- Email: [email protected]
Knowing the system
R 45 MacKenzie, W. M., Hoskin, D. W. and Blay, J. (1994) Cancer Res. 54, 3521–3526 46 Fozard, J. R., Pfannkuche, H. J. and Schuurman, H. J. (1996) Eur. J. Pharmacol. 298, 293–297
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47 Shepherd, R. K., Linden, J. and Duling, B. R. (1996) Circ. Res. 78, 627–634 48 Auchampach, J. A. et al. (1997) Circ. Res. 80, 800–809 49 Liang, B. T. and Jacobson, K. A. Proc. Natl. Acad. Sci. U. S. A. (in press)
Chemical names CGS15943: 9-chloro-2-(2-furyl)[1,2,4]triazolo[1,5-c] quinazolin-5-amine
MRS1191: 3-ethyl 5-benzyl 2-methyl-6-phenyl-4-phenylethynyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate
L249313: 6-carboxymethyl-5,9-dihydro-9-methyl-2-phenyl[1,2,4]-triazolo[5,1-a][2,7]naphthyridine
MRS1220: 9-chloro-2-(2-furyl)-5-phenylacetylamino [1,2,4]triazolo[1,5-c]quinazoline
L268605: 3-(4-methoxyphenyl)-5-amino-7-oxothiazolo[3,2]pyrimidine
MRS1334: 3-ethyl 5-(4-nitrobenzyl) 2-methyl-6-phenyl-4phenylethynyl-1,4-(±)-dihydropyridine-3,5dicarboxylate
MRS1067: 3,6-dichloro-2′-(isopropoxy)-4’-methylflavone
B Knowing the system The Kinin System edited by Stephen G. Farmer Academic Press, 1997. £65.00 (349 pages) ISBN 0 12 249340
Other than several excellent review articles and kinin conference proceedings, a comprehensive textbook summarizing recent developments in kallikrein-kinin research has not been published since the Handbook of Experimental Pharmacology Supplement in 1979. Stephen Farmer has done an excellent job in compiling this volume, entitled The Kinin System, of The Handbook of Immunopharmacology, one of a series of texts that are being produced to reflect three major themes: (1) cell types and inflammatory mediators; (2) organ systems and their diseases; and (3) drugs used to treat inflammation and diseases of the immune system. The kininogen-kallikrein-kinin-kininase system has had a major impact on the first two and the third is already an important feature of clinical medicine, not only regarding the use of angiotensin converting
enzyme (ACE, kininase II) inhibitors for the treatment of hypertension and reperfusion ischaemia injury of the myocardium, but also with second-generation peptide-based bradykinin receptor antagonists that have undergone clinical trials for the treatment of diseases such as asthma, rhinitis and head trauma. Each chapter is written by an expert in his or her respective field, and the volume encompasses almost every area in which the kininogenkallikrein-kinin-kininase system is involved in physiology and pathophysiology. These areas are as diverse and apparently as unrelated as salt and water metabolism, thrombosis and haemostasis, gastrointestinal and urinary tract function, cardiac function, bone metabolism, angiogenesis, and growth factor function, in addition to the more obvious targets of inflammation and pain. All the molecular probes and genetic approaches available are now being applied to all areas of the kininogen-kallikrein-kinin-kininase system. Recent developments in the immuno- and molecular pharmacology of bradykinin receptors have clearly identified subtype and species variants and these are extensively described in an excellent series of chapters. Together with the recently targeted disruption of the
O
O
K
S
bradykinin B2 receptor researchers now have available appropriate tools that will be invaluable for a greater understanding of the functional roles of these receptors. This book also contains a description of significant advances in kininogen research, which highlight the multi-functional roles of these proteins in relation to the contact system, platelets, endothelial cells and leukocytes, the implications of which are far more widespread than their traditional role as substrates for kinin generation. This is clearly a fertile area for future research in an exciting and evolving field of vascular biology that has tremendous therapeutic potential. The book covers most of the traditional areas of interest with respect to physiological roles, pathological functions and areas of therapeutic potential, particularly with respect to B2 and B1 receptor antagonists and alternative approaches to bradykinin potentiation other than ACE inhibitors. However, this book is particularly pleasing and refreshing as it includes areas of research that are often given a low profile or not mentioned at all in general reviews. These include the sections dealing with the role of the kallikrein-kinin system in inflammation-induced bone metabolism, as growth and
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angiogenic factors, in CNS injury and inflammation and urinary tract pathophysiology. I found these sections particularly interesting, in addition to the section dealing with the molecular pharmacology of kinin receptors. It is clear from the book that major advances have been made in all areas of kininogenkallikrein-kinin-kininase-research and there is major interest in the development of potent and selective B2 and B1 receptor antagonists as therapeutics. However, it should not be assumed that kinins are naturally pro-inflammatory or pathological and it is apparent from some of the sections that kinins per se may have protective functions other than the now well-documented cardioprotective effects. Current knowledge of the
