Atividade da NADH-redutase de metemoglobina em hemolisado e membranas eritrocitárias de pacientes hansenianos sob tratamento sulfônico
DOI:
https://doi.org/10.47878/hi.1998.v23.36461Palavras-chave:
Hanseníase, NADH-redutase, Diaforase, NADH-metemoglobina-redutaseResumo
Nós efetuamos determinações da série vermelha, dosagem da sulfonemia, dosagem de metemoglobina, contagem de reticulócitos e dosagem da atividade enzimática da NADHdiaforase no hemolisado e nas membranas dos eritrócitos livres de hemoglobina em 72 pacientes portadores de hanseníase, todos ingerindo doses diárias de 100 mg de diaminodifenil-sulfona. Idênticos testes, exceto dosagem de sulfona, foram efetuados no sangue de 72 pessoas normais, não ingerindo medicamentos oxidantes. Foram encontradas diferenças estatísticas significativas nas variáveis da série vermelha, metemoglobina, reticulócitos e na atividade enzimática da NADH-redutase nas membranas eritrocitárias entre os dois grupos. A atividade enzimática nas membranas eritrocitárias foi inferior e estatisticamente significativa com relação ao grupo-controle. A atividade enzimática da NADH-redutase no hemolisado não apresentou diferença estatística significativa quando feita a correção pela taxa de hemoglobina. O nível de metemoglobina foi superior nos portadores de hanseníase em relação ao grupocontrole, provavelmente devido à ação oxidante da sulfona. Tendo em vista termos encontrado níveis inferiores de atividade enzimática nas membranas eritrocitárias dos hansenianos e níveis
coincidentes no hemolisado, em comparação com um grupo-controle, podemos afirmar que, provavelmente, isto se deve ao deslocamento enzimático da membrana celular para o citoplasma, com o objetivo de manter o eritrócito em equilíbrio hemoglobínico constante, apesar da ação oxidante da sulfona.
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Referências
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2. BALAKRISHNAN, S., KARTHIKEYAN, S., RAMU, G. Investigations into haemolytic effects of dapsone therapy in leprosy patients. Indian J. Med., v.61,
p.10-16, 1989.
3. BANZATO, C.E.M., MAGNA L.A. In vitro effect of Dapsone on NADH-methemoglobin reductase. Int. J. Leprosy, v.59, p.486-487, 1991.
4. BERNARD, J., et al. Anatomia e fisiologia do eritrócito e da série eritroblástica. In: ______ Manual de hematologia. Santos, 1989. p.15-35.
5. BEUTLER, E., BALUDA, M.C. Metemoglobin reduction. Studies of the interaction between cell populations and of the role of methylene blue. Blood, v.22, p. 323-33, 1963.
6. BUNN, H. F. Distúrbios da hemoglobina - metemoglobinemia. In: HARRISSON, T.R. Medicina interna. 13. ed. São Paulo: Mc Graw Hill, 1995. v.2., p.1823-1824.
7. CAMPBELL, J.M. , CAMPBELL, J.B. Cálculo baseado no coeficiente de extinção molar de um produto de reação com absorbânc ia. In: ______ Matemática de laboratório -cálculo de enzimas aplicações médicas e biológicas. 3.ed. São Paulo: Roca, 1986. p.214.
8 . CATICHA-ALFONSO, O.S., MAGNA, L.A., BEIGUELMAN, B. NADH - r e d u t a s e d e metemoglobina e reticulocitose. Ciência e Cultura, v.37, p.280-283,1985.
9. CHOURY, D., LEROUX, A. , KAPLAN, J.C. Membrane-bound cytochrome b5 reductase (methemoglobin reductase) in human erythrocytes. J. Clin. Invest., v.67, p.149-51, 1981.
10. COHEN, G., HOCHSTEIN, P. Generation of hydrogen peroxide in erythrocytes by hemolytic agents. Biochemistry, v.3, p.895-900, 1964.
11. CONROY, J.M., BAKER, J.D., MARTIN, W.J. et al. Acquired methemoglobinemia from multiple oxidants. Soot. Med. J., v.86, p.1156-1159, 1993.
12. CREAM, J. J., SCOTT, G.L. Anaemia in dermatitis herpetiformis. The role of Dapsone- induced haemolysis and malabsorption. Brit. J. Derm., v.82, p.333-342, 1970.
13. DODGE, J.T., MITCHELL, C., HANAHAN, D.J. The preparat ion and character ist ics of hemoglobin-free ghost of human erythrocytes. Arch. Biochem. Biophys., v.100, p.119-130, 1963.
