This thesis explores the impact of type 2 diabetes among Indian and Pakistani migrants. Indians and Pakistanis living in the UK have a high incidence of type 2 diabetes and associated complications. Research is needed in order to understand factors that make it difficult to adhere to lifestyle advice about diet, exercise and medication. Drawing on data collected during a sixteen-month ethnographic investigation, this thesis explores Indians’ and Pakistanis’ perceptions of diabetes. The research revealed that Indians and Pakistanis related the onset of diabetes to processes of migration and settling in the UK as well as to stress and depression. In particular, holding on to negative thoughts and worries, were perceived by respondents as directly affecting the body by causing stress, depression and eventually illness. Struggles over diabetes control were also perceived as to cause distress. Specifically, respondents struggled to adhere to a healthy diet regime, since food, especially taste, played a crucial role in forming, reinforcing and demarcating social relations and in ensuring cultural continuity. In addition, respondents struggled to ‘adhere’ to their prescriptions of diabetes medications due to the uncomfortable side effects that they experienced, particularly in the stomach. Respondents, however, counteracted side effects by turning to alternative medications which were perceived to facilitate flow within the circulatory and digestive system. Thus, in spite of the difficulties that Indians and Pakistanis experienced in following biomedical recommendations for diabetes control, they still actively engaged in searching and using different treatments available to them in order to control the disease.

Den arena där socker och sötma förstärs har förändrats i och med att socker har gått från en global handelsvara, endast tillgänglig ett fåtal, till en lokal som når de stora massorna. Detta kanske kan ses som en mindre revolution i mathållningen. Men varför äter människan socker och varför finner hon smaken så åtråvärd? Syftet med studien var att ur ett evolutionärt samt kulturellt perspektiv undersöka varför människan finner den söta smaken åtråvärd. Metoden som har använts i föreliggande studie var en litteraturstudie av vetenskapliga artiklar där artiklar som berör hälsoaspekter som socker och sötma orsakar diskuteras emot bakgrundens evolutionära samt kulturella aspekter. Resultatet visade att människan fann den söta smaken åtråvärd baserat både på medfödda samt kulturellt inlärda preferenser. Av diskussionen framgick att det fanns en medfödd preferens för sötma men att den kulturellt betingade preferensen tog över genom den inlärning hon får från sin första måltid av modersmjölk och framåt. Människan förknippade därför sött med både trygghet, lugn, belöning, tröst men framförallt med mat. För om sötma endast vore evolutionärt betingat skulle människan kunna äta socker direkt ur påsen. / B-uppsatser

The sense of taste is one of the most important factors in regulating ingestive decisions. This is central to a number of disease conditions including but not limited to obesity, diabetes, anorexia, hypertension, coronary artery diseases and malnutrition. The detection of the molecules eliciting taste qualities in food is mediated by the coordinated actions of distinct types of taste sensory cells (TSCs) housed in taste buds within specialized papillae throughout the oral cavity. Taste receptors in the taste sensory cells that detect food molecules are the key players in selecting dietary nutrients. One such example is L-amino acids, a critical part of one's diet. L-glutamate is the prototypical umami compound and is known to increase palatability of food. A unique characteristic of umami taste is the response potentiation of glutamate by 5' ribonucleotide monophosphates, such as inosine 5' monophosphate (IMP), which is also capable of eliciting an umami taste. Candidate receptors for umami taste include a heterodimer T1r1+T1r3, brain variants of mGluR1 and mGluR4, and the truncated variants of mGluR1 and mGluR4. Studies using heterogeneous expression of T1r1+T1r3 suggest it is an umami and a broadly tuned L-amino acid receptor. While much attention is devoted to understanding glutamate transduction, the detection mechanisms for other L-amino acids by TSCs are less well understood. Here calcium imaging of isolated TSCs and taste cell clusters from the circumvallate and foliate papillae of C57BL/6J and T1r3 knockout mice was performed to determine if other receptors are involved in the detection of L-amino acids and IMP. Ratiometric imaging with Fura-2 was used to study calcium responses to IMP and four L-amino acids (monopotassium L-glutamate, L-serine, L-arginine, and L-glutamine) with and without IMP. The results of these experiments showed that the response patterns elicited by L-amino acids varied significantly across TSCs. Only a small subset of cells responded to all stimuli. Interestingly, L-amino acids other than glutamate elicited synergistic responses in a subset of TSCs. Additionally IMP alone elicited a response in a large number of TSCs. Our data indicate that synergistic and non-synergistic responses to L-amino acids and IMP are mediated by multiple receptors or possibly a receptor complex. Next the roles of mGluR1 and mGluR4 in the detection of the IMP and L-amino acids were investigated. Selective agonists for mGluR1, (RS)-3, 5-dihydroxyphenylglycine (DHPG; a group I mGluR agonist), and mGluR4, L-(+)-2-amino-4-phosphonobutyric acid (L-AP4; a group III mGluR4 agonist) elicited responses in TSCs. In addition, TSCs responsive to these agonists were also responsive to L-amino acids and IMP. More importantly, selective antagonists against different mGluRs such as (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; a group I mGluR antagonist), and (RS)-α-methylserine-O-phosphate (MSOP; a group III mGluR antagonist) significantly suppressed L-amino acid- and IMP-mediated responses in TSCs of T1r3 knockout mice. Collectively, these data provide evidence for the involvement of taste and the brain variants of mGluR1 and mGluR4 in L-amino acid and IMP taste responses in mice, and support the hypothesis that multiple receptors contribute to the IMP and L-amino acid tastes.

