bluuebunny/crossref_metadata_2025 huggingface dataset:
Voir Dire and Jury Selection
Authors: Kovera Margaret Bull , Dickinson Jason J. , Cutler Brian L.
Published: November 2003

During the pretrial proceeding of voir dire, attorneys use a wide range of techniques to select potential jurors who will be favorably disposed to their case. Traditionally, attorneys have drawn on intuition, courtroom experience, and implicit theories of juror behavior to select favorable jurors. In contrast, scientific jury selection refers to the use of surveys and other social scientific tools to identify demographic characteristics, personality traits, or attitudes that predict jurors' verdict inclinations. There is a long‐standing debate within the legal and scientific communities whether either method of jury selection effectively identifies jurors favorable to a given case. This chapter describes the legal framework in which attorneys execute jury selection (i.e., voir dire), the procedures underlying traditional and scientific jury selection, and the history behind the development of scientific jury selection. The chapter provides a detailed review of the empirical research assessing the effectiveness of both traditional and scientific jury selection. The chapter concludes with a discussion of the limitations of this empirical research and a recommendation for a social‐psychological approach to the study of scientific jury selection that may remedy the current theoretical stagnation and advance research in the area.
Forensic Evaluation in Americans with Disabilities Act Cases
Authors: Foote William E.
Published: November 2003

The Americans with Disabilities Act (ADA) came into effect in the early 1990s. The legislation was developed to provide disabled people with legal remedies to address discrimination and to require reasonable accommodation for disabilities in many aspects of daily life. The ADA also provides psychologists with opportunities for evaluation and consultation related to litigation. However, the ADA presents the inquiring professional with a daunting array of definitions and regulations. A goal of this chapter is to address the considerable ADA literature in the context of a practical forensic approach. The chapter introduces the reader to some general information about disability in the workplace and how the ADA fits into existing disability systems. The second section reviews mental disabilities under the ADA. The third section will deal with how psychologists may work with employers to accommodate workers with disabilities. The fourth section will examine litigation‐related psychological evaluations and how psychologists may assist the court in determining damages in cases of discrimination and failure to provide reasonable accommodation. A final section will provide some concluding remarks.
Forensic Evaluation in Delinquency Cases
Authors: Grisso Thomas
Published: November 2003

Mental health professionals have provided forensic evaluations in delinquency cases throughout the one‐hundred‐year existence of the juvenile court. Yet little research has been available to assist the development of this mental health service, and professional guidance through literature and specialized training has lagged far behind other areas of forensic mental health practice. The first section of this chapter describes these conditions historically and suggests that a “new field” of juvenile forensic evaluation has recently emerged due to increased attention to problems of youth violence and increasing evidence of elevated prevalence rates of mental disorders among delinquent youths.

Three types of assessments in delinquency cases are reviewed in the three main sections of this chapter: disposition (rehabilitation) assessments, evaluations for estimating risk of future violence, and assessments for psycholegal concepts in delinquency cases (e.g., waiver to criminal court, competence to stand trial, and youths' capacities to waive Miranda rights). Each section reviews the fundamental questions that these evaluations address, from a legal and psychological perspective, then review concepts and methods that have been developed to assist clinicians in obtaining data and making inferences to address those questions. The final section reviews anticipated future advances in forensic assessment in delinquency cases.
Evaluation of Criminal Responsibility
Authors: Goldstein Alan M. , Morse Stephen J. , Shapiro David L.
Published: November 2003

Unlike traditional clinical assessments that are usually concerned with present functioning, forensic assessments of criminal responsibility focus on a defendant's actions and mental states that may have occurred days, weeks, months, or years ago. This chapter considers the basic doctrines of criminal liability. Specific attention is given to mental state issues relevant to culpability: negation ofmens rea, provocation/passion, extreme mental or emotional disturbance, voluntary and involuntary intoxication, imperfect self‐defense, and duress. The history of the insanity defense, including its development, changes, and recent reforms, is discussed. Those ethical issues and conflicts that frequently arise when clinicians conduct retrospective forensic mental state evaluations are reviewed. A generic model for conducting forensic assessments, with specific application to evaluating defendants' mental states at the time of the offense, is presented. The structure of mental state at the time of the offense assessments is described, including the need to review third‐party information and the administration of appropriate psychological testing.
Sentencing Determinations in Death Penalty Cases
Authors: Cunningham Mark D. , Goldstein Alan M.
Published: November 2003

