A CONTABILIDADE E O REAL VALOR DAS EMPRESAS: FOCO NO CAPITAL INTELECTUAL

Este trabalho mostra que a contabilidade pode não estar a evidenciar o real valor do património das empresas (um dos seus objectivos), constatamos nos últimos tempos, que os relatórios fornecidos pela contabilidade financeira não retratam certas realidades das empresas, visto que o valor contabilístico se distancia cada vez mais do valor de mercado, principalmente nas empresas de alta tecnologia e serviços, assim sendo as demonstrações financeiras podem estar experimentando uma perda de relevância para a tomada de decisões de investimentos, de crédito e de gestão. Dentro deste contexto, ressaltamos a necessidade de a contabilidade evidenciar naquelas demonstrações tais informações para que possa divulgar aos vários utentes da informação o real valor da empresa. Visto que o Capital Intelectual é importante para as empresas, torna-se necessário relatar não só informações financeiras como também não financeiras. Este trabalho apresenta um estudo descritivo/quantitativo da empresa CVTelecom, com o objectivo de avaliar o grau de divulgação do Capital Intelectual na empresa. A principal constatação foi o seguinte: uma participação activa da empresa em divulgar o Capital Intelectual, uma forma não normalizada através da divulgação voluntária do Capital Intelectual cujo veículo de divulgação, é o Relatório de Gestão e o Balanço Social. This work shows that the Accounting cannot be evidencing the Real value of the patrimony of the enterprises (one of their objectives), we verified in the last times, that the reports supplied by the Financial Accounting don't portray certain realities of the enterprises, because the value Accounting of the enterprises go away more and more of his market value, mainly in the companies of high technology and services, soon the financial demonstrations are trying a loss of relevance for socket of decisions of investments, of credit and of administration. Inside of this context, we emphasized the need of the Accounting to evidence in the demonstrations such financial information so that it can publish to the several users of the information the Real value of the company. Because the Intellectual Capital is important for the enterprises, it becomes necessary to tell not only financial information as well as any financial. This work presents a descriptive-quantitative study of the enterprise CVtelecom, with the objective of evaluating the degree of popularization of the Intellectual Capital in the enterprise and the impact in the performance of this enterprise. The main verification was the following: A participation active of the company in publishing the Intellectual Capital in spite of being in a way no normalized but a voluntary popularization of the Intellectual Capital, whose popularization vehicle is the Report of Administration and the Social Swinging.

Análise Económica e Financeira como Instrumento de Apoio ao Processo Decisório

O foco central deste relatório consiste em mostrar a total importância da Análise Económica e Financeira como instrumento de apoio ao processo decisório. No contexto actual onde a concorrência é cada vez mais forte e a busca pela competitividade é uma necessidade constante, as empresas necessitam de informações precisas e oportunas para apoiar o processo decisório. A escassez de recursos financeiros e o elevado custo, aliado com a falta de planeamento e controle, têm contribuído para que muitas empresas encerrem suas actividades. A tomada de boas decisões torna-se, então, um factor crucial para assegurar a sobrevivência, crescimento e permanência da empresa no mercado. Neste sentido, buscamos trazer para todos os interessados alguns conceitos e técnicas fundamentais de análise e medição da performance económica e financeira das empresas que será igualmente útil, quer a nível académica, como também a nível profissional. Procuramos evidenciar a importância de se conhecer os indicadores que podem ser vistos como alertas de possíveis falências de empresas e com base nisso, tomar decisões que determinam que estratégias utilizar para enfrentar a concorrência. A finalizar este relatório procedemos a uma pesquisa Estudo de Caso que engloba uma análise económica e financeira, baseada na análise das Demonstrações Financeiras e demais informações complementares da TRANSCOR-SV, S.A. Foram explorados alguns conceitos relacionados com o tema, mostrando de forma simples e objectiva a situação de como a empresa vem actuando no mercado. Constámos algumas deficiências, pois, foram verificados alguns pontos fracos. Diante dos problemas, sugerimos formas de mudanças e de viabilidade dos mesmos. Esperamos, então, que este relatório contribua para a empresa analisar melhor a forma de administrar a parte económica e financeira e demais sectores.The central focus of this report consists of showing to total importance of the Analysis Economic and Financial as support instrument to the ruling process. In the context actual where the competition is more and more strong and the search for the competitiveness is a constant need, the companies need necessary and opportune information to support the ruling process. The shortage of financial resources and the high cost, ally with the planning lack and control, they have been contributing so that a lot of companies contain their activities. The socket of good decisions becomes, then, a crucial factor to assure the survival, growth and permanence of the company in the market. In this sense, we looked for to bring for all the interested parties, some concepts and fundamental techniques of analysis and measurement of the performance economic and financial of the companies, which will be equally useful, he/she wants to academic level, as well as at professional level. We tried to evidence, the importance of knowing the indicators that you/they can be seen as alerts of possible bankruptcies of companies and with base in that, to make decisions that determine which strategies to use to face the competition. To conclude this report we proceeded to a research Study of Case that includes an analysis economic and financial, based on the analysis of the Financial Demonstrations and other complementary information of TRANSCOR-S.V., S.A. Some concepts related with the theme were explored, showing the situation of simple form and objective of as the company is acting in the market. It was verified some deficiencies, because, some weak points were verified. Before the problems, we suggested forms of changes and of viability of the same ones.We waited, then, which this report contributes to company to analyze the form better of administering the part economic and financial and other sectors.

