The open drug discovery journal最新文献

{"title":"The Protective Effects of Ischemic Postconditioning against Stroke: From Rapid to Delayed and Remote Postconditioning.","authors":"Heng Zhao","doi":"10.2174/1877381801002010138","DOIUrl":"10.2174/1877381801002010138","url":null,"abstract":"<p><p>The author reviews the protective effects of ischemic postconditioning, a recently emerging strategy with broad implications in the search for new treatments in stroke and myocardial ischemic injury. Ischemic postconditioning, which refers to a series of brief ischemia and reperfusion cycles applied immediately at the site of the ischemic organ after reperfusion, results in reduced infarction in both cerebral and myocardial ischemia. Conventional postconditioning induced within a few minutes after reperfusion is arbitrarily defined as rapid postconditioning. In contrast, postconditioning performed hours to days after stroke is defined as delayed postconditioning. In addition, postconditioning can be mimicked using anesthetics or other pharmacological agents as stimuli to protect against ischemia/reperfusion injury or performed in a distant organ, which is known as remote postconditioning. In this article, the author discusses the conceptual origin of classical rapid ischemic postconditioning and its evolution into a term that represents a broad range of stimuli or triggers, including delayed postconditioning, pharmacological postconditioning, and remote postconditioning. Thereafter, various in vivo and in vitro models of postconditioning and its potential protective mechanisms are discussed. Since the concept of postconditioning is so closely associated with that of preconditioning and both share some common protective mechanisms, whether a combination of preconditioning and postconditioning offers greater protection than preconditioning or postconditioning alone is also discussed.</p>","PeriodicalId":89503,"journal":{"name":"The open drug discovery journal","volume":"5 ","pages":"138-147"},"PeriodicalIF":0.0,"publicationDate":"2011-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3204606/pdf/nihms312530.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40127889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting TRPV1: Challenges and Issues in Pain Management~!2009-12-02~!2010-03-08~!2010-07-26~!","authors":"M. Trevisani","doi":"10.2174/1877381801002030037","DOIUrl":"https://doi.org/10.2174/1877381801002030037","url":null,"abstract":"","PeriodicalId":89503,"journal":{"name":"The open drug discovery journal","volume":"2 1","pages":"37-49"},"PeriodicalIF":0.0,"publicationDate":"2010-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68151870","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}

{"title":"TRPV1 in GU Disorders~!2009-12-24~!2010-02-25~!2010-07-26~!","authors":"A. Charrua","doi":"10.2174/1877381801002030050","DOIUrl":"https://doi.org/10.2174/1877381801002030050","url":null,"abstract":"","PeriodicalId":89503,"journal":{"name":"The open drug discovery journal","volume":"2 1","pages":"50-54"},"PeriodicalIF":0.0,"publicationDate":"2010-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68151888","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}

{"title":"Editorial: [TRP Channels as Drug Targets]","authors":"A. Szallasi","doi":"10.2174/1877381801002030036","DOIUrl":"https://doi.org/10.2174/1877381801002030036","url":null,"abstract":"","PeriodicalId":89503,"journal":{"name":"The open drug discovery journal","volume":"2 1","pages":"36-36"},"PeriodicalIF":0.0,"publicationDate":"2010-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68151779","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}

{"title":"Review: Friedreich Ataxia and Erythropoietin","authors":"S. Boesch, B. Sturm, W. Nachbauer, S. Hering, H. Steinkellner, R. Schneider, W. Poewe, B. Scheiber-Mojdehkar","doi":"10.2174/1877381801002010018","DOIUrl":"https://doi.org/10.2174/1877381801002010018","url":null,"abstract":"In vitro and in vivo studies have provided evidence for neuroprotective properties of Erythropoietin in neurodegenerative disorders. Although the magnitude of effect is still controversial, very recent findings point to neuronal protection in the central nervous system by Erythropoietins. Erythropoietin is a powerful growth factor which enhances cellular size and ultimatively increases the number of mitochondria. Friedreich Ataxia (FA), an inherited neurodegenerative disorder is caused by a loss of function mutation in the first intron on chromosome 9. FA patients therefore suffer a marked reduction of Frataxin, a mitochondrial protein which is involved in mitochondrial iron homeostasis and/or assembly of iron-sulfur (FeS) proteins and heme synthesis. Mitochondrial dysfunction results in a deleterious energy deficit especially in tissues highly dependent on oxidative phosphorylation such as neurons, muscle cells or pancreatic insular cells. Beneficial effects of recombinant human Erythropoietin (rhuEPO) may derive from an increase in Frataxin levels through currently unknown post-transcriptional and/or post-translational mechanisms. Moreover, additional effects via BDNF and through mitochondrial iron chelation may complete the spectrum of rhuEPOs actions in FA and may be part of its beneficial treatment effects. However, there are clear limitations to chronic rhuEPO treatment. Apart from hematopoietic side effects, tumor growth may be enhanced by rhuEPO application. In this review we provide an overview of studies using rhuEPO in FA and discuss potential beneficial effects of Erythropoietin in FA.","PeriodicalId":89503,"journal":{"name":"The open drug discovery journal","volume":"2 1","pages":"18-24"},"PeriodicalIF":0.0,"publicationDate":"2010-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68151635","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}

