Potentiation of polarized intestinal Caco-2 cell responsiveness to probiotics complexed with secretory IgA.

The precise mechanisms underlying the interaction between intestinal bacteria and the host epithelium lead to multiple consequences that remain poorly understood at the molecular level. Deciphering such events can provide valuable information as to the mode of action of commensal and probiotic microorganisms in the gastrointestinal environment. Potential roles of such microorganisms along the privileged target represented by the mucosal immune system include maturation prior, during and after weaning, and the reduction of inflammatory reactions in pathogenic conditions. Using human intestinal epithelial Caco-2 cell grown as polarized monolayers, we found that association of a Lactobacillus or a Bifidobacterium with nonspecific secretory IgA (SIgA) enhanced probiotic adhesion by a factor of 3.4-fold or more. Bacteria alone or in complex with SIgA reinforced transepithelial electrical resistance, a phenomenon coupled with increased phosphorylation of tight junction proteins zonula occludens-1 and occludin. In contrast, association with SIgA resulted in both enhanced level of nuclear translocation of NF-κB and production of epithelial polymeric Ig receptor as compared with bacteria alone. Moreover, thymic stromal lymphopoietin production was increased upon exposure to bacteria and further enhanced with SIgA-based complexes, whereas the level of pro-inflammatory epithelial cell mediators remained unaffected. Interestingly, SIgA-mediated potentiation of the Caco-2 cell responsiveness to the two probiotics tested involved Fab-independent interaction with the bacteria. These findings add to the multiple functions of SIgA and underscore a novel role of the antibody in interaction with intestinal bacteria.

Affaires de patrons, usages de la frontière : géographie des réseaux marchands entre Niger, Bénin et Nigéria

