bluuebunny/crossref_metadata_2025 huggingface dataset:
The Benthamite Theory of Democracy
Authors: Pratt R. Cranford
Published: June 2006

Successful political movements are frequently accompanied by, and well served by, theoretical defences of their positions which later reflection shows to be inadequate for purposes other than popular political polemics. The history of the reform movement in England in the early decades of the nineteenth century provides an excellent example. The defence of political democracy offered by Jeremy Bentham, James Mill, and their followers gave the Radicals of the 1820's and 1830's their main intellectual arguments for the Great Reform Act. A close examination of this theory suggests, however, that it is inadequate in its view both of the nature of a democratic society and of the process of policy formation therein. It is, moreover, also apparent that Bentham's theory of democracy is sharply inconsistent with the main body of Benthamite doctrines.

The basic problem in Bentham's political theory is a product of the manner in which he resolved a contradiction that exists between his ethical and his psychological theory. Utilitarian ethics rests on the principle that the rightness or wrongness of an act is decided by its effect on the happiness of the greatest number. Bentham's psychological theory, however, is egoistic and hedonistic. He offered no hope that a man will act other than in pursuit of his own interests, and little hope that these interests will naturally be associated with the interests of others.

If this psychology is valid, individuals will choose, voluntarily, the ethically proper act only when, by chance, it coincides with that act which they perceive will maximize their own personal pleasure. Bentham realized this. As a consequence, he argued that if individuals are to be brought into harmony and if the greatest happiness is to be achieved, then legal sanctions and incentives must be introduced to influence individual hedonistic calculations in favour of acts that do not diminish the happiness of others more than they increase the happiness of the doer.
The Discoveries and Mercantilism: An Essay in History and Theory
Authors: Dales J. H.
Published: June 2006

The study of Mercantilism (an ill-defined concept at best) has usually been a study of Mercantilist pamphlets. Historians have used the pamphlets to piece together a picture of the economic policy of the age; theorists have discussed the doctrines they contain, more or less sympathetically, but usually in the light of classical economic theory and therefore frequently in a faintly patronizing manner. But each age must write its own history and in a neomercantilistic world we cannot be content to view Mercantilism so narrowly. We must, I suggest, stand back from the pamphlets and take a wider view of the matter.

Some five years ago Professor Charles Wilson wrote a paper in which he attempted to do just that. In particular, he sought to identify certain objective economic conditions in the Mercantilist world which would account for Mercantilist trade practices. Behind this approach was the idea that Mercantilism was not merely an economic ideology invented by ex parte pamphleteers, but a rational economic policy reflecting the economic facts of the age. Furthermore, Professor Wilson suggested that the economic facts of the Mercantilist period bore a certain resemblance to the economic facts of the contemporary world. Heresy received its due, for the late Professor Heckscher immediately brought the weight of his authority to bear on Professor Wilson's article and gently but firmly tried to push the whole problem back into the well-worn grooves of traditional Mercantilist scholarship.
Common Property Resources and Factor Allocation
Authors: Crutchfield J. A.
Published: June 2006

Two recent articles by Professors H. Scott Gordon and Anthony Scott present an interesting analysis of the conditions for economic maximization in a renewable resource industry the primary raw material for which is drawn from the public domain. While their criticism of the concepts which now govern fishery conservation programmes will be generally accepted among the handful of economists dealing with the fishing industry, some aspects of the problem call for additional consideration. In this paper I should like to elaborate and modify the general outlines of the analysis, largely in terms of a specific and important case: the Pacific halibut fishery.

As Gordon and Scott point out, the core of the “over-fishing” problem inheres in the fact that the basic resource is incapable of ownership in any meaningful sense. When the demand for a given species exceeds the level at which supplies can be drawn from local waters at relatively constant costs, further exploitation of the fishery gives rise to higher costs at both intensive and extensive margins. The catch per unit of fishing effort will decline in the closer, more populous grounds as stocks are reduced, and greater costs must be incurred in pushing fishing activities to more distant grounds. If the grounds could be and were privately owned, the incremental income resulting from, say, secular growth in demand would, of course, accrue as rent in a purely Ricardian sense. Since they are not, and since there are no substantive barriers to the entry of new vessels, the increasing aggregate returns will simply be dissipated in excess capacity and higher monetary and real costs. If the reduction in stocks, viewed with grave alarm by biologist and legislator alike, now gives rise to restrictions on the catch designed to hold fish populations at some predetermined level or to rebuild them, the increases in price, aggregate returns, and excess capacity will continue. There is obviously no assurance that the final effect on economic output over time relative to total factor inputs is the same, better, or worse than in the absence of such restrictions.
The Science of Politics in the United States
Authors: Crick Bernard
Published: June 2006