Bilateral renal artery entrapment by diaphragmatic crura: a rare cause of renovascular hypertension with a specific management.

We present the case of a young man with compression of both renal arteries by the crura of the diaphragm. Correct diagnosis of renal artery entrapment is difficult but crucial. The investigations rely on an high index of suspicion and include Doppler ultrasound and spiral computed tomography angiography, which permits visualization of the diaphragm and its relationships with the aorta. This pathology, unlike common renal artery stenoses, requires surgical decompression and sometimes aortorenal bypass graft.

High Specificity of C4d/CD68 Staining for the Diagnosis of Late Antibody-Mediated Rejection in Heart Transplantation.

In heart transplantation (HTx), acute antibody-mediated rejection (AMR) is infrequent but carries high mortality and increased risk of graft vasculopathy. The diagnosis requires evidence of acute graft dysfunction, capillary lesions on endomyocardial biopsy (EMB), and immunopathological criteria of antibodymediated injury. Multiple markers of antibody-mediated injuries have been proposed, but there is ample debate on their usefulness. In kidney transplantation, C4d deposition in peritubular capillaries is a reliable marker of alloantibody-dependant graft injury. In this study, we prospectively screened all EMBs for C4d and CD68 in new HTx recipients, and correlated pathological fi ndings with immunological evidence of donor-specifi c antibodies (DSA) and graft dysfunction. Methods Between Nov 05 and Aug 08, we had 22 HTx, and 17 cases were analysed. All recipients received polyclonal rabbit anti-thymocytes globulin, calcineurin inhibitors, mycophenolate mofetil, and corticosteroids (weaning in 6 -12 months). They had EMB every 1-2 weeks in the fi rst 3 months, and then monthly for 9 months. C4d and CD 68 were assessed by immunochemistry. Echocardiography and DSA assessment or crossmatch (early phase) were realised if C4d or CD68 staining was positive. Results There was 1 early and 1 late AMR. Table 1 C4d and CD68 positive, at least 1 EMB 6 / 17; 35% 1 treated C4d and CD68 positive, at least 2 consecutive EMBs 3 / 17; 17.5% 1 treated C4d and CD68 positive, and graft dysfunction 1 / 17; 6% 1 treated C4d and CD68 positive, with DSA and crossmatch + 1 / 17; 6% 1 treated Table 2 C4d and CD68 positive, at least 1 EMB 1 / 17; 6% 1 treated C4d and CD68 positive, at least 2 consecutive EMBs 1 /17; 6% 1 treated C4d and CD68 positive and graft dysfunction 1 / 17; 6% 1 treated C4d and CD68 positive, and + DSA 1 / 17; 6% 1 treated Conclusion In this single-center experience, C4d / CD68 positive staining was frequent in the early phase and raised the question of false positive cases of AMR. However, these markers showed high specifi city for the diagnosis of AMR in the late phase. Of course these data need to be confi rmed in larger multi-center studies.

