bluuebunny/crossref_metadata_2025 huggingface dataset:
Monopoly and Free Trade in Dutch-Asian Commercial Policy: Debate and Controversy within the VOC
Authors: Arasaratnam S.
Published: April 2011

The Dutch East India Company (VOC) secured in March 1602, by charter from the States General of the Netherlands, a monopoly of eastern trade. Throughout its history of two centuries, it sought zealously to maintain and safeguard this monopoly against all interlopers and against any attempts at private trade by its own officers. With its establishment and expansion in the east the Company extended this concept of monopoly to embrace as much of Asian trade as it could master. It developed early the policy of acquiring a monopoly of certain key commodities of Asian trade by controlling the areas of production and hence the supply. It soon went further and declared a total monopoly of the entire seaborne trade of specific trading areas by virtue of conquest, enforced contracts and naval domination. Thus the close monopoly of the Europe/Asia trade and of large areas of their inter-Asian trade constituted a commercial system to which the Company's Directors and its officers in Asia became closely attached and it formed a major plank in its commercial policy in the two centuries of its existence. Through this period, its energies and exertions were largely directed to the acquisition and maintenance of this many-sided monopoly system. Monopolistic policies and practices in trading dominated the thinking and activities of the Company at all levels of operation. The VOC was held as the archetype of such a trading body.
The Anti-Federation Movement in Malaya, 1946–48
Authors: Wah Yeo Kim
Published: April 2011

The early postwar years witnessed serious and acrimonious controversies over the constitutional order the British intended to introduce in Malaya (including Singapore). The first set of proposals called the Malayan Union Scheme encountered strong Malay opposition. Partly because of this, the British advanced an alternative known as the Federation Proposals. This in turn was condemned by the non-Malays. Together with leftwing Malay leaders, non-Malay politicians organised an anti Federation movement, consisting of the Pan-Malayan Council of Joint Action (PMCJA) and the Pusat Tenaga Ra'ayat (PUTERA), to oppose the Federation Proposals. This paper examines the origin, leadership and organisation of the PMCJA-PUTERA as well as its agitation against the Federation scheme during the years, 1946–48.
The Abolition of Elective Local Government in Penang
Authors: Tennant Paul
Published: April 2011

The demise of elective local government in the State of Penang, Malaysia, is worth examining for several reasons. George Town, the state capital, was the first British settlement in the Far East; traces of elective local government appeared in the city early in the nineteenth century and the subsequent development of local government in the city followed British theory and practice to such a degree that at the time of Malayan Independence in 1957 the George Town City Council was a remarkable replica of a British town council. To study the George Town Council after Independence is thus to study a transplanted western institution which failed to survive within an Asian political system. Of more significance, however, is the light which a study of elective local government in Penang casts upon the fundamental transformations now underway in local government throughout Malaysia. Penang was the only state in the Federation to attain fully developed elective local government. Penang was one of the two states (the other was Malacca) in which all state territory and all state citizens were within the jurisdiction of local authorities. Penang however, was the only state in which every local authority consisted entirely of elected members and the only state in which every local authority was financially autonomous of the state government. Yet in 1966 the George Town Council was suspended and in 1971 the remaining local authorities were suspended as well. Penang became the first state in the federation to have no elective local government at all. It now seems likely that the other Malaysian states will follow Penang's lead (indeed, Malacca did so in early 1972), since it is now clear that the sanguine view of elective local government originally held by state and central officials has given way to one of pessimism and distrust. In July 1971 the Minister of Local Government indicated in Parliament that the central government believed that elective local government should be abolished. For these reasons, and for others which will become apparent in this paper, a study of the decline of elective local government in Penang provides an opportunity not only to test the hypotheses which have already been advanced to explain the demise of elective local government in the State itself, but also to test wider hypotheses advanced to explain the actions of national and state government towards elective local government throughout Malaysia.
The Growth of the Rubber Economy of Southern Thailand
Authors: Stifel Laurence D.
Published: April 2011

In 1934 the Siamese Council of Ministers agreed to participate in an international rubber control scheme without understanding either the dynamics of the expansion process or the extensiveness of the planting of small stands of rubber trees in peninsular Siam. The area estimates and export statistics available in Bangkok caused the government to believe that the quota offered by the International Rubber Regulation Committee was generous, and they consequently signed agreements with the producers' organizations and cooperating countries subject only to the ratification of the People's Assembly. The State Councilors were so confident of perfunctory approval of what appeared to be a technical issue that they delayed submitting the proposal until three months after the effective date of the agreement. But when the debate opened the representatives from the South sharply challenged the government estimates for failing to account for the areas of immature trees or to recognize that low prices had depressed production below current capacity. Neither Premier Bahol's plea that negotiations with countries “which are already civilised require something substantial in the way of evidence, such as statistics,” nor the need to honor the government's commitment dissuaded them.1 A minor political crisis was precipitated as the Assembly rejected the proposal and Siam's first constitutional government resigned.
The ‘Double-Seventh’ Incident, 1937: Singapore Chinese Response to the Outbreak of the Sino-Japanese War
Authors: Seng Pang Wing
Published: April 2011