The study of politics in the United States today is something in size, content, and method unique in Western intellectual history. As Professor Pendleton Herring has recently said: “Political science as a subject of systematic enquiry started with Aristotle but as a profession it has won its greatest recognition in the United States and within our generation. One fact is clear: no other country in the world has so large, so well trained, so competent a profession dedicated to the teaching and analysis of government… . This profession … is now part of our national strength.” Not merely has the size of “the profession” grown so much since Aristotle's day, but the method has also markedly changed. American methods have consciously aspired to the modern concepts of natural science. There has been an advocacy of an integrated science of society, resting especially on concepts drawn from modem physics, biology, and psychology, and on a marked displacement of speculative philosophy and historical study. There now follow, from a sceptical foreigner, some reflections on the claims of Professor Herring. It is surely important for friends and neighbours to make some judgment on how a political science profession can become a “partof … national strength” and how relevant these new methods can be to the peculiar historical experience of the United States.
Ghana, the West, and the Soviet Union
Authors: Anglin Douglas G.
Published: June 2006

Ghana is the first truly African state to emerge from colonial status. Her attitude towards and relations with the Western powers and the Communist bloc are, therefore, of considerable importance both in themselves and as indications of the policies other independent African nations are likely to pursue. While Ghana’s foreign policy is still not fully defined, the broad pattern which is emerging is sufficiently discernible to merit discussion.

The present position was defined by Dr. Kwame Nkrumah on the eve of Independence. “We of Ghana feel,” the Prime Minister declared, and has since repeated,

that at this stage our country should not be committed in any aspect of its foreign policy and that it should not be aligned with any particular group of powers or political bloc. At the same time, our new state does not intend to follow a neutralist policy in its foreign policy. It is our intention to preserve our independence and to act as we see best at any particular time.

The same view was expressed more succinctly in June, when it was stated that “Ghana will neither join any power bloc nor maintain a blind policy of neutrality and non-alignment.” These formulations of Ghanaian policy are deliberately vague. They do, however, admirably fulfil the pressing need which every country feels of having a foreign policy of its own, and at the same time they leave the Government free to pursue almost any particular course of action it might later choose.
Economic Scholarship in Canada
Authors: Taylor K. W.
Published: June 2006

Economics first appeared in a Canadian university curriculum more than eighty years ago; thirty years later several universities were offering groups of courses in economics that could qualify a student for the equivalent of an honours degree in economics; but it is only in the past thirty-five years that a steady flow of scholarly writing in Canadian economics has developed. The twenty-fifth anniversary of the founding of this Journal provides an appropriate occasion to review briefly the expansion of economic scholarship in Canada.

The first university course in political economy to be offered in Canada was in 1878 when the Department of Philosophy at Queen's University introduced a course of lectures based on Adam Smith, Mill, and Jevons. Ten years later, in 1888, Adam Shortt was appointed lecturer in political economy and in 1891 he became the Sir John A. Macdonald Professor of Political Science. The University of Toronto appointed its first professor of political science in 1888, and (Sir) William Ashley gave lectures in both political economy and constitutional history. McGill entered the field in 1899 when Dr. LeRossignol of Colorado was appointed visiting professor for one year. In 1900 Stephen Leacock was appointed lecturer in political science, and in 1901 (Sir) William Flux was brought over from England to occupy McGill's first chair in economics. The succeeding chairs of political economy in Canadian universities were occupied by A. L. McCrimmon at McMaster in 1904, E. Bouchette at Montreal in 1907, and A. B. Clark at Manitoba in 1909.
Social Economic Policy
Authors: Knight Frank H.
Published: June 2006

It is well to state explicitly at the outset that the society considered in this essay is the sovereign democratic state, that is, a modern Western nation, where law is made and enforced by a responsible government within the context of representative institutions. Only a free society living under democratic government confronts or deals with social problems—problems of and for society as a unit. It is assumed that public opinion is committed to the general ideal of a practical maximum of individual freedom and freedom of association, hence to a minimum of enforced or “jural” law, prescribing or restricting personal conduct. That is, it holds to the ideal of association by free agreement or assent, subject to the state and its laws. The concepts are imprecise, and to make them workable and definite is a major function of law and government.

The field of association to be chiefly considered here is that of “economic” relations. In the form now prevalent in the Western world, free economic association is a historical novelty, in origin closely intertwined with democracy or political freedom. It will be argued that these and other modes of freedom are in fact inseparable aspects of “liberal” culture. “Liberal” culture arose through a radical and historically swift transformation of the order which prevailed in mediaeval Western Europe. Without looking farther back in history, what is important is the antithetical character in essential respects of mediaeval and contemporary society in their structure and operation and in their accepted ideals.
The Political Economy of Central Africa's Experiment with Inter-Racial Partnership
Authors: Barber William J.
Published: June 2006

In 1953 a new formula for dealing with the complicated racial problems of the settler communities was introduced into the African scene. This innovation—the doctrine of inter-racial partnership—was launched with the merger of the territories of Southern Rhodesia, Northern Rhodesia, and Nyasaland into a federal state. In its brief life, government under the “partnership” banner can already claim several noteworthy reforms in this community of some 280,000 Europeans, 34,000 Asians and persons of mixed race, and more than 7,300,000 Africans. A new university has been established which opens its doors to members of all races. In Southern Rhodesia, the long-established legal bars to the ownership of urban property by Africans have been relaxed. In Northern Rhodesia, the first breach in the industrial colour bar has been made in the important copper fields. Further, serious discussion has been given to several proposals with more sweeping implications, for example the draft bill which would scrap segregation in the trade unions of Southern Rhodesia and proposals which would extend the franchise to substantial numbers of Africans.
Immigration into Canada, 1851–1920
Authors: McDougall Duncan M.
Published: June 2006

