It is our wish that readers discover the importance of polymyxin structure in relation to the mechanisms of activity, resistance and toxicity. We emphasized that reliable analytic methods for polymyxins are critical when investigating their pharmacokinetics (PK) and pharmacodynamics (PD). The complicated dose definitions and different pharmacopoeial standards have already compromised the safe use of polymyxins in patients. Therefore, informed by the latest pharmacological information, scientifically-based dosing recommendations have been proposed for intravenous polymyxins. Considering the PK/PD limitations and potential development of resistance, polymyxin combinations are encouraged; however, the current literature has not shown definite microbiological benefits, possibly because most clinical studies to date overlooked key PK/PD principles. Nephrotoxicity is the major dose-limiting factor and it is imperative to elucidate the mechanisms and develop novel approaches to minimize polymyxin-associated toxicities. In addition, the anti-endotoxin effect of polymyxins supports their clinical use to treat Gram-negative sepsis. Fortunately, the discovery of new-generation polymyxins with wider therapeutic windows has benefited from the latest achievements in polymyxin research.

Microbiology and Molecular Diagnosis in Pathology: A Comprehensive Review for Board Preparation, Certification and Clinical Practice reviews all aspects of microbiology and molecular diagnostics essential to successfully passing the American Board of Pathology exam. This review book will also serve as a first resource for residents who want to become familiar with the diagnostic aspects of microbiology and molecular methods, as well as a refresher course for practicing pathologists. Opening chapters discuss issues of laboratory management, including quality control, biosafety, regulations, and proper handling and reporting of laboratory specimens. Review chapters give a quick overview of specific clinical infections as well as different types of bacteria, viruses, fungal infections, and infections caused by parasites. Following these, coverage focuses on diagnostic tools and specific tests: media for clinical microbiology, specific stains and tests for microbial identifications, susceptibility testing and use of antimicrobial agents, tests for detecting antibodies, antigens, and microbial infections. Two final chapters offer overviews on molecular diagnostics principles and methods as well as the application of molecular diagnostics in clinical practice. - Takes a practical and easy-to-read approach to understanding microbiology at an appropriate level for both board preparation as well as a professional refresher course - Covers all important clinical information found in larger textbooks in a more succinct and easy-to-understand manner - Covers essential concepts in microbiology in such a way that residents, fellows, and clinicians understand the methods and tests without having to become specialists in the field - Offers a quick overview of specific clinical infections as well as different types of bacteria, viruses, fungal infections, and infections caused by parasites

This volume is the first-ever complete treatise on polymyxins and presents the most comprehensive and up-to-date reviews of all major research and clinical topics from chemistry, microbiology, pharmacology, clinical use, to drug discovery. All chapters were written by internationally leading researchers and clinicians in the field. It is our wish that readers discover the importance of polymyxin structure in relation to the mechanisms of activity, resistance and toxicity. We emphasized that reliable analytic methods for polymyxins are critical when investigating their pharmacokinetics (PK) and pharmacodynamics (PD). The complicated dose definitions and different pharmacopoeial standards have already compromised the safe use of polymyxins in patients. Therefore, informed by the latest pharmacological information, scientifically-based dosing recommendations have been proposed for intravenous polymyxins. Considering the PK/PD limitations and potential development of resistance, polymyxin combinations are encouraged; however, the current literature has not shown definite microbiological benefits, possibly because most clinical studies to date overlooked key PK/PD principles. Nephrotoxicity is the major dose-limiting factor and it is imperative to elucidate the mechanisms and develop novel approaches to minimize polymyxin-associated toxicities. In addition, the anti-endotoxin effect of polymyxins supports their clinical use to treat Gram-negative sepsis. Fortunately, the discovery of new-generation polymyxins with wider therapeutic windows has benefited from the latest achievements in polymyxin research. This book provides extensive pharmacological information on polymyxins to infectious diseases clinicians, pharmacists, clinical microbiologists, antimicrobial pharmacologists, and pharmaceutical scientists, and is an essential read for those who aim to develop novel polymyxins and improve their clinical use as a last-line defense against Gram-negative ‘superbugs’.

Advances in the Biosciences, Volume 82: Presynaptic Receptors and Neuronal Transporters documents the proceedings of the Official Satellite Symposium to the IUPHAR 1990 Congress held in Rouen, France on June 26-29, 1990. The first part of this book deals with the extensive and still increasing list of presynaptic release-modulating auto and heteroreceptors, emphasizing the various subtypes of presynaptic receptors that are characterized by functional studies, both in vitro and in vivo, using a number of experimental approaches. The next chapters are devoted to the molecular pharmacology of presynaptic receptors, of which can interfere with G proteins and modify the activity of adenylate cyclase, guanylate cyclase, or protein kinase C. The purification and molecular biology of transporter systems, including cloning and sequencing of the neuronal sodium-ion coupled GABA transporter are also discussed. This compilation concludes with insights on the function of presynaptic receptors and neuronal transporters both in the periphery and in the CNS, as well as their ubiquitous locations and physiological roles. This publication is a good reference for students and individuals researching on the presynaptic autoreceptors and neurotransmitters.

When Antibiotics I was published in 1967, the teleological view was held by some that" antibiotics" were substances elaborated by certain microorgan isms for the purpose of competing with other microorganisms for survival in mixed ecological environments. However, not only had J. EHRLICH and his associates shown 15 years earlier that chloramphenicol was produced by Strepto myces venezuelae in cultures of sterilized soils but not in parallel cultures of the same soils which were not sterilized, but operationally, the search for anti cancer antibiotics was actively under way (Antibiotics I reporting on numerous such substances), although the concept of antibiosis could not logically justify such undertakings. This editor hesitates to accept the use of the term "antibiotic" for anti microbial agents of non microbiological origins which is sometimes encountered, but neither does he subscribe to the view that antibiotics are in some fundamental manner different from chemotherapeutic substances of other origins. Modes and mechanisms of action of chemotherapeutic compounds are not systematic functions of their origins nor of the taxonomical position of the target organisms. Consequently, in the selection of topics for Antibiotics III (published in 1975), synthetic drugs and natural products of higher plants (alkaloids) were represented, along with antibiotics in the strict sense of the definition. We now present Antibiotics V, for whose assembly the same selection criteria were applied as for Antibiotics Ill. The aggregate length of the contributions rendered it impractical to place the entire text between the covers of one book.

This volume covers all aspects of the antibiotic discovery and development process through Phase II/III. The contributors, a group of highly experienced individuals in both academics and industry, include chapters on the need for new antibiotic compounds, strategies for screening for new antibiotics, sources of novel synthetic and natural antibiotics, discovery phases of lead development and optimization, and candidate compound nominations into development. Beyond discovery , the handbook will cover all of the studies to prepare for IND submission: Phase I (safety and dose ranging), progression to Phase II (efficacy), and Phase III (capturing desired initial indications). This book walks the reader through all aspects of the process, which has never been done before in a single reference. With the rise of antibiotic resistance and the increasing view that a crisis may be looming in infectious diseases, there are strong signs of renewed emphasis in antibiotic research. The purpose of the handbook is to offer a detailed overview of all aspects of the problem posed by antibiotic discovery and development.