Morphological aspects of the myocarditis and myositis in Calomys callosus experimentally infected with Trypanosoma cruzi: fibrogenesis and spontaneous regression of fibrosis

Calomys callosus a wild rodent, is a natural host of Trypanosoma cruzi. Twelve C. callosus were infected with 10(5) trypomastigotes of the F strain (a myotropic strain) of T. cruzi. Parasitemia decreased on the 21 st day becoming negative around the 40th day of infection. All animals survived but had positive parasitological tests, until the end of the experiment. The infected animals developed severe inflammation in the myocardium and skeletal muscle. This process was pronounced from the 26 th to the 30th day and gradually subsided from the 50 th day becoming absent or residual on the 64 th day after infection. Collagen was identified by the picro Sirius red method. Fibrogenesis developed early, but regression of fibrosis occurred between the 50th and 64th day. Ultrastructural study disclosed a predominance of macrophages and fibroblasts in the inflammatory infiltrates, with small numbers of lymphocytes. Macrophages had active phagocytosis and showed points of contact with altered muscle cells. Different degrees of matrix expansion were present, with granular and fibrilar deposits and collagen bundles. These alterations subsided by the 64th days. Macrophages seem to be the main immune effector cell in the C. callosus model of infection with T. cruzi. The mechanisms involved in the rapid fibrogenesis and its regression deserve further investigation.

A new function of the Fas-FasL pathway in macrophage activation.

Upon infection with the protozoan parasite Leishmania major, susceptible BALB/c mice develop unhealing lesions associated with the maturation of CD4(+)Th2 cells secreting IL-4. In contrast, resistant C57BL/6 mice heal their lesions, because of expansion and secretion of IFN-gamma of CD4(+) Th1 cells. The Fas-FasL pathway, although not involved in Th cell differentiation, was reported to be necessary for complete resolution of lesions. We investigate here the role of IFN-gamma and IL-4 on Fas-FasL nonapoptotic signaling events leading to the modulation of macrophage activation. We show that addition of FasL and IFN-gamma to BMMø led to their increased activation, as reflected by enhanced secretion of TNF, IL-6, NO, and the induction of their microbicidal activity, resulting in the killing of intracellular L. major. In contrast, the presence of IL-4 decreased the synergy of IFN-gamma/FasL significantly on macrophage activation and the killing of intracellular L. major. These results show that FasL synergizes with IFN-gamma to activate macrophages and that the tight regulation by IFN-gamma and/or IL-4 of the nonapoptotic signaling events triggered by the Fas-FasL pathway affects significantly the activation of macrophages to a microbicidal state and may thus contribute to the pathogenesis of L. major infection.

Desequilibri 234Th/238U per a l'estudi del cicle de partícules al Mediterrani nord-occidental

El desequilibri 238U/234Th s’utilitza per traçar el cicle de les partícules a la part més superficial dels oceans. Això és possible degut a les diferències entre els seus períodes de semidesintegració (T1/2 (234Th)=24,1 d; T1/2 (238U)=4,5 10 9 anys) i a les seves característiques biogeoquímiques: el Th presenta una gran afinitat per les partícules mentre que l’U és conservatiu en aigua de mar. En absència de partícules s’esperaria tenir equilibri secular entre ambdós radionúclids, però com que l’oceà no està lliure de partícules, el 234Th és exportat des de les capes més superficials produint-se un dèficit respecte el seu pare, l’238U. El període de semidesintegració del 234Th és molt adequat per traçar processos d’escales temporals de dies a setmanes, del mateix ordre que el desenvolupament de la floració del fitoplàncton i a la posterior exportació de partícules. En aquest treball es presenten dades obtingudes durant dues campanyes oceanogràfiques realitzades en el marc del Projecte FAMOSO (2009) en el Mediterrani nordoccidental, abans i després de la floració de fitoplàncton de primavera a la zona. Una de les peculiaritats d’aquesta regió és el procés de convecció profunda d’hivern, el qual suposa un important mecanisme de fertilització. A partir dels fluxos de 234Th obtinguts a la columna d’aigua es poden establir les pautes temporals que ha seguit el fitoplàncton en les setmanes prèvies al mostreig. Aquesta informació es compara amb els fluxos obtinguts utilitzant trampes de sediment a la deriva instal·lades durant ambdues campanyes.

Adaptació del model europeu (EEES) de les assignatures relacionades amb organització i mètodes de treball de la Diplomatura de relacions Laborals

L'adaptació dels estudis a l'Espai Europeu d'Educació Superior (EEES) comporta l'establiment d'un nou paradigma docent centrat en l'estudiant, l'ús d'una nova unitat de valoració de l'activitat acadèmica, el crèdit europeu, i enfortir i repensar l'avaluació de l'aprenentatge. Aquesta adaptació representa una transformació profunda en el paper que juga tant el professor com l'alumne. En aquest context, es fa molt necessari adaptar les metodologies docents, els continguts i les eines d'interacció amb els alumnes. La finalitat d'aquest projecte consisteix en adaptar les assignatures troncals d'Organització i Mètodes de Treball de la Diplomatura de Relacions Laborals a aquest nou entorn. Per a tal fi, a part d'elaborar un pla docent consistent al EEES, també s'han de desenvolupar continguts, eines d'interacció i metodologies d'avaluació que permetin millorar el nivell de formació i el rendiment acadèmic de l'estudiant. Aquest projecte comprèn sis accions específiques per aconseguir-ho: 1) L'elaboració de la guia docent (objectius, capacitats a treballar, continguts, metodologia, avaluació, etc.); 2) L'elaboració del programa d'activitats (on es concreten les activitats d'aprenentatge que l'estudiant ha de dur a terme per assolir els objectius formatius: projectes tutoritzats, estudis de casos , lectures orientades, etc.) 3) Elaboració del material teòric. Aquesta acció té com a objectiu realitzar un llibre bàsic que comprengui la totalitat de la matèria relacionada amb OMT. 4) Elaboració del material pràctic. 5) Creació d'una pàgina web per aquest material. Aquesta web pretén ser un espai de treball comú pels estudiants de Relacions Laborals que cursin assignatures d'OMT a la UAB i la UPF. 6) Realitzar un projecte pilot tutoritzat. Aquesta prova pilot sorgeix arran de converses informals mantingudes amb alumnes de la diplomatura i la coordinadora d'estudis.

