1. A quantitive understanding of the nucleosynthesis process requires the knowledge of the production rates, the masses and the ?-decay characteristics of exotic neutron-rich nu- clei. Nuclear fission is a suitable method of producing such nuclei with masses from 60 - 150. Neutron-rich nuclei close to the r-process path can be produced via photo-fission at the Rossendorf superconducting linear accelerator of high brilliance and low emittance (ELBE) or by means of nuclear reactions at relativistic energies (for example at GSI). If the fission prod- ucts are identified and also their charge numbers are obtained, it will be principally possible to investigate their structure by means of beta-gamma spectroscopy. 2. For the purpose of fission-fragment detection a double time-of-flight (TOF) spectrometer has been developed. The key component of the TOF spectrometer is a TOF detector consisting of multichannel-plate (MCP) detectors with a position-sensitive readout, a foil for secondary electron (SE) production and an electrostatic mirror. The fission fragments are detected by measuring the SEs impinging on the position-sensitive anode after emission from the foil, ac- celeration and deflection by the electrostatic mirror. 3. In the first part of the work, special attention is paid to the relevant methods of building a spectrometer of such type. The functionality of the different detector components is proven in detail. A unique method for the determination of the SE foil thickness with ?-particles is pre- sented. Values for the mirror transmission and scattering are deduced. A dedicated SIMION 3D simulation showed that introducing serpentine like wires with pitch distance of 1 mm is capable of providing transparency of more than 90% without significant impact on the time resolution. 4. Since the performance of the MCP detectors is crucial, optimised schemes for their high- voltage supplies have been implemented successfully. Further enhancement of the setup was achieved by introducing surface-mount device (SMD) elements for signal decoupling, positioned close to the detector surface. Thus, we succeeded in avoiding signal deterioration coming from the additional capacitances and inductivities caused by extra cable lengths. Because the MCP signal decoupling takes place by means of rings with not well-defined impedance, impedance- matching problems arise, causing signal ringing and distortion. An approach towards solving this problem was to build a special fast, wide-band transimpedance amplifier. Using its circuit mounted close to the detectors, a significant reduction of the signal ringing was observed while maintaining the rise time of the detector signal. In order to process the multichannel-plate de- tector signals optimally, a new state-of-the-art constant-fraction discriminator (CFD) based on the amplitude and rise time compensated (ARC) technique with very low threshold capabilities and optimised walk properties has been developed and incorporated into the setup. 5. In our first laboratory test measurements conducted with an ?-particle source, we demonstrated ability of the setup to resolve pattern images placed directly in front of the MCP detector or reflected by the electrostatic mirror. The obtained position resolution for the second case is in the order of 2 mm. We showed that the detection efficiency of the system for ions like He is less than 30 %. This is mainly due to the low number of the electrons liberated from the SE foil. In a setup consisting of two mirror MCP detectors, we could successfully observe the TOF spectrum of a mixed (226Ra, 222Rn, 210Po, 218Po, 214Po) ?-source and found a good agreement with a SRIM simulation. 6. Measurements performed at the FZ Dresden-Rossendorf 5 MV tandem accelerator en- abled us to learn more about the response of the TOF detectors to various beams of heavy ions. The first in-beam experiments clearly showed that the applied setup consisting of two mirror detectors is capable of resolving different 35Cl beam charge states. In a combination with the specially designed wide-band amplifier and dedicated CFDs based on the ARC technique, we managed to achieve an in-beam time resolution of 170 ps per TOF detector. Measurements with ions of Z > 30 resulted in detection efficiencies of greater than 90%. At foil accelerating potentials approximately two times larger than the mirror deflection voltage, most of the SEs gain enough energy to pass through the electrostatic mirror without being deflected towards the MCP surface. Thus, an abrupt drop of the efficiency curve was observed - the “transparent” mode of the mirror. 7. Properties of electrons ejected from thin foils from heavy ions have been also investigated. From the MCP pulse-height-distribution spectra, a number for the forward-emitted SEs ejected by 35Cl beam was deduced. A method for obtaining widths of the SE energy distributions from the drop of the efficiency curve for various ions has been proposed. Assuming that the efficiency curve as a function of the accelerating voltage follows an error function, its standard deviation gives the standard deviation of the SE energy distribution. Another method based on the TOF technique for reconstructing the secondary electron velocity and energy distribution was also invented. It was found that the resulting mean SE velocity closely approaches the one of the beam ions. This phenomenon was attributed to the so-called “convoy” electrons. 