Depuis la réforme du droit des procédures collectives par la loi de sauvegarde des entreprises du 26 juillet 2005, deux régimes de cession aux conséquences juridiques dissemblables restent applicables lors des réalisations d’actifs en liquidation judiciaire. Le fonds de commerce, bien particulier à la définition lacunaire, présente la particularité d’être éligible tant à l’application du régime de la cession d’entreprise des articles L 642-1 et suivants du Code de Commerce, qu’à celle de la cession de biens isolés de l’article L 642-19 du Code de Commerce. Les éléments guidant la répartition des ensembles cédés sous l’un ou l’autre régime restent cependant à ce jour imprécis, compromettant la sécurité juridique des différents acteurs de la procédure. Suite à l’étude des causes théoriques et pratiques de cette confusion, des propositions de réforme de ces régimes peuvent être formulées afin d’offrir aux intervenants à la procédure, qu’ils soient parties à la cession, créanciers, ou salariés, une meilleure lisibilité de leurs droits et obligations / Since the reform of the collective procedures by the July 26, 2005 Companies backup Act, two regimes of sales, of dissimilar legal consequences, can be applied during the divestments of the assets that takes place in the final stages of the judicial liquidation. The goodwill, specific asset of lacunar definition, has the particularity to be eligible both for the application of the system of transfer of companies mentionned at the article L 642-1, to that of isolated assets divestment regime mentionned at the article article L 642-19 of the French Commercial Code. Elements guiding the distribution of sets sold under one or the other regime remain however to this day unclear, compromising the legal security of the different actors in the process. Following the study of the theory and practice of this confusion causes, proposals for reform of these regimes can be formulated to provide to the participants in the proceedings, may they be parties to the sales, creditors or employees, a better readability of their rights and obligations

Nós investigamos as relações entre a diversidade e a estrutura do componente arbóreo com as variáveis ambientais, em quatro posições microtopográficas (MPs), ao longo de um gradiente formado entre zonas úmidas depressionais florestadas e terras firmes em jaboticabais (FDWs) no Planalto Sul-Brasileiro. A riqueza específica e a diversidade foram similares nas terras firmes e menores nas zonas úmidas, enquanto que os parâmetros estruturais diferiram pouco entre as MPs. Uma análise de espécies indicadoras mostrou que poucas espécies são indicadoras das terras firmes, revelando que a distribuição das espécies foi relativamente uniforme em comparação às zonas úmidas. Os mesmos padrões foram revelados por uma análise de correspondência canônica (CCA), que mostrou que os alagamentos foram os principais determinantes da zonação de espécies arbóreas. Aparentemente, Plinia peruviana (Poir.) Govaerts (Myrtaceae) é a única espécie com distribuição praticamente restrita às MPs estudadas, mas os jaboticabais podem ter uma importância desproporcionalmente maior na preservação de espécies que são pouco abundantes em outras florestas na região. A ocorrência exclusiva de solos distróficos nas áreas de estudo, em uma região onde solos eutróficos predominam, indicam que as terras firmes estudadas representam zonas transicionais entre as zonas úmidas e a matriz florestal. Como estudo pioneiro em zonas úmidas depressionais florestadas no Planalto Sul-Brasileiro, nossos resultados sugerem que ao menos toda a área correspondente às depressões topográficas deve ser protegida, até que estudos complementares proponham zonas de amortecimento apropriadas, com base em critérios biológicos. Jaboticabais são ecossistemas únicos cuja restauração, manejo e preservação são cruciais para manter ambientes espacialmente heterogêneos e, consequentemente, a riqueza específica e as funções e serviços ecossistêmicos. / We investigated the relationships between tree component diversity and structure with environmental variables of four microtopographic positions (MPs) along a wetland-upland gradient in forested depressional wetlands (FDWs) on the South Brazilian Plateau. Species richness and diversity were quite similar in the uplands and lowest in the wetlands, while structural parameters differed little among MPs. An indicator species analysis showed that few species were indicators of the upland sites, suggesting that species distribution was relatively uniform in comparison to the wetlands. The same patterns were revealed by a canonical correspondence analysis (CCA) that showed flooding to be the main factor driving tree species zonation. Apparently, Plinia peruviana (Poir.) Govaerts (Myrtaceae) is the only tree species with practically restricted distribution to the studied ecosystems, although FDWs and their surrounding uplands can have a disproportionately higher importance in the preservation of species that are under-represented in other regional forests. The occurrence of exclusively dystrophic soils in the study areas, in a region where eutrophic soils predominate, indicates that the studied uplands represent transitional zones between the FDWs and the forest matrix. As a pioneer study in FDWs on the South Brazilian Plateau, our findings suggest that the whole area of the topographic depressions should be protected at least until complementary studies propose proper buffer zones based on biological criteria. FDWs are unique ecosystems whose restoration, management and preservation are crucial to maintain spatial environmental heterogeneity and consequently species richness and ecosystem functions and services.