Increased connexin43 expression in human sphenous veins in culture is associated with intimal hyperplasia

Résumé Objectif : L'hyperplasie intimale est un processus de remodelage vasculaire qui apparaît après une lésion vasculaire. Les mécanismes impliqués dans l'hyperplasie intimale sont la prolifération, la dédifférentiation et la migration des cellules musculaires lisses depuis la média vers l'espace sous-intimal. Nous avons émis l'hypothèse que les jonctions communicantes de type gap, qui coordonnent certains processus physiologiques tels que la croissance et la différentiation cellulaire, pouvaient participer au développement de l'hyperplasie intimale. Méthodes : Des segments de veines saphènes humaines prélevées chirurgicalement lors de pontages, ont été ouverts longitudinalement avec la surface luminale placée vers le haut et maintenus en culture pendant 14 jours. Des fragments veineux ont été préparés pour une évaluation histologique, pour des mesures de l'épaisseur de la néointima, et pour des analyses immunocytochimiques de l'ARN messager ainsi que des protéines. Résultats : Parmi les 4 connexines (Cxs 37, 40, 43 et 45) qui forment les jonctions communicantes dans les veines, nous avons focalisé notre étude sur l'expression des Cxs 43 et 40; nous avons démontré que la Cx43 est exprimée dans les cellules musculaires lisses et les cellules endothéliales alors que la Cx40 est uniquement présente dans l'endothélium. Après 14 jours en culture, des analyses histomorphométriques ont montré une augmentation significative de l'épaisseur de l'intima démontrant la présence d'hyperplasie intimale. Une analyse temporelle a révélé une augmentation progressive de la Cx43 jusqu'à une augmentation maximale de six à huit fois au niveau de l'ARN messager et des protéines après 14 jours en culture. Au contraire, l'expression de la Cx40 n'était pas modifiée. Des analyses par immunofluorescence ont montré également une augmentation de la Cx43 dans les membranes des cellules musculaires lisses de la média. Le développement de l'hyperplasie intimale in vitro est diminué en présence de fluvastatin et cette diminution est associée à une réduction de l'expression de la Cx43. Conclusions : Ces données démontrent que la Cx43 est augmentée in vitro pendant le processus d'hyperplasie intimale et que la fluvastatin prévient cette induction. Ces résultats suggèrent un rôle crucial joué par la communication intercellulaire impliquant la Cx43 dans la veine humaine durant le développement de l'hyperplasie intimale. Abstract Objective: Intimal hyperplasia is a vascular remodelling process that occurs after a vascular injury. The mechanisms involved in intimal hyperplasia are proliferation, dedifferentiation, and migration of medial smooth muscle cells towards the subintimal space. We postulated that gap junctions, which coordinate physiologic processes such as cell growth and differentiation, might participate in the development of intimal hyperplasia. connexin43 (Cx43) expression levels may be altered in intimal hyperplasia, and we therefore evaluated the regulated expression of Cx43 in human saphenous veins in culture in the presence or not of fluvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity. Methods: Segments of harvested human saphenous veins, obtained at the time of bypass graft, were opened longitudinally with the luminal surface uppermost and maintained in culture for 14 days. Vein fragments were then processed for histologic examination, neointimal thickness measurements, immunocytochemistry, RNA, and proteins analysis. Results: Of the four connexins (Cx37, 40, 43, and 45), we focused on Cx43 and Cx40, which we found by real-time polymerase chain reaction to be expressed in the saphenous vein because they are the predominant connexins expressed by smooth muscle cells and endothelial cells. Afrer 14 days of culture, histomorphometric analysis showed a significant increase in the intimal thickness as observed during the process of intimal hyperplasia. Atime-course analysis revealed a progressive upregulation of Cx43 to reach a maximal increase of sixfold to eightfold at both transcript and protein levels after 14 days in culture. In contrast, the expression of Cx40, abundantly expressed in the endothelial cells, was not altered. Immunofluorescence showed a large increase in Cx43 within smooth muscle cell membranes of the media layer. The development of intimal hyperplasia in vitro was decreased in presence of fluvastatin and was associated with reduced Cx43 expression. Conclusions: These data show that Cx43 is increased in vitro during the process of intimal hyperplasia and that fluvastatin could prevent this induction, supporting a critical role for Cx43-mediated gap-junctional communication in the human vein during the development of intimal hyperplasia. (J Vasc Surg 2005;41:1043-52.)