8. The obtained position resolution for beams like 35Cl, 79Br and 107Ag at stable detection efficiency was better than 1.8 mm. It was demonstrated that with increasing the foil accelerat- ing voltage, the position resolution improves due to the minimised SE angular spread. Such a mode of operation was favoured until the mirror “semi-transparency” regime was reached, after which increasing further the accelerating potential could lead to a position resolution worsen- ing. An explanation of the fact could be the deterioration of the anode timing signals or some defocusing effects arising from the mirror wires field at high accelerating voltages. 9. Testing photo-fission experiments were performed at the bremsstrahlung facility at the ELBE accelerator. For the first time a spectrometer of this kind was successfully employed for bremsstrahlung-induced photo-fission measurements. The setup consisted of two mirror detectors (first arm) and a 80 mm diameter MCP detector (second arm) with a 238U target positioned in between. TOF measurements with two bremsstrahlung end-point energies of 12.9 and 16.0 MeV were carried out. A clear cut separation of the TOF peaks for the medium- mass and heavy fission fragments was observed. At these experimental test runs, we did not aim at one-by-one fission fragment mass resolution, since this may be the purpose of a more specific experiment utilising a much thinner fissile source than the one applied here (minimum straggling of the fragments inside the target is required) and considerably better statistics. It was possible to estimate the photo-fission production rate for the two measuring cases and to compare the obtained results with data from other measurements.

Les bactéries du genre xanthomonas sont responsables de nombreuses maladies des plantes, telles que la nervation noire des brassicacées causée par x. campestris pv. campestris (xcc). Lors des phases précoces du processus infectieux, ces bactéries doivent identifier des sites favorables à leur pénétration dans les tissus et les atteindre afin de s'internaliser dans les tissus végétaux et s’y multiplier. Le chimiotactisme est le mécanisme par lequel les bactéries détectent des signaux et se dirigent vers des attractants ou s’éloignent de signaux répulsifs. L’objectif de ce travail est de comprendre les rôles du chimiotactisme et de la mobilité flagellaire dans la fitness des xanthomonas. Nous avons montré que la mobilité flagellaire n’est pas une caractéristique partagée par tous les xanthomonas mais qu’environ 5% des souches perdent cette capacité sans altération majeure de leur fitness in planta. Un senseur du chimiotactisme, dénommé hsb1, probablement acquis par transfert horizontal, présente un groupe d’allèles spécifique à x. campestris. Une mutation de hsb1 dans la souche xcc atcc 33913 entraine une diminution de l’internalisation de cette souche dans les tissus de plantes hôtes combinée à une augmentation de l’internalisation dans les tissus des plantes non-hôtes. Hsb1 perçoit un signal émis par les blessures des feuilles de chou. Un glucosinolate, la sinigrine, et un acide aminé, la l-phénylalanine, sont détectés in vitro par ce senseur, mais ne sont pas métabolisés. Des travaux complémentaires seront nécessaires pour identifier le signal détecté par ce senseur et envisager la conception de méthodes de lutte basées sur la confusion d’informations. / Xanthomonads are responsible for plant diseases such as black rot of Brassicaceae caused by X. campestris pv. campestris (Xcc). During the early stages of the infection, pathogenic bacteria such as Xcc must detect favorable sites and ingress into host plant tissues to colonize and multiply in the apoplast or the xylem vessels. Chemotaxis is the mechanism used by bacteria to detect attractants and repellents and adapt in consequence its direction. The aim of this work is to understand the roles of chemotaxis and flagellar motility in the fitness of xanthomonads. We showed that flagellar motility is not a general feature of xanthomonads. About 5 % of tested strains lost this ability without major impact on their fitness in planta. A chemotaxis sensor, named Hsb1, probably acquired by horizontal transfer shows a group of alleles that are specific of X. campestris. In Xcc ATCC 33913, a mutation in hsb1 resulted in a decreased penetration of this strain in the host plant tissues combined with an increase penetration in the non-host plant tissues. Hsb1 sense a signal from wounds of cabbage leaves. In vitro, a glucosinolate, the sinigrin, and an amino acid, the L-phenylalanine are detected by Hsb1 but are not metabolized. Further work is needed to identify the signal detected by the sensor and to design control methods based on confusion.