Magister Scientiae Dentium - MSc(Dent) / Introduction: Dental caries has one the highest incidences in children and the host’s diet may be a major factor in determining susceptibility to the disease. A proposed tool to screen and identify high risk individuals uses a bitter compound 6-n-propylthiouracil (PROP). The goal of this screening tool is to identify mothers and children who are Non-tasters (those who cannot taste PROP) and to educate them about their possible affinity towards sugar substances and its harmful effects on oral and general health. It is suggested that Non-taster children could be prioritized when providing preventative dental treatment. Aim: To validate the use of PROP as a screening tool for determining high caries risk individuals by identifying the taster status of mothers and children, their preference towards sugar, and its impact on their caries status. Methodology: 75 mother/ child pairs were recruited to participate in this study. Caries experience, sugar preference and taster status were determined for all the subjects. Comparisons were made between mothers and their children to find a possible association. Results: Caries experience was greater in individuals who were Non-tasters when compared to Super-tasters. A significant association between taster status and DMFT score was established (p<0.000). A significant association between taster status and sugar preference was established (p<0.000). A positive correlation with regard to taster status, sugar preference and caries experience was observed in mother/child pairs.

O crítico de arte americano Clement Greenberg dedica especial atençãoà teoria estética em seus textos dos anos 1970, sobretudo ao juízo de gosto. Esta pesquisa busca evidenciar um aspecto importante na discussão estética em Greenberg, qual seja, a possibilidade de aprimoramento do gosto. Para tal, também se faz necessária uma compreensão de seu sistema crítico, articulando os Seminários por ele ministrados nos anos 70 e seus textos críticos desde os anos 30. Dentro da teoria estética moderna formulada por Greenberg, os textos reunidos em Estética Domésticaservem de base para a investigação do ponto central da pesquisa. Apesar disso, não se pode perder de vista o grande espectro coberto pela obra do crítico, uma vez que seus textos dialogam entre si, retomando e alinhavando os diversos temas abordados. / The american art critic Clement Greenberg pays special attention to the aesthetics in his texts of the 1970s, and to the taste judgement most of all. This study try to put light over an important aspect of Greenberg theory: the taste improvement possibility. To do so, it\'s imperative to comprehend Greenberg\'s critical system, considering his Seminars and also his critics since the 30s. The essays presented on Homemade Estheticswill base the investigations about the central point of interest in this study, having in mind the modern theory formulated by Greenberg. But it\'s necessary, beside this, to consider the great diversity of his work, once his texts can have a dialogue.