14. EDELHOCH, H., HAYAISHI, O., TEPLY, L.J. The preparat ion and properties of a soluble diphosphopyridine nucleotide cythocrome c reductase. J. biol. chem , v.197, p. 97-104, 1952.
15. EVELIN, K.A., MALLOY, H.T. Microdetermination o f o x y h emo g l o b i n , me t h emo g l o b i n a n d sulfhemoglobin in a single sample of blood. J.
biol. chem., v.126, p. 655-662, 1938.
16. FEIG, S.A., NATHAN, D.G., GERALD, P.S. et al. Congenital methemoglobinemia- the result of age-dependent decay of methemoglobin reductase. Blood, v.39, p.407, 1972.
17. FINCH, C. A. Me t h emo g l o b i n emi a a n d sulfhemoglobinemia. The New Engl. J. of Med.v. 239, p.470-478, 1948.
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19. HARLEY, J.D., MAUER, A.M. Studies on the formation of Heins bodies. II. The nature and significance of heins bodies. Blood, v.17, p.418-33, 1961.
20. HEGESH, E., CALMANOVICI, N., AVRON, M. - New method for determining ferrihemoglobin reductase (NADH-Methemoglobin Reductase) in
erythrocytes. J. Lab & Clin. Med.. v. 72, p.339-44, 1968.
21. HENRY, J.B. Hemoglobina. In: TODD, SANFORD, DAVIDSON. Diagnósticos clínicos e conduta terapêutica por exames laboratoriais. 16. ed., São Paulo: Manole, 1982. V.I, p. 946-54.
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24. JANDL, J.H., ENGLE, L.K., ALLEN, D.W. Oxidative hemolysis and precipitation of hemoglobin. I. Heinz body anemias as an acceleration of red cell aging. J. Clin. Invest., v.39, p.1818-36, 1960.
25. KITAJIMA, S., YASUKOCHI Y., MINAKAMI, S. Purification and properties of human erythrocyte membrane NADH-cytochrome b5 reductase. Arch. Biochem. Biophys. v.210, p.330-9, 1981.
26. KUMA, F., ISHIZAWA, S., HIRAYAMA, K , NAKAJIMA, H. Studies on methemoglobin redutase. I. Comparative studies of diaphorases f rom normal and methemoglobinemic erythrocytes. J. Biol. Chem., v.247, p.550-5, 1972.
27. KUMA, F., PROUGH, R.A., MASTER, B. S. S. Studies on methemoglobin reductase. Immunochemical similarity of soluble methemoglobin reductase and cytochrome b5 of human erythrocytes with NADH-citochrome b5 reductase and cytochrome b5 of rat liver microsomes. Arch. Biochem. Biophys. v.172, p.600-7, 1976,
28. LEROUX, A., TORLINSKI, L., KAPLAN, J.C. Soluble and microsomal forms of NADH-cytochrome b5 reductase from human placenta: Similarity with
NADH-methemoglobin reductase from human erythrocytes. Biochim. Biophys. Acta, v.481, p.50, 1977.
29. MAGNA L. A. , BEIGUELMAN, B. NADHMethemoglobin reductase and methemoglobinemia among leprosy patients. Int. J. Lepr.. v.52, p.475-81, 1984
30. MATSUKI, T., TAMURA, M., TAKESHITA, M. et al. Age-dependent decay of cytochrome b5 and cytochrome b5 reduc tase in human erythrocytes. Biochem. J., v.194, p.327-30, 1981.
31. MELDOLESI J., CORTE, G., PIETRINI, G. et al. Localization and biosynthesis of NADHcytochrome b5 reductase, an integral membrane protein, in rat liver cells. J. Cell Biol., v.85, p.516-26, 1980.
32. MIHARA, K., SATO, R., SAKAKIBARA, R. et al. Reduced nicotinamide adenine dinucleotide - cytochrome b5 reductase: Location of the hydrophobic, membrane-binding region at the carboxyl-terminal end and the masked amino terminus. Biochemistry, v.17, p.2829-34, 1978.
33. MILLER, A., SMITH, H.C. The intracellular and membrane effects of oxidant agents on normal red cells. Brit. J. Haem., v.19, p.417-28, 1970.
34. MILLS, G.C., RANDALL, H.P. - Hemoglobin catabolism II. The protection of hemoglobin from oxidative breakdown in the intact erythrocyte. J. Biol. Chem., v.232, p.589- 98, 1958.
35. NORDEEN, S.K., LOPES BRAVO, L., SUNDARESAN, T.K. Mise au point - nomble estimatif de cas de lepre dans le monde. Acta Lepr., v.8, p.121-5, 1993.
36. ORGANIZACION MUNDIAL DE LA SALUD. Una guia para el control de la lepra. Madri: Ministerio de Sanidad Y Consumo, 1988..
