Recent advances in cardiovascular drug discovery最新文献

{"title":"Combination of Vasopressin -Epinephrine as a Novel Candidate in Patients with Cardiac Arrest.","authors":"Nasim Ghafourian, Nader H Maniae, M. Taherikalani, Maryam Mehrazi, Mahnaz Hossieni, Firouzeh Valian, S. Karami, Yazdan Rahmatian, N. Tavakoli","doi":"10.2174/157489011001160111163856","DOIUrl":"https://doi.org/10.2174/157489011001160111163856","url":null,"abstract":"OBJECTIVES\u0000Out-hospital Cardiac arrest is considered as a global disease, which causes high rate of morbidity and mortality. Although, the return of spontaneous circulation occurs in 10 to 60 percent of cases in OHCA, with variety of treatment, the most patients faced with multiple organ failure and ultimately death. The investigations demonstrated that endogenous vasopressin levels in patients with successful resuscitation is more than died patients. Therefore, it seems the administration of vasopressin during cardiopulmonary resuscitation could be useful. The current study aimed to investigate the administration of vasopressin and epinephrine on neurological surviving of cardiac-respiratory arrest via evaluation of S100b serum factor.\u0000\u0000\u0000METHODS\u0000For this reasons, after collecting of sera from two vasopressin-epinephrine and epinephrine receiving patients, sera were subjected for ELISA to evaluate S100b.\u0000\u0000\u0000RESULTS\u0000The findings demonstrated that the great reductions of S100b in sera of patients that receiving vasopressinepinephrine in comparison with those patients that only got the epinephrine. Although no significant difference was observed between two groups, but survival rates after hospital discharge in group that receiving vasopressin-epinephrine was significantly higher than those patients that only got only epinephrine.\u0000\u0000\u0000CONCLUSION\u0000Today, no advantages of vasopressin over epinephrine have been observed in clinical trials and more studies needed to improve the OHAC patient's surveillance. But, The combination vasopressin-epinephrine in the current study demonstrated that efficacy of this combination should be noted.","PeriodicalId":90959,"journal":{"name":"Recent advances in cardiovascular drug discovery","volume":"65 1","pages":"65-9"},"PeriodicalIF":0.0,"publicationDate":"2015-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77154667","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":"NOAC or Warfarin for Atrial Fibrillation: Does Time in Therapeutic Range Matter?","authors":"Ioannis Merinopoulos,&nbsp;Paul Venables,&nbsp;Isobel Chalmers,&nbsp;Vassilios Vassiliou","doi":"10.2174/1574890110666150914121856","DOIUrl":"https://doi.org/10.2174/1574890110666150914121856","url":null,"abstract":"<p><p>Atrial fibrillation (AF) is the commonest cardiac arrhythmia currently affecting 1-2% of the general population, with stroke being one of its most fearsome complications. Dose-adjusted warfarin is an established treatment for reduction of thromboembolic risk but mandates dietary restrictions and need for routine blood monitoring. Novel oral anticoagulants (Dabigatran - patent: US20110082299A1, manufactured by Boehringer Ingelheim; Rivaroxaban - patent: US20150175590A1, manufactured by Bayer; Apixaban - patent: US20140335178A1, manufactured jointly by Pfizer and Bristol-Myers Squibb; Edoxaban - patent: WO2013026553A1, manufactured by Daiichi Sankyo) have recently been introduced that might provide at least equal reduction in thromboembolic risk to patients; negating the need for dietary restrictions and routine blood tests. The most recent National Institute of Health and Care Excellence, UK guidelines from August 2014 suggest consideration of one of the novel oral anticoagulants if the time in therapeutic range is less than 65%. In this study, the evidence for four novel oral anticoagulants is reviewed and the anticoagulation success with warfarin with atrial fibrillation and mechanical heart valves assessed in a large UK District General Hospital. Fifty-eight patients were identified with mechanical heart valve and 2737 patients with atrial fibrillation. Patients with atrial fibrillation had a significantly better TTR when compared with the patients included in the NOAC trials. Our results were similar with the Auricula registry. However, 25% of patients had TTR<65% and they would need to be considered for NOACs. Our data suggest that the degree of benefit seen in the NOAC trials might not be expected in our cohort of patients with atrial fibrillation. Interestingly, our patients with atrial fibrillation had a much better mean TTR