Orientador: Sonia Aparecidas Alem Marrach / Banca: Hélia Sonia Raphael / Banca: Paschoal Quaglio / Banca: Ivan Aparecido Manoel / Banca: Marcia Regina Tosta Dias / Resumo: Este trabalho de pesquisa analisa o processo histórico da criação da Faculdade de Filosofia, Ciências e Letras de Marília nos limites temporais que se iniciam em 1957 quando ainda era um Instituto Isolado de Ensino Superior (IIES) junto com outros espalhados pelo interior do estado de São Paulo e findam em 1976. Nesse processo de expansão da educação de nível superior pelo interior paulista, convergiam fatores de ordem política, econômica e social vigentes no período, como também as mudanças trazidas pela nova conjuntura política instaurada no Brasil com o golpe militar de 1964 e a Reforma Universitária de 1968. Além da análise bibliográfica, fontes documentais, jornais, legislação e documentos oficiais, a pesquisa sustenta-se na interpretação de dados dos episódios selecionados da memória dos indivíduos participantes desta experiência, presentes nas entrevistas localizadas no CEDEM/UNESP. Os dados foram correlacionados a fim de evidenciar fragmentos da história dos Institutos Isolados de ensino superior no interior do estado de São Paulo, mais precisamente da Faculdade de Filosofia, Ciências e Letras de Marília. Com a criação da Faculdade de Filosofia, que tinha como proposta formar professores e pesquisadores unidos a uma tradição humanística, Marília conquista uma situação diferenciada com relação ao ensino superior no interior do estado de São Paulo como parte de um processo de interiorização da cultura. Em 1976, a Faculdade de Filosofia, Ciências e Letras de Marília (FFCL) foi incorporada à Universidade Estadual Paulista (UNESP), fato resultante dos critérios de racionalização, integração e planejamento. / Abstract: This work deals with the historical process concerning the creation of the Faculdade de Filosofia, Ciências e Letras - FFCL - (Faculty of Philosophy, Sciences and Letters) of Marília. The research covers from 1957, when it was a Instituto Isolado de Ensino Superior (Isolated Institute of Higher Education), - together with others spread inland in the state of São Paulo -, to 1976. In that process of expansion of higher level education toward the Paulista hinterland several different kinds of factors such as political, economic and social converged. On the other hand, a new one influenced it when the country was taken over by the military in 1964 that put forward a reform for the university in 1968, carried out in after years. In addition to bibliographical analysis, documentary sources, newspapers, official legislation and documents, this research is based on interpretation of episodes data selected from participant individuals' memory who were involved in that experience, present in the interviews belonging to the CEDEM/UNESP. Data were correlated to make clear fragments of the history of the Isolated Institutes of higher education in the interior of the state of São Paulo, particularly those related to the Faculty of Philosophy, Sciences and Letters of Marília. With the creation of the Faculty of Philosophy whose purpose was to form teachers and researchers, closely related to a humanistic tradition, Marília reached an outstanding situation with regard to the higher education in the interior of the state of São Paulo, as part of a process of culture moving inland too. IN 1976, the Faculty of Philosophy, Sciences and Letters (FFCL) of Marília was incorporated to the Universidade Estadual Paulista - UNESP - (Paulista State University), according to rationalization, integration and planning criteria. / Doutor