This book chapter provides a comprehensive discussion of psychological evaluations in death penalty cases. Current demographic data regarding death row is described. The history of how a series of U.S. Supreme Court decisions in the modern era have shaped the parameters of death penalty sentencing is detailed. Ethical considerations are explored with particular attention to pitfalls unique to death penalty evaluations. These include participation in the death sentencing process, informed consent, and hazards of the team approach. Both conceptual frameworks and practical procedures for forensic assessments in capital cases are described. While various evaluations from pretrial to execution are considered, the primary emphasis is on sentencing assessments. Research findings that can inform evaluations of mitigation are outlined, including empirical data linking adverse developmental factors to violent criminal outcome. The methodology and statistical data important to reliable violence risk assessments at capital sentencing are described. Included are tables that summarize violence rates among capital offenders and murderers in prison, identification of common errors in capital risk assessments, and discussion of challenges to the application of group statistical data to these cases. The contributions of evaluating witness and teaching witness testimony at the sentencing phase proceedings are differentiated.
Violence Risk Assessment
Authors: Monahan John
Published: November 2003

This chapter considers, first, why and in what ways law is concerned with anticipating violence, and how evidence in the form of violence risk assessments is legally evaluated in the United States after the Supreme Court's 1993Daubert v. Merrill Dow Pharmaceuticalsdecision on the admissibility of scientific evidence. It then contrasts clinical from actuarial or statistical methods of risk assessment, and addresses key issues and controversies pertinent to each. Finally, the chapter argues that the future violence risk assessment is likely to involve more precise depictions of which specific risk factors are validly associated with violence in which specific types of people. Violence risk assessment is likely to continue to move strongly in an actuarial direction, including the introduction of violence risk assessment software. Due to the questionable validity generalization of many actuarial instruments and to the possibility of rare risk or protective factors being present in a given case, clinical judgment is unlikely to be supplanted by actuarial techniques. Increased attention is likely to be given to how estimates of risk are best communicated to those who have to make decisions based on them, and to how risk, once communicated, is to be clinically managed.
Forensic Psychology, Public Policy, and the Law
Authors: Krauss Daniel A. , Sales Bruce D.
Published: November 2003

The authors explore critical points in the interaction between forensic practice and law and policy. Using forensic assessment and testimony as primary examples, the authors argue that changes in the law as well as forensic practice have transformed the responsibilities of both forensic practitioners and legal actors. The difficulties posed by these changes are discussed in the context of the new evidentiary admissibility requirements created by the U.S. Supreme Court decision inDaubert v. Merrell Dow Chemical(1993), and a number of dilemmas are raised that forensic practitioners, judges, and policy makers will face as a result of this new standard. Additionally, a number of central lessons that can be gleaned from the complex interaction of forensic psychology, law, and policy to date are highlighted and discussed. Finally, future directions for the field of forensic practice are also offered, including the role that forensic practitioners should play in shaping future policy and law.
Stability and Change in Industrial and Organizational Psychology
Authors: Borman Walter C. , Klimoski Richard J. , Ilgen Daniel R.
Published: November 2003

As single volume nested within a handbook for all of psychology, our purpose was to provide the depth and breadth that would capture the domain of industrial and organizational psychology in a way valuable for scholars and students in that field. We also hoped to create a volume to which those outside the field could turn in order to gain an appreciation of the latest thinking and research in the area. This opening chapter first discusses some of the major accomplishments and new directions that have advanced this field since publication of the 2nd edition of theHandbook of Industrial and Organizational Psychology(Dunnette & Hough, 1990). These “milestones” include the elaboration of models of job performance; completion of Project A, a long‐term selection and classification research program in the U.S. Army; development of the Occupational Information Network (O*NET), a database of occupational information about job requirements; advances in thinking about levels of analysis; renewed interest in viewing workers as individuals and as members of teams; considerable progress in learning about relations between variables using meta‐analysis and other methods; and increased consideration of topics within a strategic human resource management framework. Finally, we commented on each of the 23 topical chapters, providing a preview of this volume's content.
Personnel Selection and Employee Performance
Authors: Schmitt Neal , Cortina Jose M. , Ingerick Michael J. , Wiechmann Darin
Published: November 2003

This paper is organized around a model of job performance in which personality and ability constructs (KSASOs) are seen as leading to procedural and declarative knowledge and motivation which, in turn, lead to task proficiency and contextual and adaptive behavior. These latter individual performance variables are thought to have implications for a set of distal variables, many of which can be conceptualized as organizational level constructs (e.g., social responsibility and litigation). Our sense is that job analyses are means of developing performance models. Some important and relatively new developments in this area include the job information tool known as O*NET. Adding distal variables to a performance model means that we must consider levels of analysis issues. Literature on applicant reactions to selection procedures and the implications of those reactions is discussed as is the notion that withdrawal behavior is a general concern that includes tardiness, absenteeism, counterproductive behavior, and turnover. Still other new developments include the use of technology in measurement, use of our procedures in other cultures, and the critical consideration of time in our analyses of the relationship of various variables with individual differences. Finally, the notion that performance itself is multidimensional is being addressed as a result of recent theorizing about its nature.
Work Groups and Teams in Organizations
Authors: Kozlowski Steve W. J. , Bell Bradford S.
Published: November 2003