The purpose of the paper is to provide more firmly based estimates of some aspects of Canadian population growth. In Part I estimates are derived of the natural increase in the Canadian population by decades from 1851 to 1931 based on survival rates derived from life tables. The figures on natural increase then permit the derivation of net migration estimates. In Part II new estimates of immigration are developed that, together with the net migration figures of Part I, yield estimates of emigration by decades. Part III tests some of the results by an examination of the limited information available on other aspects of Canada's economic development in the period.

The life table is a basic tool of population study. The most recent application of the life table to the problem of the reconstruction of Canadian population growth was made by Nathan Keyfitz. While the same method is used here, we feel that we have made more realistic assumptions in deriving a life table designed to represent the mortality characteristics of early Canadian populations.
Labour-Management Relations in the Construction Industry: The Findings of the Goldenberg Commission
Authors: Crispo John H. G.
Published: June 2006

Since the Second World War there has been a growing awareness that labour relations in the construction industry do not lend themselves to legislative frameworks designed to cope with union-management relations in general. In the United States this has given rise to a number of provisions in the federal legislation which have particular reference to the labour problems of the construction industry. Under the Taft-Hartley Act, for example, there was the banning of the closed shop and the prohibition of jurisdictional disputes and certain types of secondary boycotts. More recently, under the Landrum-Griffin Act, unions in the building trades were exempted from some of the restrictions which apply to union-security arrangements and to the employment of secondary boycotts in industry and commerce generally.

That there is also the need for a special legislative approach to the labour relations problems of the construction industry in at least one jurisdiction in Canada has been shown by the work of the Goldenberg Commission in the Province of Ontario. After setting this work in perspective, this article will focus on the implications of the Commission's findings for the applicability of both the Ontario Labour Relations Act and such protective labour statutes as the Industrial Standards Act.
The Rowell-Sirois Report, Provincial Autonomy, and Post-War Canadian Federalism
Authors: Smiley D. V.
Published: June 2006

On May 3, 1940, the Royal Commission on Dominion-Provincial Relations presented its report to the Prime Minister of Canada. This report, along with the specialized studies undertaken by direction of the commission, constitutes the most comprehensive investigation of a working federal system that has ever been made. In spite of the scope and quality of the commission's work, its analysis of federal-provincial relations has had surprisingly little influence on the directions that the theory and practice of Canadian federalism have taken since 1945. More specifically, the concept of provincial autonomy which is central to the commission's argument has been denied explicitly or implicitly by such influential writings on the Canadian federal system as the so-called Green Book proposals submitted by the federal government at the Dominion-Provincial Conference on Reconstruction in 1945, the Report of the Royal Commission on National Development in the Arts, Letters and Sciences, Mr. Maurice Lamontagne's book, Le Fédéralisme canadien, and the Report of the Quebec Royal Commission on Constitutional Problems, as well as by the actual developments in federal-provincial relations since the Second World War.

At the present time of uncertainty in the Canadian federal system it seems desirable to re-examine the perspectives of the Rowell-Sirois Report. This paper attempts to analyse one of these perspectives—provincial autonomy in the fields of health, welfare, and education.
Educational Shortage and Excess
Authors: Bowman M. J.
Published: June 2006

Be he economist, educator, or politician, the man who will say of any industrially advanced country today that it provides an excess of education is rare indeed. It is not that education is viewed as a good thing in itself, so good that it is virtually impossible to have too much of it. The pronouncements in favour of ever more education are supported above all by assertions concerning the economic value of education. Never before has there been so much education. Yet never before has there been so much talk of the shortages of trained people or of the need to expand education as an investment in the formation of human capital. In an Alice-in-Wonderland sort of way it seems that the more we have the greater the shortage. Shortage is “in,” along with the “affluent society.”
Flexible Exchange Rates and Employment Policy
Authors: Mundell Robert
Published: June 2006

The theory of employment that grew out of the Great Depression was not long in influencing government policy-makers and revolutionizing older concepts of fiscal policy. The most important of Keynes's practical lessons, that policies which promote investment and exports and inhibit saving and imports increase employment and output, has now hardened into a dogma and filtered down into almost all the elementary textbooks. The lesson, by and large, was a good one, but the dogma presents the danger that the lesson might be uncritically applied in situations where other government policies render it invalid. This paper is concerned with the most important exception to the rule.