Minimal clinically meaningful differences for the eortc QLQ-C30 and eortc QLQ-Bn20 scales in brain cancer patients

Objective: The aim of this study was to determine the smallest changes in health-related quality of life (HRQOL) scores in the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) and the EORTC Brain Cancer Module (QLQ-BN20), which could be considered as clinically meaningful in brain cancer patients. Methods: World Health Organization (WHO) performance status (PS) and the Mini Mental State Examination (MMSE) were used as clinical anchors to determine minimal clinically important differences (MCID) in HRQOL change scores (range 0 - 100) in the EORTC QLQ-C30 and QLQ-BN20. Anchor-based MCID estimates less than 0.2SD (small effect) were not recommended for interpretation. Other selected distribution-based methods were also used for comparison purposes. Results: Based on WHO PS, our findings support the following whole number estimates of the MCID for improvement and deterioration respectively: physical functioning (6, 9), role functioning (14, 12), cognitive functioning (8, 8), global health status (7, 4*), fatigue (12, 9) and motor dysfunction (4*, 5). Anchoring with MMSE, cognitive functioning MCID estimates for improvement and deterioration were (11, 2*) and those for communication deficit were (9, 7). The estimates with asterisks were less that the set 0.2 SD threshold and are therefore not recommended for interpretation. Our MCID estimates therefore range from 5-14. Conclusion: These estimates can help clinicians to evaluate changes in HRQOL over time and, in conjunction with other measures of efficacy, help to assess the value of a health care intervention or to compare treatments. Furthermore, the estimates can be useful in determining sample sizes in the design of future clinical trials.

The pro-allergic influences of helminth parasites

Parasitic infection is highly allergenic, and the present paper illustrates how parasites might disrupt the regulation of IgE synthesis, resulting in heightened Th-2 responses. The study of parasites, and dysregulation of the IgE ntwork, could in turn provide information relating to the aetiology of allergic diseases such as asthma and atopic dermatitis.

Redundant Notch1 and Notch2 signaling is necessary for IFNγ secretion by T helper 1 cells during infection with Leishmania major.

The protective immune response to intracellular parasites involves in most cases the differentiation of IFNγ-secreting CD4(+) T helper (Th) 1 cells. Notch receptors regulate cell differentiation during development but their implication in the polarization of peripheral CD4(+) T helper 1 cells is not well understood. Of the four Notch receptors, only Notch1 (N1) and Notch2 (N2) are expressed on activated CD4(+) T cells. To investigate the role of Notch in Th1 cell differentiation following parasite infection, mice with T cell-specific gene ablation of N1, N2 or both (N1N2(ΔCD4Cre)) were infected with the protozoan parasite Leishmania major. N1N2(ΔCD4Cre) mice, on the C57BL/6 L. major-resistant genetic background, developed unhealing lesions and uncontrolled parasitemia. Susceptibility correlated with impaired secretion of IFNγ by draining lymph node CD4(+) T cells and increased secretion of the IL-5 and IL-13 Th2 cytokines. Mice with single inactivation of N1 or N2 in their T cells were resistant to infection and developed a protective Th1 immune response, showing that CD4(+) T cell expression of N1 or N2 is redundant in driving Th1 differentiation. Furthermore, we show that Notch signaling is required for the secretion of IFNγ by Th1 cells. This effect is independent of CSL/RBP-Jκ, the major effector of Notch receptors, since L. major-infected mice with a RBP-Jκ deletion in their T cells were able to develop IFNγ-secreting Th1 cells, kill parasites and heal their lesions. Collectively, we demonstrate here a crucial role for RBP-Jκ-independent Notch signaling in the differentiation of a functional Th1 immune response following L. major infection.

An infrared reflection-absorption spectroscopic (IRRAS) study of the interaction of lipid A and lipopolysaccharide Re with endotoxin-binding proteins.

Lipopolysaccharides (LPS, endotoxins) are main constituents of the outer membranes of Gram-negative bacteria, with the 'endotoxic principle' lipid A anchoring LPS into the membrane. When LPS is removed from the bacteria by the action of the immune system or simply by cell dividing, it may interact strongly with immunocompetent cells such as mononuclear cells. This interaction may lead, depending on the LPS concentration, to beneficial (at low) or pathophysiological (at high concentrations) reactions, the latter frequently causing the septic shock syndrome. There is a variety of endogenous LPS-binding proteins. To this class belong lactoferrin (LF) and hemoglobin (Hb), which have been shown to suppress and enhance the LPS-induced cytokine secretion in mononuclear cells, respectively. To elucidate the interaction mechanisms of endotoxins with these proteins, we have investigated in an infrared reflection-absorption spectroscopy (IRRAS) study the interaction of LPS or lipid A monolayers at the air/water interface with LF and Hb proteins, injected into the aqueous subphase. The data are clearly indicative of completely different interaction mechanisms of the endotoxins with the proteins, with the LF acting only at the LPS backbone, whereas Hb incorporates into the lipid monolayer. These data allow an understanding of the different reactivities in the biomedicinal systems.