Contemporary work organizations make heavy use of work teams to meet both immediate and strategic objectives. This chapter addresses the nature and dynamics of work teams. It emphasizes the types of teams that are commonly used in work settings and the processes that are key to their success. The extensive literature on work teams is reviewed and organized around the shifting demands the team's life cycle—from formation to disbanding. Special emphasis is given to research needs relative to team training and development and the role of team leadership.
Customer Service Behavior
Authors: Ryan Ann Marie , Ployhart Robert E.
Published: November 2003

This chapter provides a contingency approach to the understanding, prediction, and influence of customer service behavior. Customer service behavior is defined as any activities of an employee specifically directed toward affecting service quality. Specific characteristics of services that influence how organizations promote customer service behavior are described: service intangibility, simultaneity of service production and consumption, coproduction or active customer participation, relationship vs. encounter nature of the service, role‐prescribed vs. extra‐role nature of the behavior, standard vs. customized nature of the service, and the nature and level of customer contact. These characteristics of services are then discussed in relation to research on customer service behavior in the areas of performance management, employee selection, organizational climate and employee attitudes, emotions, training, motivation, and job design. The manner by which the characteristics of services would alter how one approaches interventions in each of these areas are discussed, and questions for future research are raised.
Work Design
Authors: Morgeson Frederick P. , Campion Michael A.
Published: November 2003

In this chapter we review Industrial/Organizational Psychology research on work design. To do so, the chapter is divided into seven sections. First, the five major work design perspectives are reviewed, including scientific management, job enrichment approaches, sociotechnical systems theory, the social information processing perspective, and the interdisciplinary model of job design. Second, contextual influences (social and structural) on work design are identified. Third, research that has examined the characteristics of work is investigated, including the structure of work, whether work can be viewed as objective characteristics or subjective perceptions, and measurement concerns with existing work design research. In addition, copies of the scales that have been used to operationalize the most common work characteristics are provided. Fourth, the mediating mechanisms assumed to be responsible for work design outcomes are reviewed. Fifth, the outcomes of work design are identified, which includes psychological and behavioral outcomes, as well as individual differences in reactions to work design. Sixth, based on the review, an integrated work design framework is developed (Figure 1). Finally, several additional issues in work design are discussed, including the changing nature of work, tensions inherent in work design approaches, and important work design research needs.
Judgment and Decision Making
Authors: Connolly Terry , Ordóñez Lisa
Published: November 2003

Judgment and decision‐making (JDM) research embraces a broad interdisciplinary array of topics concerned with human choice. It includes both descriptive studies, aimed at understanding what real decision makers actually do and normative (or prescriptive) work, aimed at advising people how they might make better choices. Core processes include making inferences about what is currently happening, making predictions about what might happen next, and developing preferences about these possible future states. A variety of choice processes have been identified by which these elements can be brought together in selection of preferred actions, either at a single point in time or as a series of interventions over time. Though most research attention has considered individual decision makers, there is also important work in two‐person (negotiation, bargaining) processes and in multiperson decisions made in groups. Across these many topics there is recurrent disparity between what people are seen to be doing and what some putatively normative model suggests they should be doing, suggesting that either model or behavior is in error. This tension, and the obvious applicability of the resolution to important practical decisions, has kept the field highly energized for several decades. The creative furor continues.
Human Factors and Ergonomics
Authors: Howell William C.
Published: November 2003

Humanfactors and ergonomics(HF/E) is rooted in two fundamental concepts:user‐oriented designand thehuman‐machine systemmodel. The former embodies the principle that the utility and safety of artifacts that people create cannot be optimized unless human strengths, weaknesses, and tendencies are considered explicitly in their design. The latter regards the artifact and its human user as interactive components of a composite system that functions best when the components mesh. Thus the field is involved in research on all aspects of human performance and in the application of that knowledge to the design of all manner of systems. As technology has evolved and the role of the operator has changed, the scope of HF/E has shifted and expanded. From the era of manual tasks and a focus on information displays and manual controls, it has followed technology into the information age where the emphasis is on cognitive engineering, software design, and complex systems. Although it still draws heavily on psychological content and methods, its disciplinary composition has also expanded greatly. Once an applied extension ofexperimentalpsychology, its interests now extend into the domains ofindividual differences, I/O, and socialpsychology, along with anthropology, biomechanics, neuroscience, computer science, and a host of evolving disciplines. Institutional linkages with these specialties and disciplines have been hampered by longstanding traditions and internal HF/E controversies, but there are signs that the situation is improving.
History of Quantitative Structure‐Activity Relationships
Authors: Selassie C. D.
Published: November 2003