Les milieux ruraux, souvent distants du réseau électrique principal, sont particulièrement adaptés au déploiement de microréseaux (MR). Ce type de réseau permet une restructuration du réseau électrique d’aujourd’hui afin d'intégrer plus efficacement un plus grand nombre des sources d’énergie renouvelable. Le biogaz,obtenu par la méthanisation des déchets agricoles, est une ressource d’énergie renouvelable disponible dans les zones rurales. Cette ressource, facilement stockable en grande quantité, est particulièrement intéressante pour les réseaux faibles comme le MR. Les sources d’énergies valorisant le biogaz sont plus fiables et moins dépendantes de phénomènes stochastiques comme le vent ou l’éclairement solaire.Après un état de l’art sur les différentes technologies valorisant le biogaz, ilressort qu’un système hybride composé d’une pile à combustible de type SOFC et d’une microturbine (MT) permet d’atteindre le meilleur rendement électrique avec un faible impact environnemental.L’objectif global de la thèse est d’étudier le système SOFC/MT comme source principale dans un contexte MR rural isolé. Dans ce but, une modélisation du système a été réalisée en se focalisant sur les éléments ayant un impact sur la dynamique des signaux électriques du système. Le système hybride a ensuite été dimensionné dans le but de conserver un rendement électrique optimal et un unique convertisseur multiniveau de type 3LNPC est utilisé pour l'intégrer au MR. Comme une pile à combustible est sensible aux variations de charges (affectant son rendement et sa durée de vie), le premier objectif de la stratégie de commande appliquée au convertisseur 3LNPC est de réguler la puissance de la SOFC à sa valeur nominale. Le MR devant pouvoir fonctionner en autonomie lors de son ilotage, le deuxième objectif de cette stratégie est de fixer la tension et la fréquence du réseau.Les contrôleurs de la stratégie de commande sont conçus en attachant une importance particulière à la robustesse des correcteurs. Le fonctionnement du système hybride SOFC/MT, piloté par un unique convertisseur de type 3LNPC équipé d’une stratégie de commande originale, a été testé et validé en simulation puis expérimentalement sur la plateforme MR d’ESTIA-Recherche. / Rural areas, often far away from the main electric grid, are particularly suitablefor the deployment of microgrids (MG). This type of grid allows a restructuring oftoday's power grid in order to integrate more efficiently renewable power sources.Biogas, produced by anaerobic digestion of agricultural wastes, is a renewable energyresource available in rural areas. This resource, easily stored in large quantities, isparticularly interesting for weak grids like a MG. Energy sources using biogas are morereliable and less dependent on stochastic phenomena such as wind or solarillumination.After a state of the art on the different technologies enhancing biogas, it is clearthat a hybrid system consisting of a SOFC type fuel cell and a microturbine (MT)achieves the best electric efficiency with low environmental impact.The overall objective of the thesis is to study the SOFC / MT system as themain power source in an isolated rural MG context. For this purpose, a model of thesystem was carried out by focusing on the elements that affect the dynamics of thesystem's electrical signals. The hybrid system was then sized in order to maintainoptimal electrical performance, and a unique 3LNPC multilevel converter is used tointegrate the hybrid system to the MG. As a fuel cell is sensitive to load changes(affecting its performance and lifespan), the first objective of the control strategyapplied to the 3LNPC converter is to regulate the power of the SOFC at its nominalvalue. The MG must be able to operate autonomously when islanded, thus the secondobjective of this strategy is to set the grid voltage and frequency.The controllers of the control strategy are designed paying particular attention tothe robustness. The operation of the SOFC / MT hybrid system, driven by a single3LNPC type converter equipped with an innovative control strategy, has been testedand validated in simulation and experimentally in the MG platform of ESTIAResearch.