L'un des principaux leviers technologiques permettant le développement industriel de process de production énergétique renouvelable et à haute efficacité, consiste en l'élaboration d'une solution innovante de stockage de l'énergie. Ce système de stockage doit permettre de lisser la période de production et ainsi de suivre au plus près les besoins des consommateurs. Parmi les solutions existantes, le stockage thermique par chaleur latente présente de nombreux avantages qui font qu'aujourd'hui il fait l'objet de plusieurs travaux de recherche et de développement. Cette technologie est basée sur le principe que certaines classes de matériaux, appelés matériaux à changement de phase (MCP), libèrent (transition liquide/solide) ou accumulent (transition solide/liquide) de l'énergie lorsqu'ils sont soumis à un changement de phase. En amont du développement d'un design de stockage, il est essentiel de comprendre et de maitriser les processus thermiques entrant en jeu lors des phases de fusion et de solidification du matériau et cette compréhension passe par le développement de modèles numériques adaptés aux problématiques rencontrées. Dans le cadre de ce manuscrit, la filière technologique qui nous intéresse est celle des centrales solaires à concentration. Porté par l'ADEME dans le cadre du projet STARS (Stockage Thermique appliqué à l'extension de pRoduction d'énergie Solaire thermodynamique), le travail réalisé au sein du LaTEP consiste à analyser les performances d'une solution de stockage via la modélisation de cette dernière en considérant les phénomènes thermiques et hydrauliques. Le travail de modélisation est effectué à l'aide du logiciel de CFD libre de droit OpenFOAM dans lequel est développé et implémenté, par le laboratoire, un module dédié au problème qui nous concerne, à savoir la résolution eulérienne (maillage fixe) des équations de conservation pour un fluide incompressible, en présence d'un changement de phase solide-liquide dominé par des mouvements convectifs (convection-dominated phase change). Concernant les problèmes de transition de phase, diverses méthodes mathématiques et numériques ont été développées pour rendre compte finement de la physique de ces phénomènes. Après avoir effectué une revue de ces dernières dans la première partie du manuscrit, nous avons sélectionné deux formulations que nous avons implémenté dans OpenFOAM. Une fois ce travail réalisé nous avons taché de comparer les résultats renvoyés par ces différentes formulations en les confrontant aux résultats expérimentaux disponibles dans la littérature. Cela nous a permis d'une part de nous conforter dans l'utilisation de nos solveurs et sur la pertinence des résultats obtenus avec ces derniers et d'autre part de mettre en évidence les écarts entre les solutions renvoyées par chaque formulation. Fort de ce constat, nous avons souhaité évaluer l'impact de l'équation d'état utilisée pour relier l'enthalpie et la température, indispensable à la fermeture thermodynamique du système d'équations. Cette comparaison s'est faite par la simulation d'un échangeur type stockage thermique (simulations en 2D) et par l'analyse des performances de ce dernier lors des phases de stockage, de déstockage et au cours de plusieurs séries de cycles. Les résultats obtenus nous ont permis de conclure sur l'importance d'une bonne caractérisation des MCP afin de pouvoir modéliser leur comportement au plus juste via la formulation mathématique et la loi d'état la plus adaptée / A major technological lever to the industrial development of renewable energy production processes with high efficiency, is the development of an innovative solution to store the energy. This storage device should help to smooth the production period and to follow closely the demand. Among the existing solutions, latent heat thermal storage has many advantages that make today it is the subject of several research and development projects. This technology is based on the principle that certain classes of material, called phase change materials (PCMs), release (during liquid to solid transition) or accumulate (during solid to liquid transition) energy when subjected to a phase change. Upstream of the development of a new storage