RESUMO
Poly (ADP-ribose) polymerase is a cellular repair enzyme synthesised following damage to DNA. 3-Aminobenzamide (3-AB) is an inhibitor of this repair enzyme. To study repair efficiency in leprosy patients, who usually show a significantly higher frequency of spontaneous chromosome aberrations and sister-chromatid exchanges (SCEs), their blood lymphocyte cultures were treated with 3-AB. A marginal increase in the frequency of chromosome aberrations was observed following treatment with 3-AB in controls as well as in patient groups. There was also no significant difference in the frequency of SCEs in control cultures with or without 3-AB. A significant increase in the frequency of SCEs was observed in lymphocyte cultures of paucibacillary (PB) and multibacillary (MB) patients treated with 3-AB when compared with controls. Observation of a significant increase in the frequency of SCEs in 3-AB-treated cultures over the untreated value indicates that DNA damage caused in leprosy patients following mycobacterial infection is not repaired because of the presence of the inhibitor of repair enzyme.
Assuntos
Benzamidas/farmacologia , Reparo do DNA/efeitos dos fármacos , Hanseníase/genética , Poli Adenosina Difosfato Ribose/fisiologia , Células Cultivadas , Aberrações Cromossômicas , Humanos , Linfócitos/ultraestrutura , Masculino , Inibidores de Poli(ADP-Ribose) Polimerases , Troca de Cromátide Irmã/efeitos dos fármacosRESUMO
The effects of a bifunctional alkylating agent mitomycin C (MMC), an effective inducer of chromosome aberrations and sister-chromatid exchanges (SCEs), have been studied in untreated leprosy patients. This was done to study the mutagen sensitivity of the leprosy patients. The frequency of chromosomal aberrations induced by MMC (conc. 0.01 microgram/ml) was 2.5% in controls, 3.6% in paucibacillary (PB), and 6.8% in multibacillary (MB) patients. The difference in the frequency of MMC-induced chromosome aberrations between the 3 groups studied was highly significant (p less than 0.01). Cultures grown with MMC showed the frequency of SCEs/cell to be 12.70 +/- 1.19 in controls, 19.97 +/- 3.51 in PB, and 29.66 +/- 5.92 in MB patients. The differences in the frequency of MMC-induced SCEs between the 3 groups were found to be highly significant (p less than 0.01). The enhanced frequencies of spontaneous and MMC-induced chromosome aberrations and SCEs observed in PB and MB patients indicate a clear differential mutagen sensitivity between PB and MB patients who are known to have different immunological status and thereby differ in the severity of the disease.
Assuntos
Cromossomos/efeitos dos fármacos , Hanseníase/genética , Linfócitos/efeitos dos fármacos , Mitomicinas/toxicidade , Mutagênicos/farmacologia , Células Cultivadas , Aberrações Cromossômicas , Hanseníase/microbiologia , Linfócitos/microbiologia , Linfócitos/ultraestrutura , Masculino , Mitomicina , Troca de Cromátide IrmãRESUMO
We describe how macrophages are activated and phagocytose mycobacteria in lepromatous leprosy. The differentiation of macrophages into epithelioid cells and into giant cells in borderline leprosy is shown. Close apposition between macrophages and lymphocytes is seen in those areas where mycobacteria disintegrate inside macrophages.
Assuntos
Hanseníase/patologia , Linfócitos/ultraestrutura , Macrófagos/ultraestrutura , Biópsia , Comunicação Celular , Diferenciação Celular , Humanos , Hanseníase/microbiologia , Ativação de Macrófagos , Macrófagos/microbiologia , Microscopia Eletrônica , Mycobacterium leprae/ultraestrutura , Pele/patologiaRESUMO
The ultrastructure of 10 lepromatous lesions in the face and the palatal mucosa after different duration and length of treatment was studied. Biopsies taken from patients who showed erythema nodosum leprosum (ENL) revealed different ultrastructural characteristics from those taken from 'burnt out' and non-medicated cases. Multiple secondary lysosomes were rarely seen in non-ENL cases. The presence of Mycobacterium leprae and an increased lysosomal activity in ENL reactive cases is interpreted as a reaction to the lysis of the cytoplasmic matrix of M. leprae; however, drug-specific (diaminodiphenylsulphone) reactions must also be considered.
Assuntos
Eritema Nodoso/patologia , Dermatoses Faciais/patologia , Hanseníase/patologia , Doenças da Boca/patologia , Adolescente , Adulto , Criança , Epitélio/ultraestrutura , Eritema Nodoso/tratamento farmacológico , Dermatoses Faciais/tratamento farmacológico , Feminino , Humanos , Hanseníase/tratamento farmacológico , Linfócitos/ultraestrutura , Lisossomos/ultraestrutura , Macrófagos/ultraestrutura , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Doenças da Boca/tratamento farmacológico , Mycobacterium leprae/ultraestruturaRESUMO
Mice of the inbred strains C57BL and C3H were inoculated in the foot-pads with Mycobacterium lepraemurium (MLM) and the inflammatory reaction was studied using light and electron microscopy. In C57BL mice a granulomatous reaction developed 3-4 weeks after inoculation. The inflammatory exudate at this stage showed numerous lymphocytes, monocytes and macrophages. The latter cell type often contained many lysosomes and appeared activated. The bacilli which were all within phagosomes showed extensive electron dense aggregates of the cytoplasm suggesting severe damage. Lymphocytes and macrophages in close contact with each other were often observed. In macrophages which contained damaged bacilli, spherical lipid-like bodies surrounded by granular endoplasmic reticulum were observed. It is suggested that this cell product could be of some significance for the bactericidal function of the macrophage. Contrary to these findings, the cellular infiltrate developing in C3H mice showed no lymphocytes and consisted exclusively of macrophages. These were all heavily loaded with bacilli. The vast majority of bacilli encountered in this strain was morphologically intact and presumably viable. Lipid-like bodies similar to those observed in infected C57BL macrophages were not encountered in C3H mice. It is concluded that unless the infected macrophages become immunologically activited they are unable to cause bacterial damage or to inhibit the growth of MLM.