{"title":"In vitro studies on anti asthmatic, analgesic and anti convulsant activities of the medicinal plant Bryonia laciniosa.Linn","authors":"Jayarama Reddy, D. Gnanasekaran, D. Vijay, T. V. Ranganathan","doi":"10.2174/1877381801002020001","DOIUrl":"https://doi.org/10.2174/1877381801002020001","url":null,"abstract":"The study was carried out to ascertain anti asthmatic, analgesic and anti convulsant activities of the medicinal plant Bryonia Laciniosa . The anti asthmatic activity was estimated by mesenteric mast cell count by Atopic allergy method. Eddy's hot plate and Analgesiometer tests were used to assess the analgesic activity of Bryonia Laciniosa . Anticonvulsant activity was evaluated by Maximum electroshock- induced seizure test. The results indicated that 70% alcoholic extract of Bryonia laciniosa increased the antiasmatic activity, analgestic activity and also anticonvulsant activity. Keywords: Bryonia Laciniosa , Atopic allergy method, Eddy's hot plate analgesio meter, Electric shock method.","PeriodicalId":89503,"journal":{"name":"The open drug discovery journal","volume":"2 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2010-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68151678","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}

{"title":"Effect of Recombinant Human Erythropoietin in a Rat Model of Moderate Chronic Renal Failure - Focus on Inflammation, Oxidative Stress and Function/Renoprotection","authors":"P. Garrido, F. Reis, E. Costa, A. Almeida, B. Parada, E. Teixeira-Lemos, P. Santos, R. Alves, J. Sereno, R. Pinto, Cristina Tavares, A. Figueiredo, P. Rocha-Pereira, L. Belo, A. Santos-Silva, F. Teixeira","doi":"10.2174/1877381801002020025","DOIUrl":"https://doi.org/10.2174/1877381801002020025","url":null,"abstract":"Background/Aims: Chronic renal failure (CRF) patients develop anaemia, thus promoting cardiovascular complications, which seems to be favoured by the low kidney erythropoietin (EPO) production. The renal insufficiency degree might determine the moment to start recombinant human EPO (rhEPO) therapy. It has been attributed important non-hematopoietic effects to rhEPO, which might underlie cardio and renoprotection. This work aimed to evaluate the effect of rhEPO in a rat model of moderate CRF, focusing on inflammation, oxidative stress and function/renoprotection. Methods: Four groups (n=7) of male Wistar rats were evaluated during a 15 week follow-up period: control (without treatment); rhEPO (50 IU/Kg/wk Recormon ® ); CRF and CRF+rhEPO. Blood samples were collected at the beginning and 3, 9 and 12 weeks afternephrectomy, in order to evaluate: renal function, haematological parameters, iron metabolism and serum proliferative (TGF- 1), inflammatory (TNF- , CRP, IL-2 and IL-1 ) and redox status (MDA, TAS and 3-NT) markers. Kidney gene expression of Il2, Vegf, Nos2 and Nos3 were assessed by real-time PCR. Blood pressure, heart rate and tissues trophy indexes were also estimated. Results: Our data are consistent with a sustained moderate degree of CRF with development of moderate and corrected anaemia and hypertension. The remnant kidney showed a proliferative profile, with increased mass (hypertrophism), upregulated tissue Vegf gene expression, accompanied by increased levels of serum TGF- 1. Serum 3-NT was augmented, suggesting oxidative stress, which was accompanied by a trend to higher kidney Nos gene expression of both isoforms. rhEPO treatment was able to partially attenuate renal function markers, totally correct anaemia, also demonstrating a proliferative and antioxidant action, suggesting renoprotection. Conclusion: This study suggests that rhEPO therapy might be recommended in moderate CRF stages in order to efficiently correct not only the anaemia but also the underlying deleterious mechanisms, due to a proliferative and antioxidant action on the remnant kidney.","PeriodicalId":89503,"journal":{"name":"The open drug discovery journal","volume":"2 1","pages":"25-32"},"PeriodicalIF":0.0,"publicationDate":"2010-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68151719","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}