A preocupação crescente com o desenvolvimento de hábitos saudáveis e uma alimentação adequada vêm promovendo o avanço nas ciências dos alimentos, como também nas relações entre estes e o homem. Nas últimas décadas, a qualidade da análise sensorial tem sido estudada não apenas com base na interação entre o homem e o alimento, mas através da compreensão dos fatores subjetivos e emocionais que influenciam os consumidores. O interesse pelos aspectos emocionais que influenciam essas escolhas amplia os estudos para o terreno das ciências psicológicas, que procuram entender as bases neurocognitivas e analíticas do funcionamento cerebral como motivadores desses processos no homem. O trabalho em neurociência cognitiva tem vislumbrado novos paradigmas, com o desenvolvimento de novas técnicas de observação do cérebro, visando conhecer sua estrutura e função, além de permitir a associação de um comportamento clinico ou experimentalmente observado, não só a um correlato mental presumido, mas também a marcadores específicos da atividade mental observada. Neste sentido, a atividade elétrica cerebral adquirida usando-se o eletroencefalograma (EEG) vem sendo, recentemente, muito usada para monitoramento de eventos cerebrais. Portanto, este trabalho tem como objetivo propor um modelo de análise sensorial que permita avaliar quantitativamente a ação do estímulo gustativo no contexto cognitivo, utilizando o EEG. O experimento foi realizado no laboratório de Física Aplica e Computacional (LAFAC), na Universidade Estadual de São Paulo (USP), Campus Pirassununga, no período de maio/2011 a maio/2012, com 23 voluntários (13 do sexo feminino e 10 do sexo masculino), com idade entre 19 e 24 anos. Foram coletados os sinais de EEG destes voluntários no momento em que experimentavam 27 amostras do sabor doce, sendo nove delas a 0% (água), nove com 0,15% de sacarose (limiar) e nove com 5,0% (concentração máxima). Desta amostragem, foi selecionado um grupo de 7 voluntários (5 do sexo feminino e 2 do sexo masculino) para análise dos dados. Neste estudo constatou-se que quatro voluntários do sexo feminino e um do sexo masculino foram capazes de identificar, através de dados obtidos com o EEG, as diferentes dosagens de sacarose. Os resultados permitem concluir que o modelo de análise sensorial proposta, com a utilização de EEG, para avaliar os estímulos gustativos no contexto cognitivo foi satisfatória e permitiu com a utilização de processamento de sinais digitais e AGR (Análise Adaptativa de Gabor) quantificar com eficiência a percepção dos voluntários as diferentes dosagens apresentadas no experimento. Sugere-se que as diferentes percepções dos voluntários no geral, encontradas no EEG, representam as suas singularidades quanto aos significados atribuídos ao sabor e suas correlações. / The growing concern with the development of healthy habits and a balanced diet allows the progress in Food Science as well as in the relationship between human beings and food. In the last decades the quality of the sensorial analysis has been studied not based only on the interaction between human beings and food but also through the comprehension of subjective and emotional factors that influence customers. The interest in emotional aspects which influence such choices extends the studies to the field of Psychological Science that attempts to understand neurocognitive and analytical bases of brain functioning as motivating elements of those human processes. The work in Cognitive Neuroscience has glimpsed new paradigms due to the development of new techniques about brain observation with the purpose of getting to know its structure and function other than allowing the association of behavior observed experimentally or clinical behavior not considering only a presumed mental correlative but also specific markers of mental activity observed in advance. In that aspect the brain electrical activity acquired through electroencephalogram has been recently used to monitor brain events. Therefore, the aim of this work is to propose a sensorial analysis pattern which allows to evaluate quantitatively the action of taste stimuli within a cognitive context using electroencephalogram. The experiment was carried out in the Laboratory of Applied and Computational Physics (LAFAC) in the University of the State of São Paulo (USP), Pirassununga Campus, from May 2011 to May 2012 with 23 volunteers (13 women and 10 men) aging between 19 and 21 years old. The volunteers\' electroencephalogram signals were collected when they tasted 27 sweet flavored samples, being 9 of them with 0% of sucrose (water), 9 with 0.15% of sucrose (threshold), and 9 with 5% of sucrose (maximum concentration). Seven volunteers were selected from this experiment (5 women and 2 men) whose data was analyzed. In this study was found that four women and one man were able to identify, through the EEG data obtained with the different concentrations of sucrose. The results obtained allowed to conclude that the proposed sensorial analysis pattern using electroencephalogram to evaluate taste stimuli within the cognitive context was satisfactory and allowed, along with the use of digital signals processing and Gabor Adaptive Analysis (AGR), to analyze and to quantify efficiently the volunteers\' perception of different doses presented in the experiment. It is suggested that the different perceptions of volunteers in general, encountered in EEG, representing singularities as to the meanings attributed to taste and their correlations.

This thesis is a report on the analysis of family data gathered to test the simple recessive hypothesis for the inability to taste phenyl-thio-urea (P.T.C.). The simple recessive hypothesis states that the inability of a minority of persons to taste high concentrations of P.T.C. is due to the action of an autosomal recessive gene in the homozygous condition.

Male rats have been found to extinguish a conditioned taste aversion slower than females. It has also been found that female rats that have been "handled" (i.e., exposed to daily brief isolation from siblings and mother) during the preweaning period extinguish a taste aversion faster than nonhandled females. The present study sought to combine and extend these findings by testing handled and nonhandled females and males in a conditioned taste aversion under the methodological conditions used in the sex difference research.