The presence of a CD4+ CD25high CD45RO+ CD127high T-cell population correlates with the clinical status of kidney transplant recipients

Background: Recent data have suggested that a population of CD4+ CD25high T cells, phenotypically characterized by the expression of CD45RO and CD127, is significantly expanded in stable liver and kidney transplant recipients and represents alloreactive T cells. We analyzed this putative new alloreactive cellular marker in various groups of kidney transplant recipients. Patients and methods: Flow cytometry was used to analyze the expression of CD25, CD45RO and CD127 on peripheral CD4+ T cells. Of 73 kidney recipients, 59 had a stable graft function under standard immunosuppressive therapy (IS), 5 had biopsy-proven chronic humoral rejection (CHR), 8 were stable under minimal IS and one was an operationally "tolerant" patient who had discontinued IS for more than 3 years. Sixty-six healthy subjects (HS) were studied as controls. Results: Overall, the alloreactive T cell population was found to be significantly increased in the 73 kidney recipients (mean ± SE: 15.03 ± 1.04% of CD4+ CD25high T cells) compared to HS (5.93 ± 0.39%) (p <0.001). In the 5 patients with CHR, this population was highly expanded (31.33 ± 4.16%), whereas it was comparable to HS in the 8 stable recipients receiving minimal IS (6.12 ± 0.86%), in 4 patients who had been switched to sirolimus (4.21 ± 0.53%) as well as in the unique "tolerant" recipient (4.69%). Intermediate levels (15.84 ± 0.93%) were found in the 55 recipients with stable graft function on standard CNI-based IS. Regulatory T cells, defined as CD4+ CD25high FoxP3+ CD127low, were found to be significantly reduced in all recipients except in those with minimal or no IS, and this reduction was particularly striking in recipients with CHR. Conclusion: After kidney transplantation, an alloreactive T cell population was found to be significantly expanded and it correlates with the clinical status of the recipients. Interestingly, in stable patients with minimal (or no) IS as well as in patients on sirolimus, alloreactive T cells were comparable the healthy controls. Measuring circulating CD4+ CD25high CD45RO+ CD127high T cells may become a useful monitoring tool after transplantation.

Exclusion of lumbar arteries by aortic endovascular grafts: can angiography demonstrate sealing characteristics?

BACKGROUND: This study evaluates sealing characteristics of two designs of endovascular grafts by angiographic demonstration of exclusion of porcine lumbar arteries. METHODS: 6 endovascular grafts (3 self-expandable with integrated polyurethane wall versus 3 nitinol structures covered with polyester fabric) were implanted in 6 porcine aortae. Perfusion of lumbar arteries was assessed by angiography after implantation and by angiography and dissection at graft explantation after 4 +/- 2 months. Tissue healing was evaluated by light and scanning electron microscopy. RESULTS: Immediate exclusion of the lumbar arteries was achieved in 14/31 vessels (12 by polyurethane grafts and 2 by polyester grafts, p < 0.001). Follow-up angiography and dissection at explantation revealed perfusion of 30/31 lumbar arteries with a collateral network in most cases. Another reason for reperfusion of initially excluded branches was distention of the polyurethane grafts with resulting shortening allowing reperfusion of 8 of the 31 originally covered branches. Histological examination revealed a complete neointimal lining and a tight contact between endovascular grafts and aorta. CONCLUSIONS: The immediate angiographic demonstration of exclusion of lumbar arteries predicts sealing characteristics of endovascular grafts. Later angiographic reappearance is due to development of a collateral network and possible shortening of self-expandable devices.

