Pub Date : 2013-04-19DOI: 10.2174/1874143601307010001
D. Gregori, D. Chiffi
In Italy, the National Health System (NHS) costs are controlled by the regional governments (which are financially accountable for health care expenditure, including hospital drug budgets), but agreements regarding price and discounts are decided in AIFA (Italian Medicine Agency). For this reason, some regional governments ask the pharmaceutical companies to produce a "Health Technology Assessment" before deciding to introduce a drug in the regional hospital list of accepted drugs. Thus, in terms of public policy maker and its decision process, the choice of well-specified points of view is an essential ingredient in the critical assessment of economic evaluation, which becomes more effective when information is presented in the general terms of a cost of illness analysis (COI), or, in a disaggregated way by means of a list of the costs and the
{"title":"Editorial: Evaluating Impact of High-Cost Cancer Drugs at Regional Level: The Case of Veneto (Italy)","authors":"D. Gregori, D. Chiffi","doi":"10.2174/1874143601307010001","DOIUrl":"https://doi.org/10.2174/1874143601307010001","url":null,"abstract":"In Italy, the National Health System (NHS) costs are controlled by the regional governments (which are financially accountable for health care expenditure, including hospital drug budgets), but agreements regarding price and discounts are decided in AIFA (Italian Medicine Agency). For this reason, some regional governments ask the pharmaceutical companies to produce a \"Health Technology Assessment\" before deciding to introduce a drug in the regional hospital list of accepted drugs. Thus, in terms of public policy maker and its decision process, the choice of well-specified points of view is an essential ingredient in the critical assessment of economic evaluation, which becomes more effective when information is presented in the general terms of a cost of illness analysis (COI), or, in a disaggregated way by means of a list of the costs and the","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"185 1","pages":"1-1"},"PeriodicalIF":0.0,"publicationDate":"2013-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79755536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-06-17DOI: 10.2174/1874143601206010045
L. Corless, H. Tsai
Aims: To review current issues in the diagnosis and treatment of primary sclerosing cholangitis. Methods: search of PubMed using the terms "primary sclerosing cholangitis", "PSC", "cholangitis" and "cholestasis", as well as by review of current guidelines from the major international liver societies. Results: Primary sclerosing cholangitis is still a challenging condition to diagnose and manage, but newer imaging modalities like MRCP and timing of liver transplantation point the way forward.
{"title":"Primary Sclerosing Cholangitis - Current Issues in Clinical Practice","authors":"L. Corless, H. Tsai","doi":"10.2174/1874143601206010045","DOIUrl":"https://doi.org/10.2174/1874143601206010045","url":null,"abstract":"Aims: To review current issues in the diagnosis and treatment of primary sclerosing cholangitis. Methods: search of PubMed using the terms \"primary sclerosing cholangitis\", \"PSC\", \"cholangitis\" and \"cholestasis\", as well as by review of current guidelines from the major international liver societies. Results: Primary sclerosing cholangitis is still a challenging condition to diagnose and manage, but newer imaging modalities like MRCP and timing of liver transplantation point the way forward.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"1 1","pages":"45-51"},"PeriodicalIF":0.0,"publicationDate":"2012-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91210073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-05-21DOI: 10.2174/1874143601206010034
V. M. F. Lima, José P. Castro, W. Hanke
In this century, the IT technology will spread intelligent systems based on cameras, sensors and computers across all fields of the human endeavor. The systematization of knowledge will reach new levels of organization and applications. Scientific knowledge will not be an exception. In this paper we present the results of validation tests made with the in vitro retina model in order to propose the systematization of pharmacological knowledge in experimental platforms supplied with data banks. Data banks can be made either for the speeding up of pre-clinical research or for the control of quality of pure substances or pharmaceutical preparations. These applications and other implementations of using the retinal spreading model in pharmacological research will be useful for the users, manufacturers and authorities of regulation of public health.
