Journal of Controversies in Biomedical Research最新文献

{"title":"N-Acetylcysteine: An Old Drug With Variable Anti-Influenza Properties","authors":"Tomás Casanova, M. Garigliany","doi":"10.15586/JCBMR.2016.13","DOIUrl":"https://doi.org/10.15586/JCBMR.2016.13","url":null,"abstract":"N-acetylcysteine (NAC) is a mucolytic drug commonly used as an adjuvant therapy in patients with respiratory conditions associated with excessive mucus production. NAC also has antioxidant activities which proved useful in the management of oxidative stress. These antioxidant capacities of NAC are mostly indirect, via a pro-glutathione effect where NAC provides L-cysteine residues required for glutathione synthesis. This activity is thought to be the basis of the protective effect of NAC administration in influenza patients and in mouse models of the disease. NAC was shown to limit lung inflammation, damage associated with the virus, and limit viral growth, at least in vitro. However, the antiviral activity was highly variable depending on the influenza A strain. The reasons for these inter-strain variations are still unknown but might be related to the level of NF-κB activation required for the virus to achieve its infectious cycle.","PeriodicalId":185190,"journal":{"name":"Journal of Controversies in Biomedical Research","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122633615","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":"Beyond confusion and controversy, can we evaluate the real efficacy and safety of cholesterol-lowering with statins?","authors":"M. Lorgeril, M. Rabaeus","doi":"10.15586/JCBMR.2015.11","DOIUrl":"https://doi.org/10.15586/JCBMR.2015.11","url":null,"abstract":"A strong controversy has emerged about the reality of safety and efficacy of statins as stated by company-sponsored reports. However, physicians need credible data to make medical decisions, in particular about the benefit/harm balance of any prescription. This study aimed to test the validity of data on the company-sponsored statin trial by comparing them over time and then comparing statins with each other. Around the years 2005/2006, new stricter Regulations were introduced in the conduct and publication of randomized controlled trials (RCTs). This would imply that RCTs were less reliable before 2006 than they were later on. To evaluate this, we first reviewed RCTs testing the efficacy of statins versus placebo in preventing cardiovascular complications and published  after  2006. Our systematic review thereby identified four major RCTs, all testing rosuvastatin . They unambiguously showed that  rosuvastatin  is not effective in secondary prevention, while the results are highly debatable in primary prevention. Because of the striking clinical heterogeneity and the inconsistency of the published data in certain RCTs, meta-analysis was not feasible. We then examined the most recent RCTs comparing statins to each other: all showed that no statin is more effective than any other, including  rosuvastatin . Furthermore, recent RCTs clearly indicate that intense cholesterol-lowering (including those with statins) does not protect high-risk patients any better than less-intense statin regimens. As for specific patient subgroups, statins appear ineffective in chronic heart failure and chronic kidney failure patients. We also conducted a MEDLINE search to identify all the RCTs testing a statin against a placebo in diabetic patients, and we found that once secondary analyses and subgroup analyses are excluded, statins do not appear to protect diabetics. As for the safety of statin treatment – a major issue for medical doctors – it is quite worrisome to realize that it took 30 years to bring to light the triggering effect of statins on new-onset diabetes, manifestly reflecting a high level of bias in reporting harmful outcomes in commercial trials, as has been admitted by the recent confession of prominent experts in statin treatment. In conclusion, this review strongly suggests that statins are not effective for cardiovascular prevention. The studies published before 2005/2006  were  probably flawed, and this concerned in particular the safety issue. A complete reassessment is mandatory. Until then, physicians should be aware that the present claims about the efficacy and safety of statins are not evidence based. Supplementary files:  The supplementary files of this article are found under 'Article Tools' at the right  side bar.","PeriodicalId":185190,"journal":{"name":"Journal of Controversies in Biomedical Research","volume":"5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129573655","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":"Overview of Marfan Syndrome: knowns and unknowns","authors":"Pratiek N. Matkar, Hao-Hui Chen, H. Leong-Poi, K. Singh","doi":"10.15586/JCBMR.2015.10","DOIUrl":"https://doi.org/10.15586/JCBMR.2015.10","url":null,"abstract":"Marfan syndrome (MFS) is a relatively rare disease of the connective tissue that affects several organs of the body. Cardiovascular abnormalities such as aortic root dilatation and mitral valve prolapse are the two main life-threatening complications associated with MFS. The complete pathogenesis of MFS is yet unclear. However, fibrillin-1 ( FBN1 ) gene mutations and mutations in the transforming growth factor-β (TGFβ) signaling pathway are the leading causes of this lethal disease. Detailed assessment based on several major and minor clinical manifestations has led to the evolution of different nosologies for MFS diagnoses with reliable accuracies. Nevertheless, heterogeneous disease advancement and overlapping clinical outcomes make MFS diagnosis challenging. Rapid strides in research and surgical avenues over the last two decades have improved the life expectancy and the quality of life of MFS patients remarkably. More specific diagnostic criteria have been established, novel therapeutic targets for pharmacotherapy have been identified and validated, and newer surgical techniques have been tested. Current research efforts are focusing on the identification of prognostic biomarkers, gene modifiers, drug targets, and surgical procedures. This review aims to provide a brief overview of these aspects associated with MFS.","PeriodicalId":185190,"journal":{"name":"Journal of Controversies in Biomedical Research","volume":"61 3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131888766","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":"How Medical Practice Has Gone Wrong: Causes of the Lack-of-Reproducibility Crisis in Medical