T2R receptors are the classical bitter taste receptors which detect and transduce bitter taste in a subset of taste receptor cells (TRCs). The TRPM5-dependent T2Rs are G-protein coupled receptors (GPCRs) and are linked to G protein, gustducin to initiate an intracellular signaling cascade for the transduction of bitter tastants. Nicotine is bitter. However, at present the transduction mechanisms for the detection of nicotine in are poorly understood. Previous studies from our laboratory using TRPM5 knockout (KO) mice demonstrated that the T2R pathway is insufficient in explaining the taste perception of nicotine. TRPM5 KO mice elicited chorda tympani (CT) taste nerve responses to nicotine, albeit significantly smaller than the wild type (WT) mice and still responded to nicotine as an aversive stimulus. Following addition of mecamylamine (Mec), a non-specific blocker of neuronal nicotinic acetylcholine receptors (nAChRs), CT responses to nicotine were partially inhibited in both WT and TRPM5 KO mice. Mec also decreases the aversive response to nicotine in both WT and TRPM5 KO mice. These studies led to the hypothesis that both a TRPM5-independent and TRPM5-dependent pathways are responsible for the detection and transduction of the bitter taste of nicotine in TRCs. The TRPM5-independent pathway most likely utilizes the nAChRs expressed in TRCs and function as bitter taste receptors for nicotine. We have subsequently demonstrated the expression of nAChRs in a subset of TRPM5-positive TRCs. However, this mechanism is not well understood in other cell types, particularly undifferentiated epithelial cells, such as HEK293T cells. The specific aims of this project were: (i) To identify which components of T2R-dependent taste reception as well as components of nAChRs are expressed in HEK293T cells; (ii) To determine if HEK293T cells co-express these components; (iii) To identify if exposure to nicotine modulates the expression of T2R and nAChR dependent components in HEK293T cells; (iv) To determine if TRCs express functional nAChR ion channels; and (v) To determine if nAChRs are involved in the release of neuropeptides, such as brain-derived neurotrophic factor (BDNF) in HEK293T cells. The data obtained in HEK293T cells was compared with parallel studies on adult cultured human fungiform taste cells (HBO) done independently by Dr. Jie Qian, a postdoctoral fellow in Dr. Vijay Lyall’s lab. The results of combined studies on HBO and HEK293T cells indicates that TRPM5-positive cells also co-express ionotropic nAChRs, comprising a and β subunits. The nAChRs are capable of forming ion pores and when stimulated by nicotine and create a parallel TRPM5-independent pathway for the detection of nicotine. Using molecular and immunocytochemical techniques, our results demonstrate that mRNAs and proteins for bitter taste receptors and downstream intracellular signaling components as well as subunits necessary for the formation of nAChRs are expressed in HBO and HEK293T cells. Results demonstrated that TRPM5-positive HEK293T cells co-expressed nAChR subunits throughout the entire population. Nicotine increased the influx of Ca2+ in a dose dependent manner, which was somewhat reduced by the addition of TRPM5 blocker, triphenylphosphine oxide (TPPO). Both mRNA and protein expression were altered in a biphasic pattern with a maximum increased observed at 0.5 µM nicotine with a decrease in expression at higher concentrations. The synthesis of neurotrophic factor BDNF, required for maturation of taste bud cells and their innervating nerves, increased in HEK293T cells exposed to nicotine, however, nicotine did not trigger the release of BDNF. These results were then compared and contrasted with HBO cells to better understand the comparative effects of nicotine on both undifferentiated and differentiated cells. The data on HBO cells is presented in the Appendix.

