949 resultados para Burn wound infections


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SUMMARY : Skin wound repair is a complex and highly coordinated process, where a variety of cell types unite to regenerate the damaged tissue. Several works have elucidated cellular and molecular mechanisms, in which mesenchymal-epidermal interactions play an essential role for the regulation of skin homeostasis and repair. Peroxisome Proliferator-Activated Receptors (PPARs) are ligand-activated transcription factors that belong to the nuclear receptor superfamily. Three related isotypes (PPARα, PPARß/δ and PPARγ) have been found, which exhibit distinct tissue distribution and specific physiological functions. PPARß/δ was identified as a crucial player of skin homeostasis. In the mouse skin, PPARß/δ has been described to control proliferation-differentiation state, adhesion and migration, and survival of the keratinocytes during healing. PPARß/δ has been implicated as well in the development of the hair follicles, in which mesenchymal-secreted hepatocyte growth factor (HGF) is involved. These data suggest that the biological activity of PPARß/δ is modulated by mesenchymal-epidermal interactions and that, in turn, PPARß/δ also modulates some of these signals. The aim of the present work was to elucidate the nature of the signals exchanged between the epidermis and dermis compartments, and more particularly those which are under the control of PPARß/δ. In the first part of the study, we showed that PPARß/8 in dermal fibroblasts down-regulates the mitotic activity of keratinocytes by inhibiting the IL-1 signalling pathway via the production of secreted IL-1 receptor antagonist (sIL-1Ra), a natural antagonist of this signalling. The regulation of IL-1 signalling by PPARß/δ is required for anon-pathological skin wound repair. These findings provide evidence for a novel homeostatic control of keratinocyte proliferation and differentiation mediated by the regulation of IL-1 signalling via dermal PPARß/δ fibroblasts. Proteolysis of the extracellular matrix (ECM) is a key process involved in wound repair and modifications in its activity are often associated with an alteration óf the wound closure. This process implies specific proteinases, as matrix metalloproteinases (MMPs), which are finely modulated by IL-1 signalling. In line with the first results, the second part of the work showed that MMP8 and MMP13, which are two important collagenases involved in mouse skin wound repair, are regulated by PPARß/δ. Their expression is indirectly down-regulated by dermal PPARß/δ, via the production of sIL-1Ra, resulting in the inhibition of IL-1 signalling, known to regulate the expression of numerous MMPs. We suggest that, in absence of PPARß/δ, the positive regulation of these two collagenases could participate to the delay of skin wound healing, which has been observed in mice deleted for PPARßlS. The potential therapeutic role of PPARß/b could be as well extending to inflammatory and hyperproliferative skin diseases involving IL-1 signalling, such as psoriasis or skin cancers. Quite interestingly, MMP1 (analogue of mouse MMP13) plays an essential role in human photoaging, suggesting that PPARß/δ could as well be an attractive target for photoprotection. RESUME : La cicatrisation est un processus complexe et extrêmement organisé, impliquant un grand nombre de cellules qui s'unissent pour régénérer le tissu endommagé. De nombreux travaux nous ont éclairés sur les mécanismes cellulaires et moléculaires, dans lesquels les interactions épidermo-mésenchymateuses détiennent un rôle capital à la fois dans la régulation de l'homéostasie et dans la réparation de la peau. PPAR (Peroxisome proliferatar-activated receptor), qui appartient à la superfamille des récepteurs nucléaires, se définit comme un facteur de transcription activé par des ligands très spécifiques. Trois isotypes (PPARa, PPARß/δ et PPARy) ont été décrits et sont caractérisés par une distribution tissulaire et des fonctions physiologiques clairement définies. PPARß/δ a été identifié comme étant un important acteur dans l'homéostasie de la peau. Chez la souris, il a été décrit comme contrôlant l'état de prolifération et de différenciation, le processus d'adhésion et de migration, ainsi que la survie des kératinocytes au cours de la cicatrisation. PPARßIS a également été défini comme contrôlant le développement des follicules pileux, impliquant la sécrétion par le mésenchyme du facteur de croissance HGF. Ces données suggèrent que l'activité biologique de PPARß/δ est modulée par des interactions épidermo-mésenchymateuses, et qu'en retour, il possède la capacité de moduler certains de ces signaux. L`objectif de ce travail a été d'élucider la nature des signaux échangés entre les compartiments épidermique et dermique, et plus particulièrement ceux qui sont sous le contrôle de PPARß/δ. Dans la première partie de l'étude, nous avons montré que les fibroblastes exprimant PPARß/δ réduisent l'activité mitotique des kératinocytes en inhibant la voie de signalisation IL-1, via la production de sIL-1Ra (secreted IL-1 receptor antagonist), défini comme un antagoniste naturel de cette voie de signalisation. La régulation de cette dernière par PPARß/δ est donc nécessaire pour une cicatrisation de type non pathologique. Ces résultats offrent donc une nouvelle preuve du contrôle de l'homéostasie et de l'état de prolifération/différenciation des kératinocytes par les fibroblastes exprimant PPARß/δ, en régulant la voie de signalisation IL-1. Le mécanisme de dégradation de la matrice extracellulaire (MEC) est une étape essentielle lors du processus de cicatrisation. Ainsi des modifications de cette activité protéolytïque sont souvent associées à une altération de la fermeture de la plaie. Ce processus implique des protéinases, comme les MMPs, qui sont finement modulés par la voie de signalisation IL-1. En accord avec les premiers résultats, la seconde partie des nos travaux a montré que les collagénases MMP8 et MMP13, connues pour être d'importantes molécules impliquées lors de la réparation tissulaire chez la souris, sont modulées par l'activité de PPARß/δ. Leurs expressions sont indirectement régulées par PPARß/δ, via la production. de sIL-1 Ra, entraînant ainsi l'inhibition de la voie de signalisation IL-1, décrite pour réguler l'expression de nombreuses MMPs, Nous suggérons donc qu'en absence de PPARß/δ, la régulation de ces deux collagénases pourrait être impliquée dans le retard de cicatrisation, observé chez les souris déficientes pour PPARß/δ. L'activité biologique de PPARß/δ pourrait être ainsi étendue à des maladies hyperproliferatives et inflammatoires de la peau, impliquant la voie de signalisation IL-1, comme le psoriasis ou certains cancers de la peau, et ce à des fins thérapeutiques. Il est aussi intéressant de relever que chez l'homme, MMP1 (présenté comme l'analogue de MMP13 de la souris} joue un rôle primordial dans le photo-vieillissement, nous suggérons donc que PPARß/δ pourrait ainsi être une cible attrayante concernant la photoprotection.

