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Gen. Pharmac. Vol. 13, pp. 531 to 534, 1982 Pergamon Press Ltd. Printed in Great Britain BOOK REVIEWS Progress in Enzyme and Ion Selective Electrodes--Edited by D. W. Lubbers, H. Acker, R. P. Buck, G. Eisenman, M. Kessler and W. Simon. 239pp. 1981. Spriuger-Verlag, Berlin. US$34.30. DM 58. This is the proceedings of a meeting on the theory and application of ion selective electrodes in Physiology and Medicine held in Dortmund in 1980. There are good accounts how to manufacture different types of electrodes. It is relatively easy to get extracellular electrodes that can measure Na +, K +, Li ÷, H +, NH~, Ca 2+, Mg 2+, 02, CI', HCO~. It is also possible to get intracellular electrodes that will measure these ions. Recent developments have been the use of ion exchange liquids in the electrodes, and the use of enzymes such as urease adsorbed onto a stationary phase in the electrodes. If urease is present in the electrode it enables urea to be measured by converting urea to am- monia and the ammonium ion is measured. Similarly lac- tate oxidase in the electrode will enable lactate to be measured. The main problems are selectivity of the elec- trode, speed of response and stability of the measuring systems. This volume describes the extent to which these problems have been overcome and the developments that should be possible in the near future. Biosynthesis of lsoprenoid Compounds--Edited by J. W. Porter and S. L. Spurgeon. Volume 1, 558 pp. 1981. John Wiley, New York. £44. This, the first of two volumes, deals with the historical background to isoprenoid biosynthesis, the formation of the isopentenoid unit, the biosynthesis of monoterpenes, sesquipterpenes, diterpenes and triterpenes (sterols). Im- portant monoterpenes are found in essential plant oils, limonene, terpinolene, cineol, in camphor, pepperment, pinene, and thujone. The isomerization of farnesyl pyro- phosphate to nerolidyl pyrophosphate is discussed in re- lation to the biosynthesis of sesquiterpenes. The synthesis of squalene, plant steroids and other triter- penoids gives further insight into the plant and animals' mastery of complex chemical syntheses. The second volume will deal with the carotenoids, ubiquinone, doli- chols, rubber, vitamin A, abscisic acid, ecdysteroids and insect juvenile hormone. Electrophoresis 81--Edited by R. C. Allen and P. Arnaud. 1021 pp. 1981. Walter de Gruyter, Berlin. DM 245. This volume contains 105 of the presentations made at the Third International Congress on Electrophoresis held in Charleston, South Carolina in 1981. The chapters are arranged in 4 sections. Section l--Theory and Methods. Section lI--High Resolution Two Dimensional Electro- phoresis. Section Ill--Biomedical and Biological Appli- cation. Section IV Isotachophoresis and Free Flow Elec- trophoresis. The book is well illustrated with graphs, photographs and colour pictures of electrophoretograms. In most cases the details of the methods are fully given so that there is a good chance of the reader being able to reproduce the technique. The volume is an excellent up-to-date account of the state of present day electrophoretic separation and those workers interested in improving their technique would do well to consult this volume. Composition and Function of Cell Membranes. Application to the Pathophysiology of Muscle Diseases--Edited by Stewart Wolf and Allen K. Murray. Advances in Experi- mental Medicine and Biology. Volume 140. 287 pp. 1981. Plenum Press, New York. US$35. This symposium with 23 contributors describes in detail the present concepts of the structure of muscle membrane and the changes that are seen in membranes of RBC, cul- tured fihroblasts and muscles in diseased conditions such as Duchenne dystrophy. There is some indication that RBC from dystrophic patients can show differences in the spin label of fatty acid labelled in the 5th position using electron proton resonance. The RBC from normal patients had a more intense EPR signal than those from Duchenne patients but the spectral intensity of the two samples kept at 37 ° became the same. There is evidence that Duchenne RBC membrane lipids are in a more rigid state than those of normal patients. The muscle creatine phosphokinase (CPK) leaks through the Duchenne muscle membrane into the serum. EM studies showed that there were often defects in the muscle fibre plasmat membrane that would allow increase of extracellular fluid into the abnormal dystrophic muscle fibres. Penicillamine will reduce the symptoms of avian muscu- lar dystrophy by (1) maintenance of intracellular levels of reduced sulfhydryl compounds. (2) Protection of SH enzymes and membrane proteins. (3) Removal of deleter- ious oxydising agents, free radicals, and peroxides, and (4) solubilise collagen thereby relieving contractures. As with many symposia the reports are presented in an edited form but with much of the atmosphere of the free discussion still present. Though this is of value, and the editors have inserted a general summary at the end of each chapter, it would have helped if this summary was more detailed with specific examples. Basic and Clinical Aspects of Immunity to Insulin--Edited by K. Keck and P. Erb. 442 pp. 1981. Waiter de Gruyter, Berlin. DM 140. The injection of insulin derived from pigs, beef, or sheep, into a different host often leads to the production of anti- bodies to the foreign insulin. This, together with the im- munological aspects of insulin resistance, and the autoim- mune aspects of juvenile diabetes has led to careful study of the production of antibodies to insulin. The mouse, (much used in experimental studies of insulin antibodies) has two insulins which differ from each other by two amino acids in the B chain. The five naturally occuring insulins and the 47 chemically synthesised insulin ana- logues provide good chemical models for stimulating anti- bodies and studying their specificity. The immune response genes 0r-genes) are inherited dominantly. They are located within the H-2 locus. The A chain loop is antigenic whilst the eight amino acids around the histidine at the 10th pos- ition of the B chain cause the proliferative response of T cells. Active immunisation of guinea pigs against insulin can lead to marked destruction of the islets of Langerhans (insulitis) 4 weeks after immunization. Diabetics on insulin treatment often develop immune reactions, i.e. skin rash, urticaria, inflammatory reactions of subcutaneous fat tissue, insulin resistance. There are some indications that diabetic retinopathy may be related to the development of 531

