David A. Rubenstein

Bio: David A. Rubenstein is an academic researcher from Stony Brook University. The author has contributed to research in topics: Platelet activation & Endothelial stem cell. The author has an hindex of 21, co-authored 71 publications receiving 1906 citations. Previous affiliations of David A. Rubenstein include State University of New York System & Oklahoma State University–Stillwater.

Electronic cigarette aerosols suppress cellular antioxidant defenses and induce significant oxidative DNA damage.

Abstract: Background Electronic cigarette (EC) aerosols contain unique compounds in addition to toxicants and carcinogens traditionally found in tobacco smoke. Studies are warranted to understand the public health risks of ECs. Objective The aim of this study was to determine the genotoxicity and the mechanisms induced by EC aerosol extracts on human oral and lung epithelial cells. Methods Cells were exposed to EC aerosol or mainstream smoke extracts and DNA damage was measured using the primer anchored DNA damage detection assay (q-PADDA) and 8-oxo-dG ELISA assay. Cell viability, reactive oxygen species (ROS) and total antioxidant capacity (TAC) were measured using standard methods. mRNA and protein expression were evaluated by RT-PCR and western blot, respectively. Results EC aerosol extracts induced DNA damage in a dose-dependent manner, but independently of nicotine concentration. Overall, EC aerosol extracts induced significantly less DNA damage than mainstream smoke extracts, as measured by q-PADDA. However, the levels of oxidative DNA damage, as indicated by the presence of 8-oxo-dG, a highly mutagenic DNA lesion, were similar or slightly higher after exposure to EC aerosol compared to mainstream smoke extracts. Mechanistically, while exposure to EC extracts significantly increased ROS, it decreased TAC as well as the expression of 8-oxoguanine DNA glycosylase (OGG1), an enzyme essential for the removal of oxidative DNA damage. Conclusions Exposure to EC aerosol extracts suppressed the cellular antioxidant defenses and led to significant DNA damage. These findings emphasize the urgent need to investigate the potential long-term cancer risk of exposure to EC aerosol for vapers and the general public.

Differences Between Mainstream and Sidestream Cigarette Smoke Extracts and Nicotine in the Activation of Platelets Under Static and Flow Conditions

Abstract: Background— Cigarette smoke is a primary risk factor for cardiovascular diseases. Enhanced function of the hemostatic system, in which platelets play a major role, is a significant underlying mechanism in cardiovascular disease and its progression. Epidemiological studies, complemented by physiological and biochemical data, show that cigarette smoke adversely affects platelet function, both in smokers and in nonsmokers exposed to sidestream smoke. Methods and Results— The thrombogenic potential of platelets subjected to mainstream smoke extracts, sidestream extracts, and nicotine was measured in vitro under static and dynamic flow conditions. Platelet activation state was measured with a modified prothrombinase-based method. Mainstream and sidestream smoke extracts caused increased platelet activation. Although low-tar mainstream extracts activated platelets less than high-tar extracts, the sidestream extracts were almost equally potent. Modification of the filters of low-tar cigarettes, by blocking the a...

Platelet activation, adhesion, inflammation, and aggregation potential are altered in the presence of electronic cigarette extracts of variable nicotine concentrations.

Abstract: Tobacco smoke extracts prepared from both mainstream and sidestream smoking have been associated with heightened platelet activation, aggregation, adhesion, and inflammation. Conversely, it has been shown that pure nicotine inhibits similar platelet functions. In this work, we 1) evaluated the effects of e-cigarette extracts on platelet activities and 2) elucidated the differences between the nicotine-dependent and non-nicotine dependent (e.g. fine particulate matter or toxic compounds) effects of tobacco and e-cigarette products on platelet activities. To accomplish these goals, platelets from healthy volunteers (n = 50) were exposed to tobacco smoke extracts, e-cigarette vapor extracts, and pure nicotine and changes in platelet activation, adhesion, aggregation, and inflammation were evaluated, using optical aggregation, flow cytometry, and ELISA methods. Interestingly, the exposure of platelets to e-vapor extracts induced a significant up-regulation in the expression of the pro-inflammatory gC1qR and cC1qR and induced a marked increase in the deposition of C3b as compared with traditional tobacco smoke extracts. Similarly, platelet activation, as measured by a prothrombinase based assay, and platelet aggregation were also significantly enhanced after exposure to e-vapor extracts. Finally, platelet adhesion potential toward fibrinogen, von Willebrand factor, and other platelets was also enhanced after exposure to e-cigarette vapor extracts. In the presence of pure nicotine, platelet functions were observed to be inhibited, which further suggests that other constituents of tobacco smoke and electronic vapor can antagonize platelet functions, however, the presence of nicotine in extracts somewhat perpetuated the platelet functional changes in a dose-dependent manner.