Résumé L'objectif de la thèse est de comprendre le mode d'organisation économique spécifique aux petits centres urbains qui composent les espaces frontaliers sahéliens, en s'interrogeant sur leur concurrence ou leur complémentarité éventuelle à l'intérieur d'un régime de spatialité particulier. En s'appuyant sur l'exemple du carrefour économique de Gaya-Malanville-Kamba situé à la frontière entre le Niger, le Bénin et le Nigeria, il questionne le rôle de la ville-frontière ainsi que le jeu des acteurs marchands localement dominants, à partir de quatre grandes interrogations : Quelles sont les spécificités de l'Afrique sahélienne qui obligent à renouveler les approches géographiques de l'espace marchand? Quels sont les facteurs déterminants de l'activité économique frontalière? Les formes d'organisation de l'espace qui concourent à la structuration de l'économie sont-elles concurrentes ou coopératives? Les logiques économiques frontalières sont-elles compatibles avec l'orientation des programmes de développement adoptés par les pays sahéliens et leurs partenaires bi- ou multilatéraux? Dans une première partie, un modèle territorial de l'Afrique sahélienne permet de rendre compte de la prédominance des logiques circulatoires sur les logiques productives, une propriété essentielle de toute organisation économique confrontée à l'instabilité climatique. Dans une seconde partie, l'étude considère les facteurs déterminants de l'activité économique frontalière que sont le degré d'enclavement des territoires, la libre circulation des biens et des personnes, les relations concurrentielles ou coopératives qui lient les marchés ainsi que les liens clientélistes qui unissent patron et obligés. Une troisième partie est consacrée aux productions agricoles de tente organisées sous forme de coopératives paysannes ou d'initiatives privées. Une quatrième partie s'intéresse aux réseaux de l'import-export et du commerce de détail qui bénéficient de l'augmentation des besoins engendrée par l'urbanisation sahélienne. L'économie spatiale qui résulte de ces flux est organisée selon deux logiques distinctes : d'une part, les opportunités relatives à la production agricole conduisent certains investisseurs à intensifier l'irrigation pour satisfaire la demande des marchés urbains, d'autre part, les acteurs du capitalisme marchand, actifs dans l'import-export et la vente de détail, développent des réseaux informels et mobiles qui se jouent des différentiels nationaux. Les activités commerciales des villes-marchés connaissent alors des fluctuations liées aux entreprises productives et circulatoires de ces patrons, lesquelles concourent à l'organisation territoriale générale de l>Afrique sahélienne. Ces logiques évoluent dans un contexte fortement marqué par les politiques des institutions financières internationales, des agences bilatérales de coopération et des ONGs. Celles-ci se donnent pour ambition de transformer les économies, les systèmes politiques et les organisations sociales sahéliennes, en faisant la promotion du libéralisme, de la bonne gouvernance et de la société civile. Ces axes directeurs, qui constituent le champ de bataille contemporain du développement, forment un ensemble dans lequel la spécificité sahélienne notamment frontalière est rarement prise en compte. C'est pourquoi l'étude conclut en faveur d'un renouvellement des politiques de développement appliquées aux espaces frontaliers. Trois grands axes d'intervention peuvent alors être dégagés, lesquels permettent de réconcilier des acteurs et des logiques longtemps dissociés: ceux des espaces séparés par une limite administrative, ceux de la sphère urbaine et rurale et ceux du capitalisme marchand et de l'investissement agricole, en renforçant la coopération économique transfrontalière, en prenant en considération les interactions croissantes entre villes et campagnes et en appuyant les activités marchandes. Abstract: Urbanisation in West Africa is recent and fast. If only 10 % of the total population was living in urban areas in 1950, this proportion reached 40 % in 2000 and will be estimated to 60 % in 2025. Small and intermediate cities, located between the countryside and large metropolis, are particularly concerned with this process. They are nowadays considered as efficient vectors of local economic development because of fiscal or monetary disparities between states, which enable businessmen to develop particular skills based on local urban networks. The majority of theses networks are informal and extremely flexible, like in the Gaya - Malanville - Kamba region, located between Niger, Benin and Nigeria. Evidence show that this economic space is characterised by high potentialities (climatic and hydrological conditions, location on main economic West African axis) and few constraints (remoteness of some potentially high productive areas). In this context, this PhD deals with the economic relationships between the three market cities. Focusing on the links that unite the businessmen of the local markets - called patron; - it reveals the extreme flexibility of their strategies as well as the deeply informal nature of their activities. Through the analysis of examples taken from the commerce of agricultural products, import and export flows and detail activities, it studies the changes that have taken place in the city centres of Gaya, Malanville and Kamba. Meanwhile, this research shows how these cities represent a border economical area based on rival and complementary connections. In the first Part, it was necessary to reconsider the usual spatial analysis devoted to the question of economic centrality. As a matter of fact, the organisation of West African economic spaces is very flexible and mobile. Centrality is always precarious because of seasonal or temporary reasons. This is why the first chapters are devoted to the study of the specificity of the Sahelian territoriality. Two main elements are relevant: first the population diversity and second, the urban-rural linkages. In the second part, the study considers three main factors on which the cross-border economic networks are dependent: enclosure that prevents goods to reach the markets, administrative constraints that limit free trade between states and cities and the concurrent or complementary relationships between markets. A third part deals with the clientelist ties engaged between the patrons and their clients with the hypothesis that these relationships are based on reciprocity and inequality. A fourth part is devoted to' the study of the spatial organisation of commercial goods across the borders, as far as the agriculture commercial products, the import-export merchandises and the retail products are concerned. This leads to the conclusion that the economic activity is directly linked to urban growth. However, the study notices that there is a lack of efficient policies dealing with strengthening the business sector and improving the cross-border cooperation. This particularity allows us to favour new local development approaches, which would take into account the important potential of private economical actors. In the same time, the commercial flows should be regulated with the help of public policies, as long as they are specifically adapted to the problems that these areas have to deal with.

