Grant N. Pierce - Böcker

Diabetes and cardiovascular disease together account for the largest portion of health care spending compared to all other diseases in Western society. This work seeks to provide an understanding of the causes of diabetes and its cardiovascular complications. As this understanding becomes more widely appreciated, it may serve as a foundation for evidence-based care and wider acceptance of sound science. The International Conference on Diabetes and Cardiovascular Disease, held in Winnipeg, in June 1999, was organized to bring together a multi-disciplinary group of researchers dedicated to further knowledge amongst researchers, care givers, and the managers of the health system. The invited speakers submitted their works for publication, which serves as the basis for this book. Major themes include: epidemiology of diabetes mellitus, metabolic risk factors in diabetes and cardiovascular disease, hypertension in diabetes mellitus, cardiac function in diabetes, glycemic control and improved cardiovascular function, diabetes management, and endothelial function in diabetes.

Heart Hypertrophy and Failure brings together leading basic scientists and clinicians, presenting improved knowledge of the pathophysiology and treatment of the condition. The result is a synthesis of state-of-the-art information on molecular biology, cellular physiology and structure-function relationships in the cardiovascular system in health and disease. The papers presented describe fundamental mechanisms underlying changes in the cellular machinery during the development of cardiac hypertrophy and heart failure. Audience: Students, scientists, clinical and experimental cardiologists who seek to understand and manage the perplexing problems of hypertrophy and heart failure.

Experimental techniques are the life blood of science. The better the methodology is, the more reliable and accurate the results will be. Ultimately, this will lead to a clearer interpretation of those results and firmer conclusions from any set of experiments. Experimental methodology in the area of cardiovascular biochemistry and molecular biology has advanced considerably in the last decade. Because of these factors, it was thought that a focused issue of Molecular and Cellular Biochemistry dedicated to the novel, latest technological advances in the field was warranted. We must thank Dr Naranjan S. Dhalla, Editor-in-Chief of Molecular and Cellular Biochemistry, for his willingness to publish an issue with such a focus. We have attracted some of the leaders in the field of cardiovascular biology to submit articles describing some of the most novel, significant techniques currently in use in their laboratories. The purpose of the manuscripts was not to describe the recent experimental findings from each laboratory as is done in most conventional manuscripts. Instead, the purpose of the articles found within this focused volume of Molecular and Cellular Biochemistry was to describe how the technique is performed on the laboratory bench so that others less familiar with the technique may be able to use it in their own labs. The subjects described in this volume can be generally subdivided into three categories: molecular biology, cell biology and basic biochemistry. The methods cover wide areas including various DNA and RNA expression technologies, transfection techniques, quantification of ion flux movement, measurements of lipid metabolism, advances in the culture of specific cardiovascular cell populations, and the use of confocal microscopy to examine cell structure and function. We thank all of the authors who have contributed so much of their time and efforts and, most importantly, shared the `secrets' of these valuable techniques with the rest of the cardiovascular research community.

The papers ofthis Special Issue of Molecular and Cellular Nutraceuticals are also known as 'health foods' but they also Biochemistry are invited, peer-reviewed submissions from include any product derived from animal or plant sources speakers who attended the 2nd World Conference of the which ultimately can provide a medical benefit. F our symposia International Society for MolecuIar Nutrition & Therapy. This on various aspects concerning nutraceutical products and the Conference was held fromAugust 2--4th, 1997 in Winnipeg, marketing ofthese compounds was addressed. It is hoped that Canada. The goal of the Conference was to advance our these interactions represent the start of a new, highly interesting knowledge concerning the molecular events which link scientific venture uniting the nutraceutical industry with the nutrition to various disease processes in the body. Attending main stream academic medical research community. The the meeting were scientists from 18 countries ineluding nutraceutical industry is expected to be a multibillion dollar Canada, the United States, Japan, the United Kingdom, a year business world-wide by the turn of the century.The Franee, the Czeeh Republie, Germany, the Netherlands, identification of the active ingredients in any number of Bahrain, Hong Kong, India, Israel, China, Kuwait,Argentina, health foods reputed to be medieally beneficial would be just Sweden, Australia and Mexieo. There were 56 Distinguished one of the goals of such a scientific interaction.