A produção e liberação de substâncias vasodilatadoras pelas células endoteliais requer uma elevação sustentada na concentração intracelular de cálcio; essa elevação é consequente a um influxo de cálcio. Porém, a identidade do (s) canal (is) envolvido (s) nesse influxo ainda não foi (ram) determinada (s) conclusivamente. Existem evidências de que o gene TRPV4 (que codifica uma proteína permeável a cátions, inclusive ao cálcio) é expresso em células endoteliais. Porém, a falta de agentes que modulem especificamente a função dessa proteína não permitiu que o papel do TRPV4 no controle da função endotelial pudesse ser elucidado. Recentemente foram descritos dois novos compostos, o GSK1016790A (GSK) e o HC-067047 (HC), com ação ativadora e bloqueadora seletiva desse canal, respectivamente. Consequentemente, nesta dissertação descrevemos e interpretamos os resultados obtidos em experimentos concebidos para caracterizar o efeito do GSK1016790A (e com fins comparativos o efeito do 4PDD) em artérias isoladas de várias espécies. Para isso, empregamos anéis de artérias suspensos em cubas para órgão isolado para registro da tensão desenvolvida por esses anéis durante a contração isométrica provocada pela adição de fenilefrina; todos os experimentos foram realizados com solução de Krebs contendo diclofenaco (10 M). Inicialmente verificamos mediante imunohistoquímica a presença de imunorreatividade para o TRPV4 no endotélio da aorta torácica de rato. A adição de concentrações isoladas ou cumulativas de GSK produziu relaxamentos dependentes da concentração na aorta torácica de rato (CE50=0,5 nM; IC95%=0,35-0,72 nM; n=7); o 4PDD (1-10 µM), em concentrações isoladas, também produziu relaxamentos na aorta torácica de rato. Resultados semelhantes foram observados para o GSK na aorta torácica de coelho (CE50= 4,3 nM; IC95%=3,58-5,14 nM; n=5), de camundongo (CE50=1,4 nM; IC95%=0,85-2,24 nM; n=3) e de cobaia (CE50=0,2 nM; IC95%=0,12-0,22 nM; n=4). GSK relaxou também a aorta abdominal (CE50=6,5 nM; IC95%=3,71-11,3 nM; n=3) e a artéria femoral de coelho (CE50=17 nM; IC95%=16,8-18,7 nM; n=4); Os relaxamentos produzidos por ambas as drogas apareceram 1-2 min após a adição e atingiram o máximo em 5-8 min, foram reversíveis e não apresentaram taquifilaxia. Em todas as artérias os relaxamentos foram estritamente dependentes de endotélio e da presença de cálcio no meio extracelular. Na aorta torácica de rato, a pré-incubação com HC (5 minutos) aboliu o efeito do GSK sem afetar os relaxamentos produzidos pela acetilcolina. Em todas as artérias testadas os efeitos do GSK e do 4PDD foram revertidos completamente pelo HC (1-3 µM) ou pelo vermelho de rutênio (aorta torácica de rato e artérias de coelho, 1µM, VR). Esses resultados demonstram que os canais TRPV4 estão presentes na célula endotelial e que a sua ativação leva à produção de fatores relaxantes. Como corolário, esses resultados constituem indícios de que os canais TRPV4 podem participar da regulação da função das células endoteliais em situações fisiológicas e/ ou fisiopatológicas. / Production and release of vasodilator substances by endothelial cells require a sustained elevation of intracellular calcium which depends on calcium influx. The identity of the channels involved in this influx remains to be established. There is evidence that the TRPV4 gene (which encodes for a cation permeable channel including calcium) is expressed in endothelial cells; the lack of pharmacologic agents that selectively modulate the activity of TRPV4 channels has hindered the elucidation of its function in endothelial cells. Recently two new compounds, GSK1016790A (GSK) and HC-067047 (HC), which selectively activate or block TRPV4 channels, respectively, were described. This dissertation consists in the description and interpretation of results from experiments conceived to characterize the effect of GSK (and of 4PDD for comparison) in isolated arterial rings from several animal species. To this aim we used arterial rings mounted in isolated organ chambers; we recorded continuously the tension developed by them during isometric contractions elicited