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Made available in DSpace on 2016-06-02T19:23:00Z (GMT). No. of bitstreams: 1 DissAAV.pdf: 1362349 bytes, checksum: 68cba4c2d130812fd38174505062b5a0 (MD5) Previous issue date: 2005-03-21 / Universidade Federal de Sao Carlos / Cardiovascular responses are integrated at different levels of the central nervous system (CNS). Particularly the hypothalamus and brainstem areas are involved in the control of autonomic responses and among them the cardiovascular responses. Different areas in the brainstem, like the nucleus tract solitarii (NTS), the rostroventrolateral medulla (RVLM), caudoventrolateral medulla (CVLM) and the nucleus ambigus are important to cardiovascular control. These areas of the brainstem that control the cardiovascular system receive information from receptors present in different parts of the body, specially the pressoreceptors and chemoreceptores and control the activity of the autonomic efferents. Injection of the excitatory amino acid glutamate into the NTS in anesthetized rats produces depressor response and bradycardia like barorreflex activation. Differently, in unanesthetized rats, injection of the glutamate into the NTS produces pressor response and bradycardia, similar to chemoreflex activation. The neuropeptide substance P may act as neurotransmitter or neuromodulator of differents cardiovascular reflexes and when injected into the NTS produces pressor response. The RVLM is the main site of sympathetic output to the intermediolateral cell column of the spinal cord. Injection of glutamate into the RVLM increases sympathetic activity and induces pressor response. Hypotalamic areas are also involved in the control of cardiovascular responses. For example, electrolytic lesions in the paraventricular nucleus of the hypothalamus (PVN), reduce the pressor response to chemoreflex activation with potassium cyanide (KCN) iv Another hypothalamic area important for cardiovascular control is the anteroventral third ventricle (AV3V) region. Electrolytic lesion of the AV3V region reduces the cardiovascular responses produced by central colinergic and angiotensinergic activation and abolish many forms of the experimental hypertension in animals. In the present study, in unanesthetized rats, we investigated the effects of acute (1 day) and cronic (15 days) AV3V lesions in the pressor responses produced by NTS activation with injection of the excitatory amino acid glutamate and substance P or injection of glutamate into the RVLM. The responses to activation of the baroreflex and chemoreflex were also tested. Rats with sham or electrolytic lesions of the AV3V region and stainless steel cannulas implanted into the NTS or RVLM were used. Mean arterial pressure (MAP) and heart rate (HR) were recorded in unanesthetized rats. A polyethylene tubing was inserted into the abdominal aorta through the femoral artery on day before the experiments. A second polyethylene tubing was inserted in the femoral vein for the baroreflex and chemoreflex tests. The central injections were made using 5 µl Hamilton syringes. The volume of the central injections into the NTS and RVLM was 100 nl. In sham rats, the injection of glutamate (5 nmol) into the NTS produce pressor response (28 ± 3 mmHg). The same dose of glutamate in acute AV3V-lesioned rats produce hypotension (-26 ± 8 mmHg) in the first day after lesion or did not modify the MAP (2 ± 8 mmHg) fifteen days after AV3V lesion. The bradycardic responses produced by injection of the glutamate into the NTS in acute (-65 ± 23 bpm) or cronic (-90 ± 29 bpm) AV3Vlesioned rats were not different from the bradycardic responses produced by glutamate into the NTS in sham-lesioned rats (-76 ± 13 e -90 ± 15 bpm). Differently, the pressor response produced by injection of substance P (0,5 e 1 nmol) into the NTS in acute (16 ± 2 and 20 ± 2 mmHg, respectively) or chronic AV3V-lesioned rats (18 ± 1 and 20 ± 1 mmHg) were not different from the pressor responses produced by the same doses of substance P into the NTS in acute (20 ± 5 and 22 ± 3 mmHg) or chronic sham rats (19 ± 3 and 25 ± 3 mmHg). The tachycardic responses produced by injection of substance