Les lambeaux périostes: bases anatomiques des sites de prélèvement

Sans résuméTravail présenté à la First International Conference of China on Anatomical Sciences, Guangzhou, 7–9 décembre 1988     

Occupational health in Brazil

Brazil is a recently industrialised country with marked contrasts in social and economic development. The availability of public/private services in its different regions also varies. Health indicators follow these trends. Occupational health is a vast new field, as in other developing countries. Occupational medicine is a required subject in graduation courses for physicians. Specialisation courses for university graduated professionals have more than 700 hours of lectures and train occupational health physicians, safety engineers and nursing staff. At the technical level, there are courses with up to 1300 hours for the training of safety inspectors. Until 1986 about 19 000 occupational health physicians, 18 000 safety engineers and 51 000 safety inspectors had been officially registered. Although in its infancy, postgraduation has attracted professionals at university level, through residence programmes as well as masters and doctors degrees, whereby at least a hundred good-quality research studies have been produced so far. Occupational health activities are controlled by law. Undertakings with higher risks and larger number of employees are required to hire specialised technical staff. In 1995 the Ministry of Labour demanded programmes of medical control of occupational health (PCMSO) for every worker as well as a programme of prevention of environmental hazards (PPRA). This was considered as a positive measure for the improvement of working conditions and health at work. Physicians specialising in occupational medicine are the professionals more often hired by the enterprises. Reference centres (CRSTs) for workers' health are connected to the State or City Health Secretariat primary health care units. They exist in more populated areas and are accepted by workers as the best way to accomplish the diagnosis of occupational diseases. There is important participation by the trade unions in the management of these reference centres. For 30 years now employers organisations have also kept specialised services for safety and occupational health. Although they are better equipped they are less well used by the workers than the CRSTs. At the federal level, activities concerned with occupational health are connected to three ministries: Labour, Health and Social Security. The Ministry of Labour enacts legislation on hygiene, safety and occupational medicine, performs inspections through its regional units and runs a number of research projects. The Ministry of Health provides medical care for workers injured or affected by occupational diseases and also has surveillance programmes for certain occupational diseases. The Ministry of Social Security provides rehabilitation and compensation for registered workers. In spite of a decrease in the number of accidents at work during the past 25 years, working conditions have not improved. Changes in the laws of social security in the 1970s discouraged registration and reporting of occupational injuries and diseases. In consequence death rates due to accidents increased. With the implementation of the CRSTs, the recorded incidence of occupational diseases has risen, not only because of improved diagnosis, but also because of stronger pressure from the unions and better organisation of public services and enterprises. Received: 24 February 1997 / Accepted: 14 March 1997     

Decreased in situ expression of interleukin-10 receptor is correlated with the exacerbated inflammatory and cytotoxic responses observed in mucosal leishmaniasis

Human infection with Leishmania braziliensis can lead to cutaneous leishmaniasis (CL) or mucosal leishmaniasis (ML). We hypothesize that the intense tissue destruction observed in ML is a consequence of an uncontrolled exacerbated inflammatory immune response, with cytotoxic activity. For the first time, this work identifies the cellular sources of inflammatory and antiinflammatory cytokines, the expression of effector molecules, and the expression of interleukin-10 (IL-10) receptor in ML and CL lesions by using confocal microscopy. ML lesions displayed a higher number of gamma interferon (IFN-gamma)-producing cells than did CL lesions. In both ML and CL, CD4+ cells represented the majority of IFN-gamma-producing cells, followed by CD8+ cells and CD4- CD8- cells. The numbers of tumor necrosis factor alpha-positive cells, as well as those of IL-10-producing cells, were similar in ML and CL lesions. The effector molecule granzyme A showed greater expression in ML than in CL lesions, while inducible nitric oxide synthase did not. Finally, the expression of IL-10 receptor was lower in ML than in CL lesions. Thus, our data identified distinct cytokine and cell population profiles for CL versus ML patients and provide a possible mechanism for the development of ML disease through the demonstration that low expression of IL-10 receptor is present in conjunction with a cytotoxic and inflammatory profile in ML.     

Histopathological outcome of Leishmania major-infected BALB/c mice is improved by oral treatment with N-acetyl-l-cysteine

Leishmania major infected BALB/c mice were treated with N-acetyl-l-cysteine (NAC), a glutathione precursor, to evaluate the role of in vivo glutathione on lesion pathology and cytokine profiles following infection. Mice were maintained on NAC-containing water 2 days before infection for a total of 14 weeks. The BALB/c response to L. major infection was improved by oral administration of NAC, at the level of histopathological outcome, lesion progression and cytokine profile. A significantly improved histopathological outcome of the footpad lesion, characterized by a mixed inflammatory infiltrate organized in a focal pattern with little tissue destruction and a reduced parasite load, was observed in NAC-treated BALB/c mice. Histopathological modulation was accompanied by a modified cytokine pattern from popliteal lymph node cells, demonstrated by a sustained higher frequency of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha)-producing cells. This work points to an important role for glutathione in the modulation of effector responses in BALB/c mice.     