The mercantilist element in Keynesian policies is definitely inapplicable to countries whose central banks do not peg the price of foreign exchange or gold. Tariffs, trade controls, and export subsidies are likely to worsen employment and output in all those situations in which, with a fixed exchange rate, they would improve employment and output. Moreover, if exchange rates are flexible, an increase in investment or government spending, and a reduction in saving or taxation, will have a substantially different effect on employment than that predicted by the traditional foreign trade multiplier. The reason lies in the fact that equilibrium in the balance of payments is automatically maintained by variations in the price of foreign exchange.
Parliament's Power to Advise
Authors: Forsey Eugene
Published: June 2006

No one questions the power of Parliament to approve or condemn the actions of the Queen's ministers. But has it or has it not also the power to advise, to ask the Crown to take or not to take some particular action? May says that the British Parliament, at any rate, has: “An Address to Her Majesty is the form ordinarily employed by both Houses of Parliament for making their desires and opinions known to the Crown.” The subjects of such Addresses “have comprised every matter of foreign or domestic policy; … the administration of justice; … and, in short, representations upon all points connected with the government and welfare of the country.”

Edward Blake was equally clear and emphatic that the Canadian Parliament also possessed this power. Replying on April 30, 1890, to Sir John Thompson's contention that it would be unconstitutional for the Government to disallow a provincial Act after announcing that it would not disallow, Blake said flatly that this was wrong, because Thompson's doctrine might

thwart, annul or affect the power of Parliament to express its opinion by Address, requesting His Excellency to exercise his power to disallow. … The Parliament of the country has a power not merely to approve and to condemn, but it has also a more important power with reference to every political and executive act-it has a power to advise. … Neither the approval nor the condemnation of an accomplished act serves any purpose save that of criticism. The power of advice is the great power of Parliament, a power to be exercised with reserve, but to be maintained in efficiency; and to preserve effectively that power, it is necessary that we should deem that it has not passed beyond the domain of Parliament to advise within the twelve months, no matter what the Executive may do. … It is of very little use for Parliament to say to Ministers, who have decided that they think an Act ought to be allowed: “Gentlemen, we think you are wrong; we condemn you; we censure you.” Are we to be told that if the twelve months still remain unexpired, we may condemn the Administration, forsooth, but the Act must remain operative; that we cannot make our advice effective; that we cannot take a step which will cause that to be done which the great council of the country decides in the interest of the country ought to be done? The power of Parliament itself would be thwarted by the proposition of the hon. Minister of Justice.
Hats and the Fur Trade
Authors: Crean J. F.
Published: June 2006

This paper is an attempt to describe developments in the European hatting industry as a background to the evolution of the North American beaver trade. Most studies of the fur trade trace the movement of the furs no further than the fur market; interest is centred on production and marketing with insufficient attention directed to the ultimate sources of the demand. Vague references to style changes usually suffice as explanations of long-run demand movements. There were, however, certain technological discoveries and evolutions in hat-making which underlie both the style changes and the long-run demand fluctuations. My intent is to examine these developments and to relate them to the Canadian fur trade.

The cornerstone of this essay is L'Art de faire des chapeaux, by M. I'Abbé Nollet, published at Paris in 1765. This mid-eighteenth century work examines the sources of raw materials, the methods of production, and the history of the French hatting industry. In order to understand the industrial background against which this book was written and to explain several of the references Nollet makes, it is necessary to begin with a history of the felt hat industry. In sketching this history I have drawn extensively on other sources. Some of the hypotheses advanced in Section I may be open to question; the evidence upon which they are based is fragmentary, and I have had to content myself with material in secondary sources. In later parts of the paper I shall compare L'Art de faire des chapeaux with the article on hatting in Diderot's Encyclopedia published in 1753.
Regional Interests and Policy in a Federal Structure
Authors: Hodgetts J.E.
Published: June 2006

Almost overnight, regionalism in Canada has become the current fashion and a subject for much intellectual speculation as well as administrative experimentation. This symposium is but one of many testimonials to the growing interest in the subject. In 1964, the Committee on Statistics of the Canadian Political Science Association considered the problem. Early in 1965, Queen's University sponsored a conference on areas of economic stress that was the forerunner to a much larger conference on regionalism convened by the Province of Ontario. The Institute of Public Administration of Canada selected regionalism as the theme for its autumn conference. Recent reports of a royal commission in New Brunswick and of a legislative committee in Ontario are implicitly concerned with regionalism in so far as they propose basic remodelling of the local government services in their respective provinces. The Resources Ministers Council is grappling with the concept, as are also the federal departments of Industry and of Agriculture. On the international plane, the St. Lawrence Seaway and the Columbia River development have projected more grandiose conceptions of regionalism. In short, regionalism, with concomitant regional administrative structures, is being advanced as an answer to the new problems of interdependence that cut across traditional political boundary lines, whether they be municipal, provincial, or national.