Face au manque de médicaments spécifiquement conçus et mis au point pour répondre aux besoins thérapeutiques de la population pédiatrique, les autorités nationales et européennes se sont vues dans l’obligation d’établir un cadre réglementaire visant à encourager le développement de médicaments à usage pédiatrique. Un médicament destiné à l’enfant nécessite une présentation galénique spécifique et adaptée à son âge, pour permettre une administration simple et sûre. L’Académie nationale de Pharmacie a également travaillé sur le sujet et élaboré un rapport en juin 2005 avec certaines propositions notamment favoriser les formes orales solides dispersibles ou orodispersibles. Cependant, les formes orales solides posent le problème de l’acceptabilité et de l’évaluation de la palatabilité, condition requise qui représente un véritable défi. L’objectif de ce travail était (i) de développer des techniques de masquage du goût d’un principe actif modèle, l'acétaminophène, (ii) de mettre au point des méthodes d’évaluation du masquage de goût et de caractérisation des particules obtenues et, (iii) d'élaborer un procédé de fabrication d’une forme dispersible : des minigranules à désintégration rapide. Le caséinate de sodium et la lécithine, excipients potentiellement tolérables et sans danger pour un usage pédiatrique, ont été utilisés pour encapsuler le principe actif par atomisation-séchage. Le masquage de goût est évalué in vitro de façon indirecte par des études de libération du principe actif. Nous avons développé une méthode simple avec une pompe à seringues qui utilise de faibles volumes et débits de tampon et simule le flux salivaire. La méthode d’évaluation de masquage de goût développée donne des résultats en accord avec ceux d’autres méthodes existantes comme la langue électronique. La caractérisation des particules obtenues, notamment grâce à la spectroscopie par Rayons X qui permet d’obtenir une cartographie de la composition à la surface des particules enrobées, a montré une différence de composition en fonction du ratio caséinate de sodium/lécithine utilisé lors de l’atomisation. Cette différence a pu être mise en relation avec l'efficacité de masquage de goût. Une étude a ensuite été menée pour évaluer l'effet des paramètres du procédé et de la formulation sur l'efficacité de masquage de goût. Un plan factoriel complet a permis de déterminer les variables les plus importantes influant sur la quantité de principe actif libéré durant les premières minutes, soit la quantité de caséinate de sodium et de lécithine. L’optimisation par la méthode du simplex a permis d’obtenir une formulation optimisée pour laquelle la quantité libérée était 7 fois inférieure à celle du principe actif initial durant les deux premières minutes de l’essai de libération. Une autre approche visant à améliorer l'effet de masquage de goût incluait l'utilisation de caséinate de calcium à la place de caséinate de sodium. Le caséinate de calcium a été montré capable de retarder la libération du principe actif de façon plus importante lors de son association avec de la lécithine, ce qui améliore le masquage de goût. En effet, le masquage de goût est obtenu quand sur une courte période de temps (1 à 2 minutes), soit le principe actif n’est pas détecté, soit la quantité détectée est sous le seuil de perception du patient. Une forme galénique multiparticulaire à base de minigranules à désintégration rapide a ensuite été élaborée par extrusion-sphéronisation suivie d’une lyophilisation. Les minigranules présentent des qualités appropriées à savoir, une bonne sphéricité, une faible friabilité, la capacité d’incorporer une quantité élevée de principe actif et de plus, ces minigranules sont presque immédiatement désintégrés en présence d'eau lors de la mesure du temps de désagrégation avec l'analyseur de texture. Ce type de minigranules promet une forme galénique adaptée à la population pédiatrique grâce à la facilité d’administration et la flexibilité de dosage. / The development of paediatric formulations involves an urgent need but also presents many difficulties, e.g. the safety data of existing and new excipients in children stay restrictive; the development of palatable formulations for better compliance is requisite and challenging; the appropriateness of dosage form faces to dysphagia issue and flexibility of dosing for a large range of age. The aim of this work was (i) to develop a taste-masking formulation of a model drug (acetaminophen) on the one hand, and (ii) to elaborate a process for manufacture of fast disintegrating minigranules on the other hand. Sodium caseinate and lecithin, potentially tolerable and safe excipients for paediatric use, were utilized in order to encapsulate the drug through spray-drying. Taste-masking effect was demonstrated by in vitro drug release study and electronic tongue analysis. The characterization of spray-dried particles showed a difference in the surface composition according to the sodium caseinate/lecithin ratio, which related to the taste-masking efficiency. A study was subsequently undertaken to evaluate the effect of process and formulation parameters on the taste-masking efficiency. A full factorial design allowed screening for the most important variables that affect the released amount of drug during the early minutes, i.e. quantity of sodium caseinate and lecithin. An optimized formulation was successfully achieved by simplex design that released the drug 7-fold less than the unmasked drug during the first two minutes. Another approach to improve the taste-masking effect included the use of calcium caseinate rather than sodium caseinate. Calcium caseinate was showed to be more effective in delaying the drug release to a higher extent in association with lecithin. Indeed, the lower the released amount, the better the taste-masking. A multiparticulate dosage form of fast disintegration was developed through extrusion-spheronization followed by freeze-drying. The pellets exhibited suitable quality, e.g. good sphericity, low friability, ability of high drug loading, and moreover, almost immediately disintegrated in contact with water during measurement of disintegration by texture analyzer. This type of pellets promises age-appropriate dosage form for pediatric population thank to facility of administration and flexibility of dosing.