The QSAR paradigm is delineated as it evolved and as it is presently used. The methodology used to select appropriate substituents/compounds, parameters, and approaches is addressed. Parameters that are routinely used to define a QSAR are sequestered according to their electronic, hydrophobic, and steric attributes. Indicator variables and molecular structure descriptors are also described. The types of QSAR models that are featured include the linear and parabolic models elucidated by Hansch and the bilinear model developed by Kubinyi. Applications of QSAR are drawn from isolated receptor systems as well as cellular and whole animal studies. The utility of a comprehensive QSAR database that allows for lateral validation from physical organic reactions and other biological systems is described and illustrated.
Molecular Modeling in Drug Design
Authors: Marshall Garland R. , Beusen Denise D.
Published: November 2003

This chapter examines the approaches to molecular modeling and drug design and emphasizes their limitations. Useful information to guide the design and synthesis of potential novel therapeutics can be developed from an analysis of structure‐activity data in the three‐dimensional framework provided by current molecular modeling techniques. Although most of the techniques and approaches described have broader application than shown, the examples chosen should be sufficient to illustrate their use.
Chemical Information Computing Systems in Drug Discovery
Authors: Henry Douglas R.
Published: November 2003

An important component of drug discovery is the storage, searching, and manipulation of chemical structures and reactions. Over the past three decades, the science of chemical information management has grown along with advances in computer hardware, software, and database systems. This chapter discusses the evolution of chemical information storage in the corporate environment, from flat files to specialized databases to relational database systems. An example methodology for storing and searching structures in a relational database system is described. The recent deluge of information from high throughput chemistry is leading to the appearance of chemical data marts, data warehouses, and structural data mining, which are briefly discussed. Finally, a short look is taken into the future of chemical information and knowledge management, with respect to databases, software, and hardware. This review focuses on chemical structure database management. Other chapters describe the generation of chemical structures and their properties and the use of this data in the drug discovery process.
X‐Ray Crystallography in Drug Discovery
Authors: Livingston Douglas A. , Buchanan Sean G. , D'Amico Kevin L. , Milburn Michael V. , Peat Thomas S. , Sauder J. Michael
Published: November 2003

The focus of this chapter is the methods, recent advances, and the applications of X‐ray protein crystallography in the discovery of new drug targets and candidate drugs. It begins with a basic description of the various steps involved in solving a structure, including recent advances in technique and technology, and the major challenges that are faced in executing the process. The underlying theory, various crystallization methods, data collection equipment and techniques, and computational reduction of the data to give the final structure are all covered in this section. The accessible databases that contain large collections of structures are also described. The application to drug discovery is then briefly addressed with a discussion of co‐crystallization methods and issues, which is followed by a comprehensive table enumerating the published structures of the known drug targets and close homologs. Applications to discovering and validating protein targets of therapeutic relevance are then covered in a section on the very new field of structural genomics. Genome annotation by structural homology, elucidating pathways and the potential for the rational design of multitarget drugs, and advances in the field of protein structure modeling that are enabled by crystallographic databases are described and exemplified with very recent results from the field.
Combinatorial Chemistry and Multiple Parallel Synthesis
Authors: Mitscher Lester A. , Dutta Apurba
Published: November 2003

The methodologies used in combinatorial chemistry and multiple parallel synthesis of large and small molecules are explicated. The impact of these new technologies on drug seeking are discussed.
Rapid, High Content Pharmacology
Authors: Brown Steven J. , Clark Imran B. , Pandi Bala
Published: November 2003

High‐throughput pharmacology will play an increasingly important role in drug development as companies strive to limit the likelihood that a compound will be removed from the market or fail phase II and III clinical trials because of unexpected side effects or toxicity. Identification of the correct compounds to advance from hit to lead‐compound candidate requires the determination of efficacy and evaluation of potential compound liabilities (solubility, adsorption, toxicity) and specificity of action. We propose that the characterization of the response of hit compounds against a broad panel of natural human cells will be very useful in making the correct selection. Because genes are not overexpressed in these cells, the signaling pathways are not altered by changes in protein stoichiometry. In addition, our cell bank has been genetically indexed and characterized for responses to known pharmacological agents and stored in a database. Thus, the pattern of functional responses (such as membrane potential, changes in intracellular calcium, cAMP etc.) obtained with test compounds can be compared with the known responses and gene expression, allowing for the ready identification of compounds with unexpected toxicities and effects. In addition,
in vitro
assays for evaluation of the adsorption and metabolism properties of compounds can be used to screen for compounds with drug‐like properties. These systems and methods provide high definition, content‐rich information about cellular responses and have sufficient throughput for use in screening hit compounds.
Oligonucleotide Therapeutics
Authors: Crooke Stanley T.
Published: November 2003

Antisense technology expolits oligonucleotide analogs to bind to cognate RNA sequences through Watson‐Crick hybridization resulting in the destruction or disablement of the target RNA. Durign the past decade, programs on all fronts has continued and there are satisfactory consensus to all the basic questions.