Novel anesthetics and other treatment strategies for refractory status epilepticus

Refractory status epilepticus (RSE)-that is, seizures resistant to at least two antiepileptic drugs (AEDs)-is generally managed with barbiturates, propofol, or midazolam, despite a low level of evidence (Rossetti, 2007). When this approach fails, the need for alternative pharmacologic and nonpharmacologic strategies emerges. These have been investigated even less systematically than the aforementioned compounds, and are often used, sometimes in succession, in cases of extreme refractoriness (Robakis & Hirsch, 2006). Several possibilities are reviewed here. In view of the marked heterogeneity of reported information, etiologies, ages, and comedications, it is extremely difficult to evaluate a given method, not to say to compare different strategies among them. Pharmacologic Approaches Isoflurane and desflurane may complete the armamentarium of anesthetics,' and should be employed in a ''close'' environment, in order to prevent intoxication of treating personnel. c-Aminobutyric acid (GABA)A receptor potentiation represents the putative mechanism of action. In an earlier report, isoflurane was used for up to 55 h in nine patients, controlling seizures in all; mortality was, however, 67% (Kofke et al., 1989). More recently, the use of these inhalational anesthetics was described in seven subjects with RSE, for up to 26 days, with an endtidal concentration of 1.2-5%. All patients required vasopressors, and paralytic ileus occurred in three; outcome was fatal in three patients (43%) (Mirsattari et al., 2004). Ketamine, known as an emergency anesthetic because of its favorable hemodynamic profile, is an N-methyl-daspartate (NMDA) antagonist; the interest for its use in RSE derives from animal works showing loss of GABAA efficacy and maintained NMDA sensitivity in prolonged status epilepticus (Mazarati & Wasterlain, 1999). However, to avoid possible neurotoxicity, it appears safer to combine ketamine with GABAergic compounds (Jevtovic-Todorovic et al., 2001; Ubogu et al., 2003), also because of a likely synergistic effect (Martin & Kapur, 2008). There are few reported cases in humans, describing progressive dosages up to 7.5 mg/kg/h for several days (Sheth & Gidal, 1998; Quigg et al., 2002; Pruss & Holtkamp, 2008), with moderate outcomes. Paraldehyde acts through a yet-unidentified mechanism, and appears to be relatively safe in terms of cardiovascular tolerability (Ramsay, 1989; Thulasimani & Ramaswamy, 2002), but because of the risk of crystal formation and its reactivity with plastic, it should be used only as fresh prepared solution in glass devices (Beyenburg et al., 2000). There are virtually no recent reports regarding its use in adults RSE, whereas rectal paraldehyde in children with status epilepticus resistant to benzodiazepines seems less efficacious than intravenous phenytoin (Chin et al., 2008). Etomidate is another anesthetic agent for which the exact mechanism of action is also unknown, which is also relatively favorable regarding cardiovascular side effects, and may be used for rapid sedation. Its use in RSE was reported in eight subjects (Yeoman et al., 1989). After a bolus of 0.3 mg/kg, a drip of up to 7.2 mg/kg/h for up to 12 days was administered, with hypotension occurring in five patients; two patients died. A reversible inhibition of cortisol synthesis represents an important concern, limiting its widespread use and implying a careful hormonal substitution during treatment (Beyenburg et al., 2000). Several nonsedating approaches have been reported. The use of lidocaine in RSE, a class Ib antiarrhythmic agent modulating sodium channels, was reviewed in 1997 (Walker & Slovis, 1997). Initial boluses up to 5 mg/kg and perfusions of up to 6 mg/kg/h have been mentioned; somewhat surprisingly, at times lidocaine seemed to be successful in controlling seizures in patients who were refractory to phenytoin. The aforementioned dosages should not be overshot, in order to keep lidocaine levels under 5 mg/L and avoid seizure induction (Hamano et al., 2006). A recent pediatric retrospective survey on 57 RSE episodes (37 patients) described a response in 36%, and no major adverse events; mortality was not given (Hamano et al., 2006 Verapamil, a calcium-channel blocker, also inhibits P-glycoprotein, a multidrug transporter that may diminish AED availability in the brain (Potschka et al., 2002). Few case reports on its use in humans are available; this medication nevertheless appears relatively safe (under cardiac monitoring) up to dosages of 360 mg/day (Iannetti et al., 2005). Magnesium, a widely used agent for seizures elicited by eclampsia, has also been anecdotally