P into the NTS in acute (54 ± 15 and 71 ± 15 bpm) and chronic AV3V-lesioned rats (70 ± 11 and 66 ± 11 bpm) were also not different from the tachycardic responses produced by substance P into the NTS in acute (75 ± 14 and 72 ± 12 bpm) or chronic sham rats (53 ± 16 e 84 ± 7 bpm). The pressor responses produced by injections of glutamate (1, 5 and 10 nmol) into the RVLM in acute (9 ± 4, 39 ± 6 e 37 ± 4 mmHg, respectively) or chronic AV3V-lesioned rats (13 ± 6, 39 ± 4 and 43 ± 4 mmHg, respectively) were significantly reduced compared to the pressor responses of the same doses of glutamate into the RVLM in acute (33 ± 5, 54 ± 3 and 56 ± 8 mmHg, respectively) or chronic sham rats (29 ± 3, 50 ± 2 and 58 ± 3 mmHg, respectively). Glutamate into the RVLM in acute or chronic sham or AV3V lesioned rats produced no significant change in the heart rate. The baroreflex responses produced by iv phenylephrine (5 µg/kg of body weight), sodium nitroprussiade (30 µg/kg of body weight), or the responses produced by chemoreflex activation with iv injection of potassium cyanide (20 and 40 µg/rato) were not modified by acute or chronic AV3V lesion. The results show the importance of the AV3V region for the cardiovascular responses dependent on the activation of the sympathetic nervous system and specially the pressor responses to glutamatergic activation in the NTS and RVLM. The integrity of the AV3V region is important for the pressor responses to injection of glutamate into the NTS and into the RVLM, but not for the pressor response to injection of substance P into the NTS, which suggests that the AV3V lesion does not non specifically affect any pressor mechanism. The AV3V lesions do not modify the baro and chemoreflex responses, suggesting that the sympatoexcitatory responses to chemoreflex activation do not depend unique and exclusively on glutamatergic neurotransmission in the NTS and RVLM. / Respostas cardiovasculares podem ser integradas em diferentes níveis do sistema nervoso central (SNC). Em particular, o hipotálamo e o bulbo estão muito envolvidos com o controle de respostas autonômicas, entre as quais estão as repostas cardiovasculares. No bulbo estão vários núcleos importantes para o controle cardiovascular como o núcleo do trato solitário (NTS), as áreas rostroventrolateral (RVL) e caudoventrolateral (CVL) e o núcleo ambíguo. Um circuito envolvendo essas áreas bulbares é responsável pelo controle básico do sistema cardiovascular, podendo receber informações dos receptores localizados em diferentes partes do organismo, em especial dos pressorreceptores e quimiorreceptores e, integrando essas informações de diversas origens, comandar as eferências autonômicas. Injeção do aminoácido excitatório glutamato no NTS de ratos anestesiados produz resposta hipotensora e bradicárdica semelhante à ativação do barorreflexo. Diferentemente, em animais não anestesiados, a injeção de glutamato no NTS provoca resposta pressora e bradicárdica, semelhante á ativação do quimiorreflexo. A substância P é um neuropeptídeo que também quando injetada no NTS produz efeito pressor, podendo atuar como neurotransmissor ou neuromodulador dos diferentes reflexos cardiovasculares. A área RVL é o principal sítio de saída simpática para a coluna intermédio lateral (IML). Injeção de glutamato na área RVL produz disparos dos neurônios simpáticos para a IML produzindo resposta pressora. É bem relatado, que áreas hipotalâmicas exercem forte modulação sobre respostas cardiovasculares. Uma dessas áreas é o núcleo paraventricular do hipotálamo (NPV), cuja lesão eletrolítica reduz a resposta pressora à ativação do quimiorreflexo com cianeto de potássio i.v. Uma outra área hipotalâmica muito importante para o controle cardiovascular é a região anteroventral do terceiro ventrículo (AV3V), cuja lesão reduz as respostas cardiovasculares produzidas pela ativação colinérgica e angiotensinérgica central e impede o desenvolvimento de diversas formas de hipertensão em animais. No presente estudo o objetivo foi estudar em ratos não anestesiados, os efeitos da lesão aguda (1 dia) e crônica (15 dias) da região AV3V sobre as respostas pressoras produzidas pela ativação do NTS com injeção