In this review, progress in the medicinal chemistry and molecular pharmacology of antisense is reviewed. Further, progress in understanding thepharmacokinetic, pharmacodynamic and toxicologic properties of first and second generations antisense drugs is reviewed. Additionally, a summary of clinical data on a significant number of antisense drugs is provided.
Carbohydrate‐Based Therapeutics
Authors: Musser John H.
Published: November 2003

Carbohydrates have emerged as a significant new approach to drug discovery. The impact can be seen in the carbohydrate‐based therapeutics recently approved for marketing. For example, the trend with low molecular weight heparin‐based products has culminated in the approval of a synthetic pentasaccharide for preventing venous thromboembolism after orthopedic surgery. Also, in the treatment of viral infection, two monosaccharide glycomimetic drugs that block neuraminidase are now available for the treatment of influenza. Indeed, at least two new carbohydrate‐based drugs were approved on an annual basis as therapeutics during the last decade. Considering the carbohydrate therapeutics now in development, this pace should continue. To continue long term, several objectives must be reached. Technologies to supply carbohydrates in quality and quantity must be refined or discovered. This includes any combination of automated, solid and solution phase, and enzymatic synthesis. Work demonstrating that carbohydrate multivalency is a successful approach to drug discovery needs to be done. Likewise, examples that illustrate how carbohydrate‐based libraries can accelerate drug discovery are also needed. An important factor for the success of carbohydrate‐based therapeutics in the last decade is the combination of glycobiology and carbohydrate chemistry.
Principles of Drug Metabolism
Authors: Testa Bernard , Soine William
Published: November 2003

The focus of this chapter is mainly on drug metabolism reactions and connected information of significance to medicinal chemists. The types, selectivities, and consequences of drug metabolism are presented in the introduction. Oxidoreductases are discussed in the next section, together with a systematic and extensive treatment of the chemical groups they target and the functionalization reactions they catalyze. Particular attention is paid to cytochromes P450 and their multiplicity, specificities, and relative importance. Section 3 is dedicated to the transferases and the conjugation reactions they catalyze, e.g., glucuronidation and glutathione conjugation. The various biological factors influencing drug metabolism are examined in Section 4. These are subdivided into interindividual factors (that depend on the genome) and intraindividual factors (that can vary with time or because of external influences). The last section, which is particularly close to the interests of medicinal chemists, discusses structure‐metabolism relationships, prodrug design, and toxophoric groups.
Retrometabolism‐Based Drug Design and Targeting
Authors: Bodor Nicholas , Buchwald Peter
Published: November 2003

Retrometabolic approaches represent systematic drug design methodologies that thoroughly integrate structure—activity and structure—metabolism relationships and are aimed to design safe compounds with an improved therapeutic index. They incorporate two major concepts aimed to design soft drugs and chemical delivery systems, respectively. Soft drugs are new, active therapeutic agents that undergo predictable metabolism to inactive metabolites after exerting their desired therapeutic effect. Chemical delivery systems are biologically inert molecules that provide enhanced and targeted delivery of an active drug to a particular organ or site through a designed sequential metabolism that involves several steps. The present comprehensive review includes an overview of the general retrometabolic drug design principles and provides a variety of specific examples to illustrate the concepts. If possible, the rationale for the design as well as the pharmacokinetic and pharmacodynamic properties of the new therapeutic agents are briefly summarized and compared to those of the other compounds used in the same field.
Physicochemical Characterization and Principles of Oral Dosage Form Selection
Authors: Amidon Gregory E. , He Xiaorong , Hageman Michael J.
Published: November 2003

Identifying an active lead molecule, selecting a viable drug candidate, and developing a marketable product are profoundly influenced by molecular properties and dosage form design. This chapter discusses the importance of a molecule's physicochemical properties and the link with oral dosage form design strategies. The Biopharmaceutics Classification Scheme (BCS) is used to identify oral dosage form options that have the best chance of overcoming drug delivery problems. Physicochemical characterization not only can guide the selection of formulation strategies but, if incorporated into the lead selection process, can influence analog selection and lead optimization. The end result of considering physicochemical properties is to reduce the risk of failure by facilitating the identification of appropriate dosage form design options and, at the same time, allow discovery chemists to maximize chances of identifying commercially viable leads.
Cardiac Drugs: Antianginal, Vasodilators, and Antiarrhythmics
Authors: Joshi Gajanan S. , Burnett James C. , Abraham Donald J.
Published: November 2003