reported in RSE (Fisher et al., 1988; Robakis & Hirsch, 2006), but with scarce results even at serum levels of 14 mm. The rationale may be found in the physiologic blockage of NMDA channels by magnesium ions (Hope & Blumenfeld, 2005). Ketogenic diet has been prescribed for decades, mostly in children, to control refractory seizures. Its use in RSE as ''ultima ratio'' has been occasionally described: three of six children (Francois et al., 2003) and one adult (Bodenant et al., 2008) were responders. This approach displays its effect subacutely over several days to a few weeks. Because ''malignant RSE'' seems at times to be the consequence of immunologic processes (Holtkamp et al., 2005), a course of immunomodulatory treatment is often advocated in this setting, even in the absence of definite autoimmune etiologies (Robakis & Hirsch, 2006); steroids, adrenocorticotropic hormone (ACTH), plasma exchanges, or intravenous immunoglobulins may be used alone or in sequential combination. Nonpharmacologic Approaches These strategies are described somewhat less frequently than pharmacologic approaches. Acute implantation of vagus nerve stimulation (VNS) has been reported in RSE (Winston et al., 2001; Patwardhan et al., 2005; De Herdt et al., 2009). Stimulation was usually initiated in the operation room, and intensity progressively adapted over a few days up to 1.25 mA (with various regimens regarding the other parameters), allowing a subacute seizure control; one transitory episode of bradycardia/asystole has been described (De Herdt et al., 2009). Of course, pending identification of a definite seizure focus, resective surgery may also be considered in selected cases (Lhatoo & Alexopoulos, 2007). Low-frequency (0.5 Hz) transcranial magnetic stimulation (TMS) at 90% of the resting motor threshold has been reported to be successful for about 2 months in a patient with epilepsia partialis continua, but with a weaning effect afterward, implying the need for a repetitive use (Misawa et al., 2005). More recently, TMS was applied in a combination of a short ''priming'' high frequency (up to 100 Hz) and longer runs of low-frequency stimulations (1 Hz) at 90-100% of the motor threshold in seven other patients with simple-partial status, with mixed results (Rotenberg et al., 2009). Paradoxically at first glance, electroconvulsive treatment may be found in cases of extremely resistant RSE. A recent case report illustrates its use in an adult patient with convulsive status, with three sessions (three convulsions each) carried out over 3 days, resulting in a moderate recovery; the mechanism is believed to be related to modification of the synaptic release of neurotransmitters (Cline & Roos, 2007). Therapeutic hypothermia, which is increasingly used in postanoxic patients (Oddo et al., 2008), has been the object of a recent case series in RSE (Corry et al., 2008). Reduction of energy demand, excitatory neurotransmission, and neuroprotective effects may account for the putative mechanism of action. Four adult patients in RSE were cooled to 31_-34_C with an endovascular system for up to 90 h, and then passively rewarmed over 2-50 h. Seizures were controlled in two patients, one of whom died; also one of the other two patients in whom seizures continued subsequently deceased. Possible side effects are related to acid-base and electrolyte disturbances, and coagulation dysfunction including thrombosis, infectious risks, cardiac arrhythmia, and paralytic ileus (Corry et al., 2008; Cereda et al., 2009). Finally, anecdotic evidence suggests that cerebrospinal fluid (CSF)-air exchange may induce some transitory benefit in RSE (Kohrmann et al., 2006); although this approach was already in use in the middle of the twentieth century, the mechanism is unknown. Acknowledgment A wide spectrum of pharmacologic (sedating and nonsedating) and nonpharmacologic (surgical, or involving electrical stimulation) regimens might be applied to attempt RSE control. Their use should be considered only after refractoriness to AED or anesthetics displaying a higher level of evidence. Although it seems unlikely that these uncommon and scarcely studied strategies will influence the RSE outcome in a decisive way, some may be interesting in particular settings. However, because the main prognostic determinant in status epilepticus appears to be related to the underlying etiology rather than to the treatment approach (Rossetti et al., 2005, 2008), the safety issue should always represent a paramount concern for the prescribing physician. Conclusion The author confirms that he has read the Journal's position on issues involved in ethical publication and affirms that this paper is consistent with those guidelines.