O contributo da contabilidade numa gestão transparente das OSFL - Caso: ADECO

Na actualidade, tem-se cada vez mais a consciência da necessidade e da importância de ter uma informação financeira credível e em tempo oportuno. A informação financeira passou a ser a base para avaliação do desempenho dos gestores, assim como para análise da situação económico-financeira das Organizações. A informação só é útil para tomada de decisão se tiverem as seguintes características qualitativas: Compreensibilidade, Relevância, Fiabilidade e Comparabilidade. No ambiente concorrencial em que as Organizações estão inseridas, a Contabilidade tem um papel fulcral como instrumento de tomada de decisão. As Organizações que têm como objectivos acções sociais, actuam nas áreas como: culturais e recreativas, solidariedade social, promoção do desenvolvimento comunitário, educacionais, de protecção ao ambiente, Saúde e da promoção da higiene, entre outros. Como essas Organizações não têm com objectivo o lucro, é necessário ter uma boa gestão e para que isso seja possível, é preciso ter-se instrumentos capazes para que isso seja possível e é neste âmbito que a Contabilidade entra como um auxílio para a gestão, como ferramenta capaz de mensurar e controlar processos, resultados e impactos nos projectos executados, a fim de que seus objectivos sociais sejam alcançados de uma forma consistente com o planeado. A sustentabilidade, a necessidade de demonstração e de aplicação dos recursos obtidos é um forte desafio que as Organizações do terceiro sector têm de ultrapassar e, neste âmbito, a Contabilidade pode constituir um meio importante para atingir esses objectivos, através da demonstração dos resultados alcançados. Nesta base, o contributo da Contabilidade na gestão das OSFL tem-se acentuado cada vez mais, demonstrando transparência na apresentação das suas contas, facilitando na captação de recursos e na fidelização dos seus parceiros e financiadores. Nowadays it has become increasingly aware of the need and importance of having credible and timely financial information. The financial information started to be the base for evaluation of the managers acting, as well as for analysis of the economicfinancial situation of the company. The information is only useful for socket of decision if they have the following qualitative characteristics: Comprehensive, Relevance, Reliable and Comparability. In the atmosphere concurrencies in that the Organizations are inserted the accounting has a crucial paper as instrument of socket of decision in the Organizations. The Organizations that have as purpose social action as for instance: cultural and recreational, social solidarity, promotion of the development community, education, of protection to the atmosphere, health and of the promotion of the hygiene, among others. As those Organizations don't have with objective the profit, it is necessary to have a good administration and for that to be possible, it is necessary to have capable instruments for that to be possible and it is in this extent that the accounting enters as an aid for the administration, as tool capable to measure and to control processes, results and impacts in the executed projects, so that their social objectives are reached in a solid way with the planed. Sustainability, the demonstration of the achieved results and the application of resources collected are strong challenges that the Organizations of the third sector have to overcome. To that extent, Accounting can contribute as an important way to reach those objectives through the demonstration of resources collected. In this base, the contribution of the Accounting has been accentuating more and more in the administration of the nonprofit organizations, demonstrating transparency in the presentation of their finance statements, facilitating the fundraising of Organizations and loyal partners and funders.

Tetracycline-regulated expression of VEGF-A in beta cells induces angiogenesis: improvement of engraftment following transplantation.

Early revascularization of pancreatic islet cells after transplantation is crucial for engraftment, and it has been suggested that vascular endothelial growth factor-A (VEGF-A) plays a significant role in this process. Although VEGF gene therapy can improve angiogenesis, uncontrolled VEGF secretion can lead to vascular tumor formation. Here we have explored the role of temporal VEGF expression, controlled by a tetracycline (TC)-regulated promoter, on revascularization and engraftment of genetically modified beta cells following transplantation. To this end, we modified the CDM3D beta cell line using a lentiviral vector to promote secretion of VEGF-A either in a TC-regulated (TET cells) or a constitutive (PGK cells) manner. VEGF secretion, angiogenesis, cell proliferation, and stimulated insulin secretion were assessed in vitro. VEGF secretion was increased in TET and PGK cells, and VEGF delivery resulted in angiogenesis, whereas addition of TC inhibited these processes. Insulin secretion by the three cell types was similar. We used a syngeneic mouse model of transplantation to assess the effects of this controlled VEGF expression in vivo. Time to normoglycemia, intraperitoneal glucose tolerance test, graft vascular density, and cellular mass were evaluated. Increased expression of VEGF resulted in significantly better revascularization and engraftment after transplantation when compared to control cells. In vivo, there was a significant increase in vascular density in grafted TET and PGK cells versus control cells. Moreover, the time for diabetic mice to return to normoglycemia and the stimulated plasma glucose clearance were also significantly accelerated in mice transplanted with TET and PGK cells when compared to control cells. VEGF was only needed during the first 2-3 weeks after transplantation; when removed, normoglycemia and graft vascularization were maintained. TC-treated mice grafted with TC-treated cells failed to restore normoglycemia. This approach allowed us to switch off VEGF secretion when the desired effects had been achieved. TC-regulated temporal expression of VEGF using a gene therapy approach presents a novel way to improve early revascularization and engraftment after islet cell transplantation.