do aminoácido excitatório glutamato e da taquicinina substância P ou pela injeção de glutamato na área RVL, além de se testar as respostas à ativação tanto do barorreflexo quanto do quimiorreflexo. Para isso foram utilizados ratos com lesão eletrolítica ou lesão fictícia da região AV3V aguda ou crônica e com cânulas de aço inoxidável implantadas no NTS ou na área RVL. A pressão arterial média (PAM) e a frequência cardíaca (FC) foram registradas em ratos não anestesiados que tiveram a artéria femoral canulada com tubo de polietileno (PE 10) no dia anterior ao do registro. A veia femoral também foi canulada para injeções das drogas periféricas para os teste de baro e quimiorreflexo. As injeções centrais no volume de 100 nl foram feitas com auxílio de uma seringa Hamilton de 5 µl. Enquanto que nos ratos com lesão fictícia (1 e 15 dias), a injeção de glutamato (5 nmol) no NTS produziu respostas pressoras (28 ± 3 mmHg), a mesma injeção nos ratos com lesão da região AV3V produziu hipotensão (-26 ± 8 mmHg) no 1o dia após a lesão ou não modificou a PAM (2 ± 8 mmHg) 15 dias após a lesão da região AV3V. A resposta bradicárdica produzida pela injeção de glutamato no NTS de ratos com lesão eletrolítica aguda (-65 ± 23 bpm) e crônica (-90 ± 29 bpm) não foram diferentes das respostas bradicárdicas produzidas pela injeção de glutamato no NTS nos respectivos controles com lesão fictícia (-76 ± 13 e -90 ± 15 bpm). Diferentemente do ocorrido com injeções de glutamato, as respostas pressoras produzidas pelas injeções de substância P (0,5 e 1 nmol) no NTS de ratos com lesão da região AV3V aguda (16 ± 2 e 20 ± 2 mmHg, respectivamente) ou crônica (18 ± 1 e 20 ± 1 mmHg) não foram diferentes das respostas pressoras produzidas pela injeção das mesmas doses de substância P no NTS de ratos com lesão fictícia aguda (20 ± 5 e 22 ± 3 mmHg) ou crônica (19 ± 3 e 25 ± 3 mmHg). As respostas taquicárdicas produzidas pela injeção de substância P no NTS de ratos com lesão da região AV3V aguda (54 ± 15 e 71 ± 15 bpm) e crônica (70 ± 11 e 66 ± 11 bpm) não foram diferentes das respostas taquicárdicas produzidas pela injeção de substância P no NTS de ratos com lesão fictícia aguda (75 ± 14 e 72 ± 12 bpm) ou crônica (53 ± 16 e 84 ± 7 bpm). Por outro lado, as respostas pressoras produzidas pelas injeções de glutamato (1, 5 e 10 nmol) na área RVL de ratos com lesão da região AV3V aguda (9 ± 4, 39 ± 6 e 37 ± 4 mmHg, respectivamente) ou crônica (13 ± 6, 39 ± 4 e 43 ± 4 mmHg, respectivamente) foram significativamente reduzidas em relação às respostas pressoras produzidas pelas injeções das mesmas doses de glutamato na área RVL de ratos com lesão fictícia aguda (33 ± 5, 54 ± 3 e 56 ± 8 mmHg, respectivamente) ou crônica (29 ± 3, 50 ± 2 e 58 ± 3 mmHg, respectivamente). Não se observaram diferenças nas respostas bradicárdicas produzidas pelas injeções de glutamato nos ratos com lesão da região AV3V (aguda ou crônica) em relação aos ratos com lesão fictícia. As respostas barorreflexas produzidas pelas injeções i.v. de fenilefrina (5 µg/kg de peso corporal) ou nitroprussiato de sódio (30 µg/kg), assim como nas respostas produzidas pela ativação do quimiorreflexo com injeções i.v. de cianeto de potássio (20 e 40 µg/rato) também não foram modificadas pela lesão da região AV3V tanto aguda como crônica. Esses resultados mostram a grande importância que a região AV3V têm para as respostas cardiovasculares dependentes da ativação do sistema nervoso simpático e, nesse caso em especial, respostas pressoras à ativação glutamatérgica de áreas bulbares. Pelos resultados obtidos, pode-se sugerir, que a região AV3V participa de uma forma decisiva nas respostas pressoras resultantes da injeção de glutamato no NTS e na área RVL, mas não na resposta pressora à injeção de substância P no NTS. Isso demonstra que o efeito da lesão da região AV3V não depende de um comprometimento inespecífico de mecanismos pressores. Um outro resultado importante desse estudo, é que a lesão da região AV3V não modifica as respostas baro e quimiorreflexa, podendo sugerir, que a resposta simpato-excitatória do quimiorreflexo não depende única e exclusivamente da neurotransmissão glutamatérgica em área bulbares.