The title chosen for this symposium suggests that regional interests are, indeed, a reality within the Canadian federal structure and that policy must accommodate itself not only to the familiar strains of dominion-provincial tensions but to the newer cross-currents of regionalism. The detailed implications of regionalism cannot be considered here, but resort to the analytical tools of the new school of systems analysts may help to develop certain general conclusions.
Contributions to Canadian Political Science Since the Second World War
Authors: Smiley Donald V.
Published: June 2006

Although most of this essay relates to the work of political scientists, some of it deals with the writings of others who have contributed to our understanding of the government and politics of Canada. It would be a perverse and superficial student of our political institutions indeed who confined himself to the scholarship of political scientists without familiarizing himself at least in a general way with the writings, for example, of historians Ramsay Cook and W. L. Morton, sociologists S. D. Clark and John Porter, economists John Dales and Harry Johnson, legal scholars Edward McWhinney and Frank Scott, and, outside the bounds of Academia proper, journalists Peter Newman and Claude Ryan, and practising public administrators A. W. Johnson and Herbert Balls.
Interorgan ammonia, glutamate, and glutamine trafficking in pigs with acute liver failure
Authors: Ytrebø Lars M. , Sen Sambit , Rose Christopher , Ten Have Gabrie A. M. , Davies Nathan A. , Hodges Stephen , Nedredal Geir I. , Romero-Gomez Manuel , Williams Roger , Revhaug Arthur , Jalan Rajiv , Deutz Nicolaas E. P.
Published: June 2006

Ammonia reduction is the target for therapy of hepatic encephalopathy, but lack of quantitative data about how the individual organs handle ammonia limits our ability to develop novel therapeutic strategies. The study aims were to evaluate interorgan ammonia metabolism quantitatively in a devascularized pig model of acute liver failure (ALF). Ammonia and amino acid fluxes were measured across the portal drained viscera (PDV), kidneys, hind leg, and lungs in ALF pigs. ALF pigs developed hyperammonemia and increased glutamine levels, whereas glutamate levels were decreased. PDV contributed to the hyperammonemic state mainly through increased shunting and not as a result of increased glutamine breakdown. The kidneys were quantitatively as important as PDV in systemic ammonia release, whereas muscle took up ammonia. Data suggest that the lungs are able to remove ammonia from the circulation during the initial stage of ALF. Our study provides new data supporting the concept of glutamate deficiency in a pig model of ALF. Furthermore, the kidneys are quantitatively as important as PDV in ammonia production, and the muscles play an important role in ammonia removal.
20-Hydroxyeicosatetraenoic acid is a potent dilator of mouse basilar artery: role of cyclooxygenase
Authors: Fang Xiang , Faraci Frank M. , Kaduce Terry L. , Harmon Shawn , Modrick Mary L. , Hu Shanming , Moore Steven A. , Falck J. R. , Weintraub Neal L. , Spector Arthur A.
Published: June 2006

20-Hydroxyeicosatetraenoic acid (20-HETE), an arachidonic acid (AA) metabolite synthesized by cytochrome P-450 ω-oxidases, is reported to produce vasoconstriction in the cerebral circulation. However, we find that like 14,15-epoxyeicosatrienoic acid (14,15-EET), 20-HETE produces dilation of mouse basilar artery preconstricted with U-46619 in vitro. Indomethacin inhibited the vasodilation produced by 20-HETE but not by 14,15-EET, suggesting a cyclooxygenase (COX)-dependent mechanism. Metabolic studies indicated several mechanisms that may play a role in this process. Mouse brain endothelial cells (MBEC) converted 20-HETE to 20-OH-PGE2, which was as potent as PGE2in dilating the basilar artery. 20-HETE also stimulated AA release and PGE2and 6-keto-PGF1αproduction in MBEC. Furthermore, the basilar artery converted 20-HETE to 20-COOH-AA, which also produced COX-dependent dilation of the basilar artery. 20-COOH-AA increased AA release and PGE2and 6-keto-PGF1αproduction by the MBEC, but to a lesser extent than 20-HETE. Whereas the conversion of 20-HETE to 20-OH-PGE2and production of endogenous prostaglandins probably are primarily responsible for vasodilation, the production of 20-COOH-AA also may contribute to this process.
Heat shock protects cardiac cells from doxorubicin-induced toxicity by activating p38 MAPK and phosphorylation of small heat shock protein 27
Authors: Venkatakrishnan C. D. , Tewari Arun K. , Moldovan Leni , Cardounel Arturo J. , Zweier Jay L. , Kuppusamy Periannan , Ilangovan Govindasamy
Published: June 2006

Doxorubicin (DOX) and its derivatives are used as chemotherapeutic drugs to treat cancer patients. However, production of DOX-mediated reactive oxygen species (ROS) by prolonged use of these drugs has been found to cause dilative cardiomyopathy and congestive heart failure. Thus various preventive modalities have been developed to avoid this side effect. We have found that the DOX-mediated oxidant-induced toxicity in cardiac cells could be minimized by hyperthermia-induced small heat shock protein 27 (HSP27); that is, this protein acts as an endogenous antioxidant against DOX-derived oxidants such as H2O2. Heat shock-induced HSP27 was found to act as an antiapoptotic protein (reducing ROS and Bax-to-Bcl2 ratio) against DOX, and its phosphorylated isoforms stabilized F-actin remodeling in DOX-treated cardiac cells and, hence, attenuated the toxicity. Protein kinase assays and proteomic analyses suggested that higher expression of HSP27 and its phosphorylation are responsible for the protection in heat-shocked cells. Two-dimensional gel electrophoresis showed six isoforms (nonphosphorylated and phosphorylated) of HSP27. Matrix-assisted laser desorption/ionization time of flight analyses showed α- and β-isoforms of HSP27, which are phosphorylated by various protein kinases. Ser15and Ser85phosphorylation of HSP27 by MAPK-assisted protein kinase 2 was found to be the key mechanism in reduction of apoptosis and facilitation of F-actin remodeling. The present study illustrates that hyperthermia protects cells from DOX-induced death through induction and phosphorylation of HSP27 and its antiapoptotic and actin-remodeling activities.
Role of CYP pharmacogenetics and drug-drug interactions in the efficacy and safety of atypical and other antipsychotic agents
Authors: Murray Michael
Published: June 2006