In his two pioneer studies on the Nanyang Chinese national salvation movement between 1908 and 1941, Professor Yoji Akashi stresses developments in China, and the extension of KMT and CCP structures in the Nanyang as basic “to any investigation of Nanyang Chinese political motive and orientation”. These developments, if viewed from a rather Sino-centric standpoint, are indeed important in explaining why the Singapore hua-ch'iao (overseas Chinese) responded as they did to the Double-Seventh Incident of 1937. However, contemporary local sources reveal that forces and conditions in Singapore played a decisive part in shaping the stand and modus operandi adopted by Singapore Chinese at the outbreak of the 1937 Sino-Japanese War.
The United States, Viet-Nam, and the Cold War: A Reappraisal
Authors: Siracusa Joseph M.
Published: April 2011

The Viet-Nam War was without qualification the most unpopular war in United States history. By May 1971, 61 per cent of the 1,502 persons interviewed by the Gallup Poll thought it had been a mistake for the United States to become involved in Viet-Nam. (The question asked was, “In view of the developments since we entered the fighting in Viet-Nam, do you think the United States made a mistake sending troops to fight in Viet-Nam?” 28 per cent answered, “No”, and 11 per cent had no opinion.) The significance of the May poll lay in the fact that it marked a complete reversal of public opinion since Gallup first started asking the question in August 1965.
Malayan Union Citizenship: Constitutional Change and Controversy in Malaya, 1942–48
Authors: Lau Albert
Published: April 2011

Responding to the new forces unleashed by the Second World War, Whitehall planners devised a new scheme that envisaged the creation of Malayan Union Citizenship. In a fundamental break from past practice, the new scheme sought to confer citizenship privileges on Malaya's non-Malay population. In the aftermath of the War the implementation of the new policy embroiled the Colonial Office in a major constitutional controversy that threatened not only Britain's traditional relationship with the indigenous Malay community but also the bases of British rule in Malaya.
The Philippine Congress and the Barrio Electoral Process
Authors: Villanueva A. B.
Published: April 2011

Filipino barrios are mostly rural villages. They are, in legal parlance, the smallest political subdivisions in the Philippine system of local governments. Before the fifties barrio government was virtually non-existent. Although there were barrio lieutenants appointed by municipal mayors, it was not until the mid-fifties that councils began to give the barrios a semblance of government — mostly in form rather than in substance —similar to the commission plan of American local government. Under the unitary system of Filipino government, all local governments, except those in the chartered cities, are governed by the Revised Administrative Code. To give the barrio a government of its own and to grant its citizens the right to vote for their own officials would require an amendment to this Code by the Philippine Congress. Thus, the establishment of the first elective barrio councils in 1956 was the result of an amendment to an appropriate section of that Code. Later in 1959 the Philippine Congress became more generous by granting the barrios a general charter which defined in more definitive terms the scope and nature of barrio councils and the manner in which members of these councils were chosen. The purpose of this article is to identify the major issues on the barrio electoral process which confronted the Philippine Congress and to provide some insight into the manner in which these issues were resolved.
Political Rituals in Developing Nations: The case of the Philippines
Authors: Suhrke Astri
Published: April 2011

Systematic manipulation of symbols is present to varying degrees in all political processes. Such rituals may or may not suggest further substantive action, and when they do, such action may or may not be forthcoming. The term ritualism (or ritualistic behaviour) will here refer to activity which can be subsumed under the general concept of formalism. While some political scientsists describe formalism as a concern to establish an institution rather than to ensure its functioning, our use of the term is less specific: both structure and function may be symbols and parts of a ritual which, if suggesting further activity which is not forthcoming, constitutes ritualism.
New Zealand and the Singapore Base between the Wars
Authors: McIntyre W. David
Published: April 2011

New Zealand was one of the first parts of the British Empire to offer Britain help in the building of the Singapore naval base and was the only Dominion to do so. It is true that considerable financial help was given by the Straits Settlements. Hong Kong, the Federated Malay States and the Sultan of Johore. Australia's naval programme was, also, based on the assumption that the base would be built. But the Reform Party Ministry in New Zealand was the only democratically elected government which supported the United Kingdom Government with a vote of funds.
Archaeological Investigations of Pattani History
Authors: Welch David J. , McNeill Judith R.
Published: April 2011

Archaeological research at the Yarang complex of moated sites in Pattani demonstrates that this was an early historic Buddhist ceremonial centre and a later Islamic fortification, but probably not the early trade centre called Langkasuka. At Kerisik archaeological evidence supports the identification of this complex as the location of the fifteenth-eighteenth century trading port city of Patani.
The Impact of Missionary Christianity Upon Marginalized Ethnic Minorities: The Case of the Hmong
Authors: Tapp Nicholas
Published: April 2011

This paper combines historical with anthropological evidence on the relationship between Christianity and messianism among the Hmong of Southeast Asia and China. The lack of literacy is a motivating factor in Hmong Christian conversions. Messianism is seen as a reaction to Christian conversion, which encourages the alienation of minority groups.
The Political Structure of the State of Kedah 1879–1905
Authors: Ahmat Sharom
Published: April 2011