design, it is essential to understand and master the thermal processes involved in the melting and solidification phase of the material and this knowledge comes through the development of numerical models adapted to the problems encountered. In the particular context of this Phdthesis, the technological process that interests us is that of CSP (Concentrated Solar Power). Funded by ADEME under the STARS Project (Thermal STorage Applied to the expansion of pRoduction of thermodynamic Solar energy), the work done by the LaTEP is to analyze the performance of a storage solution by modeling the latter, considering the thermal and hydraulic phenomena. The modeling work is done with the free source OpenFOAM CFD software in which is developed and implemented by the laboratory, a new module dedicated to the problem we are concerned, namely the resolution of Eulerian (fixed grid) conservation equations for an incompressible fluid in the presence of a solid-liquid phase change dominated by convective motions. Regarding the phase transition problems, various mathematical and numerical methods have been developed to finely consider the physics of these phenomena. After conducting a review of methods in the first part of the Phd thesis, we selected two formulations that we have implemented in OpenFOAM. Once this work done, we have managed to compare the results returned from these formulations by comparing them with experimental results available in the literature and also with analytical cases. This allowed us firstly to strengthen us in the use of our solvers and the accuracy of the obtained results and secondly to highlight the differences between the solutions returned by each formulation. After that, we wanted to assess the impact of the equation of state used to connect the enthalpy to the temperature, essential for closing the thermodynamic equations. This comparison was made by the simulation of a thermal storage exchanger (2D simulation) and by analyzing the performance of this latter during the charge phase, the discharge one and during several series of cycles. The obtained results allowed us to conclude about the importance of a good characterization of PCM in order to model their behavior as accurately via the mathematical formulation and the most suitable state law

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La inflamació s’ha considerat tradicionalment com un mecanisme de defensa, molt lligat a la supervivència de l’espècie, per la seva capacitat de combatre les infeccions o restaurar el dany produït. No obstant, un estat d’inflamació crònic produeix un efecte totalment contrari, que s’associa a un mal funcionament de teixits i òrgans. L’objectiu d’aquest treball és l’estudi de la proteïna quimioatraient de monòcits-1 (MCP-1), una proteïna descrita per la seva funció en l’atracció de monòcits a la lesió arterioscleròtica, i que pot tenir un paper rellevant en el metabolisme. Els resultats mostren que MCP-1 està implicada en el control del metabolisme dels lípids i de la glucosa, i que l’expressió hepàtica de MCP-1 està sobre-expressada per la dieta i que contribueix al desenvolupament i progressió de l’esteatosi hepàtica en el model LDLr-/-. Precisament, l’últim treball demostra que l’estudi dels canvis metabolòmics en el teixit hepàtic ens pot ajudar a entendre aquesta patologia / Inflammation has been traditionally regarded as a defense mechanism, closely linked to the survival of the species for their ability to fight infections or restore the damage. However, a state of chronic inflammation produced a completely opposite effect, which is associated with tissue and organ malfunction. The aim of this work is the study of monocyte chemoattractant protein-1 (MCP-1), a protein described by its role in attracting monocytes to atherosclerotic lesions, which may also play an important role in metabolism. The results show that MCP-1 is involved in the control of lipids and glucose metabolism. Hepatic MCP-1 is over-expressed by diet and contributes to the development and progression of fatty liver disease (NASH) in LDLr-/- model. Indeed, the latest study shows that metabolomic changes in the liver can help us to understand the NASH progression.