Mechanisms of Symptomatic Spinal Cord Ischemia After TEVAR: Insights From the European Registry of Endovascular Aortic Repair Complications (EuREC).

Abstract Purpose: To test the hypothesis that simultaneous closure of at least 2 independent vascular territories supplying the spinal cord and/or prolonged hypotension may be associated with symptomatic spinal cord ischemia (SCI) after thoracic endovascular aortic repair (TEVAR). Methods: A pattern matching algorithm was used to develop a risk model for symptomatic SCI using a prospective 63-patient single-center cohort to test the positive predictive value (PPV) of prolonged intraoperative hypotension and/or simultaneous closure of at least 2 of 4 the vascular territories supplying the spinal cord (left subclavian, intercostal, lumbar, and hypogastric arteries). This risk model was then applied to data extracted from the multicenter European Registry on Endovascular Aortic Repair Complications (EuREC). Between 2002 and 2010, the 19 centers participating in EuREC reported 38 (1.7%) cases of symptomatic spinal cord ischemia among the 2235 patients in the database. Results: In the single-center cohort, direct correlations were seen between the occurrence of symptomatic SCI and both prolonged intraoperative hypotension (PPV 1.00, 95% CI 0.22 to 1.00, p = 0.04) and simultaneous closure of at least 2 independent spinal cord vascular territories (PPV 0.67, 95% CI 0.24 to 0.91, p = 0.005). Previous closure of a single vascular territory was not associated with an increased risk of symptomatic spinal cord ischemia (PPV 0.07, 95% CI 0.01 to 0.16, p = 0.56). The combination of prolonged hypotension and simultaneous closure of at least 2 territories exhibited the strongest association (PPV 0.75, 95% CI 0.38 to 0.75, p<0.0001). Applying the model to the entire EuREC cohort found an almost perfect agreement between the predicted and observed risk factors (kappa 0.77, 95% CI 0.65 to 0.90). Conclusion: Extensive coverage of intercostal arteries alone by a thoracic stent-graft is not associated with symptomatic SCI; however, simultaneous closure of at least 2 vascular territories supplying the spinal cord is highly relevant, especially in combination with prolonged intraoperative hypotension. As such, these results further emphasize the need to preserve the left subclavian artery during TEVAR.

Small airways function declines after allogeneic haematopoietic stem cell transplantation.

Bronchiolitis obliterans (BO) following allogeneic haematopoietic stem cell transplantation (HSCT) affects peripheral airways. Detection of BO is presently delayed by the low sensitivity of spirometry. We examined the relationship between peripheral airway function and time since HSCT, and compared it with spirometry and clinical indices in 33 clinically stable allogeneic HSCT recipients. The following measurements were performed: lung function, exhaled nitric oxide, forced oscillatory respiratory system resistance and reactance, acinar (S(acin)) and conductive airways ventilation heterogeneity and lung clearance index (LCI) measured by multiple breath nitrogen washout. 22 patients underwent repeat visits from which short-term changes were examined. Median time post HSCT was 12 months. Eight patients were clinically diagnosed as having BO. In multivariate analysis, time since HSCT was predicted by S(acin) and forced expiratory volume in 1 s % predicted. 20 patients had abnormal S(acin) with normal spirometry, whereas none had airflow obstruction with normal S(acin). S(acin) and LCI were the only measures to change significantly between two visits, with both worsening. Change in S(acin) was the only parameter to correlate with change in chronic graft-versus-host disease grade. In conclusion, peripheral airways ventilation heterogeneity worsens with time after HSCT. S(acin) may be more sensitive than spirometry in detecting BO at an early stage, which needs confirmation in a prospective study.