The structure and organization of the Kedah political system, like those of the other patriachal Malay states in the Peninsula, was based essentially on that of the Malacca Sultanate. Under this system, the apex and centre of the organisation was the Sultan, whose political authority was strengthened by the belief that he was endowed with the magical attributes of a “divine king”. This is evident in his title, Yang di-Pertuan (He who is made Lord); and is also manifested in the elaborate court ceremonials and rituals; the clothing, weapons, domestic adornments and a special vocabulary reserved exclusively for royalty. The political functions of the Sultan were very comprehensive covering the fields of internal administration, the defence of the country, and matters relating to external affairs.
The Labour Movement and the Practice of Professional Management in Thailand
Authors: Mabry Bevars D.
Published: April 2011

The professionalization of management is a function of the stage of economic development, both of the enterprise and the economy in which it operates, for these stages influence the size, number, nature, and complexity of problems to which the enterprise is exposed. The nature of personnel problems, for example, are influenced by the relative maturation of the labour force in motivation, commitment and skill development, and management's responses to these problems evolve with the inducement of professionalism from the growing size, complexity, and diversity of industrial institutions. Compared to 1950, the labour force of Thailand in 1986 is more urban, better educated, more materially motivated, more ethnically uniform, and better disciplined to factory work. Hence, it should be more receptive to modern management practices. Yet, by American or Japanese standards, the Thai labour force is still comparatively primitive, and personnel are administered in a diverse milieu of work environments that condition the style and progress of management. As a consequence, the practice of management varies as widely in Thailand as it does in other developing countries between metropolitan and provincially located establishments, between large and small firms, among Thai, Thai-Chinese, Japanese, or Western firms.
Comparison of macrobenthic assemblages of three fish estuarine nurseries and their importance as foraging grounds
Authors: Selleslagh Jonathan , Lesourd Sandric , Amara Rachid
Published: April 2011

Macrobenthic assemblages were examined in three fish estuarine nurseries and related to environmental variables, as well as fish and macrocrustaceans, in order to assess and compare the potential foraging ground value of these systems. Macrobenthos was sampled in spring 2007 in the Canche, Authie and Somme estuaries (eastern English Channel, France). A total of 17, 28 and 23 macrobenthic taxa, with a clear dominance of amphipods (mainly Bathyporeia sarsi), polychaetes and bivalves, were recorded in the three estuaries respectively. Although predators (fish and macrocrustaceans) were abundant, relatively high densities of macrobenthos were observed: 876.2 ± 389.1, 595.4 ± 197.2 and 854.3 ± 281.2 ind. m-2 in the Canche, Authie and Somme, respectively. No significant difference in species richness, Shannon–Wiener diversity and density (total and dominant groups) of macrobenthos was observed between the three estuaries. Although the analysis of similarity and similarity percentages analyses indicated that macrobenthic assemblage was variable between Authie and Somme, results showed that macrobenthos resource was relatively high and similar in the three estuaries. Taking into account these considerations, the present study indicated a similar relative importance of the Canche, Authie and Somme estuaries as foraging grounds for fish and macrocrustaceans during spring. Multivariate analysis showed that macrobenthic assemblages were mainly driven by salinity and sediment characteristics in the Canche and Authie estuaries while in the Somme estuary sediment characteristics were the most influencing parameters.
Social Policy by Popular Demand
Authors: Rehm Philipp
Published: April 2011

Why are unemployment benefits more generous in some countries? This article argues that citizens trade off the redistributive and insuring effect of social insurance. As a result, the distribution of risk in a society has important consequences via popular demand for social policy-making. At the microlevel, the article shows that, in addition to income, the risk of unemployment is a key predictor of individual-level preferences for unemployment benefits. Based on the microlevel findings, the article argues that at the macrolevel the homogeneity of the risk pool is an important determinant of benefit generosity: the more equally unemployment risk is distributed, the higher unemployment replacement rates are. Empirical testing at both levels finds support for this account of social policy by popular demand.
The Enemy Within: Personal Rule, Coups, and Civil War in Africa
Authors: Roessler Philip
Published: April 2011

Why do rulers employ ethnic exclusion at the risk of civil war? Focusing on the region of sub-Saharan Africa, the author attributes this costly strategy to the commitment problem that arises in personalist regimes between elites who hold joint control of the state's coercive apparatus. As no faction can be sure that others will not exploit their violent capabilities to usurp power, elites maneuver to protect their privileged position and safeguard against others' first-a rising internal threat, rulers move to eliminate their rivals to guarantee their personal and political survival. But the cost of such a strategy, especially when carried out along ethnic lines, is that it increases the risk of a future civil war. To test this argument, the author employs the Ethnic Power Relations data set combined with original data on the ethnicity of conspirators of coups and rebellions in Africa. He finds that in Africa ethnic exclusion substitutes civil war risk for coup risk. And rulers are significantly more likely to exclude their coconspirators—the very friends and allies who helped them come to power—than other included groups, but at the cost of increasing the risk of a future civil war with their former allies. In the first three years after being purged from the central government, coconspirators and their coethnics are sixteen times more likely to rebel than when they were represented at the apex of the regime.
Bilingual parents' modeling of pragmatic language use in multiparty interactions
Authors: TARE MEDHA , GELMAN SUSAN A.
Published: April 2011