by phenylephrine (Phe); all the experiments were conducted using Krebs solution containing diclofenac (10 µM). Initially, we confirmed by immunohistochemistry the presence of anti-TRPV4 immunoreactivity in the endothelium of rat thoracic aorta. In rat thoracic aortic rings pre-constricted with Phe (0.1 µM) the addition of different concentrations of GSK (either single or cumulative concentrations) caused concentration-dependent relaxations (EC50=0.5 nM, 95%CI=0.35-0.72 nM, n=7); 4PDD (in single concentrations) also caused relaxations of rat thoracic aortic rings. Similar results were observed for GSK in thoracic aortic rings from rabbit (EC50=4.3 nM, 95%CI=3.58-5.14 nM, n=5), mouse (EC50=1.4 nM, 95%CI=0.85-2.24 nM, n=3) and guinea-pig (EC50=0.2 nM, 95%CI=0.12-0.22 nM, n=4). GSK also produced relaxations of rings from rabbit abdominal aorta (EC50=6.5 nM, 95%CI=3.71-11.3 nM, n=3) and femoral artery (EC50=17 nM, 95%CI=16.8-18.7 nM, n=4). Relaxations caused by both GSK and 4PDD started 1-2 min after their addition and reached a steady-state in 5-8min; they were reversible after washing-out and did not exhibit tachyphylaxis. In all the studied arteries GSK or 4PDD induced- relaxations were strictly endothelium- and extracellular calcium- dependent. Pre-incubation of rat thoracic aortic rings with HC (1 µM for 5min) abolished the effect of GSK but did not affect relaxations elicited by Ach (1 µM). In all the arterial rings HC (1-3 µM) also completely reverted the relaxations caused by GSK or 4PDD; in rabbit and rat thoracic aortic rings ruthenium red (1 µM) also completely reverted the relaxations caused by GSK or 4PDD. The present findings showing that TRPV4 channels are present in endothelial cells and that their activation results in the production and release of relaxing factors constitute an indication that TRPV4 channels could be involved in the regulation of endothelial cell functions under physiological or patho-physiological conditions.

The ship emission already occupy the eighth position in the world biggest emitters ranking. This happens because the ship operations have a huge demand variation therefore in order to reduce the ship emissions is required an efficient operation of the generators. This work aims at integrating advanced storage systems into the operation of diesel generators. The variation of the operation point has a direct interference on the emissions and on the diesel consumption, this variation is allowed through the frequency and voltage control. The use of lithium batteries for various operation points of the generators is analyzed. The use of an energy storage system allowed the operation of the generators in a better operation point therefore there was a reduction in diesel consumption and in CO2 emissions when the diesel generators. The main result of this work could also shed light in the operation of isolated power systems equipped with advanced storage systems and diesel generators. / As emissões dos navios já ocupam a oitava posição entre os países com maior emissão no mundo. Isso pode ser explicado pelo fato de que as operações dos navios têm uma grande variação de demanda de potência, com isso a operação inteligente dos geradores a diesel é fundamental para a redução das emissões. A abordagem desenvolvida nesse trabalho integra o uso de sistemas de armazenamento avançados na operação dos geradores a diesel. A variação do ponto de operação dos geradores a diesel interfere diretamente no consumo e nas emissões, essa variação só é possível por meio do controle de frequência e tensão providos pelo sistema de armazenamento de energia. Nesse trabalho foram analisados o uso de baterias de lítio para diferentes pontos de operação do gerador a diesel. O uso das baterias possibilitou a operação dos geradores num melhor ponto de carga com isso houve uma redução das emissões e do consumo de combustível. Os resultados encontrados nesse trabalho podem ser extrapolados qualitativamente para outros sistemas de potência offshore, como plataformas de petróleo e de perfuração, que operem com sistemas de baterias avançadas e geradores a diesel.