This special issue of Molecular and Cellular Biochemistry our their mentor. The ex-students and trainees came from contains original research articles and review papers which all over Canada, the United States, Japan, Slovakia, Ger- were invitedfrom the participants ofa recent meeting organ- many, the Czech Republic, Estoniaand the Netherlands. The izedto honourthe 60th birthdayofNaranjan S. Dhalla, Ph.D., meeting wasjudged to be an overwhelming success in terms M.D. (Hon.). The meeting, organized by Drs. Morris Karma- ofthe scientific content as well as collaborative interactions zyn (London), Grant Pierce (Winnipeg) and Balwant Tuana initiated. (Ottawa), was held at the Best Western Lakeside Inn in We gratefully acknowledge the financial support from Kenora, Ontario, Canada from August 23-25th, 1996. The Pfizer, MerckFrosst, Astra, Ciba-Geigy, the Heart and Stroke meeting was entitled 'The Cellular Basis of Cardiovascular Foundation of Manitoba, the Medical Research Council of Function in Health and Disease'. There were over40 invited Canada, St.Boniface Research Foundation, the NRC Insti- speakers from 15 different countries present at the meet- tute for Biodiagnostics, the ManitobaHealth Research Coun- ing and it was attended by over 280 people. Keynote lectures cil and various sources within the University of Manitoba.

In the course of the last two decades, it has become increasingly evident that the sarcolemmal, sarcoplasmic reticular and mitochondrial membrane systems play an important role in determining the status of heart funotion in health and disease. These organelles have been shown to be intimately involved in the regulation of cation movements during the contraotion-relaxation cycle. Various proteins imbedded in the phospholipid 2+ + - + + bilayers of these membranes control Ca ,Na, Cl ,K and H concentrations within the oytoplasm by indirect or direct means. Cationic channels, Na+, + 2+ 2+ 2+ + 2+ + + K -ATPase, Ca IMg ATPase, Ca pump, Na -Ca exchanger, Na -II exchanger and adenylate cyclase affect myocardial funotion and viability through their role as regulators of specific ion movements. However, proteins are not the only important constituents of the membrane. Any disturbance in the interaction between proteins and phospholipids in the membrane has been suggested to alter the funotion of the organelles, upset ionic homeostasis and precipitate the development of abnormalities in oardiac performance.It is, therefore, orucial to understand the faotors whioh regulate membrane funotion in their totality if we are to oomprehend the nature of heart performanoe in healthy subjects. Similarly, the study of membrane dysfunotion in a wide variety of experimental models of heart disease at various stages of failure is essential if we are to fully understand the pathogenesis of heart dysfunotion and improve its treatment.

Thistext, as the tide states, is acompilationofpapersdevoted to the studyofath- erosclerosis,hypertensionanddiabetes.Thesethree distinctdisease entities,although not entirely unrelated, are three ofthe most important disease conditions in the world today.As such, this volumeofresearch papers isofobvious medical impor- tance.Thejustificationofthe energy,time and financial resources directed towards the studyofeachofthese three diseases requiressome discussion. The majority of papers amongst the three diseases that are discussed in this volume are dedicated to the studyofatherosclerosis.This is not by accident.Car- diovasculardisease isthenumberonekillertodayintheworld. IntheUnitedStates almost61 millionAmericanshaveoneormoreformsofcardiovasculardisease.These diseases claimed nearly 1million lives in 1998 alone.Although approximately 80% ofthosewho dieofcardiovasculardisease are 65 yearsofageorolder,asignificant numberofpeople are killed by cardiovascular disease below the ageof65.Ather- osclerotic heart disease in the eoronary vaseulature eausedapproximately~ million deaths in the United States in 1998.At least 12,400,000people are alive todayin the United States with a historyofmyocardial infarctions or ehest pain or both.Clearly,atherosclerotie disease inthe heart isamajormedicalproblem.This disease affeetsbothmenandwomen.Althoughmen are more likelyto experienee aheart attaekand are atgreater risk for eardiovaseular disease,more then ~ofthe people alive today with a historyofheart attacks or angina are females. As weIl,women whodo havemyoeardialinfarctionsare twice aslikely to diefromtheeventwithin afew weeks.Atheroscleroticvasculardisease isnotlimitedtojustthe heart.Anath- erosclerotic ischemic event is the primary causeofstroke today.Although it isnot weIl appreciated, stroke is the number 3 killer inAmerica today and the leading causeofdebilitatingneurological damage.Atherosclerotic vascular disease therefore, has acostintermsofhuman life,qualityoflifeandfinancialburden today thatno otherdisease canmatch.Theseriousnessofthis medicalproblemdemands research attention.