Parental input represents an important source of language socialization. Particularly in bilingual contexts, parents may model pragmatic language use and metalinguistic strategies to highlight language differences. The present study examines multiparty interactions involving 28 bilingual English- and Marathi-speaking parent–child pairs in the presence of monolingual bystanders (children's mean ages = 3 years, 2 months and 4 years, 6 months). Their language use was analyzed during three sessions: parent and child alone, parent and child with the English speaker, and parent and child with the Marathi speaker. Parents demonstrated pragmatic differentiation by using relatively more of the bystander's language; however, children did not show this sensitivity. Further, parents used a variety of strategies to discuss language differences, such as providing and requesting translations; children translated most often in response to explicit requests. The results indicate that parents model pragmatic language differentiation as well as metalinguistic talk that may contribute to children's metalinguistic awareness.
Cycle-types in the automorphism groups of countable homogeneous graphs
Authors: LOVELL S. , TRUSS J. K.
Published: April 2011

We give a classification of all the cycle types occurring in the automorphism groups of countable homogeneous graphs.
Other nature: geodiversity and geosystem services
Authors: GRAY MURRAY
Published: April 2011

The concepts of biodiversity and ecosystem services have become widely established and adopted within and beyond nature conservation circles. But biotic nature is only part of nature. The existence and importance of abiotic nature often goes unrecognized and is certainly undervalued. This Comment tries to redress the balance by outlining some recent developments in valuing and conserving abiotic nature, particularly the important concepts of geodiversity and geosystem services.
Genetic diversity and antibiotic resistance inShigella dysenteriaeandShigella boydiistrains isolated from children aged <5 years in Egypt
Authors: EL-GENDY A. M. , MANSOUR A. , WEINER M. A. , PIMENTEL G. , ARMSTRONG A. W. , YOUNG S. Y. N. , ELSAYED N. , KLENA J. D.
Published: April 2011

Diversity withinShigella dysenteriae(n=40) andShigella boydii(n=30) isolates from children living in Egypt aged <5 years was investigated.Shigella-associated diarrhoea occurred mainly in summer months and in children aged <3 years, it commonly presented with vomiting and fever. Serotypes 7 (30%), 2 (28%), and 3 (23%) accounted for most ofS. dysenteriaeisolates; 50% ofS. boydiiisolates were serotype 2.S. dysenteriaeandS. boydiiisolates were often resistant to ampicillin, chloramphenicol and tetracycline (42%, 17%, respectively), although resistance varied among serotypes. Pulsed-field gel electrophoresis separated the isolates into distinct clusters correlating with species and serotype. Genetic differences in trimethoprim/sulfamethoxazole and β-lactam-encoding resistance genes were also evident.S. dysenteriaeandS. boydiiare genetically diverse pathogens in Egypt; the high level of multidrug resistance associated with both pathogens and resistance to the most available inexpensive antibiotics underlines the importance of continuing surveillance.
Autologous embryo–cumulus cells co-culture and blastocyst transfer in repeated implantation failures: a collaborative prospective randomized study
Authors: Benkhalifa M. , Demirol A. , Sari T. , Balashova E. , Tsouroupaki M. , Giakoumakis Y. , Gurgan T.
Published: April 2011

In repeated implantation failure, the co-culture of human embryos with somatic cells has been reported to promote the improvement of embryos quality, implantation and pregnancy rate. It was reported that feeder cells can be more beneficial to the oocyte and embryo by detoxifying the culture medium and supporting embryo development via different pathways. In this study, 432 patients, each with a minimum of three repeated implantation failures, were accepted for a prospective randomized study with or without autologous cumulus cell embryo co-culture and transfer at day 3 or day 5–6. We also investigated the expression of leukaemia inhibitor factor (LIF) and platelet activating factor receptor (PAF-R) on day 3 confluent cumulus cells. The statistic analysis of the data showed significant difference of implantation and clinical pregnancy rates between classical culture and day 3 compared with co-culture and day 5–6 transfer. The molecular analysis showed that cumulus cells express the LIF and the PAF-R genes and confirmed the possible positive role of growth factors and cytokines in early embryo development. Embryo co-culture systems with autologous cells can be beneficial in routine in vitro fertilization for embryo selection and implantation improvement. More molecular investigations need to be done to improve elucidation of the complex dialogue between the embryo and feeder cells prior to implantation and to understand the involved biological function and molecular process during embryo development.
What do foreign neighbors say about the mental lexicon?
Authors: VITEVITCH MICHAEL S.
Published: April 2011

A corpus analysis of phonological word-forms shows that English words have few phonological neighbors that are Spanish words. Concomitantly, Spanish words have few phonological neighbors that are English words. These observations appear to undermine certain accounts of bilingual language processing, and have significant implications for the processing and representation of word-forms in bilinguals.
Consumer preferences and the National Treatment Principle: emerging environmental regulations prompt a new look at an old problem
Authors: LYDGATE EMILY BARRETT
Published: April 2011

