Driving further the research on mammalian alkaline phosphatase structure and function, Phosphatase Modulators collects expert contributions into one “how to” manual for basic scientists interested in initiating a drug discovery effort. While this book contains the traditional method chapters and some typical reviews on the structure and known functions of phosphatases, other contributions are meant to discuss approaches and alternatives useful in making “go/no-go” decisions in high throughput screening (HTS) and lead optimization campaigns. Many chapters focus on tissue-nonspecific alkaline phosphatase (TNAP) as well as protein phosphatases. Written for the highly successful Methods in Molecular Biology series, chapters in this volume include the kind of detail and key implementation advice that promotes reproducible results. Step-by-step and practical, Phosphatase Modulators offers a path to understanding many of the facets and complexities associated with undertaking a drug discovery effort and will serve as a roadmap to initiating those efforts.

A review and discussion of new knowledge on the structure and function of mammalian alkaline phosphatases (APs) gained over the last 25 years. It covers: * The structure, regulation and expression of the AP genes * The three-dimensional structure of APs and mutagenesis work that further defined the structural/functional domains of the isozymes * The phenotypic abnormalities of the different AP knockout mice * Our current understanding of the in vivo role of the AP isozymes. The book also describes the possible use of APs as therapeutic agents and therapeutic targets and the many uses of these enzymes in clinical medicine and in biotechnology.

Phosphatases, such as TNAP are fundamental in regulating the roles of cellular, and consequently numerous body functions. TNAP is a ubiquitous enzyme with a wide spectrum of substrates and specificity. Regulation at the cellular level and the lack of TNAP activity is a lethal condition. Recent findings of a highly specific regional, laminar and subcellular localization of TNAP in the cerebral cortex indicates that in addition to its metabolic and skeletal functions, TNAP also plays a role in regulating cerebral functions, most probably cognition. In fact, TNAP disturbance could result in complex diseases such as epilepsy, developmental retardation and Alzheimer's disease. Available data suggest that, regarding brain functions, TNAP is a potentially important target of clinical research. This book aims to provide an overview of our current understanding of the functions of TNAP in the brain and on other tissues and organs.

Therapeutic enzymes exhibit fascinating features and opportunities, and represent a significant and promising subcategory of modern biopharmaceuticals for the treatment of several severe diseases. Research and drug developments efforts and the advancements in biotechnology over the past twenty years have greatly assisted the introduction of efficient and safe enzyme-based therapies for a range of both rare and common disorders. The introduction and regulatory approval of twenty different recombinant enzymes has enabled effective enzyme-replacement therapy. This volume aims to overview these therapeutic enzymes, focusing in particular on more recently approved enzymes produced by recombinant DNA technology. This volume is composed of four sections. Section 1 provides an overview of the production process and biochemical characterization of therapeutic enzymes, while Section 2 focuses upon the engineering strategies and delivery methods of therapeutic enzymes. Section 3 highlights the clinical applications of approved therapeutic enzymes, including aspects on their structure, indications and mechanisms of action. Together with information on these mechanisms, safety and immunogenicity issues and various adverse events of the recombinant enzymes used for therapy are discussed. Section 4, provides discussion on the prospective and future developments of new therapeutic enzymes. This book is aimed at academics, researchers and students undertaking advanced undergraduate/postgraduate programs in the biopharmaceutical/biotechnology area who wish to gain a comprehensive understanding of enzyme-based therapeutic molecules.

We present to our readers the proceedings of the Second International Workshop on Phosphate. A short account of the history of the effort led to the Phosphate Workshops is appro priate and can be of interest to the reader. The idea for Phosphate Workshops was born in the early days of November, 1974. One of us (S. G. M. ) suggested the thought to a group of scientists gathered for a luncheon in one of the attrac tive small restaurants in Weisbaden, Germany. The purpose of the workshop was to bring together interested scientists to discuss the newer developments and the recent advances in the field of phosphate metabolism and the other related minerals. An Organizing Committee made of Shaul G. Massry (USA), Louis V. Avioli (USA), Philippe Bordier (France), Herbert Fleisch (Switzerland), and Eduardo Slatopolsky (USA) was formed. The First Workshop was held in Paris during June 5-6, 1975 and was hosted by Dr. Philippe Bordier. Its proceeding was already published. The Second Workshop took place in Heidelberg during June 28-30, 1976 and was hosted by Dr. Eberhard Ritz. Both of these workshops were extremely successful scientific endeavors, and the need for them was demonstrated by the great interest they generated among the scientific community. The Or ganizing Committee, therefore, decided to continue with the tradi tion to hold additional Workshops annually or every other year.

Nephrology is one of the fastest growing specialties in medicine. Nevertheless, kidney disease is one of the most serious unmet health needs in many countries. To provide healthcare access with the desirable equity worldwide, the nephrology community needs to discuss this public health issue and take part in decisions for elaboration of public health policies with more justice and equity. This book brings together key current public health problems that affect kidney function and illuminates them in contributions by an international group of nephrologists and general practitioners. The chapters review current knowledge and provide guidelines to manage these conditions and decrease the disease burden. At the end, developments in the digital era and their application to kidney disease treatment are synthesized, and a broader outlook on the future of nephrology is given. Ultimately, the publication aims to gather nephrology and public health expertise from researchers from all over the world, providing a broad vision of issues that must be discussed and overcome to guarantee a better treatment for patients with kidney diseases in the world today.