Morphine-6-glucuronide is a minor metabolite. representing 5% of an administered dose of morphine. The metabolite has analgesic activity exceeding that of morphine and may contribute to analgesia following morphine administration. The aims of the study were to attempt to identify the reasons behind the improved activity of morphine-6-glucuronide over the parent compound and to examine a series of 6-substituted compounds, based on 6-substituted benzoate esters, as potential mimics of morphine-6-glucuronide. Morphine-6-glucuronide was seen to have similar affinity to morphine at l1-opioid receptors as assessed by ligand-binding assays in mouse brain homogenates. However a three-fold improved affinity at S-opioid receptor binding sites was observed and a ten-fold reduction in affinity at K-opioid sites. Using in vitro bioassay systems the glucuronide showed a two-fold improved potency over morphine in both the guinea-pig ileum and the mouse vas deferens preparations. Following in vivo (s.c.) administration in the mouse the glucuronide was seen to be equipotent with morphine in the tail-flick test, but was of much longer duration, lasting up to 9 hours. Exvivo binding assays confirmed that morphine-like material was still present in the central nervous system six hours after administration of the glucuronide, but was not observed at a similar time after morphine administration. Activity was retained if the hydroxyl groups of the sugar moiety of the glucuronide were protected as esters. In contrast the more prevalent morphine metabolite morphine-3-glucuronide was inactive in all in vitro and in vivo tests used and did not antagonise morphine in vitro or in vivo. A group of 3-substituted derivatives containing saturated and unsaturated substituents did show affinity for opioid receptors but no agonist activity of the compounds could be demonstrated in vitro. A series of synthetic 6-substituted compounds showed a variety of affinities for, and agonist potencies at, opioid receptors, though low affinity at Kopioid receptors was a general finding. For example, morphine-6- nitrobenzoate was l1-opioid receptor preferring, while morphine-6- phthalate had improved O-opioid receptor affinity and acted via Il-opioid receptors in the mouse vas deferens and in vivo. However the compounds were weaker than morphine and the duration of action in vivo was shorter than morphine-6-glucuronide. The conclusions from these studies are that morphine-6-glucuronide and morphine have similar in vitro affinities at the l1-receptor, although morphine-6-glucuronide has somewhat improved binding affinity for Il receptor sites, it has less affinity for K receptor sites. Pharmacokinetic reasons are probably responsible for the improved activity and duration of action of morphine-6-glucuronide over morphine. None of the synthetic compounds examined are potentially useful as direct mimics of the glucuronide because morphine-6-glucuronide is more potent and has a longer duration of action than the synthetic derivatives, though alteration at the 6-position of the morphine nucleus can lead to dramatic changes in selectivity and potency of ligands for the differing opioid receptors.

Neste trabalho,estudamos o índice de Poincaré-Hopf, definido para singularidades isoladas de campos de vetores sobre variedades diferenciáveis. Além disso, investigamos algumas definições de índices de campos de vetores definido sem variedades singulares, como o índice de Schwartz e o índice GSV. Estudaremos estes invariantes no caso específico em que (V; 0) é um germe de uma interseção completa com singularidade isolada na origem / In this work, we study thePoincaré-Hopf index, defined for isolated singularities of vector fields on manifolds. Moreover, we investigate some definitions of indices of vector fields defined on singular varieties, as the Schwartz index and the GSV index. We study these invariants in the case where (V; 0) is a germ of a complete intersection with an isolated singularity at the origin

Background Affective disorders are poorly defined and studied in sub-Saharan Africa despite their substantial public health impact. Objectives Overall objective: To describe the epidemiology of selected affective disorders in rural Ethiopia. Specific objectives 1. To describe the validity and utility of the concept of minor depressive disorder (mD). 