Comprehensive clostridial toxins Botulinum Neurotoxin and Teta- nus Toxin

edited by Lance L. Simpson, Academic Press, 2989. $89.00 (xiii + 422 pages) 1SBN 0 12 644445 5

Botulinum toxin and tetanus toxin are among the most potent bio- logical agents so far known. In spite of intensive research for decades the precise mechanisms of their actions are largely obscure. For these reasons both toxins are also two of the most fascinating naturally occurring agents.

The book Bottilinum Neurotoxin and Tetanus Toxin, edited by L. L. Simpson and written by outstand- ing scientists is an almost compre- hensive I cview on the state of-the- art of both these neu~toxins. The four parts of the book cover origin and structure, pharmacology and toxicology, immunology and assay and, finally, the clinical import- ance of both neurotoxins.

Biochemists, pharmacologists and clinicians working with clos- tridial neurotoxins will certainly appreciate learning more about the organisms that produce the toxins, and about the regulation of toxin production by phages or plasmids. The recent progress in the eluci- dation of the structure of clostridial toxins, the processing of the toxins in bacteria and the delineation of the relationship between botulinurn and tetanus toxins are further topics covered in Part 1.

Our knowledge of the eukary- otic receptors for neurotoxins and the mechanism of cellular entry is still very limited. The contri- butions on those topics therefore refer in a more general manner to other bacteria? toxins, e.g. diph- theria and pseudomonas toxins, the actions of which are better understood. The data available for neurotoxins are discussed against this background. Possible mech- anisms of the intracellular action of neurotoxins are extensively reviewed. The clostridial ADP- ribosylating toxins, which are dis- tinct from neurotoxins, are also described. Further topics covered in these mostly excellent chapters

are neuronal transport, electro- physiological aspects of peripheral action of tetanus toxin and the effects of the neurotoxins on iso- lated preparations (tissue slices, cell culture, broken cells and synaptosomes).

Part 3 deals witlt the immuno- logical aspects of clostridial neuro- toxins. Development, actions and effectiveness of po~yclona~ and monoclonal antibodies or vaccines are reviewed, and assays for botu- linum and tetanus toxins are de- scribed and discussed.

The clinical issues of the clos- tridial neurotoxins are outlined in

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the last part of the book, Those. include animal models of botulism and tetanus, the clinical features of both diseases in humans and their treatment, and, finally, the rather novel aspect of clostridiaI toxins ac, therapeutic agents in blepharo- spasm, torticollis and other dystonias.

In summary, this book gives a wide panorama of clostridial ncurotoxin research. It is easy to read and therefore an excellent introduction for advanced student,3 and researchers. It will be a useful source of information and a refer- ence work for people working in this field.

KLAUS AKTORIES

Beyond the mystique of pharmacokinetics Human Drug Kinetics: A Course of Simulated Experiments

by L. Saunders, D. Ingram and S. H. D. Jackson, IRL Press, 2989. f300.00 (book and software) (261 pages) lSBN 0 29 96 3039 9

l’harmacokinetics is a quantitative subject and undergraduate students from biology and medi- cine are generally horrified when they first come across it. Conse- q:?ently it is not an easy subject to teach to such an audience. It re- quires a certain degree of skill and dedication to get students beyond the mathematical ‘mystique’ sur- rounding pharmacokinetics and onto the conceptual basis of the subject. Any teaching aid that fa- cilitates this process is therefore to be welcomed.

Human Drug Kinetics: A Course of Simulated Experiments is the ccm- panion book to a software package called MuPharm which runs on an IBM PC or compatible. MuPharm is a simulation program which has been developed over a number of years from the authors’ experience with the MacDope package. A two- compartment model is used to simulate the plasma concentra- tion- and urinary excretion-time profiles of a drug in a human subject. The user can select the route of administration (i.v. bolus, i.v. infusion, oral, oral sustained release or intramuscular), the

mode of administration (single dose or multiple dose), drug- related factors (such as dose, thera- peutic window, rate constants) and subject-related factors (such as height, weight, age, hepatic and renal function). Both tabular and graphical (Cartesian and semi-log) outputs are available. A pictorial simulation of drug levels in the various compartments of the model (plasma, tissues, metab- olites, urine) is also provided.

The program is menu driven and comes with a database containing 20 common drugs. Additional drugs can readily be added to the database and subject factors may be chansed either interactively or off-line. The textbook explains the use of the program by way of examples which increase in com- plexity. The topics covered include the kinetics following an i.v. bolus, an oral dose and multiple dosing, capacity-limited metabolism and the effect of disease on pharma- cokinetic parameters. Additional study problems (with answers) are provided to allow the student to gain further experience with the program, and there is a brief intro- duction to pha~acokine~cs at both phenomenologicat and math- ematical levels. Technical details of the simulation model are given in appendices.

The authors have clearly spent a lot of time developing the software and it is of high standard. I found it easy to use and free of bugs. The flow of the examples in the book is