Should consumers' preference for ‘green’ products help justify, from a WTO perspective, emerging regulations such as restrictions on trade in non-sustainable biofuels? Despite the role consumer preferences have played in WTO disputes, in association with the ‘like’ products concept, there has not been enough focused examination of their specific influence, particularly in disputes on ethical public policy issues, such as environmental or health regulations. To this end, this paper examines key GATT Article III disputes, pointing out that they included attempts both to measure, and also to interpret, consumer preferences. The latter approach becomes more tempting when consumer preferences are difficult to measure; import bans or restrictions associated with ethical public policy regulations can bring about such a situation. A hypothetical dispute about EC biofuels sustainability criteria demonstrates this problem. Options to make the concept of consumer preferences more coherent include limitations on how they can be invoked, and an increased commitment to capturing them through measurement.
Adherence and competence assessment in studies of CBT for psychosis: current status and future directions
Authors: Fowler D. , Rollinson R. , French P.
Published: April 2011

All good quality trials of psychological interventions need to check formally that therapists have used the techniques prescribed in the published therapy manuals, and that the therapy has been carried out competently. This paper reviews methods of assessing adherence and competence used in recent large-scale trials of Cognitive Behaviour Therapy (CBT) for psychosis in the UK carried out by our research groups. A combination of the Cognitive Therapy Rating Scale and specific versions of the Cognitive Therapy for Psychosis Adherence Scales provides an optimal assessment of adherence and competence. Careful assessment of the competence and adherence can help identify the procedures actually carried out with individuals within trials. The basic use of such assessments is to provide an external check on treatment fidelity on a sample of sessions. Such assessment can also provide the first step towards moving research towards making sense of CBT for psychosis as a complex intervention and identifying which techniques work for which problems of people with psychosis, at which stages of disorder?
Collaborative Supercomputing for Global Change Science
Authors: Nemani R. , Votava P. , Michaelis A. , Melton F. , Milesi C.
Published: April 2011

There is increasing pressure on the science community not only to understand how recent and projected changes in climate will affect Earth's global environment and the natural resources on which society depends but also to design solutions to mitigate or cope with the likely impacts. Responding to this multidimensional challenge requires new tools and research frameworks that assist scientists in collaborating to rapidly investigate complex interdisciplinary science questions of critical societal importance. One such collaborative research framework, within the NASA Earth sciences program, is the NASA Earth Exchange (NEX). NEX combines state‐of‐the‐art supercomputing, Earth system modeling, remote sensing data from NASA and other agencies, and a scientific social networking platform to deliver a complete work environment. In this platform, users can explore and analyze large Earth science data sets, run modeling codes, collaborate on new or existing projects, and share results within or among communities (see Figure S1 in the online supplement to this Eos issue (http://www.agu.org/eos_elec)).
Great Lakes Literacy Principles
Authors: Fortner Rosanne W. , Manzo Lyndsey
Published: April 2011

Lakes Superior, Huron, Michigan, Ontario, and Erie together form North America's Great Lakes, a region that contains 20% of the world's fresh surface water and is home to roughly one quarter of the U.S. population (Figure 1). Supporting a $4 billion sport fishing industry, plus $16 billion annually in boating, 1.5 million U.S. jobs, and $62 billion in annual wages directly, the Great Lakes form the backbone of a regional economy that is vital to the United States as a whole (seehttp://www.miseagrant.umich.edu/downloads/economy/11‐708‐Great‐Lakes‐Jobs.pdf). Yet the grandeur and importance of this freshwater resource are little understood, not only by people in the rest of the country but also by many in the region itself. To help address this lack of knowledge, the Centers for Ocean Sciences Education Excellence (COSEE) Great Lakes, supported by the U.S. National Science Foundation and the National Oceanic and Atmospheric Administration, developed literacy principles for the Great Lakes to serve as a guide for education of students and the public. These “Great Lakes Literacy Principles” represent an understanding of the Great Lakes' influences on society and society's influences on the Great Lakes.
Yun‐tai Chen Receives 2010 International Award
Authors: Das Shamita , Chen Yun‐tai
Published: April 2011

Yun‐tai Chen received the International Award at the 2010 AGU Fall Meeting Honors Ceremony, held on 15 December 2010 in San Francisco, Calif. The award honors “an individual scientist or a small team for making an outstanding contribution to furthering the Earth and space sciences and using science for the benefit of society in less favored nations.”
Cerebral Circulation and Histamine: 1. Participation of Vascular H1- and H2-Receptors in Vasodilatatory Responses to Carotid Arterial Infusion
Authors: Gross Paul M. , Harper A. Murray , Teasdale Graham M.
Published: April 2011