Non-metric cranial variants in Brazilian skulls

The incidence of 27 non-metric cranial variants is studied in a sample of 124 skulls from Brazil. The unilateral and bilateral frequencies of the variants are determined. The Brazilian population sample was compared with 28 population samples from different parts of the world.     

Adhesion molecule expression patterns indicate activation and recruitment of CD4+ T cells from the lymph node to the peripheral blood of early cutaneous leishmaniasis patients

Adhesion molecules play a crucial role in cell migration and recruitment. Expression of adhesion molecules that preferentially address cells to inflammatory sites is a critical event in the formation and maintenance of leishmaniasis lesions. In this work, we analyzed the expression of CD11a, CD11b and CD62L, adhesion molecules involved in cell activation and circulation, in CD4+ and CD8+ T cells from peripheral blood and lymph nodes of patients with early cutaneous leishmaniasis. The percentage of expression of CD62L, CD11a and CD11b in total lymphocytes was lower in lymph nodes as compared to peripheral blood. Moreover, differences in adhesion molecule expression between blood and lymph nodes were more striking in CD4+ than CD8+ T cells. Stimulation of PBMC from leishmaniasis patients with soluble Leishmania antigens (SLA) lead to the expansion of CD4+CD62Lhigh cells, CD4+CD11b+ cells and to an increase in the intensity of expression of CD11a in CD4+, but not CD8+ T cells. Our data suggest that early activation events that occur in the lymph nodes of patients recently infected with Leishmania lead to changes in T cell adhesion molecule expression, favoring migration to the periphery and increasing the likelihood of further recruitment to lesion sites.     

Monocytes from patients with indeterminate and cardiac forms of Chagas' disease display distinct phenotypic and functional characteristics associated with morbidity

Many studies have demonstrated that monocyte-derived macrophages display critical activities in immunity to parasites. The ability of these cells to process and present antigens, produce cytokines, and provide costimulatory signals demonstrates their pivotal role in initiating immune responses. Although potential modulatory function has been attributed to monocytes from patients with Chagas' disease, a systematic phenotypic and functional analysis of these cells has not been performed. In this work, we analyzed the ex vivo expression of important surface molecules (CD11b and HLA-DR) and immunoregulatory cytokines (interleukin-10 [IL-10], IL-12 and tumor necrosis factor alpha [TNF-alpha]) in CD14(+) and CD14(-) monocytes from Chagas' disease patients with polar clinical forms of the disease: indeterminate or severe cardiac. We also evaluated the influence of in vitro infection with T. cruzi in the expression of such molecules. We observed that monocytes from indeterminate-disease patients display lower levels of HLA-DR than those from noninfected individuals both ex vivo and after in vitro infection with T. cruzi. Although ex vivo expression of CD11b was similar among the groups, in vitro infection led to decreased expression of this molecule by monocytes from Chagas' disease patients but not from noninfected individuals. Analysis of the expression of immunoregulatory cytokines showed that while monocytes from indeterminate-disease patients are committed to IL-10 expression, a higher percentage of monocytes from cardiac-disease patients express TNF-alpha after exposure to live parasites. These results suggest that monocytes from indeterminate-disease patients display modulatory characteristics related to low HLA-DR and high IL-10 expression whereas monocytes from cardiac-disease, patients may be committed to induction of inflammatory responses related to high TNF-alpha expression.     

Activated inflammatory T cells correlate with lesion size in human cutaneous leishmaniasis

Leishmaniasis is an important parasitic disease affecting millions worldwide. In attempts to understand the clinical relevance of immunological measurements as determined using flow cytometry, several immunological phenotypes were determined for a group of well defined human leishmaniasis patients and correlated with clinical measurements of the disease (Montenegro skin test (MST) and lesion area). The analysis demonstrated a positive correlation between the MST size and the frequency of ex vivo recent activated CD4(+) T cells. In contrast, higher frequencies of recent activated CD8(+) T cells were correlated with a smaller MST size. Moreover, a positive correlation was observed between the lesion total area and the frequency of activated CD69(+) (ex vivo) and CD40L(+) (cultured with Leishmania soluble antigen (SLA)) T lymphocytes. Finally, larger lesions were also correlated with a higher frequency of SLA specific inflammatory cytokine (IFN-gamma or TNF-alpha) producing lymphocytes. These studies demonstrate that immunological markers are correlated with clinical indicators of human leishmaniasis and serve to better understand the evolution of this important parasitic disease.