In accordance with the main aim of the study, a widely accessible, modifiable tool was created for parties interested in maintaining the national electricity supply network and parties interested in informing policy on plug-in vehicle adoption schemes and recharging behaviour control. The Parry Tool enables the user to incorporate present limits to plug-in vehicle recharging demand scheduling as imposed by the state of present technology (no third party mechanism for monitoring and control of recharging), present human travel behaviour needs and existing patterns in electricity usage; into the investigation of the impacts of recharging demand impacts and the design of mitigation measures for deflecting (parrying) worst case scenarios. The second aim of the project was to demonstrate the application of the Parry Tool. The multidisciplinary/interdisciplinary information gathered by the Parry Tool was used to produce national demand profiles for plug-in vehicle recharging demand, calculated using socioeconomic and travel behaviour-estimated population sizes for plug-in eligible vehicles and vehicle usage patterns, which were added to existing national electricity demand for a chosen test week – this was the first scenario subsequently tested. The information gathered by the Parry Tool was then used to inform the design of two demand management methods for plug-in vehicle recharging: Recharging Regimes and weekly recharging load-shifting – these were the second and third scenarios subsequently tested. Unmitigated simultaneous recharging demand in scenario 1 (all vehicles assumed to recharge at home upon arrival home every day) severely exacerbated peak demand, raising it by 20% above the highest peak in existing demand for the year 2009 over half an hour from 58,554 MW to 70,012 MW – a challenge to the generation sector. This increased the difference between daily demand minima and maxima and made the new total demand have sharper peaks – a challenge for grid regulators. Recharging Regimes in scenario 2 split the estimated national plug-in vehicle populations into groups of different sizes that started recharging at different times of the day, with the word ‘regime’ being applied because the spread of start times changed over the course of the test week from workdays to weekend. This avoided exacerbation of the peak and reduced the difference between daily demand minima and maxima by raising minima, providing a load-levelling service. Scenario 3 embellished the Recharging Regimes with workday-to-weekend recharging load-shifting that therefore took better advantage of the often overlooked weekly pattern in existing demand (demand being higher on workdays than weekends), by allowing partial recharging of a segment of the plug-in vehicle population. Limited consideration of the impact of changing vehicle energy usage (for which distance travelled was assumed to proxy in this study) showed that the more vehicles used their batteries during the day, the better the levelling effect offered by Recharging Regimes. Greater utilisation of battery capacity each day, however, can also be assumed to lessen the potential for workday-to-weekend load levelling, because load-shifting depends upon vehicles being able to partially recharge or defer recharging to later days and still meet their travel needs plus keep a reserve State Of Charge (SOC) for emergency and other unplanned travel. Whilst altering vehicle energy usage did not change the finding that unmitigated simultaneous recharging exacerbated existing peak demand, it was noted that when limited mileage variation was considered this sharpened the profile of total demand – the rise and fall of the new peak far steeper than that of the original peak in existing demand. The Parry Tool combines a series of integrated methods, several of which are new contributions to the field that use UK data archives but may potentially be