Basic and clinical aspects of immunity to insulin

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Page 1: Basic and clinical aspects of immunity to insulin

Gen. Pharmac. Vol. 13, pp. 531 to 534, 1982 Pergamon Press Ltd. Printed in Great Britain

B O O K REVIEWS

Progress in Enzyme and Ion Selective Electrodes--Edited by D. W. Lubbers, H. Acker, R. P. Buck, G. Eisenman, M. Kessler and W. Simon. 239pp. 1981. Spriuger-Verlag, Berlin. US$34.30. DM 58.

This is the proceedings of a meeting on the theory and application of ion selective electrodes in Physiology and Medicine held in Dor tmund in 1980. There are good accounts how to manufacture different types of electrodes. It is relatively easy to get extracellular electrodes that can measure Na +, K +, Li ÷, H +, NH~, Ca 2+, Mg 2+, 02, CI', HCO~. It is also possible to get intracellular electrodes that will measure these ions. Recent developments have been the use of ion exchange liquids in the electrodes, and the use of enzymes such as urease adsorbed onto a stationary phase in the electrodes. If urease is present in the electrode it enables urea to be measured by converting urea to am- monia and the a m m o n i u m ion is measured. Similarly lac- tate oxidase in the electrode will enable lactate to be measured. The main problems are selectivity of the elec- trode, speed of response and stability of the measuring systems. This volume describes the extent to which these problems have been overcome and the developments that should be possible in the near future.

Biosynthesis of lsoprenoid Compounds--Edited by J. W. Porter and S. L. Spurgeon. Volume 1, 558 pp. 1981. John Wiley, New York. £44.

This, the first of two volumes, deals with the historical background to isoprenoid biosynthesis, the formation of the isopentenoid unit, the biosynthesis of monoterpenes, sesquipterpenes, diterpenes and triterpenes (sterols). Im- portant monoterpenes are found in essential plant oils, limonene, terpinolene, cineol, in camphor, pepperment, pinene, and thujone. The isomerization of farnesyl pyro- phosphate to nerolidyl pyrophosphate is discussed in re- lation to the biosynthesis of sesquiterpenes.

The synthesis of squalene, plant steroids and other triter- penoids gives further insight into the plant and animals ' mastery of complex chemical syntheses. The second volume will deal with the carotenoids, ubiquinone, doli- chols, rubber, vitamin A, abscisic acid, ecdysteroids and insect juvenile hormone.

Electrophoresis 81--Edi ted by R. C. Allen and P. Arnaud. 1021 pp. 1981. Walter de Gruyter, Berlin. DM 245.

This volume contains 105 of the presentations made at the Third International Congress on Electrophoresis held in Charleston, South Carolina in 1981. The chapters are arranged in 4 sections. Section l - - T h e o r y and Methods. Section l I - - H i g h Resolution Two Dimensional Electro- phoresis. Section I l l - -Biomedical and Biological Appli- cation. Section IV Isotachophoresis and Free Flow Elec- trophoresis.

The book is well illustrated with graphs, photographs and colour pictures of electrophoretograms. In most cases the details of the methods are fully given so that there is a good chance of the reader being able to reproduce the technique. The volume is an excellent up-to-date account of the state of present day electrophoretic separation and those workers interested in improving their technique would do well to consult this volume.