We examined the cerebral circulatory effects of intra-carotid infusion of histamine or its receptor agonists in anesthetized rats. Cerebral blood flow was measured by two methods: an intracarotid 133Xe clearance technique and tissue sampling after systemic administration of the diffusible tracer, [14C]iodoantipyrine. Brain metabolic responses were estimated by the 2-deoxyglucose method and tissue sampling. Intracarotid infusion of histamine when the blood-brain barrier was intact did not increase cerebral blood flow. Following disruption of the blood-brain barrier by carotid injection of hypertonic urea, histamine evoked dose-dependent increases (133Xe clearance method) in cerebral blood flow to a maximum of 50% (20 μg min−1 kg−1); histamine produced increases in blood flow to areas supplied by the internal carotid artery, e.g., thalamus and parietal cortex ([14C]iodoantipyrine method). Both classes of histamine receptors (H1 and H2) participated in mediating increases in cerebral blood flow after blood-brain barrier opening. Mepyramine (H1-antagonist) and metiamide (H2-antagonist) attenuated blood flow responses to histamine infusion (133Xe clearance method); metiamide was the more effective blocking agent. Pyridylethylamine (H1-agonist) and dimaprit (H2-agonist) both caused increases in regional cerebral blood flow ([14C]iodoantipyrine method). Histamine infusion after blood-brain barrier opening did not increase cerebral glucose consumption. We suggest that increases in cerebral blood flow produced by histamine are the result of stimulation of vascular H1- and H2-receptors, rather than a secondary response to metabolic activation.
Derivation of Equations for the Steady-State Reaction Velocity of a Substance Based on the Use of a Second Substance
Authors: Patlak Clifford S.
Published: April 2011

To study the transport and/or transformation of a particular molecular species, a second substance, which need not be chemically identical to that species, can be employed. Equations are derived for the steady-state velocity of the molecular species that use values found by use of the second substance.
Effects of Naftidrofuryl on Local Cerebral Glucose Utilization in the Rat
Authors: Orzi F. , Schuier F. , Fieschi C.
Published: April 2011

The effects of naftidrofuryl on local cerebral glucose utilization have been examined in 21 lightly restrained, conscious rats by means of the quantitative autoradiographic 2-deoxyglucose technique. Naftidrofuryl (15, 30, and 45 mg/kg, i.p.) did not significantly alter the rate of glucose utilization in any of the 29 gray matter or 4 white matter areas that were examined.
Effects of Immobilization Stress on Regional Cerebral Blood Flow in the Conscious Rat
Authors: Ohata M. , Fredericks W. R. , Sundaram U. , Rapoport S. I.
Published: April 2011

Immobilization stress of conscious, normotensive, freely breathing 10-month-old Wistar-Kyoto rats produced an overall decline in regional cerebral blood flow (rCBF), as measured with [14C]iodoantipyrine, except at the frontal lobe. In 14 brain regions, rCBF fell by an average of 14.3% after 5 min of immobilization and by 11.9% after 15 min. Immobilization stress also stimulated hyperventilation and thereby reduced Paco2. The slope relating rCBF to Paco2 averaged 1.5 ml 100 g−1 min−1 mm Hg−1 in 9 significantly affected regions. The findings suggest that rCBF declines during immobilization stress because of cerebrovascular constriction caused by a reduction in Paco2. Comparison of the average slope with published values indicates furthermore that were Paco2 to remain unchanged during immobilization, rCBF would increase by at most 20%.
Effect of Indomethacin on Local Cerebral Blood Flow in Awake, Minimally Restrained Rats
Authors: Dahlgren Nils , Ingvar Martin , Yokoyama Hideo , Siesjö Bo K.
Published: April 2011

The effect of indomethacin (10 mg kg−1) on local CBF (l-CBF) was studied with autoradiographic techniques in awake, minimally restrained rats. When compared with uninjected awake control animals, those given indomethacin showed a reduction of l-CBF by 25–45%. This reduction is somewhat less pronounced than that previously obtained in paralyzed animals maintained on 70% N2O (a reduction by 30–60%). An enhancement of the indomethacin response during nitrous oxide anesthesia was mainly observed in structures which show a maintained or increased CBF during anesthesia.
Autonomic Nerves in the Mammalian Choroid Plexus and Their Influence on the Formation of Cerebrospinal Fluid
Authors: Lindvall Maria , Owman Christer
Published: April 2011