adapted by researchers looking at energy issues in other nations. It presents a novel fossil-fuel based justification for targeting road transport – acknowledging energy use of fossil fuel as the originator of many global and local problems, the importance of non-energy use of petroleum products and subsequent conflicts of interest for use, and a fossil fuel dependency based well-to-wheel assessment for UK road transport for the two energy pathways: electricity and petroleum products. It presents a method for the recalculation and ranking of top energy use/users using national energy use statistics that better highlights the importance of the electricity industry. It also presents the first publicly documented method for the direct consultation and extraction of vehicle-focused statistics from the people-focused National Travel Survey database, including a travel behaviour and household income-based assessment of plug-in vehicle eligibility, used to scale up to national estimates for battery electric and plug-in electric hybrid vehicle (BEV and PHEV) national population sizes. The work presented here is meant to allow the reader to perceive the potential benefits of using several resources in combination. It details the Parry Tool, a framework for doing so, and where necessary provides methods for data analysis to suit. It should however be noted that methods were kept as simple as possible so as to be easily followed by non-specialists and researchers entering the field from other disciplines. Methods are also predominantly data-exploratory in nature: strong conclusions therefore should not be drawn. Rather, the work here should be seen as a guideline for future work that may more rigorously study these combined topics and the impacts they may have upon plug-in vehicle ownership, usage behaviour, impacts of recharging upon the national network and the design of mitigation measures to cope with this new demand.

Tesis por compendio / La exposición crónica a sustancias de abuso lleva a cambios adaptativos en el cerebro que implican alteraciones en la expresión génica. Se ha propuesto que los factores de transcripción CREB y deltaFosB serían dianas moleculares para la regulación de la plasticidad, la cual lleva a la adicción.En este trabajo hemos estudiado los cambios en la activación de CREB, en PVN y NTS, y las quinasas que mediarían su activación durante la dependencia y síndrome de abstinencia a morfina, así como la respuesta del eje HHA durante dicho síndrome. También se investigó la posibilidad de que la activación de CREB y su coactivador transcripcional TORC1 dependan de la activación de receptores adrenérgicos. Además se evaluaron las posibles modificaciones en la expresión de FosB/deltaFosB en diferentes áreas cerebrales implicadas en la adicción, así como los cambios neuroendocrinos/neuroquímicos responsables de las alteraciones metabólicas observadas durante el tratamiento crónico con morfina. / Chronic exposure to opioids and other abused drugs results in adaptive changes in the brain involving alterations in gene expression. It is proposed that the transcription factors CREB and deltaFosB be molecular targets for the regulation of plasticity, which leads to addiction.In this work we studied changes in activation of the cAMP-response element binding protein (CREB) in PVN and NTS and the kinases that may mediate this activation during dependence and morphine withdrawal and the HPA axis response after naloxone-induced morphine withdrawal. We also investigated the possibility that the activation of CREB and the transcriptional coactivator of CREB, TORC1, arises from the activation of adrenergic receptors. We also evaluated the possible modifications in FosB/deltaFosB expression in several brain areas involved in addiction and neuroendocrine/neurochemical changes that are responsible for the metabolic alterations seen during chronic morphine treatment.