Cytochrome P450 (CYP) drug oxidases play a pivotal role in the elimination of antipsychotic agents, and therefore influence the toxicity and efficacy of these drugs. Factors that affect CYP function and expression have a major impact on treatment outcomes with antipsychotic agents. In particular, aspects of CYP pharmacogenetics, and the processes of CYP induction and inhibition all influence in-vivo rates of drug elimination. Certain CYPs that mediate the oxidation of antipsychotic drugs exhibit genetic variants that may influence in-vivo activity. Thus, single nucleotide polymorphisms (SNPs) in CYP genes have been shown to encode enzymes that have decreased drug oxidation capacity. Additionally, psychopharmacotherapy has the potential for drug-drug inhibitory interactions involving CYPs, as well as drug-mediated CYP induction. Literature evidence supports a role for CYP1A2 in the clearance of the atypical antipsychotics clozapine and olanzapine; CYP1A2 is inducible by certain drugs and environmental chemicals. Recent studies have suggested that specific CYP1A2 variants possessing individual SNPs, and possibly also SNP combinations (haplotypes), in the 5′-regulatory regions may respond differently to inducing chemicals. CYP2D6 is an important catalyst of the oxidation of chlorpromazine, thioridazine, risperidone and haloperidol. Certain CYP2D6 allelic variants that encode enzymes with decreased drug oxidation capacity are more common in particular ethnic groups, which may lead to adverse effects with standard doses of psychoactive drugs. Thus, genotyping may be useful for dose optimization with certain psychoactive drugs that are substrates for CYP2D6. However, genotyping for inducible CYPs is unlikely to be sufficient to direct therapy with all antipsychotic agents. In-vivo CYP phenotyping with cocktails of drug substrates may assist at the commencement of therapy, but this approach could be complicated by pharmacokinetic interactions if applied when an antipsychotic drug regimen is ongoing.
Formulations generated from ethanol-based proliposomes for delivery via medical nebulizers
Authors: Elhissi Abdelbary M A , Karnam Kiran K , Danesh-Azari Mohammad-Reza , Gill Hardyal S , Taylor Kevin M G
Published: June 2006

Multilamellar and oligolamellar liposomes were produced from ethanol-based soya phosphatidylcholine proliposome formulations by addition of isotonic sodium chloride or sucrose solutions. The resultant liposomes entrapped up to 62% of available salbutamol sulfate compared with only 1.23% entrapped by conventionally prepared liposomes. Formulations were aerosolized using an air-jet nebulizer (Pari LC Plus) or a vibrating-mesh nebulizer (Aeroneb Pro small mesh, Aeroneb Pro large mesh, or Omron NE U22). All vibrating-mesh nebulizers produced aerosol droplets having larger volume median diameter (VMD) and narrower size distribution than the air-jet nebulizer. The choice of liposome dispersion medium had little effect on the performance of the Pari nebulizer. However, for the Aeroneb Pro small mesh and Omron NE U22, the use of sucrose solution tended to increase droplet VMD, and reduce aerosol mass and phospholipid outputs from the nebulizers. For the Aeroneb Pro large mesh, sucrose solution increased the VMD of nebulized droplets, increased phospholipid output and produced no effect on aerosol mass output. The Omron NE U22 nebulizer produced the highest mass output (approx. 100%) regardless of formulation, and the delivery rates were much higher for the NaCl-dispersed liposomes compared with sucrose-dispersed formulation. Nebulization produced considerable loss of entrapped drug from liposomes and this was accompanied by vesicle size reduction. Drug loss tended to be less for the vibrating-mesh nebulizers than the jet nebulizer. The large aperture size mesh (8μm) Aeroneb Pro nebulizer increased the proportion of entrapped drug delivered to the lower stage of a twin impinger. This study has demonstrated that liposomes generated from proliposome formulations can be aerosolized in small droplets using air-jet or vibrating-mesh nebulizers. In contrast to the jet nebulizer, the performance of the vibrating-mesh nebulizers was greatly dependent on formulation. The high phospholipid output produced by the nebulizers employed suggests that both air-jet and vibrating-mesh nebulization may provide the potential of delivering liposome-entrapped or solubilized hydrophobic drugs to the airways.
In-vitro transcutaneous delivery of ketoprofen and polyunsaturated fatty acids from a pluronic lecithin organogel vehicle containing fish oil
Authors: Richards Helen , Thomas Christopher P , Bowen Jenna L , Heard Charles M
Published: June 2006