{"title":"Induction of apoptosis by the aqueous and ethanolic leaf extract of Vitex negundo L. in MCF-7 human breast cancer cells.","authors":"C. Arulvasu, D. Prabhu, R. Manikandan, P. Srinivasan, D. Dinesh, G. Babu, S. Sellamuthu","doi":"10.2174/1877381801002010001","DOIUrl":"https://doi.org/10.2174/1877381801002010001","url":null,"abstract":"The aim of this investigation was to evaluate the anti-proliferative potential of aqueous and ethanolic extract from Vitex negundo against human breast cancer cell (MCF-7). The aqueous and ethanol extract from V. negundo potently inhibited growth of MCF-7 in a concentration-dependent manner. V. negundo pretreatment resulted in deferential cell viability and IC50 value were observed in MCF-7 cell line but not in control cell line. The above result suggested that V. negundo has a potential benefits in breast cancer cells. Keywords - Anti-cancer, anti-proliferative, breast cancer, cytotoxicity, V. negundo , MCF-7","PeriodicalId":89503,"journal":{"name":"The open drug discovery journal","volume":"2 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2010-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68151559","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}

{"title":"Protective Effect of Erythropoietin in Renal Ischemia-Reperfusion Injury","authors":"N. Yazıhan, G. Kavas","doi":"10.2174/1877381801002020003","DOIUrl":"https://doi.org/10.2174/1877381801002020003","url":null,"abstract":"Ischemia and/or reperfusion injury (IR) is one of the most common causes of acute renal failure. Erythropoietin (EPO), is main hematopoietic hormone that has recently been shown to exert important cytoprotective and anti-apoptotic effects in experimental I/R and toxicity models. Recent studies suggest that administration of exogenous EPO prevents ischemia-induced kidney damage. In this review we focused on anti-apoptotic, anti-inflammatory and anti-oxidant action of EPO in renal ischemia-reperfusion models and its application in nephropathies. EPO seems to be a very promising agent for protecting cellular survival during both acute and chronic ischemic and toxic nephropathies.","PeriodicalId":89503,"journal":{"name":"The open drug discovery journal","volume":"2 1","pages":"3-7"},"PeriodicalIF":0.0,"publicationDate":"2010-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68151688","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}

{"title":"Erythropoietin Levels in Cardiac Resynchronization Patients","authors":"Patrick B. Alexander, A. Jazrawi, S. Clifford, Martin Schmidt, M. Daccarett","doi":"10.2174/1877381801002020033","DOIUrl":"https://doi.org/10.2174/1877381801002020033","url":null,"abstract":"Cardiac resynchronization therapy (CRT) is indicated in patients with advanced heart failure secondary to severe systolic impairment and refractory symptoms despite optimized medical treatment and evidence of electro- mechanical dyssynchrony with a QRS complex greater than 120 milliseconds (msec). Approximately 20%-30% of patients who receive CRT fail to respond with little improvement in subjective symptoms, functional capacity, and left ventricular indices. To date, there fails to be a serologic marker to adequately assess the degree of ventricular dyssynchrony and electro-mechanical dissociation. Increased levels of erythropoietin (EPO), a hematopoietic cytokine, has been demonstrated in patients with more advanced stages of heart failure and is associated with an increase in mortality and hospital re-admission. A recent study demonstrated a significant response to CRT in patients with higher baseline EPO levels (> 25mU/mL) with improvements in cardiac function and reduced heart failure symptoms. The presence of elevated EPO levels in addition to traditional determinants of cardiac dyssynchrony may effectively predict those that will benefit from CRT. LETTER TO THE EDITOR Cardiac resynchronization therapy (CRT) is indicated in patients with advanced heart failure secondary to severe systolic impairment and refractory symptoms despite optimized medical treatment and evidence of electro- mechanical dyssynchrony with an ECG QRS complex greater than 120 msec. Simultaneous pacing of both the right and left ventricle (BiV pacing) has been shown to restore electro-mechanical synchrony, improve overall cardiac function, reduce hospitalizations, and confer a mortality benefit (1). Despite the cardiovascular benefits of BiV pacing demonstrated in recent trials, approximately 20%- 30% of patients who receive CRT fail to respond with little improvement in subjective symptoms, functional capacity, and left ventricular functional indices (2). Absence of electro-mechanical dyssynchrony despite prolonged QRS duration (>120ms), pre-existing right bundle branch block (RBBB), inappropriate lead placement and continued disease progression have been shown as causes for non-response to CRT. To date, there fails to be a serologic marker to adequately assess the degree of ventricular dyssynchrony and electro-mechanical dissociation. Erythropoietin (EPO), a hematopoietic cytokine, has traditionally been associated with erythropoiesis in response to anemic stress. Several studies have indicated the positive effects of EPO treatment in heart failure patients with concomitant anemia resulting in reductions in hospital re- admission, improved cardiac and renal function, as well as","PeriodicalId":89503,"journal":{"name":"The open drug discovery journal","volume":"2 1","pages":"33-35"},"PeriodicalIF":0.0,"publicationDate":"2010-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68151727","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}