The choroid plexuses of all ventricles receive a well-developed adrenergic and cholinergic innervation reaching both the secretory epithelium and the vascular smooth muscle cells. Also peptidergic nerves, containing vasoactive intestinal polypeptide, are present but primarily associated only with the vascular bed. A sympathetic inhibitory effect on the plexus epithelium has been indicated in determinations of carbonic anhydrase activity and by studies of various aspects of active transport in isolated plexus tissue. Pharmacological analysis in vitro has shown the choroidal arteries to possess both vasoconstrictory α-adrenergic and vasodilatory β-adrenergic receptors. Electrical stimulation of the sympathetic nerves, which originate in the superior cervical ganglia, induces as much as 30% reduction in the net rate of cerebrospinal fluid (CSF) production, while sympathectomy results in a pronounced increase, about 30% above control, in the CSF formation. There is strong reason to believe that the choroid plexus is under the influence of a considerable sympathetic inhibitory tone under steady-state conditions. From pharmacological and biochemical experiments it is suggested that the sympathomimetic reduction in the rate of CSF formation is the result of a combined β-receptormediated inhibition of the secretion from the plexus epithelium and a reduced blood flow in the choroid plexus tissue resulting from stimulation of the vascular α-receptors. The choroid plexus probably also represents an important inactivation site and gate mechanism for sympathomimetic amines, as evidenced by considerable local activity of catechol- O-methyl transferase and monoamine oxidase, primarily type B. The CSF production rate is also reduced by cholinomimetic agents, suggesting the presence of muscarinic-type cholinergic receptors in the choroid plexus.
Hypoglycemic Brain Injury: Phospholipids, Free Fatty Acids, and Cyclic Nucleotides in the Cerebellum of the Rat after 30 and 60 Minutes of Severe Insulin-Induced Hypoglycemia
Authors: Agardh Carl-David , Siesjö Bo K.
Published: April 2011

Previous results from this laboratory have shown that although prolonged severe hypoglycemia (30 or 60 min with cessation of electroencephalographic activity) leads to relatively extensive energy failure in the cerebellum. there is surprisingly little histopathologic evidence of cell damage and virtually complete sparing of the Purkinje cells. In the present study, we induced hypoglycemia of the above-mentioned durations and compared metabolic alterations in the cerebral cortex (a structure which shows extensive cell damage) and the cerebellum. The experiments were performed on rats ventilated on 70% N2O and 30% O2, and hypoglycemia was induced by insulin administration. After 30 and 60 min of hypoglycemia the majority of animals showed changes in cerebellar energy state considerably less pronounced than in the cerebral cortex. In some animals. useful amounts of glycogen remained even after 60 min of hypoglycemic coma. It is suggested that part of the resistance of the cerebellum in hypoglycemia is due to a better preserved substrate supply, probably since the cerebellum contains a higher density of glucose transport sites. However, this alone cannot explain the higher resistance of the tissue. Thus, in all 30-min animals the cerebellum showed some deterioration of cellular energy state, and after 60 min the majority had relatively extensive energy failure. Furthermore, the results obtained after 60 min of hypoglycemia suggested that some decrease in phospholipid content occurred. During hypoglycemia. the cerebellar concentrations of cyclic AMP and cyclic GMP rose. The concentration of cyclic GMP, but not that of cyclic AMP, showed an inverse relationship to the energy charge. In cerebellum, cyclic GMP rose to higher values than in the cerebral cortex, and in contrast to that in the cerebral cortex, cyclic AMP concentration in the cerebellum showed no tendency to secondary reduction with progressive deterioration of tissue energy state. During hypoglycemia, the concentrations of free fatty acids increased in the cerebellum, the values showing an inverse relationship to cellular energy state. However, the accumulation seemed less pronounced than in the cerebral cortex, even when the two structures were compared at similar degrees of deterioration of energy state. Since accumulation of polyenoic free fatty acids has been implicated in tissue damage in several adverse situations, the results hint that part of the resistance of the cerebellum to the hypoglycemic insult may be due to a better preserved Ca2+ homeostasis and/or a less pronounced activation of phospholipase A2.
Brain Lactic Acidosis and Ischemic Cell Damage: 1. Biochemistry and Neurophysiology
Authors: Rehncrona Stig , Rosén Ingmar , Siesjö Bo K.
Published: April 2011

This study explores the influence of severe lactic acidosis in the ischemic rat brain on postischemic recovery of the tissue energy state and neurophysiological parameters. Severe incomplete brain ischemia (cerebral blood flow below 5% of normal) was induced by bilateral carotid artery clamping combined with hypovolemic hypotension. We varied the production of lactate in the tissue by manipulating the blood glucose concentrations. A 30-min period of incomplete ischemia induced in food-deprived animals caused lactate to accumulate to 15–16 μmol g−1 in cortical tissue. Upon recirculation these animals showed: (1) a considerable recovery of the cortical energy state as evaluated from the tissue concentrations of phosphocreatine, ATP, ADP, and AMP; and (2) return of spontaneous electrocortical activity as well as of somatosensory evoked response (SER). In contrast, administration of glucose to food-deprived animals prior to ischemia caused an increase in tissue lactate concentration to about 35 μmol g−1. These animals did not recover energy balance in the tissue and neurophysiological functions did not return. In other experiments the production of lactate during 30 min of complete compression ischemia was increased from about 12 μmol g−1 (normoglycemic animals) to 20–30 μmol g−1 by preischemic hyperglycemia and. in separate animals, combined hypercapnia. The recovery of the cortical energy state upon recirculation was significantly poorer in hyperglycemic animals. It is concluded that a high degree of tissue lactic acidosis during brain ischemia impairs postischemic recovery and that different degrees of tissue lactic acidosis may explain why severe incomplete ischemia, in certain experimental models, is more deleterious than complete brain ischemia.
Brain Lactic Acidosis and Ischemic Cell Damage: 2. Histopathology
Authors: Kalimo H. , Rehncrona S. , Söderfeldt B. , Olsson Y. , Siesjö B. K.
Published: April 2011