of 76.4% and required less INR tests (12/year) compared to patients with mechanical heart valve who had a mean TTR of 61.4% and required more INR tests (26/year). </p>","PeriodicalId":90959,"journal":{"name":"Recent advances in cardiovascular drug discovery","volume":"10 1","pages":"60-4"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1574890110666150914121856","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34000886","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":"Basic and Clinical Research Against Advanced Glycation End Products (AGEs): New Compounds to Tackle Cardiovascular Disease and Diabetic Complications.","authors":"A. Nenna, C. Spadaccio, M. Lusini, L. Ulianich, M. Chello, F. Nappi","doi":"10.2174/1574890110666151104120039","DOIUrl":"https://doi.org/10.2174/1574890110666151104120039","url":null,"abstract":"Diabetes is a major risk factor for cardiovascular disease, and recent advances in research indicate that a detailed understanding of the pathophysiology of its effects is mandatory to reduce diabetes-related mortality and morbidity. Advanced Glycation End Products (AGEs) play a central role in the genesis and progression of complications of both type 1 and type 2 diabetes mellitus, and have been found to be important even in non-diabetic patients as a marker of cardiovascular disease. AGEs have a profound impact on patient's prognosis regardless of the glycemic control, and therefore pharmacologic approaches against AGEs accumulation have been proposed over the years to treat cardiovascular diseases, parallel to a more detailed understanding of AGEs pathophysiology. Compounds with anti-AGEs effects are currently under investigation in both pre-clinical and clinical scenarios, and many of the drugs previously used to treat specific diseases have been found to have AGE-inhibitory effects. Some products are still in \"bench evaluation\", whereas others have been already investigated in clinical trials with conflicting evidences. This review aims at summarizing the mechanisms of AGEs formation and accumulation, and the most relevant issues in pre-clinical and clinical experiences in anti-AGEs treatment in cardiovascular research.","PeriodicalId":90959,"journal":{"name":"Recent advances in cardiovascular drug discovery","volume":"29 1","pages":"10-33"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73645866","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":"The Challenges of Blood Pressure Control in Dialysis Patients.","authors":"V. Campese, Ravi S. Lakdawala","doi":"10.2174/1574890110666151116144725","DOIUrl":"https://doi.org/10.2174/1574890110666151116144725","url":null,"abstract":"Hypertension is very prevalent among patients with chronic kidney disease (CKD) and end-stage kidney disease (ESRD). However, there are still several unsolved issues pertaining to the definition, variability, diagnosis and management of hypertension in these patients. This manuscript critically reviews the current challenges in clinical practice in defining, diagnosing and treating hypertension in CKD and ESRD patients. Moreover, the manuscript reviews the pharmacokinetics, pharmacodynamics and safety of most anti-hypertensive drugs used in the management of these patients.","PeriodicalId":90959,"journal":{"name":"Recent advances in cardiovascular drug discovery","volume":"4 1","pages":"34-59"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80916140","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":"Hypertension in Type 2 Diabetes Mellitus: Do We Need to Redefine the Role of Sulfonylureas?","authors":"D. Sehra, S. Sehra","doi":"10.2174/157489011001160111154536","DOIUrl":"https://doi.org/10.2174/157489011001160111154536","url":null,"abstract":"BACKGROUND Within a few years of diagnosis, patients with Type 2 Diabetes Mellitus (T2DM) develop hypertension. It has been hypothesized that both are part of metabolic syndrome. However, studies on diabetic patients have been undertaken while they are on treatment for diabetes. Thus, the results of these studies and inference drawn thereon may not be due to the diabetic process per se but may also be due to the medications. METHODS A comprehensive literature search was carried out on PubMed, EMBASE and Cochrane databases and articles published between January 1970 to June 2015 were reviewed. RESULTS Sulfonylureas due to their action on SUR1 in pituitary gland may release growth hormone and anti-diuretic hormone; action on SUR2B acting upon smooth muscle may interfere with vasodilatation, thereby causing hypertension. CONCLUSIONS Sulfonylureas may cause hypertension