molecular organization, tissue-specific expression and regulation of the tissue kallikrein gene families is described with respect not only to inflammation but also to other (patho)physiological conditions in which they have been implicated. The only deficiency of note is a section dealing with kallikrein inhibitors, an area of active research both in academia and industry. The area of kininogen-kallikreinkinin-kininase research is advancing at a rapid pace, and this is reflected by three International Symposia [in Immunopharmacology (Vols 32 and 33, 1996, and Vol. 36, 1997) and Can. J. Physiol. Pharmacol., Vol. 75, 1997] published since the publication of this book, and the development of truly selective, potent and orally
active nonpeptide antagonists. However, The Handbook of Immunopharmacology provides an excellent current perspective of the kallikrein-kinin system and in particular the almost pivotal role that this system appears to play, not only as a regulator of other inflammatory mediator systems, but also in an unbelievably diverse number of physiological and pathophysiological conditions. This volume will be a useful reference source for the student and specialist alike and an excellent adjunct to the other volumes in this series edited by Clive Page. Eric T. Whalley Biogen, 14 Cambridge Center, Cambridge, MA 01845, USA.
The Trends Guide to the Internet (1997) Feeling left behind? Worried about time-wasting? This guide will lead you through those all-important first steps towards using the Internet efficiently and effectively. Written by an international panel of experts, the guide will tell you what to expect and where to find it. Articles include: • The origins of the Internet • Key terms: the jargon explained • Basic Internet facilities and how to connect • The World Wide Web • USENET: setting up and joining newsgroups • Creating your own home page • FTP: how to retrieve files from around the world • What’s new in online journals • Where to go next for help Also including a poster listing useful sites to visit. For further information concerning bulk sales, contact Thelma Reid: e-mail, [email protected]; Tel, +44 1223 311114; Fax, +44 1223 321410.
192
TiPS – May 1998 (Vol. 19)
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47 Shepherd, R. K., Linden, J. and Duling, B. R. (1996) Circ. Res. 78, 627–634 48 Auchampach, J. A. et al. (1997) Circ. Res. 80, 800–809 49 Liang, B. T. and Jacobson, K. A. Proc. Natl. Acad. Sci. U. S. A. (in press)
Chemical names CGS15943: 9-chloro-2-(2-furyl)[1,2,4]triazolo[1,5-c] quinazolin-5-amine
MRS1191: 3-ethyl 5-benzyl 2-methyl-6-phenyl-4-phenylethynyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate
L249313: 6-carboxymethyl-5,9-dihydro-9-methyl-2-phenyl[1,2,4]-triazolo[5,1-a][2,7]naphthyridine
MRS1220: 9-chloro-2-(2-furyl)-5-phenylacetylamino [1,2,4]triazolo[1,5-c]quinazoline
L268605: 3-(4-methoxyphenyl)-5-amino-7-oxothiazolo[3,2]pyrimidine
MRS1334: 3-ethyl 5-(4-nitrobenzyl) 2-methyl-6-phenyl-4phenylethynyl-1,4-(±)-dihydropyridine-3,5dicarboxylate
MRS1067: 3,6-dichloro-2′-(isopropoxy)-4’-methylflavone
B Knowing the system The Kinin System edited by Stephen G. Farmer Academic Press, 1997. £65.00 (349 pages) ISBN 0 12 249340
Other than several excellent review articles and kinin conference proceedings, a comprehensive textbook summarizing recent developments in kallikrein-kinin research has not been published since the Handbook of Experimental Pharmacology Supplement in 1979. Stephen Farmer has done an excellent job in compiling this volume, entitled The Kinin System, of The Handbook of Immunopharmacology, one of a series of texts that are being produced to reflect three major themes: (1) cell types and inflammatory mediators; (2) organ systems and their diseases; and (3) drugs used to treat inflammation and diseases of the immune system. The kininogen-kallikrein-kinin-kininase system has had a major impact on the first two and the third is already an important feature of clinical medicine, not only regarding the use of angiotensin converting