The development of novel drugs to replace and/or supplement existing therapeutics for treating various cardiac disorders continues to generate significant and growing interest and has evolved hand‐in‐hand with clinical research that has facilitated a better understanding of the underlying causes of cardiac disease. However, even with these new advances and treatments, heart disease remains the number one killer of men and women in the United States—it is estimated that approximately 40% of Americans (∼60 million between the ages of 40–70) have some form of this disease. Since the later half of the 20th century, finding safe and effective means for treating increasing incidences of heart disease worldwide has been at the forefront of the medical community's consciousness. This concern has sparked the discovery and development of a wide range of cardiac drugs, which continue to account for a large portion of sales in the pharmaceutical industry. A constant flow of new cardiovascular drugs, with greater potency and improved safety profiles, will continue to provide physicians with the means for treating cardiovascular diseases in the future. Importantly, the first draft of the human genome is a turning point in the search for new medications that will address the causes, versus the symptoms, of many human ailments—including cardiovascular diseases. This chapter is designed to serve as a general reference and reviews past treatments, significant new developments, and future trends in the development of antianginal, vasodilating, and antiarrhythmic therapeutics.
Diuretic and Uricosuric Agents
Authors: Fink Cynthia A. , McKenna Jeffrey M. , Werner Lincoln H.
Published: November 2003

Herein is presented the development and therapeutic use of diuretic agents, a topic that constitutes one of the most significant advances in medicine made during the twentieth century. Diuretics are among the most frequently prescribed therapeutic agents for the treatment of edema, hypertension, and congestive heart failure and they act primarily by inhibiting the reabsorption of sodium ions from the renal tubules in the kidney. Recent advances in renal and ion‐transport research have led to a more precise understanding of the cellular mechanisms of actions of the various classes of diuretic agents. This understanding has aided the design of newer and more effective agents. Today diuretics are grouped as loop, potassium‐sparing, thiazide, or osmotic diuretics and include compounds that have combined diuretic and uricosuric properties. Uricosuric agents increase the excretion of uric acid, a principal product of purine metabolism; and because hyperuricemia is an adverse effect sometimes observed with diuretic treatment, arising from decreased extracellular volume and increased urate reabsorption, this combined property is advantageous. However, given that diuretics themselv are convenient, inexpensive, and generally are well tolerated, they will probably continue to play a role in the treatment of hypertension.
Antihyperlipidemic Agents
Authors: Sierra Michael L.
Published: November 2003

Coronary heart disease (CHD) is the leading cause of morbidity and mortality in developed nations and atherosclerotic cardiovascular disease accounts for approximately half of all deaths attributed to CHD. Dyslipidemia, including hypercholesterolemia, hypertriglyceridemia, and hypoalphalipoproteinemia, is a major risk factor for CHD. Clinical studies have demonstrated the link between elevated serum cholesterol and coronary disease. Randomized controlled studies investigating the benefit of therapies that lower serum levels of low density lipoprotein cholesterol have demonstrated improvements in coronary morbidity and mortality in patients with or without diagnosed CHD. Furthermore, data are accumulating based on the VA‐HIT trial and several other ongoing trials with fibrates that the treatment of high serum triglycerides and low concentrations of high density lipoprotein cholesterol can also lead to improvements in coronary morbidity and mortality. This review discusses the development of the HMG‐CoA reductase inhibitors and how they have, thanks to their excellent efficacy and good safety profile, revolutionized the clinical management of hypercholesterolemia. Other treatments such as fibrates, bile acid sequestrants, cholesterol absorption inhibitors, and nicotinic acid derivatives as well as new emerging treatments are also discussed.
Oxygen Delivery by Allosteric Effectors of Hemoglobin, Blood Substitutes, and Plasma Expanders
Authors: Campanini Barbara , Bruno Stefano , Raboni Samanta , Mozzarelli Andrea
Published: November 2003

The blood is a complex body fluid containing a large variety of cells and molecules serving vital functions. In particular, hemoglobin, contained in the red cells, loads, carries, and delivers oxygen and carbon dioxide in the circulation. In the last 30 years intense efforts have been made (1) to develop allosteric effectors of hemoglobin that affect oxygen affinity to treat diseases such as sickle‐cell anemia, ischemia, hypoxia, and to improve the efficiency of radio‐ and chemotherapy; (2) to obtain blood substitutes based either on organic molecules that solubilize oxygen or on genetically and/or chemically modified hemoglobins; and (3) to formulate solutions that maintain the blood volume and oncotic pressure in surgery and hemorrhagic events. In spite of the pharmacological relevance of these molecules, only plasma expanders are already available on the U.S. market. This is an indication of the difficulties in mimicking the multifaceted roles of hemoglobin.
Insulin and Hypoglycemic Agents
Authors: Sleevi Mark
Published: November 2003

