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Author: Lucio G. Costa
Publisher: Springer Science & Business Media
ISBN: 9781402072826
Category : Medical
Languages : en
Pages : 244
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Book Description
The journey to find genes responsible for determining sensitivity or resistance to specific insecticides led to the paraoxonase (PON1) gene on human chromosome 7. This gene encodes a 355 amino acid protein that is localized on the high density lipoprotein (HDL) particles in plasma. Characterization of this gene revealed that different individuals expressed both different forms of this enzyme with amino acid substitutions at positions 55 and 192 as well as different levels of this protein. Additional studies showed that mutations in the regulatory region of the PON1 gene contributed to the very different levels of plasma PON1 among individuals. It turned out that both the level of the enzyme as well as the amino acid present at position 192 (glutamine or arginine) are important in determining resistance to the active forms of specific organophosphorus insecticides, especially diazinon and chlorpyrifos. The position 192 amino acid also determined whether an individual's plasma hydrolyzed the nerve agents soman and sarin at high or low rates. It is not yet known whether these different rates of hydrolysis observed in biochemical assays reflect differences in sensitivity of individuals to nerve agents. Taken together, all of the experiments carried out to date indicate that engineered recombinant PON1 is an excellent candidate to use for treating cases of poisoning by specific organophosphorus compounds. The available data on the relationship of PON1 levels and position 192 genotype led us to introduce the term PON1 status to describe an individual's PON1 plasma level as well as their position 192 genotype.The characterization of the genetic variations of the PON1 gene together with experiments showing that HDL can protect the lipids in low density lipoprotein particles (LDL) from oxidation and that it was PON1 that was responsible for this protection have opened an entirely new area of investigation, the role of PON1 in protecting against vascular disease.More recent reports have noted that PON1 also metabolizes a number of drugs, activating some and inactivating others.This book describes the recent advances in understanding the role of PON1 in both cardiovascular disease and toxicology of insecticide exposure as well as some of the recent information indicating an important possible role in the pharmacokinetics of drug metabolism. The final chapter of the book provides an overview of the areas of PON1 research and suggests future directions for research on PON1 as well as the related, linked genes PON2 and PON3.
Author: Lucio G. Costa
Publisher: Springer Science & Business Media
ISBN: 9781402072826
Category : Medical
Languages : en
Pages : 244
Get Book Here
Book Description
The journey to find genes responsible for determining sensitivity or resistance to specific insecticides led to the paraoxonase (PON1) gene on human chromosome 7. This gene encodes a 355 amino acid protein that is localized on the high density lipoprotein (HDL) particles in plasma. Characterization of this gene revealed that different individuals expressed both different forms of this enzyme with amino acid substitutions at positions 55 and 192 as well as different levels of this protein. Additional studies showed that mutations in the regulatory region of the PON1 gene contributed to the very different levels of plasma PON1 among individuals. It turned out that both the level of the enzyme as well as the amino acid present at position 192 (glutamine or arginine) are important in determining resistance to the active forms of specific organophosphorus insecticides, especially diazinon and chlorpyrifos. The position 192 amino acid also determined whether an individual's plasma hydrolyzed the nerve agents soman and sarin at high or low rates. It is not yet known whether these different rates of hydrolysis observed in biochemical assays reflect differences in sensitivity of individuals to nerve agents. Taken together, all of the experiments carried out to date indicate that engineered recombinant PON1 is an excellent candidate to use for treating cases of poisoning by specific organophosphorus compounds. The available data on the relationship of PON1 levels and position 192 genotype led us to introduce the term PON1 status to describe an individual's PON1 plasma level as well as their position 192 genotype.The characterization of the genetic variations of the PON1 gene together with experiments showing that HDL can protect the lipids in low density lipoprotein particles (LDL) from oxidation and that it was PON1 that was responsible for this protection have opened an entirely new area of investigation, the role of PON1 in protecting against vascular disease.More recent reports have noted that PON1 also metabolizes a number of drugs, activating some and inactivating others.This book describes the recent advances in understanding the role of PON1 in both cardiovascular disease and toxicology of insecticide exposure as well as some of the recent information indicating an important possible role in the pharmacokinetics of drug metabolism. The final chapter of the book provides an overview of the areas of PON1 research and suggests future directions for research on PON1 as well as the related, linked genes PON2 and PON3.
Author: Bharti Mackness
Publisher: Springer Science & Business Media
ISBN: 1402065612
Category : Medical
Languages : en
Pages : 322
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Book Description
In September 2006 the 2nd International Conference on Paraoxonases took place in Hajdúszoboszló, Hungary, bringing together the world's foremost experts in the field. The current book is a distillation of the plenary lectures which took place at the meeting, resulting in a comprehensive up-to-date, state-of-the-art review of current paraoxonase research. The book details a unique and novel enzyme whose physiological/pathological function(s) are just starting to be revealed.