{"title":"Intelligent Systems and the Systematization of Pharmacological Knowledge: Application of the In Vitro Retina Model","authors":"V. M. F. Lima, José P. Castro, W. Hanke","doi":"10.2174/1874143601206010034","DOIUrl":"https://doi.org/10.2174/1874143601206010034","url":null,"abstract":"In this century, the IT technology will spread intelligent systems based on cameras, sensors and computers across all fields of the human endeavor. The systematization of knowledge will reach new levels of organization and applications. Scientific knowledge will not be an exception. In this paper we present the results of validation tests made with the in vitro retina model in order to propose the systematization of pharmacological knowledge in experimental platforms supplied with data banks. Data banks can be made either for the speeding up of pre-clinical research or for the control of quality of pure substances or pharmaceutical preparations. These applications and other implementations of using the retinal spreading model in pharmacological research will be useful for the users, manufacturers and authorities of regulation of public health.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"84 1","pages":"34-44"},"PeriodicalIF":0.0,"publicationDate":"2012-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77655781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-05-09DOI: 10.2174/1874143601206010012
H. Douna, B. Bavelaar, H. Pellikaan, B. Olivier, T. Pieters
Aim: This study aimed to systematically review the preclinical data of neuroprotective agents for Parkinson's disease (PD) to support the translation of these compounds. Methods: The study consisted of two phases. In phase I, Pubmed and Scopus were systematically searched for neuroprotective agents for PD. In phase II, a systematic search was conducted for each substance identified in phase I. Articles were included if they used MPTP, 6-OHDA, rotenone or paraquat injury models. Results: Phase I led to the identification of 168 putative neuroprotective agents. Eventually ten compounds were included: melatonin, estrogen, nicotine, caffeine, riluzole, curcumin, coenzyme Q10, aspirin, EGCG and resveratrol. Phase II revealed 113 experimental studies and three reviews. Conclusion: This study clearly depicts the preclinical data of ten promising neuroprotective agents. While some of these compounds have already been tested in clinical use, none of them was studied in an appropriately designed trial to determine a neuroprotective effect. In expectation of qualitatively improved neuroprotection trials, the data from this study provide a firm foundation for future research.
{"title":"Neuroprotection in Parkinson's Disease: A Systematic Review of thePreclinical Data","authors":"H. Douna, B. Bavelaar, H. Pellikaan, B. Olivier, T. Pieters","doi":"10.2174/1874143601206010012","DOIUrl":"https://doi.org/10.2174/1874143601206010012","url":null,"abstract":"Aim: This study aimed to systematically review the preclinical data of neuroprotective agents for Parkinson's disease (PD) to support the translation of these compounds. Methods: The study consisted of two phases. In phase I, Pubmed and Scopus were systematically searched for neuroprotective agents for PD. In phase II, a systematic search was conducted for each substance identified in phase I. Articles were included if they used MPTP, 6-OHDA, rotenone or paraquat injury models. Results: Phase I led to the identification of 168 putative neuroprotective agents. Eventually ten compounds were included: melatonin, estrogen, nicotine, caffeine, riluzole, curcumin, coenzyme Q10, aspirin, EGCG and resveratrol. Phase II revealed 113 experimental studies and three reviews. Conclusion: This study clearly depicts the preclinical data of ten promising neuroprotective agents. While some of these compounds have already been tested in clinical use, none of them was studied in an appropriately designed trial to determine a neuroprotective effect. In expectation of qualitatively improved neuroprotection trials, the data from this study provide a firm foundation for future research.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"86 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2012-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73055661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-05-09DOI: 10.2174/1874143601206010027
R. B. Wong, M. Zeng, an-Horng Lee, T. S. Raju, K. Cheng
Fc glycosylation of immunoglobulins is necessary for antibody effector functions. These glycans of immunoglobulins are often referred as glycoforms and they can be heterogeneous due to the variations in glycosylation machinery present in the endoplastic reticulum (ER) and in the Golgi. In the absence of a generic culturing protocol that can render a consistent glycosylation pattern, monitoring glycoforms of monoclonal antibodies from cultured cells is becoming essential. Accordingly, quantification of glycosylated and deglycosylated heavy chains of an IgG4 monoclonal antibody was accomplished using an Agilent Bioanalyzer Lab-On-the-Chip electrophoresis system. In addition to the native antibody, completely deglycosylated antibody prepared by treating with PNGase F and a F(ab')2 fraction were evaluated for their antigen binding kinetics using Biacore surface Plasmon resonance (SPR). The equilibrium binding constants KD are found to be comparable at 1.81E-09M, 1.96E-09M, for the native and deglycosylated antibody, respectively, and 5.79E-10M for the F(ab')2. An in vitro biological activity employing a competition binding assay was also developed to demonstrate the role of the Fc glycan. The results confirm that for a neutralizing antibody therapeutic the biological activity of the native MAb-1 and deglycosylated antibody are comparable, thus indicating that the Fc glycan does not contribute to the antigen binding or the biological function. The kinetics and competitive assays performed on an SPR instrument are quick and reliable. Combined with the on-chip electrophoresis method they can be used as monitoring methods for process development and quality control.