This volume explores all aspects of vascular biochemistry and includes chapters that provide an understanding of vascular function with descriptions of tissue components present in the vascular wall as well as an exploration of the haemodynamic and metabolic activities associated with this function. In addition, some chapters explore the vasculature under conditions which mimic various disease states. The information provided in this volume will provide new insights into the mechanisms that control vascular function as well as therapies designed to treat vascular disease.

"Pathophysiology of Cardiovascular Disease" has been divided into four sections that focus on heart dysfunction and its associated characteristics (hypertrophy, cardiomyopathy and failure); vascular dysfunction and disease; ischemic heart disease; and novel therapeutic interventions. This volume is a compendium of different approaches to understanding cardiovascular disease and identifying the proteins, pathways and processes that impact it.

Heart Hypertrophy and Failure brings together leading basic scientists and clinicians, presenting improved knowledge of the pathophysiology and treatment of the condition. The result is a synthesis of state-of-the-art information on molecular biology, cellular physiology and structure-function relationships in the cardiovascular system in health and disease. The papers presented describe fundamental mechanisms underlying changes in the cellular machinery during the development of cardiac hypertrophy and heart failure. Audience: Students, scientists, clinical and experimental cardiologists who seek to understand and manage the perplexing problems of hypertrophy and heart failure.

In the course of the last two decades, it has become increasingly evident that the sarcolemmal, sarcoplasmic reticular and mitochondrial membrane systems play an important role in determining the status of heart funotion in health and disease. These organelles have been shown to be intimately involved in the regulation of cation movements during the contraotion-relaxation cycle. Various proteins imbedded in the phospholipid 2+ + - + + bilayers of these membranes control Ca ,Na, Cl ,K and H concentrations within the oytoplasm by indirect or direct means. Cationic channels, Na+, + 2+ 2+ 2+ + 2+ + + K -ATPase, Ca IMg ATPase, Ca pump, Na -Ca exchanger, Na -II exchanger and adenylate cyclase affect myocardial funotion and viability through their role as regulators of specific ion movements. However, proteins are not the only important constituents of the membrane. Any disturbance in the interaction between proteins and phospholipids in the membrane has been suggested to alter the funotion of the organelles, upset ionic homeostasis and precipitate the development of abnormalities in oardiac performance.It is, therefore, orucial to understand the faotors whioh regulate membrane funotion in their totality if we are to oomprehend the nature of heart performanoe in healthy subjects. Similarly, the study of membrane dysfunotion in a wide variety of experimental models of heart disease at various stages of failure is essential if we are to fully understand the pathogenesis of heart dysfunotion and improve its treatment.