enzyme (ACE, kininase II) inhibitors for the treatment of hypertension and reperfusion ischaemia injury of the myocardium, but also with second-generation peptide-based bradykinin receptor antagonists that have undergone clinical trials for the treatment of diseases such as asthma, rhinitis and head trauma. Each chapter is written by an expert in his or her respective field, and the volume encompasses almost every area in which the kininogenkallikrein-kinin-kininase system is involved in physiology and pathophysiology. These areas are as diverse and apparently as unrelated as salt and water metabolism, thrombosis and haemostasis, gastrointestinal and urinary tract function, cardiac function, bone metabolism, angiogenesis, and growth factor function, in addition to the more obvious targets of inflammation and pain. All the molecular probes and genetic approaches available are now being applied to all areas of the kininogen-kallikrein-kinin-kininase system. Recent developments in the immuno- and molecular pharmacology of bradykinin receptors have clearly identified subtype and species variants and these are extensively described in an excellent series of chapters. Together with the recently targeted disruption of the
O
O
K
S
bradykinin B2 receptor researchers now have available appropriate tools that will be invaluable for a greater understanding of the functional roles of these receptors. This book also contains a description of significant advances in kininogen research, which highlight the multi-functional roles of these proteins in relation to the contact system, platelets, endothelial cells and leukocytes, the implications of which are far more widespread than their traditional role as substrates for kinin generation. This is clearly a fertile area for future research in an exciting and evolving field of vascular biology that has tremendous therapeutic potential. The book covers most of the traditional areas of interest with respect to physiological roles, pathological functions and areas of therapeutic potential, particularly with respect to B2 and B1 receptor antagonists and alternative approaches to bradykinin potentiation other than ACE inhibitors. However, this book is particularly pleasing and refreshing as it includes areas of research that are often given a low profile or not mentioned at all in general reviews. These include the sections dealing with the role of the kallikrein-kinin system in inflammation-induced bone metabolism, as growth and
TiPS – May 1998 (Vol. 19)
191
B
O
O
K
S
angiogenic factors, in CNS injury and inflammation and urinary tract pathophysiology. I found these sections particularly interesting, in addition to the section dealing with the molecular pharmacology of kinin receptors. It is clear from the book that major advances have been made in all areas of kininogenkallikrein-kinin-kininase-research and there is major interest in the development of potent and selective B2 and B1 receptor antagonists as therapeutics. However, it should not be assumed that kinins are naturally pro-inflammatory or pathological and it is apparent from some of the sections that kinins per se may have protective functions other than the now well-documented cardioprotective effects. Current knowledge of the
molecular organization, tissue-specific expression and regulation of the tissue kallikrein gene families is described with respect not only to inflammation but also to other (patho)physiological conditions in which they have been implicated. The only deficiency of note is a section dealing with kallikrein inhibitors, an area of active research both in academia and industry. The area of kininogen-kallikreinkinin-kininase research is advancing at a rapid pace, and this is reflected by three International Symposia [in Immunopharmacology (Vols 32 and 33, 1996, and Vol. 36, 1997) and Can. J. Physiol. Pharmacol., Vol. 75, 1997] published since the publication of this book, and the development of truly selective, potent and orally
active nonpeptide antagonists. However, The Handbook of Immunopharmacology provides an excellent current perspective of the kallikrein-kinin system and in particular the almost pivotal role that this system appears to play, not only as a regulator of other inflammatory mediator systems, but also in an unbelievably diverse number of physiological and pathophysiological conditions. This volume will be a useful reference source for the student and specialist alike and an excellent adjunct to the other volumes in this series edited by Clive Page. Eric T. Whalley Biogen, 14 Cambridge Center, Cambridge, MA 01845, USA.
The Trends Guide to the Internet (1997) Feeling left behind? Worried about time-wasting? This guide will lead you through those all-important first steps towards using the Internet efficiently and effectively. Written by an international panel of experts, the guide will tell you what to expect and where to find it. Articles include: • The origins of the Internet • Key terms: the jargon explained • Basic Internet facilities and how to connect • The World Wide Web • USENET: setting up and joining newsgroups • Creating your own home page • FTP: how to retrieve files from around the world • What’s new in online journals • Where to go next for help Also including a poster listing useful sites to visit. For further information concerning bulk sales, contact Thelma Reid: e-mail, [email protected]; Tel, +44 1223 311114; Fax, +44 1223 321410.
192
TiPS – May 1998 (Vol. 19)