免疫球蛋白的Fc糖基化是抗体效应作用所必需的。这些免疫球蛋白的聚糖通常被称为糖型，由于存在于内质网(ER)和高尔基体中的糖基化机制的变化，它们可能是异质的。在缺乏一个通用的培养方案，可以呈现一致的糖基化模式，监测单克隆抗体的糖型从培养细胞是必不可少的。因此，使用Agilent生物分析仪lab - on - chip电泳系统完成IgG4单克隆抗体糖基化和去糖基化重链的定量。除天然抗体外，用PNGase F和F(ab')2片段处理制备的完全去糖基化抗体，用Biacore表面等离子体共振(SPR)评价其抗原结合动力学。结果表明，天然抗体和去糖基化抗体的平衡结合常数KD分别为1.81E-09M和1.96E-09M, F(ab’)2的平衡结合常数KD为5.79E-10M。采用竞争结合测定法的体外生物活性也被开发来证明Fc聚糖的作用。结果证实，对于治疗性中和抗体，天然单克隆抗体-1和去糖基化抗体的生物活性是相当的，从而表明Fc聚糖不参与抗原结合或生物学功能。在SPR仪器上进行的动力学和竞争性分析快速可靠。与片上电泳法相结合，可作为工艺开发和质量控制的监测方法。
{"title":"Functional Role of Glycosylation in a Human IgG4 Antibody Assessed by Surface Plasmon Resonance Technology","authors":"R. B. Wong, M. Zeng, an-Horng Lee, T. S. Raju, K. Cheng","doi":"10.2174/1874143601206010027","DOIUrl":"https://doi.org/10.2174/1874143601206010027","url":null,"abstract":"Fc glycosylation of immunoglobulins is necessary for antibody effector functions. These glycans of immunoglobulins are often referred as glycoforms and they can be heterogeneous due to the variations in glycosylation machinery present in the endoplastic reticulum (ER) and in the Golgi. In the absence of a generic culturing protocol that can render a consistent glycosylation pattern, monitoring glycoforms of monoclonal antibodies from cultured cells is becoming essential. Accordingly, quantification of glycosylated and deglycosylated heavy chains of an IgG4 monoclonal antibody was accomplished using an Agilent Bioanalyzer Lab-On-the-Chip electrophoresis system. In addition to the native antibody, completely deglycosylated antibody prepared by treating with PNGase F and a F(ab')2 fraction were evaluated for their antigen binding kinetics using Biacore surface Plasmon resonance (SPR). The equilibrium binding constants KD are found to be comparable at 1.81E-09M, 1.96E-09M, for the native and deglycosylated antibody, respectively, and 5.79E-10M for the F(ab')2. An in vitro biological activity employing a competition binding assay was also developed to demonstrate the role of the Fc glycan. The results confirm that for a neutralizing antibody therapeutic the biological activity of the native MAb-1 and deglycosylated antibody are comparable, thus indicating that the Fc glycan does not contribute to the antigen binding or the biological function. The kinetics and competitive assays performed on an SPR instrument are quick and reliable. Combined with the on-chip electrophoresis method they can be used as monitoring methods for process development and quality control.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"10 1","pages":"27-33"},"PeriodicalIF":0.0,"publicationDate":"2012-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78627087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-04-26DOI: 10.2174/1874143601206010001
M. Cianfriglia, V. Fiori, S. Dominici, S. Zamboni, M. Flego, M. Dupuis, A. Ascione, Mara Gellini, A. Mallano, M. Magnani
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a cell surface glycoprotein involved in intercellular binding, belonging to the immunoglobulin superfamily. It is involved in cell-cell recognition and modulates cellular processes that range from vascular angiogenesis to the regulation of insulin homeostasis and T-cell proliferation. Aberrant expression of CEACAM1 is often associated with progression and metastatic potential in melanoma, lung carcinoma and other types of tumor. Tumor-specific antigens such as CEACAM1 are ideal targets for cancer immunotherapy because they are over-expressed by the cancer cell and not on non-malignant tissues, minimizing the risk of autoimmune destruction. Many of the limitations of therapeutic use of rodent monoclonal antibodies (mAbs) can now be overcome by exploiting the use of recombinant antibody fragments and the advances in antibody engineering methods to improve tumor retention, reduce immunogenicity and modulate pharmacokinetics. In addition, a novel effective model of immunotherapeutic treatments of tumors includes antibody drug conjugates (ADCs) that combine specific mAbs and antibody fragments with cytotoxic drugs, proteins, enzymes, radionuclides and nanoparticles. This review aims to describe how these antibody engineering approaches can meet the challenges for generating new and effective antibody constructs for diagnosis and therapy of CEACAM1 expressing malignancies.