Thistext, as the tide states, is acompilationofpapersdevoted to the studyofath- erosclerosis,hypertensionanddiabetes.Thesethree distinctdisease entities,although not entirely unrelated, are three ofthe most important disease conditions in the world today.As such, this volumeofresearch papers isofobvious medical impor- tance.Thejustificationofthe energy,time and financial resources directed towards the studyofeachofthese three diseases requiressome discussion. The majority of papers amongst the three diseases that are discussed in this volume are dedicated to the studyofatherosclerosis.This is not by accident.Car- diovasculardisease isthenumberonekillertodayintheworld. IntheUnitedStates almost61 millionAmericanshaveoneormoreformsofcardiovasculardisease.These diseases claimed nearly 1million lives in 1998 alone.Although approximately 80% ofthosewho dieofcardiovasculardisease are 65 yearsofageorolder,asignificant numberofpeople are killed by cardiovascular disease below the ageof65.Ather- osclerotic heart disease in the eoronary vaseulature eausedapproximately~ million deaths in the United States in 1998.At least 12,400,000people are alive todayin the United States with a historyofmyocardial infarctions or ehest pain or both.Clearly,atherosclerotie disease inthe heart isamajormedicalproblem.This disease affeetsbothmenandwomen.Althoughmen are more likelyto experienee aheart attaekand are atgreater risk for eardiovaseular disease,more then ~ofthe people alive today with a historyofheart attacks or angina are females. As weIl,women whodo havemyoeardialinfarctionsare twice aslikely to diefromtheeventwithin afew weeks.Atheroscleroticvasculardisease isnotlimitedtojustthe heart.Anath- erosclerotic ischemic event is the primary causeofstroke today.Although it isnot weIl appreciated, stroke is the number 3 killer inAmerica today and the leading causeofdebilitatingneurological damage.Atherosclerotic vascular disease therefore, has acostintermsofhuman life,qualityoflifeandfinancialburden today thatno otherdisease canmatch.Theseriousnessofthis medicalproblemdemands research attention.

This volume explores all aspects of vascular biochemistry and includes chapters that provide an understanding of vascular function with descriptions of tissue components present in the vascular wall as well as an exploration of the hemodynamic and metabolic activities associated with this function. In addition, some chapters explore the vasculature under conditions which mimic various disease states. The information provided in this volume will provide new insights into the mechanisms that control vascular function as well as therapies designed to treat vascular disease.

Pathophysiology of Cardiovascular Disease has been divided into four sections that focus on heart dysfunction and its associated characteristics (hypertrophy, cardiomyopathy and failure); vascular dysfunction and disease; ischemic heart disease; and novel therapeutic interventions. This volume is a compendium of different approaches to understanding cardiovascular disease and identifying the proteins, pathways and processes that impact it.

Diabetes and cardiovascular disease together account for the largest portion of health care spending compared to all other diseases in Western society. This work seeks to provide an understanding of the causes of diabetes and its cardiovascular complications. As this understanding becomes more widely appreciated, it will serve as a foundation for evidence-based care and wider acceptance of sound science. The International Conference on Diabetes and Cardiovascular Disease, held in Winnipeg, in June 1999, was organized to bring together a multi-disciplinary group of researchers dedicated to further knowledge amongst researchers, care givers, and the managers of the health system. The invited speakers submitted their works for publication, which serves as the basis for this book. Major themes include: epidemiology of diabetes mellitus, metabolic risk factors in diabetes and cardiovascular disease, hypertension in diabetes mellitus, cardiac function in diabetes, glycemic control and improved cardiovascular function, diabetes management, and endothelial function in diabetes.

The papers ofthis Special Issue of Molecular and Cellular Nutraceuticals are also known as 'health foods' but they also Biochemistry are invited, peer-reviewed submissions from include any product derived from animal or plant sources speakers who attended the 2nd World Conference of the which ultimately can provide a medical benefit. F our symposia International Society for MolecuIar Nutrition & Therapy. This on various aspects concerning nutraceutical products and the Conference was held fromAugust 2--4th, 1997 in Winnipeg, marketing ofthese compounds was addressed. It is hoped that Canada. The goal of the Conference was to advance our these interactions represent the start of a new, highly interesting knowledge concerning the molecular events which link scientific venture uniting the nutraceutical industry with the nutrition to various disease processes in the body. Attending main stream academic medical research community. The the meeting were scientists from 18 countries ineluding nutraceutical industry is expected to be a multibillion dollar Canada, the United States, Japan, the United Kingdom, a year business world-wide by the turn of the century.The Franee, the Czeeh Republie, Germany, the Netherlands, identification of the active ingredients in any number of Bahrain, Hong Kong, India, Israel, China, Kuwait,Argentina, health foods reputed to be medieally beneficial would be just Sweden, Australia and Mexieo. There were 56 Distinguished one of the goals of such a scientific interaction.