The influence of severe tissue lactic acidosis during incomplete brain ischemia (30 min) on cortex morphology was studied in fasted rats. Production of lactate in the ischemic tissue was varied by preischemic infusions (i.v.) of either a saline or a glucose solution. The brains were fixed by perfusion with glutaraldehyde at 0, 5, or 90 min of recirculation. In saline-infused animals (tissue lactate about 15 μmol g−1), changes observed at 0 and 5 min of recirculation were strikingly discrete: slight condensation of nuclear chromatin. mild to moderate mitochondrial swelling, and only slight astrocyte edema. These changes had virtually disappeared after 90 min recirculation and. at this time. only discrete ribosomal changes were observed. In contrast. glucose-infused rats (tissue lactate about 35 μmol g−1) showed severe changes: marked clumping of nuclear chromatin and cell sap in all cells was already evident at 0 and 5 min recirculation, while mitochondrial swelling was mild to moderate. Although tissue fixation was inadequate at 90 min. the ultrastructural appearance indicated extensive damage. It is concluded that excessive tissue lactic acidosis during brain ischemia exaggerates structural alterations and leads to irreversible cellular damage. A tentative explanation is offered for the paucity (<0.2%) of condensed neurons with grossly swollen mitochondria. previously considered a hallmark of ischemic cell injury.
Effect of the Calcium Antagonist, Nimodipine, on Cerebral Blood Flow and Metabolism in the Primate
Authors: Harper A. M. , Craigen L. , Kazda S.
Published: April 2011

The effect of the calcium antagonist nimodipine was tested in anaesthetised primates. A rapid intravenous injection of 3 or 10 μg kg−1 produced a transient rise in end-tidal Pco2 and a fall in arterial blood pressure, but 10 min after the injection there was no significant change in CBF. A continuous intravenous infusion of 2 μg kg−1 min−1 caused a modest fall in mean arterial blood pressure and an increase in cerebral blood flow (CBF), which gradually increased to 27% above control after 50 min infusion. There was no significant change in CMRO2. A continuous intracarotid infusion of 0.67 μg kg−1 min−1 caused an increase in CBF of between 46 and 57%. This was further increased to 87% above control after disruption of the blood-brain barrier with hyperosmolar urea. Thirty minutes after the urea, the CBF returned to 43% above control. Twenty minutes after the infusion of nimodipine had been stopped, the CBF had returned to control values. EEG studies in this group showed no obvious increase in electrocortical activity. This evidence suggests that nimodipine has no effect on cerebral metabolism but increases CBF, particularly after disruption of the blood-brain barrier.
Regional Cerebral Blood Flow during Rest and Skilled Hand Movements by Xenon-133 Inhalation and Emission Computerized Tomography
Authors: Lauritzen Martin , Henriksen Leif , Lassen Niels A.
Published: April 2011

Regional cerebral blood flow (CBF) was studied in 16 normal adult volunteers during rest and in 10 the study was repeated during skilled hand movements. A fast-rotating (“dynamic”), single-photon emission computerized tomograph (ECT) with four detector heads was used. Xenon-133 was inhaled over a 1-min period at a concentration of 10 mCi/L. The arrival and washout of the radioisotope was recorded during four 1-min periods. Two slices, 2 cm thick, 7 and 12 cm above the orbitomeatal line were obtained in every study. CBF averaged 60 ml/100 g/min (SD ± 11) in the lower slice and 51 ml/100 g/min (SD ± 13) in the upper slice. A symmetric pattern comparing right to left sides was found in both slices. Finger tapping and writing with the right hand increased CBF in specific areas of the upper slice: in the contralateral hand area by 35 ± 15% ( p < 0.025), and in the supplementary motor area on both sides by 34 ± 15% ( p < 0.025).
Local Cerebral Blood Flow Values as Estimated with Diffusible Tracers: Validity of Assumptions in Normal and Ischemic Tissue
Authors: Tomita Minoru , Gotoh Fumio
Published: April 2011

A theoretical assessment is made of the validity of assumptions underlying the theory for estimating local cerebral blood flow with diffusible tracer in the tissue under normal and ischemic conditions. First, Kety's derivation of equations that have commonly been used for calculating local cerebral blood flow values is examined in order to define the problems and assumptions. Second, the brain:blood partition coefficient of diffusible tracer, λ and the diffusion-limited factor, m, under normal and ischemic conditions are reviewed. An examination of the literature suggested that contrary to common belief, λ appears to change very little in ischemia if the tissue constituents remain unchanged, whereas m does change with ischemia if the diffusible tracer used is greatly diffusion-limited in the exchange between brain and blood. Even when a gas with an m value close to unity is used as the diffusible tracer, the prolonged mean transit time of blood through the ischemic tissue would make it difficult to maintain the exponential assumptions. As part of the ischemic tissue became infarcted, which is the case with most stroke patients, so the assumptions of homogeneous perfusion would become invalid. This inevitably renders it difficult to estimate local cerebral blood flow with diffusible tracer in ischemic tissue containing an infarcted mass.