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Community studies of non-hospitalized children are essential to obtain a more thorough understanding of acute respiratory infections (ARI) and provide important information for public health authorities. This study identified a total ARI incidence rate (IR) of 4.5 per 100 child-weeks at risk and 0.78 for lower respiratory tract infections (LRI). Disease duration averaged less than one week and produced a total time ill with ARI of 5.8% and for LRI 1.2%. No clear seasonal variation was observed, the sex-specific IR showed a higher proportion of boys becoming ill with ARI and LRI and the peak age-specific IR occurred in infants of 6-11 months. Correlation with risk factors of the child (breastfeeding, vaccination, diarrheal disease, undernourishment) and the environment (crowding, living conditions, maternal age and education) showed marginal increases in the rate ratios, making it difficult to propose clear-cuts targets for action to lower the ARI and LRI morbidity. The importance of an integral maternal-child health care program and public education in the early recognition of LRI is discussed.

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Opossums (Didelphis marsupialis) captured in intensely urbanized areas of the city of Caracas, Venezuela, were found infected with Trypanosoma cruzi. The developmental cycle of trypomastigote-epimastigote-metacyclic infective trypomastigote, usually occurring in the intestine of the triatomine vector, was taking place in the anal odoriferous glands of the opossums. Material from the glands, inoculated in young, healthy opossums and white mice by different routes, subcutaneously, intraperitoneally, orally, and into the eye, induced T. cruzi infections in all animals. Parasitemia, invasion of cardiac and skeletal muscle, and intracellular multiplication of amastigotes were observed. Inoculation of metacyclics from anal glands, cultured in LIT medium, gave equivalent results. All opossums survived; all mice died. Excreta of opossums may thus transmit Chagas' disease by contamination, even in urban areas where insect vectors are not present.

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Didelphis marsupialis, the most important sylvatic reservoir of Trypanosoma cruzi, can also maintain in their anal scent glands the multiplicative forms only described in the intestinal tract of triatomine bugs. A study of 21 experimentally and 10 naturally infected opossums with T. cruzi was undertaken in order to establish the histopathological pattern under different conditions. Our results showed that the inflammation was predominantly lymphomacrophagic and more severe in the naturally infected animals but never as intense as those described in Chagas' disease or in other animal models. The parasitism in both groups was always mild with very scarce amastigote nests in the tissues. In the experimentally infected animals, the inflammation was directly related to the presence of amastigotes nests. Four 24 days-old animals, still in embryonic stage, showed multiple amastigotes nests and moderate inflammatory reactions, but even so they survived longer and presented less severe lesions than experimentally infected adult mice. Parasites were found in smooth, cardiac and/or predominantly striated muscles, as well as in nerve cells. Differing from the experimentally infected opossums parasitism in the naturally infected animals predominated in the heart, esophagus and stomach. Parasitism of the scent glands did not affect the histopathological pattern observed in extraglandular tissues.