Research","authors":"H. Bauer","doi":"10.15586/JCBMR.2015.8","DOIUrl":"https://doi.org/10.15586/JCBMR.2015.8","url":null,"abstract":"Modern medical practice has gone wrong by over-emphasizing drug-based treatment for chronic, constitutional conditions. The failure to distinguish between infectious and innate conditions was exacerbated by misinterpretation of quantitative measures, inappropriate statistical analysis, and inadequate regulation. The drug industry has become too influential as a result of these mis-steps and is a source of many conflicts of interest that are barriers to improving matters. This article summarizes some of the current problems facing medical practice and offers suggestions to address these problems.","PeriodicalId":185190,"journal":{"name":"Journal of Controversies in Biomedical Research","volume":"29 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115749709","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":"Reactive oxygen species in disease: Rebuttal of a conventional concept","authors":"L. Vitetta, S. Coulson, A. Linnane","doi":"10.15586/JCBMR.2015.7","DOIUrl":"https://doi.org/10.15586/JCBMR.2015.7","url":null,"abstract":"The production of intracellular reactive oxygen species and reactive nitrogen species has long been proposed as leading to the random deleterious modification of macromolecules (i.e., nucleic acids, proteins) with an associated progressive development of the age associated systemic diseases (e.g., diabetes, Parkinson’s disease) as well as contributing to the ageing process.   Superoxide anion (hydrogen peroxide) and nitric oxide (peroxynitrite) comprise regulated intracellular second messenger pro-oxidant systems, with specific sub-cellular locales of production and are essential for the normal function of the metabolome and cellular electro-physiology.  We have posited that the formation of superoxide anion and its metabolic product hydrogen peroxide, and nitric oxide, do not conditionally lead to random damage of macromolecular species such as nucleic acids or proteins.  Under normal physiological conditions their production is intrinsically regulated that is very much consistent with their second messenger purpose of function.   We further propose that the concept of an orally administered small molecule antioxidant as a therapy to abrogate free radical activity (to control oxidative stress) is a chimera.  As such we consider that free radicals are not a major overwhelming player in the development of the chronic diseases or the ageing process.","PeriodicalId":185190,"journal":{"name":"Journal of Controversies in Biomedical Research","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127508060","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":"Journal of Controversies in Biomedical Research - the Need of the Hour","authors":"C. Morais, L. Vitetta","doi":"10.15586/JCBMR.2015.5","DOIUrl":"https://doi.org/10.15586/JCBMR.2015.5","url":null,"abstract":"Approximately 75-89% of the peer–reviewed published literature are thought to be non-reproducible. A need exists to better address the problem of irreproducibility of research data so that contradictory, null and negative findings can be disclosed in an unbiased, non-judgemental, yet scientifically plausible manner. Journal of Controversies in Biomedical Research (JCBMR; www.jcbmr.com) is an attempt to address the ‘reproducibility crisis’ in biomedical research. JCBMR is an online-only open access journal that will publish basic science or clinical research articles that meet any of the following criteria: a) original articles that demonstrate biologically plausible negative, neutral or contentious findings; b) original articles that challenge previously published results in peer-reviewed journals; c) original articles that show effects of compounds on disease models (either in vitro or in vivo ) are contradictory to the expected outcome; d) review articles that critically evaluate and challenge established norms and offer possible solutions to the problem; e) any manuscript that will assist the scientific community to re-think and re–evaluate the established norm.","PeriodicalId":185190,"journal":{"name":"Journal of Controversies in Biomedical Research","volume":"33 10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133872982","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":"Disparity of outcomes: the limits of modeling amyotrophic lateral sclerosis in murine models and translating results clinically","authors":"P. Zwiegers, C. A. Shaw","doi":"10.15586/JCBMR.2015.3","DOIUrl":"https://doi.org/10.15586/JCBMR.2015.3","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a devastatingly progressive neurodegenerative disorder with multiple underlying etiological factors contributing to disease pathogenesis. Despite intensive research efforts and therapeutic development, disease presentation in ALS remains largely intractable to intervention. To date, the most common rodent model used in pre-clinical drug development accounts for a small proportion of the affected patient population and is predicated upon the significant overexpression of a mutant form of the human antioxidant protein, superoxide dismutase 1 (mSOD1). After more than 50 clinical trials, there is an alarming paucity of positive outcomes at the clinical level of ALS therapeutics with strong supporting pre-clinical data in mSOD1 models. Potential reasons for the negative clinical results are multifactorial in nature and include an overly reductionist model system that is heavily influenced by individual transgene level variation, as well as attempting to widely apply findings derived from a model of specific genetic causality to a patient population where the majority of cases are of unknown etiology. With such a tremendous disease burden and a lack of therapeutic options, it is critical that the research community re-evaluate the dependence on mSOD1 pre-clinical models as the gold standard prior to translating findings at the clinical level. Here we briefly review both the clinical and pre-clinical findings of select therapeutics, discuss the limitations of pre-clinical mSOD1 models, and suggest future stratagems that could aid in the clinical translation of efficacious therapeutic agents. Supplementary files:  The supplementary files of this article are found under 'Article Tools' at the right  side bar.","PeriodicalId":185190,"journal":{"name":"Journal of Controversies in Biomedical Research","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129851825","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}