This work explored the use of pluronic lecithin organogel (PLO) as a base for the delivery of bioactive polyunsaturated fatty acids from fish oil, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and ketoprofen. PLO was adapted to contain fish oil, ketoprofen, or both, and 1,8-cineole as penetration enhancer, and used to determine the in-vitro permeation from infinite and finite dosing protocols across full thickness porcine skin. Oruvail gel (2.5% ketoprofen) was included for comparison. No EPA or DHA was found to permeate skin when applied as an infinite dose. From multiple finite doses, small amount (max. 0.22%) of fish oil were found to permeate the skin. This indicates retention of fish oil within the gel matrix and that the viable domain of full thickness skin was a significant barrier. Greater amounts of EPA and DHA were delivered in the presence of ketoprofen indicating co-transport resulting from selective complexation, although no enhancement was observed using 1,8-cineole. Unlike EPA and DHA, substantial amounts of ketoprofen permeated when applied as infinite doses. Oruvail, a Carbopol 940-based hydrogel containing 2.5% ketoprofen and ethanol, delivered the greatest amount, although similar to the PLO gel containing 5% ketoprofen. The addition of propylene glycol enhanced permeation, although the presence of fish oil in the PLO gel inhibited ketoprofen permeation. When applied as multiple finite doses a maximum of 76μmcm2 (1.12%) was delivered, which was reduced by the presence of 1,8-cineole. Greater permeation was again observed with Oruvail by a factor of two and with half the ketoprofen dose. To conclude, a PLO-based gel is capable of delivering EPA and DHA via a repeat finite dosing regimen, although there is evidence for the retention of these very lipophilic molecules within the gel matrix. Although to a lesser extent than EPA and DHA, ketoprofen was also substantially retained, as exemplified by the superior delivery rates from Oruvail. Finally, this work has highlighted the importance of using an appropriate topical dosing method to match the intended use of a product.
Enhanced cellular uptake of Ara-C via a peptidomimetic prodrug, L-valyl-ara-C in Caco-2 cells
Authors: Cheon Eun-Pa , Hong Joon Hee , Han Hyo-Kyung
Published: June 2006

This study aimed to investigate the gastrointestinal stability and the cellular uptake characteristics of l-valyl-ara-C, a peptidomimetic prodrug of ara-C (cytarabine). After the synthesis of l-valyl-ara-C via the incorporation of l-valine into the N4-amino group of the cytosine ring in ara-C, the gastrointestinal stability of l-valyl-ara-C was examined using artificial gastric juice and artificial intestinal fluids. The cellular uptake characteristics of l-valyl-ara-C were also examined in Caco-2 cells. The disappearance half-life of l-valyl-ara-C was 2.2 h in artificial gastric juice, while the degradation of l-valyl-ara-C was negligible in artificial intestinal fluid and also in the supernatant above the Caco-2 cell monolayer during the 2-h incubation. The cellular accumulation of l-valyl-ara-C was 5-fold higher than that of ara-C in Caco-2 cells. Furthermore, the cellular uptake of l-valyl-ara-C did not increase proportionally to the increase in drug concentration. The cellular accumulation of l-valyl-ara-C was significantly reduced in the presence of uridine, p-aminohippurate, tetraethylammonium and small dipeptides, while it was not changed in the presence of l-valine and benzoic acid, suggesting that l-valyl-ara-C could interact with multiple uptake transporters, including peptide transporters, organic anion and cation transporters and nucleoside transporters, but might not interact with amino acid transporters. In conclusion, l-valyl-ara-C could be effective to improve the oral absorption of ara-C via the carrier-mediated transport pathway.
Aircraft Noise Perception and Annoyance at Schools near Salgado Filho International Airport, Brazil
Authors: de Oliveira Nunes Maria Fernanda , Sattler Miguel Aloysio
Published: June 2006

This article presents results of an evaluation of aircraft noise perception and annoyance in schools located in the vicinity of Salgado Filho International Airport, in the city of Porto Alegre, RS, Brazil. This research is based on indoor and outdoor acoustic measurements, in addition to questionnaires in three schools. The results indicate problems in school performance, resulting from frequent interruption of classroom communication associated with high noise levels. The research also indicates that children aged between 11 and 13 years form the most vulnerable group.
An Experimental Investigation of Cavity Flow Oscillations and Tones of an In-Flow Microphone
Authors: Fields Richard S. , Tso Jin , Soderman Paul T.
Published: June 2006

