fibrosis in the vascular wall resulting in progressive vascular remodeling. Deficiencies in antioxidant enzymes also contribute to pulmonary hypertensive states. Current therapies were developed to improve endothelial function, reduce pulmonary artery pressure, and slow the progression of vascular remodeling in the pulmonary vasculature by targeting deficiencies in either NO (PDE-type 5 inhibition) or PGI 2 (prostacyclin analogs), or excessive synthesis of ET-1 (ET receptor blockers) with the intent to improve patient clinical status and survival. New therapies may slow disease progression to some extent, but long term management has not been achieved and mortality is still high. Although little is known concerning the effects of current pulmonary arterial hypertension treatments on RV structure and function, interest in this area is increasing. Development of therapeutic strategies that simultaneously target pathology in the pulmonary vasculature and RV may be beneficial in reducing mortali

关键词： Pulmonary arterial hypertension Rosuvastatin Oxidative stress Nicotinamide adenine dinucleotide phosphate oxidase Statins

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可卡因强化性敏化与多巴胺D2受体

可卡因强化性敏化与多巴胺D2受体

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中国毒理学会第二届全国中青年学者科技论坛

作者：刘昱 David CS Roberts 北京大学中国药物依赖性研究所北京海淀区学院路38号 Wake Forest University Health Sciences Department of physiology and pharmacology Winston-Salem NC 27157USA

＜正＞目的:成瘾者给药动机的逐渐加强是成瘾行为形成和发展的主要因素,而药物强化性敏化是给药动机逐渐增强的原因之一。虽然已有实验证明多巴胺 D2受体对可卡因诱导的自发活动敏化性又显著影响,但是迄今为止还没有在动物自我给药模型...

＜正＞目的:成瘾者给药动机的逐渐加强是成瘾行为形成和发展的主要因素,而药物强化性敏化是给药动机逐渐增强的原因之一。虽然已有实验证明多巴胺 D2受体对可卡因诱导的自发活动敏化性又显著影响,但是迄今为止还没有在动物自我给药模型上确立其与

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Effects of Activation and Blockade of Serotonin 5-HT1A Receptors on the Immune Response in Rats Selected for Different Levels of Aggressiveness

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pharmacology & Pharmacy 2015年第9期6卷 451-459页

作者： Elizaveta Alperina Elena Zhukova Galina Idova Rimma Kozhemyakina Margarita Cheido Federal State Budgetary Scientific Institution Scientific Research Institute of Physiology and Basic Medicine Novosibirsk Russia Novosibirsk State University Novosibirsk Russia Federal Research Center Institute of Cytology and Genetics Siberian Branch of the Russian Academy of Sciences Novosibirsk Russia

The present study examines the effects of serotonin (5-HT) 1A receptor ligands on humoral im-mune response in two rat lines selected for over 75 generations for the enhancement or elimination of aggression. Activation of presynaptic 5-HT1A receptors with a low dose of the selective 5-HT1A receptor agonist 8-OH-DPAT (0.1 mg/kg) or the blockade of postsynaptic 5-HT1A receptors with the antagonist WAY-100635 (1.0 mg/kg) did not affect the numbers of IgM-antibody forming cells (IgM-AFC) in the spleen of highly aggressive rats, which were characterized by higher immune responsiveness compared to nonaggressive line. On the other hand, the same doses of 8-OH-DPAT and WAY-100635, as well as a higher dose of 8-OH-DPAT (1.0 mg/kg), which is known to activate postsynaptic 5-HT1A receptors, produce immunostimulation in nonaggressive rats. However, only the highest dose of 8-OH-DPAT (5.0 mg/kg) was able to cause immunosuppression in nonaggressive rats that was mainly dependent on stimulation of postsynaptic 5-HT1A receptors. In contrast to nonaggressive rats, the dose of 1.0 mg/kg 8-OH-DPAT was sufficient to produce a decrease in the numbers of IgM-AFC in highly aggressive rats. Thus, pharmacological activation of pre- and postsynaptic 5-HT1A receptors, as well as the blockade of postsynaptic 5-HT1A receptors, produced different effects on the immune response in two lines of rats selected for high level of aggression or its absence. These data may have implications for more efficient treatments of a number of mental disorders associated with abnormal aggression.

关键词： Aggressive Behavior Serotonin Pre- and Postsynaptic 5-HT1A Receptors 8-OH-DPAT WAY-100635 IgM-Immune Response

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