RESUMO
The mechanisms by which Mycobacterium leprae invades the human host are presently unknown. We investigated the ability of M. leprae to bind to human RPMI 2650 cells, a human nasal septal epithelial cell line, using both microscopic observation and an ELISA technique. The results demonstrated that M. leprae adheres to nasal cells after binding to soluble fibronectin. Furthermore, it was observed that M. leprae could bind to the beta 1 chain of the integrins in the absence of serum or mucus. These results demonstrated that M. leprae uses fibronectin and fibronectin receptors on the surface of epithelial cells to bind and possibly invade the nasal epithelial cells.
Assuntos
Fibronectinas/fisiologia , Integrinas/fisiologia , Mycobacterium leprae/metabolismo , Septo Nasal/citologia , Septo Nasal/microbiologia , Sequência de Aminoácidos , Proteínas de Bactérias , Linhagem Celular , Células Epiteliais , Epitélio/microbiologia , Humanos , Hanseníase/transmissão , Ligantes , Macrófagos/microbiologia , Dados de Sequência Molecular , Mycobacterium leprae/efeitos dos fármacos , Oligopeptídeos/farmacologia , Ligação Proteica/efeitos dos fármacos , SolubilidadeRESUMO
Haemolysis and frank anaemia from dapsone therapy of leprosy has been long recognized. However, the frequency and severity of this side-effect have not been well documented. We report herein a retrospective analysis of the effect of daily dapsone (generally 100 mg/day) on the haemoglobin concentration of 100 leprosy patients undergoing initial chemotherapy. The average haemoglobin was found to fall significantly by almost 2 g/dl, from 14.25 +/- 1.27 g/dl to a nadir of 12.31 +/- 1.61 (P less than 0.001). Eighty-three percent of patients had a fall of haemoglobin concentration of 1 g/dl or more, while in 16% of patients the haemoglobin fell greater than or equal to 3 g/dl. Increasing age was found associated with an increased magnitude of dapsone-related haemolysis (P less than or equal to 0.004). Decreasing the daily dose of dapsone was associated with an increased haemoglobin concentration (P less than 0.001%). We have concluded that dapsone commonly results in not only haemolysis but a significant decrease in haemoglobin concentration. This may have serious clinical implications, especially in endemic areas, where, owing to nutrition, malaria, and intestinal parasitism, the haemoglobin concentration is already compromised.
Assuntos
Dapsona/efeitos adversos , Hemoglobinas/análise , Hanseníase/sangue , Adolescente , Adulto , Idoso , Criança , Dapsona/uso terapêutico , Feminino , Deficiência de Glucosefosfato Desidrogenase/sangue , Deficiência de Glucosefosfato Desidrogenase/complicações , Hemólise/efeitos dos fármacos , Humanos , Hanseníase/complicações , Hanseníase/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
We found that in the years 1978 through 1981 only one of 54 previously untreated patients with Hansen's disease was found to harbor dapsone-resistant Mycobacterium leprae. That single strain was only partially resistant, ie, it was resistant to 0.0001% dapsone in a mouse diet but not to higher concentrations. During the years 1983 through 1988, M leprae from 47 previously untreated patients presenting to clinics in San Francisco, Calif, and Los Angeles, Calif, grew in mice. None of these strains was found to be dapsone resistant. Thus, from 1978 through 1988 only one of 101 M leprae isolates obtained from skin biopsy specimens from patients with leprosy was found to be resistant to dapsone. We have concluded that primary dapsone resistance still does not appear to be a significant problem in California. Owing to the fact that our single resistant case and those reported from international sources are, in general, partially resistant, the potential importance of partial dapsone resistance is discussed.