alpha-melanocyte stimulating hormone (alpha-MSH) is an important regulator of food intake, metabolic rate, and inflammation. Recently, alpha-MSH was shown to influence sympathetic activity and blood pressure regulation. In the present study, we investigated the cardiovascular effects of alpha-MSH in the nucleus tractus solitarii (NTS) of spontaneously hypertensive rats (SHR). Because nitric oxide (NO) is well-known to involve in central cardiovascular regulation, we elucidated the role of NO in the cardiovascular responses induced by alpha-MSH. In urethane-anesthetized SHR, unilateral microinjection of alpha-MSH (0.3-300 pmol) into the NTS produced dose-responsive depressor and bradycardic effects. The cardiovascular effects of alpha-MSH were abrogated by the antagonist of melanocortin receptor (MC3/4-R), SHU9119. Pretreatment with precursor of nitric oxide, L-arginine, enhanced the duration of alpha-MSH-mediated hypotensive effects, whereas prior application of L-NAME, a universal inhibitor of nitric oxide synthase (NOS), significantly attenuated the effects of alpha-MSH. Prior injection with inhibitor of inducible NOS, aminoguanidine, but not inhibitor of neuronal NOS, 7-nitroindazole, attenuated the hypotensive effect of alpha-MSH. In summary, these results indicated alpha-MSH induced depressor and bradycardic effects in the NTS of SHR. Besides, the hypotensive mechanism of alpha-MSH was mediated via MC4-R and involved with iNOS activation in the NTS of SHR.

Philosophiae Doctor - PhD / Working with Arab students pursuing a degree in English Language and Translation at the Taiz University, Republic of Yemen, has brought to the researcher‟s attention a number of errors or problems encountered in Arabic to English translation. This study aims to investigate the problems encountered by student translators (STs), novice translators (NTs) as well as more experienced translators (Ts) while translating from Arabic into English. The study starts with the assumption that Arabic and English belong to different families of languages and thus there is rarely a word-for-word equivalence in both languages. The present study is cross-sectional in nature. It is based on empirical data collected from several categories of translators. In other words, the data was collected from fourth-year students in the department of English and Translation in the Faculty of Arts, Taiz University, as well as five NTs who have previously graduated from this department and are currently working in a number of accredited translation offices in Taiz. The study also investigates the challenges faced by Ts. For this purpose, a novel, a tourist brochure, an editorial, and three academic abstracts all translated by established publishing houses and translation centres in and outside Yemen are examined. These texts are analyzed to determine to what extent the problems faced by STs and NTs reoccur in published translations produced by Ts. For its conceptual framework, the study adopts an eclectic approach that does not stick rigidly to a particular paradigm but rather draws upon multiple linguistic and translation theories. However, it is mainly based on Halliday‟s Systemic Functional Grammar (SFG) and the problems have been classified along his taxonomy of meaning metafunctions into ideational, interpersonal and textual. Extra-textual problems are also analyzed. Several SFG-based translation models such as Hatim and Mason‟s (1990) sociometic model, House‟s (1977, 1997) translation quality assessment model, Hervey et al. (1992) register analysis model and Baker‟s (1990) equivalence model are also employed in the study to help the researcher examine the problems encountered in Arabic-English translation within those four categories. In addition, Nord‟s functional model to translation which is based on Skopos theory is also taken into consideration although to a minimum extent. In addition to the analysis of translations produced by various categories of translators, the study uses several triangulation research tools such as questionnaire, Thinking Aloud Protocols (TAPs), retrospective interviews, and classroom observation. These tools are employed to assist the researcher to identify the possible causes for the problems the STs, NTs, and Ts experience from the perspective of the participants themselves. The current translation programme at Taiz University is also analyzed to determine to what extent it contributes to the poor performance of the student translators and would-be translators. The study concludes that STs, NTs and even Ts encounter several problems at the ideational, interpersonal and textual levels. They also encounter problems at the extra-textual stratum. The study attributes these problems to structural and cultural differences between the two languages, the reliance on the dictionary rather than the meaning in use of lexical items, the differences in the cohesion and coherence systems of Arabic and English, the negligence of the role of context in translation as well as unfamiliarity with text-typologies and genre conventions. In other words, participants follow a bottom-up approach in translation and come close to the source text translating it literally. This approach is very damaging because it ignores the fact that the three metafunctions might be realized differently in the two languages. Furthermore, the study concludes that the manner in which translation is taught at Taiz University as well as the syllabus contribute mainly to the lack of translation competence of the student translators and would-be translators. The programme is inadequate and it needs urgent review and improvements. The present syllabus does not keep abreast with the latest theoretical and practical developments in the discipline of translation as well as neighbouring disciplines such as contrastive linguistics, text-analysis, discourse analysis, corpus linguistics and the like. As for methodology, the study concludes that it is the transmissionist (teacher-centred) teaching approach rather than the transformational (learner-centred) which