Author: National Research Council
Publisher: National Academies Press
ISBN: 0309112982
Category : Science
Languages : en
Pages : 300
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Book Description
The new field of toxicogenomics presents a potentially powerful set of tools to better understand the health effects of exposures to toxicants in the environment. At the request of the National Institute of Environmental Health Sciences, the National Research Council assembled a committee to identify the benefits of toxicogenomics, the challenges to achieving them, and potential approaches to overcoming such challenges. The report concludes that realizing the potential of toxicogenomics to improve public health decisions will require a concerted effort to generate data, make use of existing data, and study data in new waysâ€"an effort requiring funding, interagency coordination, and data management strategies.
Author: Arnold von Eckardstein
Publisher: Springer
ISBN: 9783319096643
Category : Medical
Languages : en
Pages : 0
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Book Description
In this Handbook of Experimental Pharmacology on “High Density Lipoproteins – from biological understanding to clinical exploitation” contributing authors (members of COST Action BM0904/HDLnet) summarize in more than 20 chapters our current knowledge on the structure, function, metabolism and regulation of HDL in health and several diseases as well as the status of past and ongoing attempts of therapeutic exploitation. The book is of interest to researchers in academia and industry focusing on lipoprotein metabolism, cardiovascular diseases and immunology as well as clinical pharmacologists, cardiologists, diabetologists, nephrologists and other clinicians interested in metabolic or inflammatory diseases.
Author: Lucio G. Costa
Publisher: Springer Science & Business Media
ISBN: 1461510279
Category : Science
Languages : en
Pages : 226
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Book Description
The paraoxonase or PON family of genes resides on human chromosome 7q2t-22 in the order PONt, PON3 and PON2. PONt was one of the early genes identified as an environmentally relevant gene, in that it is important in determining an individual's sensitivity or resistance to exposure from specific organophosphorus (OP) insecticides. Paraoxonase (PONt) is an A esterase (i. e. , not inhibited by OP compounds) initially identified for its ability to catalytically hydrolyze paraoxon, the toxic metabolite (oxon form) of the insecticide parathion. Evidence accumulated in the past several years has established that this enzyme, which is present at variable levels in liver and serum of different individuals, is an important determinant of sensitivity to toxicity of specific organophosphorus compounds including chlorpyrifos oxon and diazoxon. Recent experiments have pointed out that it is the catalytic efficiency of PONt together with the levels of PONt that are important in determining the degree of resistance. Surprisingly, even though PONt has a higher catalytic efficiency than PONtQ)92 for paraoxon RJ92 hydrolysis, it does not provide significant in vivo protection against an exposure to paraoxon. Interest in this enzyme has also emerged from the finding that it displays genetic polymorphisms in most populations, with a significant number of the individuals in a given population canying a PONt gene that puts them at risk for a specific OP exposure.
Author: John F. Keaney Jr.
Publisher: Springer Science & Business Media
ISBN: 9780792386780
Category : Medical
Languages : en
Pages : 404
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Book Description
One of the major biomedical triumphs of the post-World War II era was the defmitive demonstration that hypercholesterolemia is a key causative factor in atherosclerosis; that hypercholesterolemia can be effectively treated; and that treatment significantly reduces not only coronary disease mortality but also all cause mortality. Treatment to lower plasma levels of cholesterol - primarily low density lipoprotein (LDL) cholesterol - is now accepted as best medical practice and both physicians and patients are being educated to take aggressive measures to lower LDL. We can confidently look forward to important decreases in the toll of coronary artery disease over the coming decades. However, there is still uncertainty as to the exact mechanisms by which elevated plasma cholesterol and LDL levels initiate and favor the progression of lesions. There is general consensus that one of the earliest responses to hypercholesterolemia is the adhesion of monocytes to aortic endothelial cells followed by their penetration into the subendothelial space, where they differentiate into macrophages. These cells, and also medial smooth muscle cells that have migrated into the subendothelial space, then become loaded with mUltiple, large droplets of cholesterol esters . . . the hallmark of the earliest visible atherosclerotic lesion, the so-called fatty streak. This lesion is the precursor of the more advanced lesions, both in animal models and in humans. Thus the centrality of hypercholesterolemia cannot be overstated. Still, the atherogenic process is complex and evolves over a long period of time.