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BACKGROUND: Both the human immunodeficiency virus (HIV) and hepatitis C virus (HCV), either alone or as coinfections, persist in their hosts by destroying and/or escaping immune defenses, with high morbidity as consequence. In some cases, however, a balance between infection and immunity is reached, leading to prolonged asymptomatic periods. We report a case of such an indolent co-infection, which could be explained by the development of a peculiar subset of Natural Killer (NK) cells. RESULTS: Persistently high peripheral levels of CD56+ NK cells were observed in a peculiar hemophiliac HIV/HCV co-infected patient with low CD4 counts, almost undetectable HIV viral load and no opportunistic infections. Thorough analysis of NK-subsets allowed to identify a marked increase in the CD56bright/dim cell ratio and low numbers of CD16+/CD56- cells. These cells have high levels of natural cytotoxicity receptors but low NCR2 and CD69, and lack both CD57 and CD25 expression. The degranulation potential of NK-cells which correlates with target cytolysis was atypically mainly performed by CD56bright NK-cells, whereas no production of interferon γ (IFN-γ) was observed following NK activation by K562 cells. CONCLUSIONS: These data suggest that the expansion and lytic capacity of the CD56bright NK subset may be involved in the protection of this « rare » HIV/HCV co-infected hemophiliac A patient from opportunistic infections and virus-related cancers despite very low CD4+ cell counts.

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OBJECTIVES: To determine the relationship between infections and functional impairment in nursing home residents. DESIGN: Prospective cohort study (follow-up period, 6 months). SETTING: Thirty-nine nursing homes in western Switzerland. PARTICIPANTS: A total of 1,324 residents aged 65 and older (mean age 85.7; 76.6% female) who agreed to participate, or their proxies, by oral informed consent. MEASUREMENTS: Functional status measured every 3 months. Two different outcomes were used: (a) functional decline defined as death or decreased function at follow-up and (b) functional status score using a standardized measure. RESULTS: At the end of follow-up, mortality was 14.6%, not different for those with and without infection (16.2% vs 13.1%, P=.11). During both 3-month periods, subjects with infection had higher odds of functional decline, even after adjustment for baseline characteristics and occurrence of a new illness (adjusted odds ratio (AOR)=1.6, 95% confidence interval (CI)=1.2-2.2, P=.002, and AOR=1.5, 95% CI=1.1-2.0, P=.008, respectively). The odds of decline increased in a stepwise fashion in patients with zero, one, and two or more infections. The analyses predicting functional status score (restricted to subjects who survived) gave similar results. A survival analysis predicting time to first infection confirmed a stepwise greater likelihood of infection in subjects with moderate and severe impairment at baseline than in subjects with no or mild functional impairment at baseline. CONCLUSION: Infections appear to be both a cause and a consequence of functional impairment in nursing home residents. Further studies should be undertaken to investigate whether effective infection control programs can also contribute to preventing functional decline, an important component of these residents' quality of life.

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Here we review the phenomenon of persistency in Leishmania (Viannia) braziliensis infections. In other Leishmania species where appropriate animal models exist, considerable advances in the understanding of basic immunologic mechanisms of persistency have been made; for a review see Aebisher (1994). On the contrary, the evidences of persistence in infections with L. braziliensis rest on studies of human clinical cases many of which we summarized and discussed in this work

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Granuloma size is the variable most frequently used to evaluate the immunopathogenesis of schistosome infections. However, hepatic fibrosis is at the least an equally relevant variable. Hepatic fibrosis and the size of circumoval granulomas are frequently dissociated in experimental murine Schistosoma mansoni and S. japonicum infections. Virtually nothing is known of the immunoregulation of schistosomal hepatic fibrosis. This review notes many of the studies which have found discrepancies in granuloma volume and hepatic fibrosis, attempts to put them in perspective and to evaluate different methods of calculating changes in collagen synthesis or content

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We report two patients with chronic granulomatous disease (CGD) and life-threatening infections: a 10 10/12-year-old boy had Aspergillus fumigatus spondylitis with destruction of the 11th vertebral body and paravertebral abscess formation, and an 8 5/12-year-old boy had multiple Staphylococcus aureus hepatic abscesses with subphrenic abscess formation. Both patients failed to respond to intense antimicrobial therapy but showed a remarkable recovery following surgical drainage combined with granulocyte transfusions. These results suggest that antimicrobial therapy and surgical drainage followed by granulocyte transfusions may be the ideal mode of treatment for severe infections in patients with CGD.