Characterization of CD4+ CD25+ T cells in solid organ transplant recipients

Although important progresses have been achieved in the therapeutic management of transplant recipients, acute and chronic rejections remain the leading causes of premature graft loss after solid organ transplantation. This, together with the undesirable side effects of immunosuppressive drugs, has significant implications for the long-term outcome of transplant recipients. Thus, a better understanding of the immunological events occurring after transplantation is essential. The immune system plays an ambivalent role in the outcome of a graft. On one hand, some T lymphocytes with effector functions (called alloreactive) can mediate a cascade of events eventually resulting in the rejection, either acute or chronic, of the grafted organ ; on the other hand, a small subset of T lymphocytes, called regulatory T cells, has been shown to be implicated in the control of these harmful rejection responses, among other things. Thus, we focused our interest on the study of the balance between circulating effectors (alloreactive) and regulatory T lymphocytes, which seems to play an important role in the outcome of allografts, in the context of kidney transplantation. The results were correlated with various variables such as the clinical status of the patients, the immunosuppressive drugs used as induction or maintenance agents, and past or current episodes of rejection. We observed that the percentage of the alloreactive T lymphocyte population was correlated with the clinical status of the kidney transplant recipients. Indeed, the highest percentage was found in patients suffering from chronic humoral rejection, whilst patients on no or only minimal immunosuppressive treatment or on sirolimus-based immunosuppression displayed a percentage comparable to healthy non-transplanted individuals. During the first year after renal transplantation, the balance between effectors and regulatory T lymphocytes was tipped towards the detrimental effector immune response, with the two induction agents studied (thymoglobulin and basiliximab). Overall, these results indicate that monitoring these immunological parameters may be very useful for the clinical follow-up of transplant recipients ; these tests may contribute to identify patients who are more likely to develop rejection or, on the contrary, who tolerate well their graft, in order to adapt the immunosuppressive treatment on an individual basis.

Intrahippocampal cholinergic grafts in aged rats compensate impairments in a radial maze and in a place learning task

Age-related cognitive impairments were studied in rats kept in semi-enriched conditions during their whole life, and tested during ontogeny and adult life in various classical spatial tasks. In addition, the effect of intrahippocampal grafts of fetal septal-diagonal band tissue, rich in cholinergic neurons, was studied in some of these subjects. The rats received bilateral cell suspensions when aged 23-24 months. Starting 4 weeks after grafting, they were trained during 5 weeks in an 8-arm maze made of connected plexiglass tunnels. No age-related impairment was detected during the first eight trials, when the maze shape was that of a classical radial maze in which the rats had already been trained when young. The older rats were impaired when the task was made more difficult by rendering two arms parallel to each other. They developed an important neglect of one of the parallel tunnels resulting in a high amount of errors before completion of the task. In addition, the old rats developed a systematic response pattern of visits to adjacent arms in a sequence, which was not observed in the younger subjects. None of these behaviours were observed in the old rats with a septal transplant. Sixteen weeks after grafting, another experiment was conducted in a homing hole board task. Rats were allowed to escape from a large circular arena through one hole out of many, and to reach home via a flexible tube under the table. The escape hole was at a fixed position according to distant room cues, and olfactory cues were made irrelevant by rotating the table between the trials. An additional cue was placed on the escape position. No age-related difference in escape was observed during training. During a probe trial with no hole connected and no proximal cue present, the old untreated rats were less clearly focussed on the training sector than were either the younger or the grafted old subjects. Taken together, these experiments indicate that enriched housing conditions and spatial training during adult life do not protect against all age-related deterioration in spatial ability. However, it might be that the considerable improvement observed in the grafted subjects results from an interaction between the graft treatment and the housing conditions.

