Open African Reference Pathology Data Center

Poster at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

IFN-g in human Chagas' disease: protection or pathology?

An apparently paradoxical role for IFN-g in human Chagas' disease was observed when studying the pattern of cytokine production by peripheral blood mononuclear cells (PBMC) obtained from two groups of chagasic patients after specific stimulation with Trypanosoma cruzi-derived antigens. The groups studied were 1) patients treated with benznidazole during the acute phase of Trypanosoma cruzi infection and 2) chronically infected untreated patients. In the treated group, higher levels of IFN-g were produced by PBMC from individuals cured after treatment when compared to non-cured patients. In contrast, in the chronically infected group (not treated) higher levels of IFN-g were produced by PBMC from cardiac patients in comparison with asymptomatic (indeterminate) patients. This apparently paradoxical role for IFN-g in human Chagas' disease is discussed in terms of the possibility of a temporal difference in IFN-g production during the initial stages of the infection (acute phase) in the presence or absence of chemotherapy. The maintenance of an immune response with high levels of IFN-g production during the chronic phase of the infection may favor cure or influence the development of the cardiac form of the disease

Cytokine profile and pathology in human leishmaniasis

The clinical spectrum of leishmaniasis and control of the infection are influenced by the parasite-host relationship. The role of cellular immune responses of the Th1 type in the protection against disease in experimental and human leishmaniasis is well established. In humans, production of IFN-g is associated with the control of infection in children infected by Leishmania chagasi. In visceral leishmaniasis, an impairment in IFN-g production and high IL-4 and IL-10 levels (Th2 cytokines) are observed in antigen-stimulated peripheral blood mononuclear cells (PBMC). Moreover, IL-12 restores IFN-g production and enhances the cytotoxic response. IL-10 is the cytokine involved in down-regulation of IFN-g production, since anti-IL-10 monoclonal antibody (mAb) restores in vitro IFN-g production and lymphoproliferative responses, and IL-10 abrogates the effect of IL-12. In cutaneous and mucosal leishmaniasis, high levels of IFN-g are found in L. amazonensis-stimulated PBMC. However, low or absent IFN-g levels were observed in antigen-stimulated PBMC from 50% of subjects with less than 60 days of disease (24 ± 26 pg/ml). This response was restored by IL-12 (308 ± 342 pg/ml) and anti-IL-10 mAb (380 ± 245 pg/ml) (P<0.05). Later during the disease, high levels of IFN-g and TNF-a are produced both in cutaneous and mucosal leishmaniasis. After treatment there is a decrease in TNF-a levels (366 ± 224 pg/ml before treatment vs 142 ± 107 pg/ml after treatment, P = 0.02). Although production of IFN-g and TNF-a might be involved in the control of parasite multiplication in the early phases of Leishmania infection, these cytokines might also be involved in the tissue damage seen in tegumentary leishmaniasis

Cytokines as determinants of resistance and pathology in human Schistosoma mansoni infection

The role of different cytokines in the peripheral blood mononuclear cell (PBMC) proliferative response and in in vitro granuloma formation was evaluated in a cross-sectional study with patients with the different clinical forms and phases of Schistosoma mansoni infection, as well as a group of individuals "naturally" resistant to infection named normal endemic (NE). The blockage of IL-4 and IL-5 using anti-IL-4 and anti-IL-5 antibodies significantly reduced the PBMC proliferative response to soluble egg (SEA) and adult worm (SWAP) antigens in acute (ACT), chronic intestinal (INT) and hepatosplenic (HS) patients. Similar results were obtained in the in vitro granuloma formation. Blockage of IL-10 had no significant effect on either assay using PBMC from ACT or HS. In contrast, the addition of anti-IL-10 antibodies to PBMC cultures from INT patients significantly increased the proliferative response to SEA and SWAP as well as the in vitro granuloma formation. Interestingly, association of anti-IL-4 and anti-IL-10 antibodies did not increase the PBMC proliferative response of these patients, suggesting that IL-10 may act by modulating IL-4 and IL-5 secretion. Addition of recombinant IL-10 decreased the proliferative response to undetectable levels when PBMC from patients with the different clinical forms were used. Analysis of IFN-g in the supernatants showed that PBMC from INT patients secreted low levels of IFN-g upon antigenic stimulation. In contrast, PBMC from NE secreted high levels of IFN-g. These data suggest that IL-10 is an important cytokine in regulating the immune response and possibly controlling morbidity in human schistosomiasis mansoni, and that the production of IFN-g may be associated with resistance to infection.

Cat Scratch Disease in kidney transplant receptors: is it a rare or underdiagnosed pathology?