is commonly used in teaching translation. As a result, the read-and-translate approach dominates the scene and no tasks, activities, or projects are given to the STs. The study provides some recommendations, which if implemented, can be useful in enabling Yemeni and Arab universities to improve the competence among student translators in order to improve translation teaching at academic level. A major contribution of this study is the description and classification of translation problems in Arabic-English translation on the basis of meaning systems. Unlike traditional descriptive error analysis, which is widely used to analyze the translation product, SFG-based text analysis provides a systematic description of translation problems which allows a precise articulation of the nature of problems that would otherwise be explained simply as translations which “sound unnatural or awkward” (Kim 2008; Yallop 1999). As far as the researcher knows, no study in the Arab world has yet tackled translation problems from this perspective. Other studies have tackled deviated forms produced by students or translators using an error analysis technique rather than a holistic approach based on solid theoretical knowledge. In other words, while most other studies focused on specific „errors‟ and error analysis and ended at that, the present study does not only looks at „errors‟ as „difference‟ (from contrastive analysis) but rather from several perspectives. It is also more comprehensive by triangulating several sources of data and pooling them together for a more informed understanding.

Philosophiae Doctor - PhD / This study begins with an ethnographic self-study which allows for a reflection on traditional learning experiences. This study is located in the context of the initial development of dental health professionals within those higher education institutions that endeavour to provide education and training in a rapidly changing context. This context is characterised by the simultaneous need to address the blurring of boundaries and the dichotomies that exist such as the first world and the third world, the developed and the less developed world, the rich and the poor, health and wealth, the private and the public sectors, the formal and the informal sectors, the advantaged and the disadvantaged, the privileged and the underprivileged. The definitions, concepts, theories and principles around curricula and professional development are examined in an effort to extend into discoveries of educational research usually beyond the purview of dental health practitioners, policy makers or higher education specialists involved in training these dental health practitioners. It poses key questions regarding the nature of professional competences within dental health science undergraduate studies and how the curricula are organised around these perceptions of competence. Investigative tools include participant observation, interviews and questionnaires which have included both education deliverers - the teaching staff - and education consumers - the students. The areas of access by students to programmes (input), activities whilst in the programmes (throughput) and their competences at the exit end of the programme (output) are examined. It was found that institutions and programmes are paradoxically positioned declaring missions to be globally competitive and internationally recognised and at the same time wanting to reach out to the population who are disadvantaged and who form a majority. Whilst the needs of the wider community is for basic dental services and primary health care, the resources appear to be geared for producing technologically-superior professionals who will cater for a largely urban and middle class populations. The resources available, particularly human resources, for this training, are going through a critical shortage. Simultaneously demands are being made to challenge the epistemological rationale of the curriculum practice of the training sites at both universities and technikons (now known as universities of technology). These findings reveal that the SAQA demands and the proposed transformation of higher education provided an impetus for schools and departments within universities and technikons and their institutes to look at educational concepts and to transform curricula. This shift was found to be hampered by a variety of causes which included territorial protection, lack of a deep understanding of the education and training concepts and lack of human, physical and financial resources. It was also found that traditional designs of programmes are locked into tribal boundaries which restrict movement beyond these. The boundaries are ring-fenced by historical legacies and practices which confine programmes within these borders and continue to cement the fragmented development of dental health science professionals. The education and training of the different dental health science occupational categories are fragmented between institutes, within institutes and with three separate professional regulating bodies and, seemingly, disjointed functioning national and provincial departments of health and education. This (education and training) is found to be dominated by the traditional mould of teaching, learning and assessment with pockets of change in some schools and departments. Teaching units in the form of subjects, which operate as discrete units and remain entrenched by the habituations of subjects and departments within schools, restricts movement in the competence-based direction. The framework offered by this thesis sets broader and more fluid principles and guidelines which embody the notion of knowledge, skills, attitudes and values and which course designers and educators can utilise so that renewed ways can emerge for their programmes. This allows for a cross over into each other's territories (regulatory, institutional and the health and educational services) that will allow for courses to be designed more holistically and rationally with appropriate transformatory potential.