La forma lògica de les oracions d'acció i la tesi d'Anscombe

This paper has three sections. In the first one, I expose and discuss Davidson's semantic account of adverbial sentences: the basic idea is that these sentences involve quantification over events, and I defend that view from opposing perspectives like the theory of adverbs as predicate modifiers. In the second section I defend the claim that in english constructions following the scheme: ¿X did V by T-ings¿, we are referring to the same action of X; what is sometimes called ¿The Anscombe Thesis¿. Again I discuss competing theories only to conclude that the Anscombe Thesis is true. In the third section, however, it is shown that to assume as premisses these two theses -Davidson's account and the Anscombe Thesis- leads to a serious conflict. Alternative solutions are worked out and rejected. It is also argued that the only tenable solution depends on certain metaphysical assumptions. Finally, however, I will cast doubt on this solution.

Ectodysplasin A (EDA)-EDA receptor signalling and its pharmacological modulation

L'ectodysplasine Al (EDA1 ou EDA), un ligand de la famille du TNF, et son récepteur EDAR favorisent le développement des poils, des dents et de plusieurs types de glandes. Chez l'humain, une déficience en EDA cause une dysplasie ectodermique liée à l'X, caractérisée par la genèse défectueuse des phanères. Les souris Tabby, déficientes en Eda, présentent des symptômes similaires. Nous démontrons que les souris Tabby sont en moyenne 7% plus légères que les contrôles au moment du sevrage. Ce phénotype ne dépend pas du génotype des petits, mais exclusivement de celui de la mère, suggérant que l'absence d'EDA perturbe la fonction mammaire. La glande mammaire se développe en plusieurs étapes, principalement à la puberté et pendant la grossesse. Nous avons généré des anticorps pour activer ou inhiber la signalisation d'EDAR. Les anticorps agonistes corrigent le développement de souris ou de chiens déficients en EDA, alors que les antagonistes provoquent une dysplasie ectodermique chez les souris saines. L'exposition répétée de souris Tabby aux anticorps agonistes après le sevrage accroît la taille et la fonction des glandes sébacées, démonstration pharmacologique qu'EDA contrôle l'homéostasie de la glande sébacée adulte. Ces outils seront utiles pour étudier la fonction d'EDA aux diverses étapes du développement de la glande mammaire. Fc-EDAl, un stimulateur d'EDAR, est en phase d'évaluation clinique. Nous avons montré que les structures dépendantes d'EDA qui se forment à différentes étapes du développement répondent à l'action du Fc-EDAl dans des fenêtres temporelles étroites ou larges. De plus, certaines structures peuvent être induites plusieurs jours après le début naturel de leur formation. Alors que la plupart des structures se forment suite à un seul jour d'activation d'EDAR, d'autre demandent un temps de stimulation plus long. La formation des dents est régulée par des signaux activateurs et inhibiteurs. Une forte stimulation d'EDAR spécifiquement appliquée aux deux premières molaires induit des signaux négatifs qui avortent la formation de la troisième molaire, alors qu'une forte stimulation donnée à la troisième molaire la rend hypertrophique tout en induisant parfois une quatrième molaire jamais observée chez les souris de type sauvage ou Tabby. EDA est donc un activateur important de la formation dentaire. Pris dans leur ensemble, ces résultats ont des implications pour la thérapie des dysplasies ectodermiques. - The TNF family ligand Ectodysplasin Al (EDA1 or EDA) and its receptor ED AR regulate embryonic development of hair, teeth and several types of glands. In humans, EDA mutations cause X-linked hypohidrotic ectodermal dysplasia (XLHED), a condition characterized by defective development of skin appendages. £da-deficient (Tabby) mice suffer from similar defects. We observed that Tabby pups at weaning were on average 7% smaller than WT controls, a phenotype that was curiously not linked to the genotype of pups, but to that of mothers, suggesting decreased mammary gland function in the absence of EDA. Mammary glands develop in several steps, most of which are post-natal. We generated monoclonal antibodies to block or activate EDAR signaling. Agonist antibodies rescued developmental defects when administered timely in £cfo-deficient mice and dogs, whereas blocking antibodies induced ectodermal dysplasia in WT mice. Agonist antibodies administered after weaning in £da-deficient mice for several months markedly increased both size and function of sebaceous glands, providing the first demonstration that pharmacological activation of the EDAR pathway in adults can correct important aspects of the dry skin phenotype. This also highlights a role for EDA1 in the homeostasis of adult sebaceous glands. These tools will be useful to study the function of EDA 1 at different stages of mammary gland development. Another EDAR agonist, Fc-EDAl, is currently evaluated in clinical trials. We found that EDA 1-dependent structures forming at different time points during development can respond to Fc-EDAl during time response windows that are narrow or wide. Also, some structures can be triggered up to several days after their normal time of induction. While most structures could be rescued by a single day of EDAR signaling, others required longer exposure times to form. Tooth formation is regulated by activating and inhibitory signals that impact one on the other. When strong EDAR signals were specifically given to the first two molars, overwhelming inhibitory signals completely inhibited formation of the third molar. In contrast, strong signals specifically given to the third molar induced hypertrophy of the later with occasional appearance of a fourth molar never observed in WT or £da-deficient mice. This clearly positions EDA as an important activating signal in tooth formation. Taken together, these results have implications for the therapy of ectodermal dysplasias.