Microbial crude protein (MCP) is the main source of protein supplied to ruminants. Several studies report that the efficiency of MCP production (eMCP) from tropical forages is low due to low rumen degradable protein (RDP) content. The studies reported in this thesis determined the eMCP from tropical forages varying in crude protein (CP) and dry matter digestibility (DMD), examined strategies to increase eMCP and the possible practical methods of application under extensive cattle production systems. This was done through four metabolism experiments, one rate of digestion experiment and a preference test experiment. In Experiment 1, the eMCP of 3 tropical forages (speargrass (Heteropogon contortus), Mitchell grass (Astrebla spp) and pangola grass (Digitaria eriantha)), and temperate ryegrass (Lolium multiflorum cultivar aristocrat) was measured. All tropical forages were associated with low eMCP (102 - 110 g MCP/kg digestible organic matter (DOM)) due to low CP and RDP content. The RDP content of the tropical forages ranged from 43 - 103 g RDP/kg DOM compared to 214 g RDP/kg DOM in ryegrass. Retention time of Cr-EDTA and Ytterbium in the rumen ranged from 13 - 34 and 29 - 59 h for tropical forages respectively, compared to 10.2 and 13.2 h for ryegrass. In Experiment 2, the rate of digestion of speargrass, Mitchell grass and ryegrass varied when incubated in the rumen of steers consuming speargrass hay (1.8% CP). Addition of a variety of nitrogen supplements; urea-ammonium sulphate (US), US plus branch chain amino acids (leucine, isoleucine and valine) plus phenylalanine (USAA), casein, cottonseed meal (CSM), yeast and Chlorella (Chlorella pyrenoidea) algae to supply approximately 170 g RDP/kg DOM improved the rate of digestion of all three substrates. However, there was no difference in rate of digestion of the three substrates between the different nitrogen supplements. In Experiments 3 and 4, steers fed medium quality pangola grass hay (9.9% CP and 61% DMD) or low quality Mitchell grass hay (4.5% CP and 41% DMD) were supplemented with US, casein and USAA. US was provided at 130, 170, 210 and 250 g RDP/kg DOM. The USAA treatment was provided at a RDP/DOM of 170 with US and then amino acids (USAA) were provided in the same ratio and level as the amino acids in the casein treatment at 130, 170, 250 and 300 g RDP/kg DOM. Increased RDP intake from all supplements increased the rumen ammonia-N concentration for both hays. The molar percentage of branch chain fatty acids (BCFA) increased 3 - 4 fold (6.6% of total VFA) above control with increasing intake of USAA or casein supplements for both hays. However, eMCP did not increase in response to increasing RDP intake from either supplement for both hays. The RDP supplementation also had no effect on intake, rate of digestion and retention time of Cr-EDTA in the rumen. In Experiment 5, steers fed Mitchell grass hay (3.8% CP and 44% DMD) were supplemented with US and Spirulina (Spirulina platensis) algae. The US was supplied to provide 90, 130, 170 and 210 g RDP/kg DOM and the Spirulina supplied to provide 90, 130, 170 and 290 g RDP/kg DOM. Increased RDP intake from US and Spirulina was associated with linear and quadratic increases in eMCP respectively. The eMCP at the highest level of US (93 g MCP/kg DOM) was below the minimum feeding standards value of 130 g MCP/kg DOM, whilst the highest level of Spirulina reached the higher end of the feeding standards (166 g MCP/kg DOM). Increasing RDP intake resulted in increased hay DM intake and total DOM intake, which were both higher for the Spirulina than the US supplement (24.5 vs.18.5 g DM/kg W/d and 11.9 vs. 7.6 g DOM/kg W/d). The retention time of Cr-EDTA and lignin in the rumen decreased with increasing RDP intake and were both shorter with Spirulina compared with US supplementation (15 vs. 21 h for Cr-EDTA; 45 vs. 56 h for lignin). In addition, Spirulina increased the BCFA concentration to 4.2% of total VFA. In Experiment 6, four different concentrations of Spirulina solution were offered to steers fed restricted amounts (14 g DM/kg W/d) of pangola hay (3.4% CP). Drinking water containing Spirulina was highly preferred and had no deleterious effect on water or hay intake. Steers strongly preferred Spirulina solution to water, when offered both solutions. Approximately 20.5% of imbibed water by-passed the rumen, which was not influenced by the Spirulina concentration in the drinking water. It may be concluded that RDP is the primary factor affecting eMCP. High eMCP was associated with low retention time of water in the rumen and high intake. Once RDP is not limiting eMCP, a source of RDP rich in true protein, nucleic acids, fatty acids, vitamins and minerals, such as Spirulina algae, may be required for cattle fed low quality tropical hay to achieve the maximum eMCP reported in the feeding standards.