TRENDS IN HOSPITAL MANAGEMENT OF ACUTE MYOCARDIAL INFARCTION IN SWITZERLAND, 1998 TO 2008 THE REGION MAKES THE DIFFERENCE: DISPARITIES IN MANAGEMENT OF ACUTE MYOCARDIAL INFARCTION WITHIN SWITZERLAND

The aim of this master's thesis was to assess the ten- year trends and regional differences in management and outcome of acute myocardial infarction (AMI) within Switzerland. The thesis is composed of two articles. First, in the article "Trends in hospital management of acute myocardial infarction in Switzerland, 1998 to 2008" over 102,700 cases of AMI with corresponding management and revascularization procedures were assessed. The results showed a considerable increase in the numbers of hospital discharges for AMI, namely due to the increase of between- hospital transfers. Rates of intensive care unit admissions remained stable. All types of revascularization procedures showed an increase. In particular, overall stenting rates increased with drug-eluting stents partly replacing bare stents. Second, in the article "The region makes the difference: disparities in management of acute myocardial infarction within Switzerland" around 25,600 cases of AMI with corresponding management were assessed for the period of 2007-2008 and according to seven Swiss regions. As reported by our results, considerable regional differences in AMI management were stated within Switzerland. Although each region showed different trends regarding revascularization interventions, Leman and Ticino contrast significantly by presenting the minimum and maximum rates in almost all assessed parameters. As a consequence these two regions differ the most from the Swiss average. The impact of the changes in trends and the regional differences in AMI management on Swiss patient's outcome and economics remains to be assessed. Purpose: To assess ten-year trends in management and outcome of acute myocardial infarction (AMI) in Switzerland. Methods: Swiss hospital discharge database for the 1998 to 2008 period. AMI was defined as a primary discharge diagnosis code I21 according to the CIM-10 classification of the World Health Organization. Management and revascularization procedures were assessed. Results: Overall, 102,729 hospital discharges with a diagnosis of AMI were analyzed. The number of hospital discharges increased almost three-fold from 5530 in 1998 to 13,834 in 2008, namely due to a considerable increase in between-hospital transfers (1352 in 1998, 6494 in 2008). Relative to all hospital discharges, Intensive Care Unit admission rate was 38.0% in 1998 and remained stable (36.2%) in 2008 (p for trend=0.25). Percutaneous revascularization rates increased from 6.0% to 39.9% (p for trend<0.001). Non-drug-eluting stent use increased from 1.3% to 16.6% (p for trend<0.05). Drug eluting stents appeared in 2004 and increased to 23.5% of hospital discharges in 2008 (p for trend=0.07). Coronary artery bypass graft increased from 1.0% to 3.0% (p for trend<0.001). Circulatory assistance increased from 0.2% to 1.7% (p for trend<0.001). Thrombolysis showed no significant changes, from 0.5% to 1.9% (p for trend=0.64). Most of these trends were confirmed after multivariate adjustment. Conclusion: Between 1998 and 2008 the number of hospital discharges for AMI increased considerably in Switzerland, namely due to between-hospital transfers. Overall stenting rates increased, drug-eluting stents partly replacing bare stents. The impact of these changes on outcome and economics remains to be assessed.

Homeostasis and in vivo effector function of antigen-specific CD4+CD25+ regulatory T cells in experimental transplantation.

CD4+CD25+ regulatory T cells (Tregs) play a critical role in the prevention of autoimmune diseases as well as in the induction and maintenance of dominant tolerance in transplantation models. While their suppressive function has been extensively studied in vitro, their homeostasis and mechanisms of immunoregulation still remain to be clarifi ed in vivo. Using a murine adoptive transfer and skin allograft model, we analysed the expansion, effector function and traffi cking of effector T cells in the presence or absence of donor-specifi c Tregs. Although hyporesponsive to allogeneic and polyclonal stimulation in vitro, transferred Tregs survived and expanded, in response to an allograft in vivo. When co-transferred with naive CD4+CD25- effector T cells, they specifi cally prevented donor but not 3rd party allograft rejection by inhibiting the production of effector cytokines rather than the proliferation of effector T cells in response to alloantigens. The co-transfer of donor-specifi c Tregs did not affect the homing of effector T cells towards the graft draining lymph nodes, but it markedly reduced the infi ltration of the allograft by these pathogenic cells. Furthermore, in recipients where donor-specifi c transplantation tolerance was induced, Tregs preferentially accumulated in the allograft draining lymph nodes and within the grafted skin itself. Taken together, our results suggest that the suppression of graft rejection is an active process that involves the persistent presence of Tregs at the site of antigenic challenge.