Mathematics in Catalonia: 1996-2002

The aim of this article is to present the main conclusions of the Report on research in Catalonia for the area of mathematics**. The report was prepared by Joaquim Bruna, Marta Sanz, Joan de Solà-Morales and the author of this text, and published by the Institute for Catalan Studies in 1998. In the report, scientific activity in the area of mathematics was measured essentially by examining two parameters: papers published in specialised journals and doctoral theses read. It should be recognised that a considerable amount of activity in the field of mathematics consists of applying existing knowledge to the resolution of practical technological problems that arise in particular companies. This kind of scientific activity was not measured in any way in the report due to the difficulty of obtaining objective data. This article is divided into the following sections: human resources, scientific production, funding, research publications, research centres, and conclusions.

Automatic selection of tidal volume, respiratory frequency and minute ventilation in intubated ICU patients as start up procedure for closed-loop controlled ventilation.

OBJECTIVE: Before a patient can be connected to a mechanical ventilator, the controls of the apparatus need to be set up appropriately. Today, this is done by the intensive care professional. With the advent of closed loop controlled mechanical ventilation, methods will be needed to select appropriate start up settings automatically. The objective of our study was to test such a computerized method which could eventually be used as a start-up procedure (first 5-10 minutes of ventilation) for closed-loop controlled ventilation. DESIGN: Prospective Study. SETTINGS: ICU's in two adult and one children's hospital. PATIENTS: 25 critically ill adult patients (age > or = 15 y) and 17 critically ill children selected at random were studied. INTERVENTIONS: To stimulate 'initial connection', the patients were disconnected from their ventilator and transiently connected to a modified Hamilton AMADEUS ventilator for maximally one minute. During that time they were ventilated with a fixed and standardized breath pattern (Test Breaths) based on pressure controlled synchronized intermittent mandatory ventilation (PCSIMV). MEASUREMENTS AND MAIN RESULTS: Measurements of airway flow, airway pressure and instantaneous CO2 concentration using a mainstream CO2 analyzer were made at the mouth during application of the Test-Breaths. Test-Breaths were analyzed in terms of tidal volume, expiratory time constant and series dead space. Using this data an initial ventilation pattern consisting of respiratory frequency and tidal volume was calculated. This ventilation pattern was compared to the one measured prior to the onset of the study using a two-tailed paired t-test. Additionally, it was compared to a conventional method for setting up ventilators. The computer-proposed ventilation pattern did not differ significantly from the actual pattern (p > 0.05), while the conventional method did. However the scatter was large and in 6 cases deviations in the minute ventilation of more than 50% were observed. CONCLUSIONS: The analysis of standardized Test Breaths allows automatic determination of an initial ventilation pattern for intubated ICU patients. While this pattern does not seem to be superior to the one chosen by the conventional method, it is derived fully automatically and without need for manual patient data entry such as weight or height. This makes the method potentially useful as a start up procedure for closed-loop controlled ventilation.