by their extra-pancreatic effects, further studies are needed to validate this hypothesis.","PeriodicalId":90959,"journal":{"name":"Recent advances in cardiovascular drug discovery","volume":"43 1","pages":"4-9"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87325843","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":"Streptokinase-A Drug for Thrombolytic Therapy: A Patent Review.","authors":"Adinarayana Kunamneni,&nbsp;Ravi Durvasula","doi":"10.2174/1574890110999150202150017","DOIUrl":"https://doi.org/10.2174/1574890110999150202150017","url":null,"abstract":"<p><p>Accumulation of fibrin in blood vessels significantly increases thrombosis, leading to myocardial infraction and other cardiovascular diseases. Microbial enzymes are one option for curing this pathological condition. Fibrinolytic enzymes such as urokinase (UK), tissue type plasminogen activator (t-PA) and streptokinase (SK) attracted much attention for thrombolytic therapy. Among them SK is preferable in low-resource settings because it is cost-effective. Therefore, the purpose of this review is to summarize recent patents related to the occurrence, mechanism of action, physico-chemical properties, cloning and expression, production, structure, immunogenicity, chemical modification, in vivo application and clinical trials of SK. This patent review considers the properties and characteristics of SK that make it a preferred agent for thrombolytic therapy. </p>","PeriodicalId":90959,"journal":{"name":"Recent advances in cardiovascular drug discovery","volume":"9 2","pages":"106-21"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34181268","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":"Primary and Secondary Prevention of Acute Coronary Syndromes: The Role of the Statins.","authors":"Evangelos Diamantis,&nbsp;Theodoros Troupis,&nbsp;Antonios Mazarakis,&nbsp;Giorgos Kyriakos,&nbsp;S Diamanti,&nbsp;Georgios Troupis,&nbsp;Panagiotis Skandalakis","doi":"10.2174/1574890110666150708112349","DOIUrl":"https://doi.org/10.2174/1574890110666150708112349","url":null,"abstract":"<p><p>Poor prognosis is strongly associated with Acute Coronary Syndrome (ACS) and, even though a number of treatment strategies are available, the incidence of subsequent serious complications after an acute event is still high. Statins are hypolipidemic factors and recent studies have demonstrated that they have a protective role during the process of atherogenesis and that they reduce mortality caused by cardiovascular diseases. This review tries to reveal the function of the statins as a component of the primary and secondary action of acute coronary syndrome and to describe the lifestyle changes that have the same effect as the use of statins.</p>","PeriodicalId":90959,"journal":{"name":"Recent advances in cardiovascular drug discovery","volume":"9 2","pages":"97-105"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33987355","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":"Orekhov's Method: Reassessment of In vitro Lipid Uptake Assays.","authors":"Sergei V Jargin","doi":"10.2174/1574890110666150707095340","DOIUrl":"https://doi.org/10.2174/1574890110666150707095340","url":null,"abstract":"<p><p>The large research series has become known to the international scientific community 1986 after a publication in The Lancet (2:595). In short, cultures of smooth muscle cells from the human aortic intima or blood-derived monocytes/macrophages were used for measurements of ability of drugs and plant substances to induce or prevent cholesterol deposition in the cells, cultured with the sera from atherosclerosis patients, which was interpreted as pro- or anti-atherogenic effects. However, as discussed previously, the relationship between the uptake of lipids by cultured cells and atherogenesis in vivo must be inverse rather than direct. The up-regulation of lipoprotein receptors is one of the action mechanisms of some cholesterol-lowering drugs. Accordingly, if a drug lowers the uptake of lipids by cultured smooth muscle cells or macrophages, it should be expected to elevate the blood cholesterol level in vivo. Nevertheless, following their concept of blood atherogenicity, the same researchers started to apply apheresis (extracorporeal perfusion of patients' blood for 2 hours through a column with immobilized LDL) aimed at a removal of non-lipid atherogenicity factors. In conclusion, validity of the cell culture method of serum atherogenicity measurement, and testing of pro- or antiatherogenic effects of drugs and dietary supplements is questionable. It would be useful to reproduce