Cat Scratch Disease (CSD) is an infectious disorder which appears after cat scratching particularly in children and adolescents. Bartonella henselae is the etiologic agent more frequently involved. There are only a few recent reports demonstrating the disease after transplantation, although the illness is not infrequent in immunologically competent people. Indeed CSD in transplant receptors has only been recently emphasized in the literature and it was concluded that fever and lymphadenopathy in patients who had been exposed to cats should prompt clinicians to maintain a suspicion for the infection. In this report CSD infecting a renal transplanted adolescent complaining of headache, blurred vision and fever, presenting a cat scratching lesion in the right arm, with a bilateral painful cervical lymphadenopathy was related. He also presented indirect immunofluorescency identifying that the two subtype's titles of Bartonella-henselae and quintana- were elevated. Treatment with doxicicline e rifampicin was introduced and the patient became asymptomatic in about 3 weeks.

Disabled legislators : disability and Irish colonial pathology in James Joyce's Ulysses

Why are there so many disabled characters in James Joyce's Ulysses? "Disabled Legislators" seeks to answer this question by exploring the variety and depth of disability's presence in Joyce's novel. This consideration also recognizes the unique place disability finds within what Lennard Davis calls "the roster of the disenfranchised" in order to define Joyce as possessing a "disability consciousness;" that is, an empathetic understanding (given his own eye troubles) of the damaged lives of the disabled, the stigmatization of the disabled condition, and the appropriation of disabled representations by literary works reinforcing normalcy. The analysis of four characters (Gerty MacDowell, the blind stripling, the onelegged sailor, and Stephen Dedalus) treats disability as a singular self-concept, while still making necessary associations to comparably created marginal identities-predominantly the colonial Other. This effort reevaluates how Ulysses operates in opposition to liberal Victorian paradigms, highlighting disability's connections to issues of gender, intolerance, self-identification and definition.

Ontological constructivism : Negri and the philosophical foundations of a future communism

As we find in Empire and Multitude, Antonio Negri's political project IS a thoroughly Marxist analysis and critique of global or late capitalism. By modifying and updating Marx's conceptual tools, he is able to provide a clear account of capitalism's processes, its expanding reach, and the revolutionary potential that functions as its motor. By turning to Negri's philosophical works, however, we find that this political analysis is founded on a series of concepts and theoretical positions. This paper attempts to clarify this theoretical foundation, highlighting in particular what I term "ontological constructivism" - Negri's radical reworking of traditional ontology. Opposing the long history of transcendence in epistemology and metaphysics (one that stretches from Plato to Kant), this reworked ontological perspective positions individuals - not god or some other transcendent source - as the primary agents responsible for molding the ontological landscape. Combined with his understanding of kairos (subjective, immeasurable time), ontological constructivism lays the groundwork for opposing transcendence and rethinking contemporary politics.

Wild Civility: Cultivating the Foundations of Social Justice through Participation in a Wilderness Program

This heuristic inquiry examined if the foundations of social justice knowledge and beliefs were developed as a result of participation in a wilderness program and what knowledge and beliefs were developed. There were six participants in this study. Data collection involved participants completing pre- and post- program interviews and daily journals during the program. Through inductive analysis six themes emerged. Three of these were related to the development of certain foundations of social justice: (a) experienced conflict development and resolution; (b) experienced relationship change and development; and (c) shift from “me” to “we” mentality. The remaining three themes were included as additional findings: (a) experienced personal change and development; (b) identification of specific factors of the program responsible for changes; and (c) bringing learning back to everyday life. Results highlight wilderness program impacts on participants’ social justice knowledges and beliefs and inform wilderness program providers and social justice educators.

The foundations of rhetoric

UANL

Disease, illness, sickness, pathology : faut-il en faire une maladie?

Département de linguistique et de traduction

The human right to water - normative foundations and ethical implications

La présente contribution examine les fondements normatifs ainsi que les implications éthiques du droit à l’eau, tel qu’il fut reconnu en 2002 par le comité onusien des droits économiques, sociaux et culturels. Il sera défendu que le droit à l’eau potable peut être justifié en tant que droit moral fondamental, de par son caractère indispensable en vue de la garantie des conditions basiques de survie. Cet état de fait, cependant, s’avère moins évident au vue d’un droit à l’eau d’usage non-domestique. Ici, la discussion se rapproche des débats accompagnant le concept beaucoup plus complexe des droits sociaux et économiques. Par rapport à ce groupe de droits, la question de l’allocation est des plus controversées: à qui incombe-t-il de garantir leur respect? Dans le but d’éviter cette problématique d’allocation, le présent essai soulèvera la question de savoir, si la limitation de l’accès à l’eau peut être conçue comme une violation d’autres droits moraux: bien qu’il y ait des cas où des entreprises transnationales déploient des activités nuisibles à l’égard des populations pauvres en polluant sciemment leurs ressources en eau ou en initiant et en exécutant des stratégies de privatisation les privant de leurs droits, la crise globale de l’eau ne saura être rattachée uniquement aux effets de la mondialisation. Plutôt, l’on reconnaîtra la nécessité d’efforts positifs et soutenus de la part des pays développés en vue de la réalisation d’un approvisionnement suffisant en eau pour tous.