Different effects of hyperlipidic diets in human lactation and adulthood: growth versus the development of obesity

After birth, the body shifts from glucose as primary energy substrate to milk-derived fats, with sugars from lactose taking a secondary place. At weaning, glucose recovers its primogeniture and dietary fat role decreases. In spite of human temporary adaptation to a high-fat (and sugars and protein) diet during lactation, the ability to thrive on this type of diet is lost irreversibly after weaning. We could not revert too the lactating period metabolic setting because of different proportions of brain/muscle metabolism in the total energy budget, lower thermogenesis needs and capabilities, and absence of significant growth in adults. A key reason for change was the limited availability of foods with high energy content at weaning and during the whole adult life of our ancestors, which physiological adaptations remain practically unchanged in our present-day bodies. Humans have evolved to survive with relatively poor diets interspersed by bouts of scarcity and abundance. Today diets in many societies are largely made up from choice foods, responding to our deeply ingrained desire for fats, protein, sugars, salt etc. Consequently our diets are not well adjusted to our physiological needs/adaptations but mainly to our tastes (another adaptation to periodic scarcity), and thus are rich in energy roughly comparable to milk. However, most adult humans cannot process the food ingested in excess because our cortical-derived craving overrides the mechanisms controlling appetite. This is produced not because we lack the biochemical mechanisms to use this energy, but because we are unprepared for excess, and wholly adapted to survive scarcity. The thrifty mechanisms compound the effects of excess nutrients and damage the control of energy metabolism, developing a pathologic state. As a consequence, an overflow of energy is generated and the disease of plenty develops.

Activities of amino acid metabolizing enzymes in the stomach and small intestitine of developing rats

The activities of aspartate and alanine transaminase, serine dehydratase, arginase, glutamate dehydrogenase, adenylate deaminase and glutamine synthetase were determined in the stomach and small intestine of developing rats. Despite the common embryonic origin of the intestine and stomach, their enzymes showed quite different activity levels and patterns of development, depending on their roles. Most enzyme activities were low during late intrauterine life and after birth, attaining adult levels with the change of diet at weaning. No arginase activity was found in the stomach and no changes were detected in adenylate deaminase in the stomach or intestine throughout the period studied. Alanine transaminase, serine dehydratase and, to some extent, glutamine synthetase levels, significantly higher in late intrauterine life, decreased after birth, suggesting that the foetal stomach has a transient ability to handle amino acids.

Effects of lactation upon circulating plasma metabolites in cafeteria-fed rats

1. The effects of "cafeteria feeding" on primiparous Wistar rats during lactation have been studied by measuring circulating levels of glucose, amino acids, lactate, urea and ammonia as well as glycogen levels in liver and muscle. 2. No significant changes in glucose levels were observed despite alterations in blood glucose compartmentation. 3. Compared with controls, the dams given the cafeteria diet had higher liver glycogen stores which were more easily mobilized at the peak of lactation. 4. Rats given the cafeteria diet showed a lower amino acid utilization than controls and adequately maintained circulating levels, as determined by the lower circulating levels of ammonia and urea. 5. No significant differences in body-weight were observed in the period studied despite increasing dam weight after weaning in the cafeteria-fed group. 6. The size of pups of cafeteria-fed dams was greater than that of controls, and the differences were marked after weaning, when the metabolic machinery of the cafeteria pup maintained high protein accretion and body build-up using fat as the main energy substrate characteristic of the preweaning stage. The controls, however, changed to greater utilization of amino acids as an energy substrate and adapted to high-protein (lowbiological-quality) diets with a significantly different pattern of circulating nitrogen distribution.