{"title":"CEACAM1 is a Privileged Cell Surface Antigen to Design Novel ScFv Mediated-Immunotherapies of Melanoma, Lung Cancer and Other Typesof Tumors","authors":"M. Cianfriglia, V. Fiori, S. Dominici, S. Zamboni, M. Flego, M. Dupuis, A. Ascione, Mara Gellini, A. Mallano, M. Magnani","doi":"10.2174/1874143601206010001","DOIUrl":"https://doi.org/10.2174/1874143601206010001","url":null,"abstract":"Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a cell surface glycoprotein involved in intercellular binding, belonging to the immunoglobulin superfamily. It is involved in cell-cell recognition and modulates cellular processes that range from vascular angiogenesis to the regulation of insulin homeostasis and T-cell proliferation. Aberrant expression of CEACAM1 is often associated with progression and metastatic potential in melanoma, lung carcinoma and other types of tumor. Tumor-specific antigens such as CEACAM1 are ideal targets for cancer immunotherapy because they are over-expressed by the cancer cell and not on non-malignant tissues, minimizing the risk of autoimmune destruction. Many of the limitations of therapeutic use of rodent monoclonal antibodies (mAbs) can now be overcome by exploiting the use of recombinant antibody fragments and the advances in antibody engineering methods to improve tumor retention, reduce immunogenicity and modulate pharmacokinetics. In addition, a novel effective model of immunotherapeutic treatments of tumors includes antibody drug conjugates (ADCs) that combine specific mAbs and antibody fragments with cytotoxic drugs, proteins, enzymes, radionuclides and nanoparticles. This review aims to describe how these antibody engineering approaches can meet the challenges for generating new and effective antibody constructs for diagnosis and therapy of CEACAM1 expressing malignancies.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"40 1","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2012-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79795950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-11-23DOI: 10.2174/1874143601105010001
Yuhua Wang, R. Quock, R. Keegan
Background/Aims: The role of nitric oxide (NO) in general anesthetic drug action is controversial. The present study was carried out to determine the role of NO in the loss of righting reflex induced by injectable sedative and
{"title":"Attenuation of Drug-Induced Loss of Righting Reflex Response by Pretreatment with a Nitric Oxide Donor","authors":"Yuhua Wang, R. Quock, R. Keegan","doi":"10.2174/1874143601105010001","DOIUrl":"https://doi.org/10.2174/1874143601105010001","url":null,"abstract":"Background/Aims: The role of nitric oxide (NO) in general anesthetic drug action is controversial. The present study was carried out to determine the role of NO in the loss of righting reflex induced by injectable sedative and","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"13 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2011-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84700458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-08-12DOI: 10.2174/1874143601004010036
Galya Abrham, S. Dovrat, H. Bessler, S. Grossman, U. Nir, M. Bergman
The plant Inula viscosa has been shown to possess many important medicinal benefits, including anti-inflammatory, anti-oxidant, anti-bacterial, and anti-fungal activities, but the plant metabolites that mediate these effects and their mechanism of action are poorly understood. In a previous study, we demonstrated a reduced expression of the p65 subunit of nuclear factor kappa B (NFB) in melanoma cells treated with the purified sesquiterpene lactone compounds, Inuviscolide (Inv) and Tomentosin (Tom), extracted from Inula viscosa leaves. In this study, we tested the in- vitro effect of these purified compounds on the secretion of pro-inflammatory cytokines from human peripheral blood mononuclear cells (PBMCs) upon stimulation with lipopolysaccharide (LPS) or phorbol myristate acetate (PMA). Their possible mechanism of action was also studied. The results showed that both agents caused decreased production of IL-2, IL-1� , IFN� , and slightly increased secretion of TNF� , whereas secretion of IL-6 was not affected. The elevated levels of TNFdid not appear to affect the viability of human PBMCs. Western blot analysis revealed a reduction in the protein level of both the transcription factor component p65/RelA of nuclear factor-� B (NF B) and the signal transducer and activator of transcription 1 (STAT1) through proteosomal degradation. However, no change was observed in the expression level of the nuclear factor-� B component, p50 (NF B), or the signal transducer and activator of transcription 3 (STAT3). Taken together, our results indicate the possible future use of these agents as an anti-inflammatory treatment in cases where overstimulation of cytokine secretion is the basis for the pathological symptoms.