Thèse (M.Sc.)--Université Laval, 2003. / Bibliogr.: f. 51-56. Publié aussi en version électronique.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / IntroduÃÃo: As lesÃes renais na hansenÃase tem grande importÃncia, pois podem evoluir para uma doenÃa renal de etiologia glomerular (glomerulonefrites, amiloidose) ou tubulointersticial. Objetivo: Investigar disfunÃÃes renais em pacientes com hansenÃase utilizando marcadores tradicionais de funÃÃo renal e a ProteÃna QuimiotÃtica de MonÃcitos-1 (MCP-1) urinÃria. PopulaÃÃo e Metodologia: Foi realizado estudo transversal e prospectivo de 44 pacientes com hansenÃase em todas as formas clÃnicas, antes do inÃcio do tratamento, sem estado reacional e sem outras nefropatias. Os pacientes foram acompanhados em centros pÃblicos de saÃde em Fortaleza, CearÃ, Brasil entre agosto de 2012 e agosto de 2013. O estudo foi aprovado pelo Comità de Ãtica em Pesquisa do Hospital UniversitÃrio Walter CantÃdio da Universidade Federal do Cearà (No: 267.426). Os pacientes foram comparados com um grupo controle composto por 15 indivÃduos sadios. Foi calculada a fraÃÃo de excreÃÃo de eletrÃlitos, estimada a taxa de filtraÃÃo glomerular (TFG), proteinÃria e microalbuminÃria. O estresse oxidativo urinÃrio foi quantificado pelo MalonaldeÃdo (MDA) urinÃrio e o MCP-1 urinÃrio foi quantificado atravÃs da tÃcnica do ELISA sanduÃche. Os valores foram normalizados pela creatinina urinÃria. Resultados: NÃo houve diferenÃa significativa entre a idade, sexo, peso corporal e pressÃo arterial entre os grupos. A idade mÃdia dos pacientes foi de 36Â10 anos, sendo 61 % do gÃnero masculino. O tempo de doenÃa variou de um mÃs a 8 anos, com mÃdia de 17 meses. A baciloscopia foi positiva em 26 pacientes (59,1%) e negativa em 18 (40,9%). Quanto à classificaÃÃo: 14 pacientes (31,8%) eram do pÃlo tuberculÃide (TT/DT), 19 (43,2%) eram dimorfos (DD) e 11 (25%) eram do pÃlo virchowiano (DV/VV). As provas de funÃÃo renal nÃo diferiram (p>0,05), com exceÃÃo da proteinÃria. Os pacientes com hansenÃase tiveram nÃveis elevados de proteinÃria (97,6Â69,2 vs 6,5Â4,3 mg/g-Cr, p<0,001) do MDA urinÃrio (1,77Â1,31 vs 1,27Â0,66 mmol/g-Cr, p=0,0372) e do MCP-1 urinÃrio (101Â79,8 vs 34,5Â14,9 mg/g-Cr, p=0,006) em relaÃÃo ao grupo controle respectivamente. O MCP-1 urinÃrio esteve maior nos pacientes multibacilares em relaÃÃo aos paucibacilares (122,1Â91,9 vs 72Â46,1 mg/g-Cr, p=0,023), respectivamente e se correlacionou positivamente com a baciloscopia (r=0,104; p=0,035), com a albuminÃria (r=0,171; p=0,006) e com o MDA urinÃrio (r=0,205; p=0,002). ConclusÃo: Em pacientes com hansenÃase sem doenÃa renal clÃnica, o MCP-1 urinÃrio esteve aumentado sobretudo no pÃlo virchowiano, e se associou com marcadores de progressÃo de lesÃo renal, apresentando grande utilidade como preditor de disfunÃÃo renal. / Introduction: Leprosy patients can present with kidney disease from glomerular (glomerulonephritis, amyloidosis) or tubule-intertitial etiology. Aims: To evaluate renal abnormalities in leprosy patients through traditional markers of renal disease and Monocyte Chemotactic Protein-1 (MCP-1). Methods: This is a cross-sectional study of 44 patients with clinical and laboratory diagnosis of leprosy and with no previous anti-mycobacterium treatment and reaction episode. Patients were recruited in public health centres in Fortaleza, Ceara, Brazil