Advanced Glycation End Products and Diabetic Complications

Abstract: During long standing hyperglycaemic state in diabetes mellitus, glucose forms covalent adducts with the plasma proteins through a non-enzymatic process known as glycation. Protein glycation and formation of advanced glycation end products (AGEs) play an important role in the pathogenesis of diabetic complications like retinopathy, nephropathy, neuropathy, cardiomyopathy along with some other diseases such as rheumatoid arthritis, osteoporosis and aging. Glycation of proteins interferes with their normal functions by disrupting molecular conformation, altering enzymatic activity, and interfering with receptor functioning. AGEs form intra- and extracellular cross linking not only with proteins, but with some other endogenous key molecules including lipids and nucleic acids to contribute in the development of diabetic complications. Recent studies suggest that AGEs interact with plasma membrane localized receptors for AGEs (RAGE) to alter intracellular signaling, gene expression, release of pro-inflammatory molecules and free radicals. The present review discusses the glycation of plasma proteins such as albumin, fibrinogen, globulins and collagen to form different types of AGEs. Furthermore, the role of AGEs in the pathogenesis of diabetic complications including retinopathy, cataract, neuropathy, nephropathy and cardiomyopathy is also discussed.

Cardiovascular Effects of Secondhand Smoke Nearly as Large as Smoking

Abstract: Background— Secondhand smoke increases the risk of coronary heart disease by ≈30%. This effect is larger than one would expect on the basis of the risks associated with active smoking and the relative doses of tobacco smoke delivered to smokers and nonsmokers. Methods and Results— We conducted a literature review of the research describing the mechanistic effects of secondhand smoke on the cardiovascular system, emphasizing research published since 1995, and compared the effects of secondhand smoke with the effects of active smoking. Evidence is rapidly accumulating that the cardiovascular system—platelet and endothelial function, arterial stiffness, atherosclerosis, oxidative stress, inflammation, heart rate variability, energy metabolism, and increased infarct size—is exquisitely sensitive to the toxins in secondhand smoke. The effects of even brief (minutes to hours) passive smoking are often nearly as large (averaging 80% to 90%) as chronic active smoking. Conclusions— The effects of secondhand smoke ...

Primer of Biostatistics

Abstract: This book attempts to achieve a difficult goal: to teach statistics to the novice so as to impart a liking and understanding of statistics. The book is geared toward a medical audience, since most examples are from the medical literature. The structure of the book consists of the following elements in each chapter: a small number of statistical rules of thumb, followed by a nontechnical explanation, a demonstration of how to work through the mechanics of doing the statistical test in question, a summary, and sample problems to be solved by the reader. (The answers, with explanations, are provided in an appendix.) Although a variety of univariate statistics are included, certain topics that are important in medical research are not. For example, there is little or no discussion of multiple regression, life-table techniques, or pooling of studies. These omissions, especially of multiple regression, are unfortunate. The Primer was derived from

Evolution and Modern Approaches for Thermal Analysis of Electrical Machines

Abstract: In this paper, the authors present an extended survey on the evolution and the modern approaches in the thermal analysis of electrical machines. The improvements and the new techniques proposed in the last decade are analyzed in depth and compared in order to highlight the qualities and defects of each. In particular, thermal analysis based on lumped-parameter thermal network, finite-element analysis, and computational fluid dynamics are considered in this paper. In addition, an overview of the problems linked to the thermal parameter determination and computation is proposed and discussed. Taking into account the aims of this paper, a detailed list of books and papers is reported in the references to help researchers interested in these topics.

IARC Handbooks of Cancer Prevention

Abstract: The International Agency for Research on Cancer (IARC) was established in 1965 by the World Health Assembly, as an independently funded organisation within the framework of the World Health Organization. The headquarters of the Agency are in Lyon, France. The Agency conducts a programme of research concentrating particularly on the epidemiology of cancer and the study of potential carcinogens in the human environment. Its field studies are supplemented by biological and chemical research carried out in the Agency's laboratories in Lyon and, through collaborative research agreements, in national research institutions in many countries. The Agency also conducts a programme for the education and training of personnel for cancer research. The publications of the Agency contribute to the dissemination of authoritative information on different aspects of cancer research. Information about IARC publications, and how to order them, is available via the Internet at: http:// The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city, or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. The authors alone are responsible for the views expressed in this publication.