This chapter focuses on insulin and hypoglycemic agents. It surveys the drugs available for treatment of hyperglycemia associated with diabetes mellitus: insulin and its analogs, insulinotropic agents, insulin‐sensitizing agents, and α‐glucosidase inhibitors.
Chemokine and Cytokine Modulators
Authors: Fuentes Maria Elena , Mirzadegan Tara , Wilhelm Robert S.
Published: November 2003

The ability to respond to exogenous stimuli is a key characteristic in the survival of multicellular organisms. Both chemokines and cytokines participate in this process with different mechanisms. Chemokines are mostly involved in chemoattraction of different cell types to inflamed tissues. Cytokines, on the other hand, regulate gene expression in a wide variety of cell types. Both types of molecules are mostly inducible, although some participate in homeostatic processes. Chemokines exert their action through the activation of seven‐transmembrane spanning receptors also called G‐protein‐coupled receptors. Cytokine receptors are usually formed of two or more single‐spanning membrane subunits and phosphorylation is crucial in the signaling cascade. Because of the nature of the receptors, significant information is available regarding attempts to block chemokine receptors with small molecule antagonists. The situation is quite different for cytokine receptors, in which most of the antagonists described so far are either receptor antibodies or soluble receptors. In this chapter we summarize data available for both families.
COX‐2 Inhibitors and Leukotriene Modulators
Authors: Bell Randy L. , Harris Richard R. , Stewart Andrew O.
Published: November 2003

Agents that modulate the effects of eicosanoids have proved to be important therapeutics. In the early 1990s a number of agents that modulate the actions or synthesis of leukotrienes were optimized and tested in asthma. This major effort provided for the approval of two CYSLT1 antagonists, montelukast and zafirlukast; and one 5‐lipoxygenase inhibitor, zileuton, which proved effective in the treatment of asthma. More recently, the breakthrough discovery of a second cyclooxygenase isozyme, COX‐2, provided the impetus for the discovery of selective COX‐2 agents. These agents, which include celecoxib, rofecoxib, and valdecoxib, have been shown to have significant anti‐inflammatory and analgesic effects while being gastric sparing, in contrast to nonselective cyclooxygenase inhibitors commonly referred to as NSAIDs. The gastric‐sparing properties of these agents and others currently in development should open new therapeutic modalities. One of the most exciting of these is in the prevention and treatment of cancer.
Agents Acting on Prostanoid Receptors
Authors: Jenkins David W. , Humphrey Patrick P.A. , Coleman Robert A.
Published: November 2003

The prostaglandins and thromboxanes comprise a family of C
20
fatty acids, known as the prostanoids. They are primarily synthesized from arachidonic acid and exert a multitude of physiological and pathophysiological actions through the activation of membrane‐bound receptors. The current scheme of prostanoid receptor classification proposes receptors for each of the naturally occurring prostanoids and was originally based on comparisons of prostanoid receptor agonist and antagonist potencies in functional preparations. This scheme has been confirmed and expanded by the use of molecular techniques, which have led to the cloning of the known prostanoid receptors and also the discovery of a number of prostanoid receptor subtypes and isoforms. Many compounds with varying potencies and selectivities at the known prostanoid receptors have been synthesized, although few have proved highly valuable in the clinic. The use of prostanoids in clinical practice has been largely limited to those occurring naturally, where they are used predominantly as abortifacients and in the induction of labor. Several synthetic analogs have also been used for these and other purposes, including the treatment of gastric ulcers and glaucoma. Hopefully, the next few years will lead to the further discovery of new prostanoid receptor ligands that will become successful medicines.
Vitamins
Authors: Block John H.
Published: November 2003

Vitamins are essential components of the diet that are required in small amounts. Biochemical processes cannot operate without them. Vitamins have a variety of functions and some have dual roles. Vitamin A (retinol) is both a regulator of cell division and a structural component of the visual pigment rhodopsin. Vitamin D (cholecalciferol) is a hormonal regulator of calcium transport and cell division. Vitamin K is a coenzyme for carboxylation of glutamic acid. Vitamin E (α‐tocopherol) is a lipid‐soluble antioxidant. Thiamine (vitamin B1) is a coenzyme for decarboxylation of α‐keto acids and transketolase reactions in carbohydrate metabolism. Riboflavin (vitamin B2) is the active portion of the coenzymes FMN and FAD. Niacin and niacinamide are the active portions of the coenzymes NAD and NADP. The pyridoxine group (vitamin B6), as pyridoxal phosphate (PLP), is the coenzyme for amino acid metabolism, including transaminations and decarboxylations. Pantothenic acid is a structural component of coenzyme A. Biotin is a coenzyme for four carboxylation reactions. Folic acid, as tetrahydrofolate, is a coenzyme for one‐carbon metabolism. Vitamin B12(cobalamin), with folic acid, is required for regeneration of methionine and, singly, is the coenzyme required for the rearrangement of methylmalonyl CoA. Ascorbic acid is a general free‐radical scavenger and required for at least eight biochemical reactions requiring oxidations.
Lifestyle and Over‐the‐Counter Drugs
Authors: Abu‐Izza Khawla , Li Vincent , Parr Graham
Published: November 2003