some of the cell culture experiments discussed in this letter in an independent laboratory. Verification is necessary prior to preclinical studies in animals and then humans of reportedly anti-atherogenic substances, detected by the cell culture method. </p>","PeriodicalId":90959,"journal":{"name":"Recent advances in cardiovascular drug discovery","volume":"9 2","pages":"122-5"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34267252","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":"Vorapaxar, a Protease-Activated Receptor-1 Antagonist, a Double-Edged Sword!","authors":"Bharti Bhandari,&nbsp;Bharati Mehta","doi":"10.2174/1574890110666150624100815","DOIUrl":"https://doi.org/10.2174/1574890110666150624100815","url":null,"abstract":"<p><p>Acute coronary syndrome (ACS) constitutes a group of pathophysiological entities resulting from reduced blood flow in the coronary arteries leading to decreased or improper functioning or death of heart muscle. Such patients are usually prescribed combination antiplatelet drug therapy, containing acetylsalicylic acid (aspirin) and an adenosine diphosphate receptor inhibitor to prevent recurrence of ischemic events. The combination prophylactic therapy to certain extend has been successful in preventing secondary complications including ischemic/thrombotic events in these patients. However, research is still on for newer advances in anti-thrombotic therapy that can further prevent secondary complications of Acute Coronary Syndrome. Vorapaxar is a newer drug recommended along with aspirin or clopidogril for prevention of recurrence of cardiac events. Vorapaxar, a thrombin receptor antagonist acts by reversible inhibition of the protease-activated receptor-1 (PAR-1). PAR-1 is expressed on platelets, and it inhibits platelet aggregation, both thrombin-induced and thrombin receptor agonist peptide (TRAP)-induced. Various trials world -wide have documented its efficacy as an anti-platelet agent for preventing recurrent cardiovascular ischemic events but at the expense of increased bleeding complications including intracranial haemorrhage (ICH), when compared to standard therapy alone. For the same reason, vorapaxar is contraindicated in patients with prior stroke, transient ischemic attack and ICH. U.S. Food and Drug Administration (FDA) approved vorapaxar in May 2014 as an antiplatelet agent along with standard anti-platelet therapy for the reduction of recurring thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. Vorapaxar is developed and marketed by Merck Sharp Dohme and is available by the brand name 'Zontivity' as 2.5 mg oral tablet equivalent to 2.08 mg of vorapaxar sulfate. There are two patents protecting this drug. </p>","PeriodicalId":90959,"journal":{"name":"Recent advances in cardiovascular drug discovery","volume":"9 2","pages":"73-7"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33414385","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":"ω-3 Polyunsaturated Fatty Acids Effects on the Cardiometabolic Syndrome and their Role in Cardiovascular Disease Prevention: An Update from the Recent Literature.","authors":"GianLuca Colussi,&nbsp;Cristiana Catena,&nbsp;Leonardo A Sechi","doi":"10.2174/1574890110666150724115111","DOIUrl":"https://doi.org/10.2174/1574890110666150724115111","url":null,"abstract":"<p><p>Docosahexaenoic (DHA) and eicosapentaenoic (EPA) acid of the ω-3 family of polyunsaturated fatty acids (PUFA) are abundant in fatty fish and other marine sources. Their consistent consumption has been related to an improved cardiovascular risk especially in high risk patients and populations. In this review, we presented major findings about potential mechanisms of action and clinical evidence regarding ω-3 PUFA effect on the control and prevention of cardiovascular disease. This review is an update of our previous review (Colussi et al. Recent Pat Cardiovasc Drug Discov 2007;2:13-31) in which we additionally summarize and comment new literature of the past few years. Despite clinical studies have been significantly increased in the last years, the evidence in support of a beneficial role of ω-3 PUFA in cardiovascular prevention is still relatively weak. The growing improvement of medical interventions for cardiovascular prevention might explain why these molecules appear to have limited impact on the cardiovascular risk. </p>","PeriodicalId":90959,"journal":{"name":"Recent advances in cardiovascular drug discovery","volume":"9 2","pages":"78-96"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33931262","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}