Tetanus has been known from the very beginning of medical literature since it was first described by Hyppocrates of Cos in the fifth century B.C. For 24 centuries it was considered a neuro logical disease until the breakthrough of CARLE and RATIONE (1884) who demonstrated its infectious etiology. Following the establishment of purified cultures of Clostridium tetani(KITASATO 1889), FABER (1890), and TIZZONI and CATIANI (1890) demon strated that the disease is actually an intoxication caused by a proteic neurotoxin. This toxin was shown by BRUSHCHETIINI (1892) to move retroaxonally and to act at the spinal cord level. Soon thereafter VAN ERMENGEN (1897) demonstrated that botu lism is also due to intoxication with a protein toxin produced by bacteria of the genus Clostridium. These bacteria and their spores and ubiquitous, and the majority of them do not produce neurotoxins. The selective advantage of producing such potent toxin is still a matter of speculation (see Popoff, this volume). The next major advance was the discovery that tetanus neurotoxin 1 can be converted by formaldehyde treatment to a nonpathogenic but still fully immunogenic form, and that this can be used successfully as a vaccine to prevent tetanus (RAMON and DESCOMBEY 1925). Similar vaccines (toxoids) can be prepared with botulism neurotoxins (see MiDDLEBROOK and BROWN, this volume). The prevention oftetanus by vaccination (see Galatzka and Gasse, this volume) is one of the great successes of basic research coupled with an efficient public medicine service.

Botulinum Neurotoxin and Tetanus Toxin ...

Neurotoxicology is a broad and burgeoning field of research. Its growth in recent years can be related, in part, to increased interest in and concern with the fact that a growing number of anthropogenic agents with neurotoxic potential, including pesticides, lead, mercury, and the polytypic bypro ducts of combustion and industrial production, continue to be spewed into and accumulate in the environment. In addition, there is great interest in natural products, including toxins, as sources of therapeutic agents. Indeed, it is well known that many natural toxins of broadly differing structure, produced or accumulated for predatory or defensive purposes, and toxic agents, accumulated incidentally by numerous species, function to perturb nervous tissue. Components of some of these toxins have been shown to be useful therapeutic agents and/or research reagents. Unfor tunately, the environmental accumulation of some neurotoxic ants of anthropogenic ori gin, especially pesticides and metals, has resulted in incidents of human poisoning, some of epidemic proportion, and high levels of morbidity and mortality. Furthermore, an increasing incidence of neurobehavioral disorders, some with baffling symptoms, is confronting clinicians. It is not clear whether this is merely the result of increased vigi lance and/or improved diagnostics or a consequence of improved health care. In any case, the role of exposure to environmental and occupational neurotoxic ants in the etiology of these phenomena, as well as neurodegenerative diseases, is coming under increasing scrutiny and investigation.

Clostridial Diseases of Animals is the first book to focus on clostridial diseases in domestic and wild animals, offering a comprehensive reference on these common diseases. Provides a single resource for all aspects of clostridial diseases Presents current, comprehensive information with a focus on clinical relevance Covers each disease in depth, including etiology, epidemiology, clinics, gross pathology, histopathology, diagnostics, diagnostic criteria, prophylaxis, control, and treatment Written by the world-leading experts in the field of clostridial diseases in animals Offers photographs and summary tables to support the concepts discussed in the text and aid in recognition

The extremely potent substance botulinum neurotoxin (BoNT) has attracted much interest in diverse fields. Originally identified as cause for the rare but deadly disease botulism, military and terrorist intended to misuse this sophisticated molecule as biological weapon. This caused its classification as select agent category A by the Centers for Diseases Control and Prevention and the listing in the Biological and Toxin Weapons Convention. Later, the civilian use of BoNT as long acting peripheral muscle relaxant has turned this molecule into an indispensable pharmaceutical world wide with annual revenues >$1.5 billion. Also basic scientists value the botulinum neurotoxin as molecular tool for dissecting mechanisms of exocytosis. This book will cover the most recent molecular details of botulinum neurotoxin, its mechanism of action as well as its detection and application.

Clostridia is one of the largest bacterial genera with an enormous potential for biotechnical and medical applications. Despite growing scientific, medical, and industrial interest, information on basic methods, biochemical fundamentals, clinical practice, industrial applications, and novel developments remains scattered in a variety of research ar