No description available.

Dans ce travail, nous démontrons que STIM1, un senseur calcique activé par la déplétion du Ca2+ intracellulaire du réticulum endoplasmique, est indispensable pour la signalisation calcique et la préférence oro-sensorielle du gras. Nous observons que l'acide linoléique (LA), en activant les phospholipases A2 via CD36, produit de l’acide arachidonique (AA) et de la lyso-phosphatidylcholine (lyso-PC). Cette activation déclenche un influx calcique dans les cellules CD36-positives, et induit la production du facteur CIF (Ca2+ Influx Factor). CIF, AA et lyso-PC exercent différentes actions sur l'ouverture des canaux SOC (Stored Operated Calcium Channel) constitués de protéines Orai et contrôlés par STIM1. Par ailleurs, les souris au phénotype Stim1-/- perdent la préférence spontanée pour les lipides et la libération de la sérotonine à partir des cellules gustatives dans le milieu extracellulaire chez les animaux sauvages. Nous demontrons aussi que la signalisation calcique médiée via CD36 est doublement modulée lors de l’obésité. L’augmentation de la [Ca2+]i dans les cellules gustatives observée chez le Psammomys obesus, un modèle d’obésité nutritionelle, est fortement diminuée chez les souris rendues obèses par un regime hyperlipidique. Nous avons constaté également que l’interaction de LA avec le CD36 induit l’activation des MAP Kinases de la voie MEK1/2/ERK1/2/Elk-1 qui est non seulement à l’origine de l’activation des aires cérébrales telles que le NTS, le noyau arqué, l’hippocampe mais aussi indispensable pour la préférence spontanée pour les lipides alimentaires. Nos résultats suggèrent pour la prémière fois, que la voie ERK1/2 des MAPK et la signalisation calcique lipidique controlée par STIM1 sont impliquées dans la perception oro-gustative des lipides / In this work, we demonstrate that stromal interaction molecule 1 (STIM1), a sensor of Ca2+ depletion in the endoplasmic reticulum, mediates fatty acid–induced Ca2+ signaling in the mouse tongue and fat preference. We showed that linoleic acid (LA) induced the production of arachidonic acid (AA) and lysophosphatidylcholine (Lyso-PC) by activating multiple phospholipase A2 isoforms via CD36. This activation triggered Ca2+ influx in lingual CD36-positive taste bud cells (TBCs) purified from mouse CVP. LA also induced the production of Ca2+ influx factor (CIF). STIM1 was found to regulate LA-induced CIF production and the opening of store-operated Ca2+ (SOC) channels. Furthermore, CD36-positive TBCs from Stim1–/– mice failed to release serotonin, and Stim1–/– mice lost the spontaneous preference for fat that was observed in wild-type animals. We also demonstrate that the calcium-mediated signaling via CD36 is doubly modulated in obesity. The increase in [Ca2+]i in taste bud cells observed in Psammomys obesus, a model of nutritional obesity is strongly reduced in diet-induced obese (DIO) mice. We also found that the interaction of LA with CD36 induces activation of MAP Kinases MEK1/2/ERK1/2/Elk-1 pathway that is not only responsible for the activation of NTS, arcuate nucleus, and the hippocampus in the brain but also essential for the spontaneous preference for fat food. Our results suggest for the first time, that ERK1/2 MAPK pathway and lipid-induced calcium signaling controlled by STIM1 are involved in oro-gustatory perception of dietary lipids

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