Composition and Function of Cell Membranes. Application to the Pathophysiology of Muscle Diseases--Edited by Stewart Wolf and Allen K. Murray. Advances in Experi- mental Medicine and Biology. Volume 140. 287 pp. 1981. Plenum Press, New York. US$35.

This symposium with 23 contributors describes in detail the present concepts of the structure of muscle membrane and the changes that are seen in membranes of RBC, cul- tured fihroblasts and muscles in diseased conditions such as Duchenne dystrophy. There is some indication that RBC from dystrophic patients can show differences in the spin label of fatty acid labelled in the 5th position using electron proton resonance. The RBC from normal patients had a more intense EPR signal than those from Duchenne patients but the spectral intensity of the two samples kept at 37 ° became the same. There is evidence that Duchenne RBC membrane lipids are in a more rigid state than those of normal patients.

The muscle creatine phosphokinase (CPK) leaks through the Duchenne muscle membrane into the serum. EM studies showed that there were often defects in the muscle fibre plasmat membrane that would allow increase of extracellular fluid into the abnormal dystrophic muscle fibres.

Penicillamine will reduce the symptoms of avian muscu- lar dystrophy by (1) maintenance of intracellular levels of reduced sulfhydryl compounds. (2) Protection of SH enzymes and membrane proteins. (3) Removal of deleter- ious oxydising agents, free radicals, and peroxides, and (4) solubilise collagen thereby relieving contractures.

As with many symposia the reports are presented in an edited form but with much of the atmosphere of the free discussion still present. Though this is of value, and the editors have inserted a general summary at the end of each chapter, it would have helped if this summary was more detailed with specific examples.

Basic and Clinical Aspects of Immunity to Insulin--Edited by K. Keck and P. Erb. 442 pp. 1981. Waiter de Gruyter, Berlin. DM 140.

The injection of insulin derived from pigs, beef, or sheep, into a different host often leads to the production of anti- bodies to the foreign insulin. This, together with the im- munological aspects of insulin resistance, and the autoim- mune aspects of juvenile diabetes has led to careful study of the production of antibodies to insulin. The mouse, (much used in experimental studies of insulin antibodies) has two insulins which differ from each other by two amino acids in the B chain. The five naturally occuring insulins and the 47 chemically synthesised insulin ana- logues provide good chemical models for st imulating anti- bodies and studying their specificity. The immune response genes 0r-genes) are inherited dominantly. They are located within the H-2 locus. The A chain loop is antigenic whilst the eight amino acids around the histidine at the 10th pos- ition of the B chain cause the proliferative response of T cells. Active immunisat ion of guinea pigs against insulin can lead to marked destruction of the islets of Langerhans (insulitis) 4 weeks after immunization. Diabetics on insulin treatment often develop immune reactions, i.e. skin rash, urticaria, inflammatory reactions of subcutaneous fat tissue, insulin resistance. There are some indications that diabetic retinopathy may be related to the development of

531

Page 2: Basic and clinical aspects of immunity to insulin

532 Book Reviews

antibodies. The development of biochemical engineering production of human insulin for injection may reduce many of these effects in man. Nevertheless insulin provides an excellent model for the study of the production and control of antibody formation and this volume with its 40 contributors gives a clear account of the subject and its problems.

Cardiac Glycosides Edited by K. Greeff. Handbook of Experimental Pharmacology. Volume 56. Part 1. Experi- mental Pharmacology of Cardiac Glycosides. 682pp. DM 390. Part 2. Pharmacokinet ics and Clinical Pharma- cology of Cardiac Glycosides. 394pp. DM248. 1981. Springer-Verlag. Berlin.

Two earlier contributions to this Handbook have been on Cardiac glycosides. One was by Straub in 1924 and the other by Lendle in 1935.

In the intervening years there have been considerable advances in biochemical and pharmacological measuring techniques so that by these and rad io immune assay, it is possible to get a much better understanding of the levels and life of the administered cardiac glycosides.

Volume 1 starts with a consideration of the history, chemistry and structure-activity relationship of the cardiac glycosides, starting back in 1600B.C. when the healing effects of the sea onion are described in the Egyptian Ebers Papyrus. This is followed by evaluation of the chemical and biological methods for the assay of the drugs, and the evaluation of their action on organs preparations, mem- brane receptors and enzymes.