between August 2012 and August 2013. The protocol of this study was approved by the Ethical Comitee of the Walter Cantidio University Hospital, Federal University of Ceara, Brazil (N 267.426). Also, a group of 15 healthy subjects were included as a control group. Glomerular filtration rate (GFR), protein excretion, microalbuminuria and Urinary oxidative stress (malondialdehyde-MDA) were estimated. Urinary MCP-1 was determined by sandwich enzyme-linked immunosorbent assay. All urine measurements were normalized by urinary creatinine concentration. Results: Age and gender were similar between leprosy patients and control groups. Patientsâ average age was 36Â10 years, and 61% were male. Time from symptoms to leprosy diagnosis varied from one month to 8 years, with a median time of 17 months. Twenty-six patients had skin smear-positive test (59,1%) and 18 were negative (40,1%). Clinically, there were 14 (31,8%) tuberculoid polar form (TT/BT), 19 (43,2%) boderline (BB) and 11 (25%) lepromatous polar form (LL/BL). Regarding renal function, no patient had chronic kidney disease. Leprosy patients had a higher urine protein excretion (97,6Â69,2 vs 6,5Â4,3 mg/g-Cr, p<0,001), urinary MDA (1,77Â1,31 vs 1,27Â0,66 mmol/g-Cr, p=0,0372) and urinary MCP-1 (101Â79,8 vs 34,5Â14,9 mg/g-Cr, p=0,006) than healthy controls. Urinary MCP-1 was higher in multibacillary than in paucibacillary patients (122,1Â91,9 vs 72Â46,1 mg/g-Cr, p=0,023). There was a positive correlation between urinary MCP-1 and bacteriological index in skin smear (r=0,104; p=0,035), urinary MCP-1 and albumin excretion rate (r=0,171; p=0,006) and urinary MCP1 and urinary MDA (r=0,205; p=0,002). Conclusion: Leprosy patients with no clinical kidney disease have increased urinary MCP-1 and its levels are even higher according patients approximates to lepromatous polar form. Moreover, urinary MCP-1 was associated with urinary oxidative stress and urine albumin excretion, suggesting these patients are at increased risk of developing clinical kidney disease in the future.

The interaction between CD40 ligand (CD154) expressed on activated T cells and its receptor, CD40, has been shown to play a role in the onset and maintenance of autoimmune inflammation. Recent studies suggest that CD154+T cells also contribute to the regulation of atherogenesis due to their capacity to activate CD40+cells of the vasculature, including vascular smooth muscle cells (VSMC). The present study evaluated the signalling events initiated through CD40 ligation which culminate in VSMC chemokine production. CD40 ligation resulted in the phosphorylation/activation of mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and p38, but not c-jun N-terminal kinase. Inhibition of both ERK1/2 and p38 activity abrogated CD40 stimulation of IL-8 and MCP-1 production. CD40-mediated induction of chemokines also showed dependence on the Src family kinase activity. The Src kinase inhibitor, PP2, was found to inhibit CD40-induced phosphorylation of ERK1/2 as well as activation of IκB kinase. An evaluation of Src kinases that may be important in CD40 signalling identified Lyn as a potential candidate. These data indicate that CD40 signalling in VSMC activates a Src family kinase-initiated pathway that results in the induction of MAPK activities required for successful induction of chemokine synthesis.