This special issue of Molecular and Cellular Biochemistry our their mentor. The ex-students and trainees came from contains original research articles and review papers which all over Canada, the United States, Japan, Slovakia, Ger- were invitedfrom the participants ofa recent meeting organ- many, the Czech Republic, Estoniaand the Netherlands. The izedto honourthe 60th birthdayofNaranjan S. Dhalla, Ph.D., meeting wasjudged to be an overwhelming success in terms M.D. (Hon.). The meeting, organized by Drs. Morris Karma- ofthe scientific content as well as collaborative interactions zyn (London), Grant Pierce (Winnipeg) and Balwant Tuana initiated. (Ottawa), was held at the Best Western Lakeside Inn in We gratefully acknowledge the financial support from Kenora, Ontario, Canada from August 23-25th, 1996. The Pfizer, MerckFrosst, Astra, Ciba-Geigy, the Heart and Stroke meeting was entitled 'The Cellular Basis of Cardiovascular Foundation of Manitoba, the Medical Research Council of Function in Health and Disease'. There were over40 invited Canada, St.Boniface Research Foundation, the NRC Insti- speakers from 15 different countries present at the meet- tute for Biodiagnostics, the ManitobaHealth Research Coun- ing and it was attended by over 280 people. Keynote lectures cil and various sources within the University of Manitoba.

Experimental techniques are the life blood of science. The better the methodology is, the more reliable and accurate the results will be. Ultimately, this will lead to a clearer interpretation of those results and firmer conclusions from any set of experiments. Experimental methodology in the area of cardiovascular biochemistry and molecular biology has advanced considerably in the last decade. Because of these factors, it was thought that a focused issue of Molecular and Cellular Biochemistry dedicated to the novel, latest technological advances in the field was warranted. We must thank Dr Naranjan S. Dhalla, Editor-in-Chief of Molecular and Cellular Biochemistry, for his willingness to publish an issue with such a focus. We have attracted some of the leaders in the field of cardiovascular biology to submit articles describing some of the most novel, significant techniques currently in use in their laboratories. The purpose of the manuscripts was not to describe the recent experimental findings from each laboratory as is done in most conventional manuscripts. Instead, the purpose of the articles found within this focused volume of Molecular and Cellular Biochemistry was to describe how the technique is performed on the laboratory bench so that others less familiar with the technique may be able to use it in their own labs. The subjects described in this volume can be generally subdivided into three categories: molecular biology, cell biology and basic biochemistry. The methods cover wide areas including various DNA and RNA expression technologies, transfection techniques, quantification of ion flux movement, measurements of lipid metabolism, advances in the culture of specific cardiovascular cell populations, and the use of confocal microscopy to examine cell structure and function. We thank all of the authors who have contributed so much of their time and efforts and, most importantly, shared the `secrets' of these valuable techniques with the rest of the cardiovascular research community.

The probability for exposure to damaging radiation, toxic chemicals in the environment and adverse biological agents has increased exponentially today. The more frequent and faster travel that we experience today also escalates the risk of contraction and transmission of potentially deadly infections. This has created a very real and escalating risk for injuries and deaths. This is accentuated in the military and medical staff that is more frequently exposed to radiological, chemical,  and  biological  agents  in their  normal working  environment. Understanding the mechanisms whereby these toxic agents inflict damage to our bodies is essential to prepare us for these challenges.Much of the damage is inflicted through the generation of free radicals and non-radical oxidants which then act through oxidative mechanisms to injury the body. This volume will discuss the damage caused by these radiological, chemical, and biological environmental stressors, the mechanisms through which the damage can occur and the novel strategies that can be used to reduce the injury inflicted by these toxic compounds. Using basic and clinical research approaches, the contents of this book  discuss  new  ideas  for  the  development  of  bioactive  products  and  environmental approaches to lessen or negate the biological damage inflicted by thesenoxious compounds.