植物粘菊已被证明具有许多重要的药用价值，包括抗炎、抗氧化、抗菌和抗真菌活性，但介导这些作用的植物代谢物及其作用机制尚不清楚。在之前的一项研究中，我们证明了用从粘菊叶中提取的纯化倍半萜内酯化合物Inuviscolide (Inv)和Tomentosin (Tom)处理黑色素瘤细胞中核因子κ B (NFB) p65亚基的表达降低。在这项研究中，我们测试了这些纯化的化合物在体外受脂多糖(LPS)或肉豆蔻酸酯(PMA)刺激时对人外周血单核细胞(pmcs)分泌促炎细胞因子的影响。并对其可能的作用机理进行了探讨。结果表明，两种药物均可导致IL-2、IL-1、IFN的产生降低，TNF的分泌略有增加，而IL-6的分泌不受影响。tnf水平升高似乎并不影响人类pbmc的生存能力。Western blot分析显示，核因子- B (NFB)的转录因子组分p65/RelA和转录信号换能器和激活因子1 (STAT1)的蛋白水平通过蛋白体降解而降低。然而，核因子- β组分p50 (NFB)或转录信号转导和激活因子3 (STAT3)的表达水平未见变化。综上所述，我们的研究结果表明，在细胞因子分泌过度刺激是病理症状基础的情况下，这些药物可能在未来被用作抗炎治疗。
{"title":"Inhibition of Inflammatory Cytokine Secretion by Plant-Derived Compounds Inuviscolide and Tomentosin: The Role of NFκB and STAT1~!2010-02-10~!2010-06-28~!2010-08-12~!","authors":"Galya Abrham, S. Dovrat, H. Bessler, S. Grossman, U. Nir, M. Bergman","doi":"10.2174/1874143601004010036","DOIUrl":"https://doi.org/10.2174/1874143601004010036","url":null,"abstract":"The plant Inula viscosa has been shown to possess many important medicinal benefits, including anti-inflammatory, anti-oxidant, anti-bacterial, and anti-fungal activities, but the plant metabolites that mediate these effects and their mechanism of action are poorly understood. In a previous study, we demonstrated a reduced expression of the p65 subunit of nuclear factor kappa B (NFB) in melanoma cells treated with the purified sesquiterpene lactone compounds, Inuviscolide (Inv) and Tomentosin (Tom), extracted from Inula viscosa leaves. In this study, we tested the in- vitro effect of these purified compounds on the secretion of pro-inflammatory cytokines from human peripheral blood mononuclear cells (PBMCs) upon stimulation with lipopolysaccharide (LPS) or phorbol myristate acetate (PMA). Their possible mechanism of action was also studied. The results showed that both agents caused decreased production of IL-2, IL-1� , IFN� , and slightly increased secretion of TNF� , whereas secretion of IL-6 was not affected. The elevated levels of TNFdid not appear to affect the viability of human PBMCs. Western blot analysis revealed a reduction in the protein level of both the transcription factor component p65/RelA of nuclear factor-� B (NF B) and the signal transducer and activator of transcription 1 (STAT1) through proteosomal degradation. However, no change was observed in the expression level of the nuclear factor-� B component, p50 (NF B), or the signal transducer and activator of transcription 3 (STAT3). Taken together, our results indicate the possible future use of these agents as an anti-inflammatory treatment in cases where overstimulation of cytokine secretion is the basis for the pathological symptoms.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"41 1","pages":"36-44"},"PeriodicalIF":0.0,"publicationDate":"2010-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90950247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-06-02DOI: 10.2174/1874143601004010030
C. Vinkers, R. Penning, M. Ebbens, J. Helhammer, J. Verster, C. Kalkman, B. Olivier
The stress-induced hyperthermia (SIH) response is the transient change in body temperature in response to acute stress. This body temperature response is part of the autonomic stress response which also results in tachycardia and an increased blood pressure. So far, a SIH response has been found in a variety of species (including rodents, baboons, turtles, pigs, impalas and chimpanzees), and there are indications that stress exposure alters body temperature in humans. This review aims to assess the translational potential and the different aspects of the body temperature reaction in response to stress. If stress-induced temperature changes are consistent across species, the SIH paradigm may be employed in preclinical and clinical setups and provide a tool to examine the pharmacological, genetic and mechanistic background of stress at both the preclinical and the clinical level.