Author: Ramesh C Gupta
Publisher: Academic Press
ISBN: 0080543103
Category : Technology & Engineering
Languages : en
Pages : 781
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Book Description
This text/reference book provides the most comprehensive coverage of anticholinesterase compounds (Organophosphates and Carbamates), which constitute the largest number of chemicals that are primarily used as insecticides in agriculture, industry, and around the home/garden. Some OPs (nerve agents) have been used in chemical warfare and terrorist attacks, while some OPs and CMs have been recommended as therapeutic agents in human medicine as well as in veterinary medicine. Many chemicals of both classes are extremely toxic and lack selectivity, thus their inadvertent/accidental use continues to pose a threat to human and animal health, aquatic systems and wildlife. These anticholinesterase agents produce a variety of toxicological effects in target and nontarget organs. In light of this complexicity, this multi-authored book is written by the well known scientists from many countries. The book is organized into nine sections, with a total of 49 chapters, to provide in-depth knowledge on various aspects of OP and CM compounds, including their use, classification, mechanism-based toxicity, and prophylactic and therapeutic measurements. Several chapters are written with special emphasis to cover timely topics, such as chemical warfare agents, physiologically-based pharmacokinetic modeling, structure and function of cholinesterases, paraoxonase, carboxylesterases; developmental neurotoxicity, the intermediate syndrome, oxidative stress, endocrine disruption, and DNA damage/gene expression and carcinogenesis. Section-VI with 5 chapters is specifically devoted to risk assessment, and safety and regulatory guidelines for pesticides. - Describes everything you need to know about Organophosphates and Carbamates - Extensively covers pesticides, nerve agents, therapeutic drugs, and flame retardants - Describes epidemiology of the world's major disasters involving Organophosphates and Carbamates - Covers animal, human, aquatic, and wildlife toxicity of Anticholinesterases - Insights into in-depth cholinergic and noncholinergic mechanisms of toxicity - Describes recent advancements in cholinesterases, paraoxonases, carboxylesterases, oxidative stress, endocrine disruption, cardiac and pulmonary toxicity, and carcinogenesis - Provides in vitro and in vivo models for neurotoxicity testing - Integrates knowledge of studies in lab animals and humans - Offers risk/safety assessment and national/international guidelines for permissible levels of pesticide residues - Describes management of Anticholinesterase poisoning in humans
Author: Chukwuebuka Egbuna
Publisher: Springer Nature
ISBN: 3030729990
Category : Science
Languages : en
Pages : 262
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Book Description
This book presents comprehensive coverage on the importance of good nutrition in the treatment and management of obesity, cancer and diabetes. Naturally occurring bioactive compounds are ubiquitous in most dietary plants available to humans and provide opportunities for the management of diseases. The text provides information about the major causes of these diseases and their association with nutrition. The text also covers the role of dietary phytochemicals in drug development and their pathways. Later chapters emphasize novel bioactive compounds as anti-diabetic, anti-cancer and anti-obesity agents and describe their mechanisms to regulate cell metabolism. Written by global team of experts, Dietary Phytochemicals: A Source of Novel Bioactive Compounds for the Treatment of Obesity, Cancer and Diabetes describes the potentials of novel phytochemicals, their sources, and underlying mechanism of action. The chapters were drawn systematically and incorporated sequentially to facilitate proper understanding. This book is intended for nutritionists, physicians, medicinal chemists, drug developers in research and development, postgraduate students and scientists in area of nutrition and life sciences.
Author: John Betteridge
Publisher: CRC Press
ISBN: 9780340552698
Category : Medical
Languages : en
Pages : 1328
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Book Description
This comprehensive work deals with the major health problem of high lipid levels in blood, a cause of serious heart and vascular disease. Formerly the province only of the chemical pathologist, cardiologists and general physicians are now offering treatment as new 'lipid-lowering' drugs become available. The area is also of considerable interest to public health physicians as changes in lifestyle (such as dietary and smoking habits) have significant effects on lipid levels. A prestigious team of contributors covers all aspects of the topic, from molecular biology to practical dietary management to help reduce lipid levels.
Author: N. B. Myant
Publisher: Butterworth-Heinemann
ISBN: 148328123X
Category : Science
Languages : en
Pages : 925
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Book Description
The Biology of Cholesterol and Related Steroids focuses on the study of sterols in relation to living organisms. The publication first takes a look at the analysis of sterols and related steroids and the distribution of sterols and related steroids in nature, as well as the processes of extraction and separation and presence of sterols in plants, fungi, vertebrates, and invertebrates. The text then ponders on biosynthesis of sterols and metabolism of cholesterol. Topics include formation of fatty acid esters of cholesterol, steroid hormones, biosynthetic pathway to sterols, reaction mechanisms, and comparative aspects of sterol synthesis. The manuscript examines the developmental aspects of cholesterol metabolism and sterols in biological membranes. The book also reviews cholesterol synthesis in animal tissues, sterol metabolism in isolated cells, and epidemiology of the plasma cholesterol. Discussions focus on selection of statistical populations, genetic influences, regulation of sterol synthesis, general aspects of sterol metabolism, and removal of cell cholesterol in vivo. The publication is a dependable source of data for biochemists and readers interested in the biology of cholesterol and steroids.