2. To describe the manifestation, prevalence and the short-term clinical and functional course and outcome of bipolar disorder. Subjects and methods Population: Zay community residents (age ≥16), and residents of Butajira (ages 15-49), in Southern Ethiopia. Study design: Population-based cross-sectional and longitudinal studies Case identification: For the identification of cases with bipolar disorder, a two stage process was employed. An initial screen used key informants and interview with the Composite International Diagnostic Interview (CIDI) to identify cases with probable bipolar disorder. A second confirmatory diagnostic assessment stage employed the Schedules for Clinical Assessment in Neuropsychiatry (SCAN). For the identification of cases with mD, data from the CIDI was used. Follow-up: 312 cases with bipolar disorder from Butajira were followed up for a mean of 2.5 years (ranging 1-4 years) through monthly clinical assessments and annual symptom and functional ratings. Results The CIDI was administered to 1714 adults among the Zay and to 68, 378 adults among the Butajira residents. The prevalence of mD among the Zay and Butajira was 20.5% and 2.2% respectively. Up to 80% of cases with mD had used services for their symptoms, while a third to a half of cases had thought about self harm. Up to a sixth of cases had attempted suicide. Age, marital status, education and somatic symptoms were independently associated with mD. The prevalence of bipolar disorder among the Zay was 1.8%. During a 2.5-year follow-up of 312 cases with bipolar disorder from Butajira, 65.9% relapsed (47.8% manic, 44.3% depressive and 7.7% mixed episodes) while 31.1% experienced persistent illness. Female gender predicted depressive relapse whereas male gender predicted manic relapse. Only being on psychotropic medication predicted remission (OR=3.42; 95% CI=1.82, 6.45). Disability was much worse among bipolar patients than in the general population and was predicted by symptom se3verity. Conclusions This is the largest study on mD and bipolar disorder in Africa. mD appears to have potential clinical utility in this setting given its association with service use and risk. The identified risk factors for mD also suggest potential aetiological continuity with major depression. The relatively high prevalence of bipolar disorder among the Zay may be related to genetic predisposition perhaps mediated through a founder effect, but other factors need exploring. In relation to the outcome of bipolar disorder, this study indicates that, contrary to previous assumptions, the course of bipolar disorder is characterised by both manic and depressive relapses in a relatively proportionate fashion. Bipolar disorder also leads to significant levels of disability. This is the only prospective outcome study of bipolar disorder in Africa where cases were monitored systematically at short assessment intervals. Therefore, findings are likely to be more robust than previous reports.

The lumen-to-cell transport, cellular accumulation, and toxicity of ionic cadmium (109Cd2+) and cadmium-cysteine conjugate (Cys-S-109Cd-S-Cys) were studied in isolated perfused S2 segments of the proximal tubule of the rabbit kidney. All perfusion solutions were HEPES buffered and contained 3H-L-glucose which functioned as a volume and leak marker along with 250 nM FD & C Green dye as a vital dye. When ionic cadmium, 0.73µM Cd2+, or 0.73µM cadmium-cysteine conjugate (Cys-S-109Cd-S-Cys) containing solution was perfused through the lumen of the tubule there was no visual evidence of toxicity such as blebbing of the luminal membrane, cellular vital dye uptake, and cellular swelling. Ionic Cd2+ transport was temperature dependent (87% reduction at 22°C and 100% at 11°C) and inhibited by FeCl2 (42% reduction at 10µM) and ZnCl2 (48% reduction at 20µM), and high Ca2+ concentrations (27% reduction at 1.95mM and 69% at 2.6mM). The ionic Cd2+ transport was not affected by verapamil and diltiazem. The cadmium conjugate (Cys-S-Cd-S-Cys) transport was also temperature dependent (76% reduction at 22°C and 100% at 11°C) and inhibited by the amino acids L-cystine and L-arginine (55% and 50% respectively), stimulated by L-methionine (56%), but not affected by L-aspartate, L-glutamate and Gly-Sar. 2, 3-Dimercaptopropane-1-Sulfonate (DMPS) co-perfused with Cd2+ decreased absorption of 20µM Cd2+ (39% reduction at 30 µM and 94.6% reduction at 200 µM), while DMPS added to the bathing solution has no effect on the luminal transport of Cd2+. DMPS co-perfused with 20 µM Cys-S-Cd-S-Cys substantially reduced Cd2+ transport (62% reduction at 30 µM). We conclude that cadmium can be transported at the luminal membrane of the S2 segment of the proximal tubule by multiple mechanisms, depending on the form which it is presented to membrane. Ionic cadmium appears to be transported by iron (DCT1), zinc (ZTL1) transporters and some kind of calcium-selective channel while cadmium conjugate of L-cysteine appears to be transported by L-cystine transporters (system b0+). Dipeptide transporter is not involved in the transport of cadmium. DMPS appears to be a chelator for cadmium.