{"title":"Stress-Induced Hyperthermia in Translational Stress Research","authors":"C. Vinkers, R. Penning, M. Ebbens, J. Helhammer, J. Verster, C. Kalkman, B. Olivier","doi":"10.2174/1874143601004010030","DOIUrl":"https://doi.org/10.2174/1874143601004010030","url":null,"abstract":"The stress-induced hyperthermia (SIH) response is the transient change in body temperature in response to acute stress. This body temperature response is part of the autonomic stress response which also results in tachycardia and an increased blood pressure. So far, a SIH response has been found in a variety of species (including rodents, baboons, turtles, pigs, impalas and chimpanzees), and there are indications that stress exposure alters body temperature in humans. This review aims to assess the translational potential and the different aspects of the body temperature reaction in response to stress. If stress-induced temperature changes are consistent across species, the SIH paradigm may be employed in preclinical and clinical setups and provide a tool to examine the pharmacological, genetic and mechanistic background of stress at both the preclinical and the clinical level.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"138 1","pages":"30-35"},"PeriodicalIF":0.0,"publicationDate":"2010-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79121214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-06-02DOI: 10.2174/1874143601004010015
C. Vinkers, B. Olivier, J. Bouwknecht, L. Groenink, J. Olivier
The serotonin (5-HT) system plays a key role in the pathophysiology of psychiatric disorders including mood and anxiety disorders. A role for serotonin in stress-related disorders is further supported by the fact that clinically effective treatments for these disorders alter serotonergic neurotransmission. The therapeutic potential of serotonergic pharmacological interventions has resulted in a variety of preclinical approaches to study the serotonin system. Of these, the stress-induced hyperthermia (SIH) paradigm has been extensively used to study the serotonin system at a preclinical level. The SIH response uses the transient rise in body temperature in response to a stressor which can be reduced using anxiolytic drugs including benzodiazepines, CRF receptor antagonists and serotonergic ligands. The present review aims to discuss the acute and chronic effects of 5-HT ligands on the SIH response. Also, the SIH response in genetically modified mice that lack or overexpress specific serotonergic receptor subtypes or the serotonin transporter will be summarized. 5-HT1A receptor ligands reduce the SIH response, whereas acute administration of other serotonergic drugs (including 5-HT1B, 5-HT2 and 5-HT3 modulators and SSRIs) generally does not influence the SIH response. Also, the SIH paradigm is generally insensitive to detect the anxiolytic effects of chronic serotonergic antidepressants in rodents, and serotonergic drugs that have been found to reduce the SIH response acutely do so irrespective of the healthy or pathological status of an individual.
{"title":"Stress-Induced Hyperthermia, the Serotonin System and Anxiety","authors":"C. Vinkers, B. Olivier, J. Bouwknecht, L. Groenink, J. Olivier","doi":"10.2174/1874143601004010015","DOIUrl":"https://doi.org/10.2174/1874143601004010015","url":null,"abstract":"The serotonin (5-HT) system plays a key role in the pathophysiology of psychiatric disorders including mood and anxiety disorders. A role for serotonin in stress-related disorders is further supported by the fact that clinically effective treatments for these disorders alter serotonergic neurotransmission. The therapeutic potential of serotonergic pharmacological interventions has resulted in a variety of preclinical approaches to study the serotonin system. Of these, the stress-induced hyperthermia (SIH) paradigm has been extensively used to study the serotonin system at a preclinical level. The SIH response uses the transient rise in body temperature in response to a stressor which can be reduced using anxiolytic drugs including benzodiazepines, CRF receptor antagonists and serotonergic ligands. The present review aims to discuss the acute and chronic effects of 5-HT ligands on the SIH response. Also, the SIH response in genetically modified mice that lack or overexpress specific serotonergic receptor subtypes or the serotonin transporter will be summarized. 5-HT1A receptor ligands reduce the SIH response, whereas acute administration of other serotonergic drugs (including 5-HT1B, 5-HT2 and 5-HT3 modulators and SSRIs) generally does not influence the SIH response. Also, the SIH paradigm is generally insensitive to detect the anxiolytic effects of chronic serotonergic antidepressants in rodents, and serotonergic drugs that have been found to reduce the SIH response acutely do so irrespective of the healthy or pathological status of an individual.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2010-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86430185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：