This chapter attempts to show how lifestyle drugs and over‐the counter (OTC) drugs relate to each other and the challenges that they face. It also traces the history of OTC drugs and regulations, shows how the OTC Review process works, and shows how the United States, Europe, and Japan classify OTC drugs. It briefly explains the three major criteria for Rx‐to‐OTC switch—safety, labeling, and effectiveness. The chapter also provides an overview and a generalized definition of lifestyle drugs. Four examples of lifestyle drugs are provided: hair growth drugs, smoking cessation drugs, sexual disorder drugs, and sunscreens. The selected examples cover both prescription only and OTC lifestyle drugs. The chapter ends with a look into the future for OTC and lifestyle drugs.
Microarrays and Gene Expression Profiling Applied to Drug Research
Authors: Windle Brad , Guiseppi‐Elie Anthony
Published: November 2003

DNA microarray technology combines the recent advances in genome sequence availability with high‐speed robotics. Arrays of gene sequences representing entire genomes, including the human genome, have been produced, allowing the analysis of expression for all genes in a genome in a single experiment. Global gene expression profiles of cells are being explored in a broad range of biomedical applications, from identifying cell lineages to predicting response to therapy in patients. The basic principles of microarray fabrication and analysis are presented in this chapter. Current applications of gene expression profiling to drug development, including target identification, and mechanism of action are reviewed. Finally, the potential for new applications of this technology in drug discovery and development is discussed.
SNPs: Single Nucleotide Polymorphisms and Pharmacogenomics—Individually Designed Drug Therapy
Authors: Puckett Brian J. , Terra Steven G. , Walker Joe
Published: November 2003

Pharmacogenomics is a rapidly expanding field aimed at understanding interpatient variability in drug response through the exploration and investigation of the human genome. It is an incontrovertible fact that large interpatient variability exists in response to medications. Variation in response has existed as long as medications have been used for the prevention and treatment of disease. In many ways, the field of pharmacogenomics began serendipitously in the 1950s after seminal observations describing variability in response to medications. Examples included peripheral neuropathy from isoniazid among slow acetylator, prolonged apnea from succinylcholine caused by pseudocholinesterase deficiency, and severe hypotension from debrisoquine among cytochrome P450 (CYP) 2D6 poor metabolizers. For the next 40 years, pharmacogenetic studies focused almost exclusively on the etiologies of altered variability in pharmacokinetic responses to medications. As we entered the 1990s, pharmacogenomic studies began to include studies that examined pharmacodynamic variability in drug response. Now instead of examining only differences in drug metabolizing enzymes, scientists began to focus on genes that encode drug transporters, drug targets, and ion channels. The ultimate goal of pharmacogenomics is to be able to accurately predict, based on an individual's genomic information, which medications will provide the greatest benefit with the least harm, thus transforming medicine into an era of personalized therapeutics. This chapter provides a review of pharmacogenomics and how single nucleotide polymorphisms may impact pharmacotherapy and drug discovery. The chapter further explores the abundant recent literature as well as provides insight into some of the issues, limitations, and ethical considerations of pharmacogenomics.
Plasmid DNA–Mediated Gene Therapy
Authors: Banerjee Rajkumar , Huang Leaf
Published: November 2003

Non‐viral gene delivery has earned a special position in gene therapy because of its less immunogenic and less toxic effect than the viral counter part. One of the methods is direct injection of naked DNA to the organs of interest. Plasmid DNA (pDNA) that carry recombinant genes of interest are used for introducing genes to cells and organs. Various physical methods, e.g., gene gun and electroporation, increase the efficiency of the naked DNA incorporation. Lipid‐based vectors have the advantage of protecting the DNA against degradation by endogenous DNAasein vivoand can be targeted to specific cellular site in some special cases. A variety of lipid‐based systems have been designed, mostly containing cationic lipids of different structures. Second‐generation vectors containing polymers are more stable and more targetable than the first‐generation vectors. Although significant progress has been made, non‐viral vectors are still limited by their efficiency and some cytotoxicity inherited in the bacterial pDNA. Understanding mechanisms and means to overcome the cellular barriers for the DNA delivery will undoubtly promote further development of pDNA mediated gene delivery.