An experiment was conducted to investigate the flow-induced nose-cone cavity oscillations of a B&K in-flow microphone. A 38.1-mm-diameter scale model of the B&K 12.7-mm UA 0386 nose cone was constructed and tested in a 177.8-mm-round free-jet in the Anechoic Chamber Wind Tunnel at NASA Ames Research Center at ReD up to 1.1 × 105. The results indicated that the B&K nose-cone cavity behaves much like a cavity without a screen. Detailed flow velocity measurements over the cavity screen have shown inflection points in the mean velocity profiles and high disturbance intensities in the vicinity of the cavity trailing edge. These results and the high coherence between the strong velocity and acoustic pressure oscillations at the cavity trailing edge implied that the cavity acoustic tones are the consequence of the cavity shear-layer impingement on the cavity trailing edge. The effect of cavity screen appears to be secondary in the velocity range tested. The screen seems mainly to modulate the Strouhal numbers of the higher acoustic modes.
The Rehabilitation of the Prairie Wheat Economy
Authors: Britnell G. E.
Published: June 2006

The prairies and the country north of them are in truth a diversified country about which accurate generalizations are not easily made. A series of good crop years tempts both settlers and writers to predict cultivation in the most distant situations. A series of dry years invites equally extreme predictions of restriction of settlement…. In Canada … it is refinement of observation on critical elements and seasons of precipitation that we need rather than figures of annual rainfall, which are often almost meaningless. An old plains farmer once remarked to me “Annual rainfall? We have no such thing as an annual rainfall here! Once in a long while it rains.”—[Isaiah Bowman]

Standards of living in the prairie wheat economy have been depressed by overhead costs, recurring cycles of drought, specialization in wheat, and dependence on prices determined in world markets. The record of the last eight or nine years has brought suggestions that the greater part of the area should be abandoned or allowed to revert to range use, although a more general assumption has been that drought would give way to years of greater precipitation and that wheat prices would show a measure of recovery. Drought and depression have indicated that throughout the region emphasis has shifted from problems of exploitation to problems of conservation and that, accordingly, an attempt must be made to re-establish the economy on a basis which will reduce the waste of human and economic resources in the future. Individual initiative and local group action will undoubtedly continue to play an important part in the adaptation of agricultural techniques to climatic and soil conditions, but correction of the most glaring mistakes in settlement and land utilization policies demands careful planning and constructive action on a fairly large scale by federal and provincial governments. From the national or social point of view, more is at stake than relief budgets and rehabilitation expenditures, onerous as the financial burden of these charges may be. Successive years of extreme poverty in a depressing environment have begun to sap the morale of all but the most fortunate or the most determined members of the prairie community, and continuance or recurrence of such conditions must ultimately produce a demoralized agricultural population.
Agricultural Debt Adjustment
Authors: Easterbrook W. T. , W.B.H.
Published: June 2006

The present paper is intended as the background to a more detailed discussion of the facts of agricultural debt adjustment. I propose to discuss briefly the nature and objectives of our machinery of agricultural debt adjustment, the background against which it works, and some of the more important difficulties encountered in practice. The observations are based largely upon experience acquired in the West, although the setting concerns the country as a whole.

Problems of debt adjustment are primarily problems in the economics of distribution. Measures taken in this direction affect transfers of income between individuals, groups, and sections of the country. Their chief objective is to relieve the pressure on exposed groups and to allay the tensions created thereby. They constitute a part of the machinery of adjustment so essential in an economy subject to extreme variation of income and afflicted with rigidities which obstruct or divert forces tending to equilibrium. The tendency has been to concentrate upon the economics of the long run and to ignore obstacles to the free play of such forces. The importance of these obstacles is most manifest in the lower phases of the business cycle, and the presence of corrective or compensatory measures is in large part due to the cumulative effects of the inflexibility characteristic of a continental type of development and to the difficulty of planning for an economy in which variability is so marked. The results are seen in a wide range of expedients of which debt adjustment is an example. Difficulties arise owing to the failure to distinguish between social and pecuniary costs, to the widely different interpretations of what the term “justice” implies, and to differences in points of view which range from an insistence upon a strictly legal interpretation of rights and obligations to demands for debt reductions upon the basis of present income.
Towards the Sociology of Sovereignty
Authors: Handler Benjamin
Published: June 2006

The modern state whose youth was spent in strife has entered its turbulent old age. Now, as then, the old order is marshalling its forces of arms and ideas to defend itself against the impact of the new. Just as the medieval church-state was once attacked by the protagonists of the national state, so this latter is now attacked in turn by those seeking to break the bonds of a narrow nationalism. Beneath the struggle lies the ineradicable craving for fulfilment. Where once it was expressed in terms of unity under the headship of the Vicar of Christ, since the Reformation it has taken the form of unity within a sovereign state. And where once the claims of the Pope were subjected to a merciless criticism, now the claims of the sovereign are subjected to an equally relentless stricture. The opposition is no new thing, for the history of political thought in the last five centuries revolves around the attempt to impose restrictions upon the sovereign authority of the state. But it is significant that not until recently has the argument taken the form of a denial of sovereignty. This means, of course, that the assumptions underlying the political system are being challenged. Nor is it only ideas; it is also the social and economic institutions which are being poured into the crucible of criticism. The result of the withdrawal of reverence is to illuminate the nature of sovereignty, thereby enabling us to clarify its functions and to evaluate its worth.