Midregional pro-atrial natriuretic peptide and procalcitonin improve survival prediction in VAP.

Ventilator-associated pneumonia (VAP) affects mortality, morbidity and cost of critical care. Reliable risk estimation might improve end-of-life decisions, resource allocation and outcome. Several scoring systems for survival prediction have been established and optimised over the last decades. Recently, new biomarkers have gained interest in the prognostic field. We assessed whether midregional pro-atrial natriuretic peptide (MR-proANP) and procalcitonin (PCT) improve the predictive value of the Simplified Acute Physiologic Score (SAPS) II and Sequential Related Organ Failure Assessment (SOFA) in VAP. Specified end-points of a prospective multinational trial including 101 patients with VAP were analysed. Death <28 days after VAP onset was the primary end-point. MR-proANP and PCT were elevated at the onset of VAP in nonsurvivors compared with survivors (p = 0.003 and p = 0.017, respectively) and their slope of decline differed significantly (p = 0.018 and p = 0.039, respectively). Patients with the highest MR-proANP quartile at VAP onset were at increased risk for death (log rank p = 0.013). In a logistic regression model, MR-proANP was identified as the best predictor of survival. Adding MR-proANP and PCT to SAPS II and SOFA improved their predictive properties (area under the curve 0.895 and 0.880). We conclude that the combination of two biomarkers, MR-proANP and PCT, improve survival prediction of clinical severity scores in VAP.

Building the future: the Brazilian university library in 2010

Information technology will affect academic activities as well as the nature of the high education sector. This sector besides the need to assimilate these technologies will need to attend the requisites of market globalization and, as consequence, all theses changes will be reflected in the university library. Prospectives impacts will affect the structure (emphasis in user services, outsourcing of several services), in the financing aspect (growing of consortia in order to reduce costs), in services (electronic reference, support to long distance education programs, intelligent agents) and in the clientele (attending the great demand por high education which implies a diversity of people).

Cardiologie [Cardiology]

Heart failure and atrial fibrillation are the main problems in general cardiology. Our therapeutic reflections summarize new ideas in the treatment of theses pathologies but we will not forget importance of PCI. All these therapies have proven now the clinical benefit but also reduction in more morbidity and mortality. Cardiac resynchronisation therapy has shown promising results. The art of medicine to develop will be to better identify the patients benefiting from this therapy. Interventional cardiology is focusing on the acute coronary syndrome. Not only rapid intervention but also the stent technology allow significant modification of endothelial tissue reaction and therefore improve the general benefit for the patient.

Technology and research in a global Networked University Digital Library (NUDL)

Digital Libraries (DLs) are extremely complex information systems that support the creation, management, distribution, and preservation of complex information resources, while allowing effective and efficient interaction among the several societies that benefit from DL content and services. In this paper, we focus on our experience facing challenges of building, maintaining, and developing the Networked University Digital Library (www.nudl.org), an extension of the Networked Digital Library of Theses and Dissertations (www.ndltd.org). NUDL is a worldwide initiative that addresses making the intellectual property produced in universities more accessible, stimulating international collaboration across all disciplines. We detail technological aspects of our solutions and research activities carried out to provide powerful and enriched services for the communities served by this initiative.

ETDs, NDLTD, and open access: a 5S perspective

Worldwide initiatives toward digital library (DL) support for electronic theses and dissertations (ETDs), facilitated by the work of the Networked Digital Library of Theses and Dissertations (NDLTD), are a key part of the move toward open access. When all graduate students learn to use openly available ETDs, and have experience with authoring and submission in connection with their own research results, it will be easy for them to continue these efforts through other contributions to open access. When all universities support ETD activities, they will be key participants in institutional repositories and open access, and will have engaged in discussion and infrastructure development supportive of further open access activities. Understanding of open access also can be facilitated through modeling of all of these efforts using the 5S framework, considering the key aspects of DL development: Societies, Scenarios, Spaces, Structures, and Streams.