Cardiac cell fate control by the imidazoline I1 receptor/nischarin : application in cardiac pathology

La moxonidine, un médicament antihypertenseur sympatholytique de type imidazolinique, agit au niveau de la médulla du tronc cérébral pour diminuer la pression artérielle, suite à l’activation sélective du récepteur aux imidazolines I1 (récepteur I1, aussi nommé nischarine). Traitement avec de la moxonidine prévient le développement de l’hypertrophie du ventricule gauche chez des rats hypertendus (SHR), associé à une diminution de la synthèse et une élévation transitoire de la fragmentation d’ADN, des effets antiprolifératifs et apoptotiques. Ces effets se présentent probablement chez les fibroblastes, car l’apoptose des cardiomyocytes pourrait détériorer la fonction cardiaque. Ces effets apparaissent aussi avec des doses non hypotensives de moxonidine, suggérant l’existence d’effets cardiaques directes. Le récepteur I1 se trouvé aussi dans les tissus cardiaques; son activation ex vivo par la moxonidine stimule la libération de l’ANP, ce qui montre que les récepteurs I1 cardiaques sont fonctionnels malgré l’absence de stimulation centrale. Sur la base de ces informations, en plus du i) rôle des peptides natriurétiques comme inhibiteurs de l’apoptose cardiaque et ii) des études qui lient le récepteur I1 avec la maintenance de la matrix extracellulaire, on propose que, à part les effets sympatholytiques centrales, les récepteurs I1 cardiaques peuvent contrôler la croissance-mort cellulaire. L’activation du récepteur I1 peut retarder la progression des cardiopathies vers la défaillance cardiaque, en inhibant des signaux mal adaptatifs de prolifération et apoptose. Des études ont été effectuées pour : 1. Explorer les effets in vivo sur la structure et la fonction cardiaque suite au traitement avec moxonidine chez le SHR et le hamster cardiomyopathique. 2. Définir les voies de signalisation impliquées dans les changements secondaires au traitement avec moxonidine, spécifiquement sur les marqueurs inflammatoires et les voies de signalisation régulant la croissance et la survie cellulaire (MAPK et Akt). 3. Explorer les effets in vitro de la surexpression et l’activation du récepteur I1 sur la survie cellulaire dans des cellules HEK293. 4. Rechercher la localisation, régulation et implication dans la croissance-mort cellulaire du récepteur I1 in vitro (cardiomyocytes et fibroblastes), en réponse aux stimuli associés au remodelage cardiaque : norépinephrine, cytokines (IL-1β, TNF-α) et oxydants (H2O2). Nos études démontrent que la moxonidine, en doses hypotensives et non-hypotensives, améliore la structure et la performance cardiaque chez le SHR par des mécanismes impliquant l’inhibition des cytokines et des voies de signalisation p38 MAPK et Akt. Chez le hamster cardiomyopathique, la moxonidine améliore la fonction cardiaque, module la réponse inflammatoire/anti-inflammatoire et atténue la mort cellulaire et la fibrose cardiaque. Les cellules HEK293 surexprimant la nischarine survivent et prolifèrent plus en réponse à la moxonidine; cet effet est associé à l’inhibition des voies ERK, JNK et p38 MAPK. La surexpression de la nischarine protège aussi de la mort cellulaire induite par le TNF-α, l’IL-1β et le H2O2. En outre, le récepteur I1 s’exprime dans les cardiomyocytes et fibroblastes, son activation inhibe la mort des cardiomyocytes et la prolifération des fibroblastes induite par la norépinephrine, par des effets différentiels sur les MAPK et l’Akt. Dans des conditions inflammatoires, la moxonidine/récepteur aux imidazolines I1 protège les cardiomyocytes et facilite l’élimination des myofibroblastes par des effets contraires sur JNK, p38 MAPK et iNOS. Ces études démontrent le potentiel du récepteur I1/nischarine comme cible anti-hypertrophique et anti-fibrose à niveau cardiaque. L’identification des mécanismes cardioprotecteurs de la nischarine peut amener au développement des traitements basés sur la surexpression de la nischarine chez des patients avec hypertrophie ventriculaire. Finalement, même si l’effet antihypertenseur des agonistes du récepteur I1 centraux est salutaire, le développement de nouveaux agonistes cardiosélectifs du récepteur I1 pourrait donner des bénéfices additionnels chez des patients non hypertendus.