Volume 2 describes the pharmacokinetics of Digitoxin, Digoxin, Strophanthidins, Proscillaridin; the intestinal absorption and secretion and bioavailability of the glyco- sides. The section on Clinical Pharmacology describes the effects of cardiac glycosides on the failing and non-failing heart, their side effects, interactions with other drugs, and the effect of disease on their pharmacokinetics. The high s tandard of these two volumes is what readers have come to expect from this important series of Handbooks of Ex- perimental Pharmacology. They provide an excellent sur- vey of the literature and a source foff~background infor- mation, current ideas and probable new developments for the future.

Hormone Antagonists--Edited by M. K. Agarwal. 732 pp. 1982. W. de Gruyter, Berlin. DM 180.

Considerable clinical and scientific interest in the mech- anisms of hormone action has led to the development of hormone antagonists.

In the main these have been directed against steroid hor- mones and against peptide hormones, and there are also well known antagonists such as nalaxone and antihis- tamines that are considered in this volume. Potential anti- estrogens are tamoxifen and nafodixine, cyproterone is an antagonist against androgens; spirinolactone is an anti mineralocorticoids. On the peptide front the workers are interested in developing antagonists to the Renin-Angio- tensin system, the development of anti-prolactin and anti- growth hormone receptor antibodies; and gastrin antagon- ists. The basic chemistry and biochemistry behind the research for more effective hormone antagonists is fully described in this volume and the major research groups have contributed.

The development of selective hormone antagonists is a powerful clinical and pharmacological research tool that also has important practical applications in Medicine. These discoveries are fully described in the present volume.

Glutamate Transmitter in the Central Nervous System- Edited by P. J. Roberts, J. Storm-Mathisen and G. A. R. Johnston. 226 pp. 1981. John Wiley, New York. £15.50.

Over the last 10 years the case has developed for the amino acid, glutamate as a possible excitatory transmitter on the motoneurone, the hippocampal pyramidal cells, cor- tico-striatal fibres, and the granular cells of the cerebellar cortex. Evidence is presented in this volume in terms of the ionotophoretic application of glutamate and its effect on nerve membrane potential and action potentials, the selec- tive uptake of glutamate; the binding of labelled glutamate to specific sites, differential binding of ligands: autoradio- graphic and microchemical localization of high affinity uptake and the specific release of glutamate following stimulation.

There are 14 contributors to this volume and they present the case for glutamate in a well argued manner. The main problem is that there is at present no highly specific antagonist that will block glutamate action and which can differentiate glutamate from aspartate or even ACh.

It is still possible that the active transmitter could be "like-glutamate" but not actually glutamate.

Taurine in Nutrition and Neurology--Edited by R. J. Hux- table and H. Pasantes-Morales. Advances in Experimental Medicine and Biology. Volume 139. 531 pp. 1982. Plenum Press, New York. US$59.50.

This volume is the published proceeding of a meeting held in Mexico in 1980. There are 7 major sections. Physio- chemical Properties of Taurine, Taurine in Nutrit ion and Development. Transport and Metabolism of Taurine. Taurine and the Heart. Neurochemistry of Taurine. Neuro- pharmacology of Taurine. Discussions on Taurine.

Taurine is more acidic than B-alanine. It can form direct complexes with calcium and zinc. Taurine concentrations are high in the developing brain and then fall off. H u m a n s have little ability to synthesise taurine and obtain it as infants from milk. At the beginning of lactation it is the most abundant amino acid in milk comprising 20~,~i of the total free amino acids. At the weaning stages rats obtain more of their taurine by endogenous synthesis than from milk. Guinea pigs can synthesise their taurine requirements whilst cats have little biosynthetic ability for taurine. Cats maintained on a taurine deficient diet show retinal de- generation.

Cats depend on taurine in their diet. This taurine has to be transported into cells. Deficiencies in taurine across membranes can be found in some cases of epilepsy, Fried- reich's ataxia and genetic myocardiopathy. Taurine is the most abundant free amino acid in the heart. In the rat heart it is four times higher than the concentration of free glutamate. It stabilises the membrane potential, modulates the effect of calcium, has a positive ionotropic effect, and if given orally can ameliorate the effects of genetic cardio- myopathy in hamsters.

It is doubtful if taurine is a neurotransmitter . It is more likely a modulator. In the retina whilst light/dark rapidly affects the GABA levels it takes several weeks to get changes in taurine levels. There are indications that a pre- cursor cysteine sulfinic acid (CSA) could also have modu- lator properties (it's release is calcium modulated and potassium stimulated: it stimulates formation of cAMP: it is taken up by specific acidic amino acid transport system). Depolarization of nerves can lead to release of GABA but not taurine. No specific receptors for taurine have been found in the brain. The antagonists of taurine are non- specific (strychnine and bicuculline). The majority of bind- ing sites are sodium dependent.

The volume with its 30 contributors provides an interest-