37. PANIN, G., PERNECHELE, M., GIURIOLI, R. et al. Cytochrome b5 reductase ac t ivi ty in erythrocytes and leukocytes as related to sex and age. Clin. Chem., v.30, p.701-3, 1984.
38. PASSON, P.G., HULTQUIST, D.E. Soluble cytochrome b5 reductase from human erythrocytes. Bioch. Biophys. Acta, v.275, p.62-73, 1972.
39. PETRAGNANI, N., NOGUEIRA, O.C., RAW, I. Methemoglobin reduction through cytochrome b5 reductase. Nature, v.184, p.1651. 1959.
40. RAPAPORT, S.I. Hemoglobinopatias e síndromes talassêmicas. In : ______ Introdução à hematologia. Rio de Janeiro: Harper & Row do Brasil. 1978. p.54-70.
41. Metemoglobinemia . In:________________ Introdução à hematologia. Rio de Janeiro: Harper & Row do Brasil,1978. p.109-10.
42. RASBRIDGE, M.R., SCOTT, G.L. The haemolytic action of dapsone : he efect on red-cell glycolysis . Brit. J. Haemat., v.24, p.169-81, 1973.
43. ROSS, J.D. Deficient activity of DPNH-dependent methemoglobin diaphorase in cord blood erythrocytes. Blood, v.21, p.51-62,1963
44. SCHWARTZ, J.M., JAFFÉ, E. R.Hereditary methemoglobinemia with deficiency of NADHdehydrogenase. In: STANBURY, J.B., WYNGAARDEN, J.B., FREDRICSON, D.S. eds. The metabolic basis of inherited disease. 4. ed.New York: McGraw-Hill, 1978. p.1452-64
45. SCHWARTZ, J.M., PARESS. P.S., ROSS, J.M., DIPILLO, F., RIZEK R. Unstable variant of NADH-methemoglobin reductase in Puerto Ricans with hereditary methemoglobinemia. J. Clin. Invest., v. 51, p.1594-601, 1972.
46. SCHWARTZ, J.M., REISS, A.L., JAFFÉ, E.R. Hereditary methemoglobinemia with deficiency of NADH-cytochrome b5 reductase. In: STANBURY, J.B., WYNGAARDEN, FREDRICSON, D.S., eds. The metabolic basis of inherited disease. New York: McGraw-Hill, 1983. p.1654-65.
47. SCOTT, E.M. The relation of diaphorase of humam erythrocytes to inheritance of methemoglobinemia. I. Clin. Invest., v.39, p.1176-9, 1960.
48. SCOTT, E. M., DUNCAN, I.W. , EKSTRAND, V. T h e reduced pyridine nucleotide dehydrogenases of human erythrocytes. J.Biol. Chem.,v.240, p.481-5, 1965.
49. SCOTT, E.M., GRIFFITH, I.V. The enzymic defect of hereditary methemoglobinemia- diaphorase (Preliminary notes). Biochem. and Biophys. Acta, v.34, p.584-6, 1959.
50. SCOTT, E.M., MCGRAW, J.C. Purification and properties of diphosphopyridine nucleotide diaphorase of human erythrocytes. J. Biol. Chem., v.237, p.249-52, 1962.
51. SIMPSON, I. A. Appendix. Method of sulfone estimations. Int. I. of Leprosy, v.17, p.208-10, 1949.
52. SOCIEDADE BRASILEIRA DE HEMATOLOGIA E HEMOTERAPIA. Enzimopatias eritrocitárias. In _______Manual de Técnicas e Recomendações
Hematológicas. São Paulo: 1975. p.125-23.
53. SPATZ, L., STRITTMATTER, P. A form of reduced nicotinamide adenine dinucleotide-cytochrome b5 reductase containing both the catalytic site
and an additional hydrophobic membranebinding segment. J. Biol. Chem. v.248, p.793-9, 1973.
54. SUGITA, Y., NOMURA, S., YONEYAMA, Y. Purification of reduced pyridine nucleotide dehydrogenase from human erythrocytes and methemoglobin reduction by the enzyme. I. BioL Chem., v.246, p.6072-78. 1971.
2. BALAKRISHNAN, S., KARTHIKEYAN, S., RAMU, G. Investigations into haemolytic effects of dapsone therapy in leprosy patients. Indian J. Med., v.61,
p.10-16, 1989.
3. BANZATO, C.E.M., MAGNA L.A. In vitro effect of Dapsone on NADH-methemoglobin reductase. Int. J. Leprosy, v.59, p.486-487, 1991.
4. BERNARD, J., et al. Anatomia e fisiologia do eritrócito e da série eritroblástica. In: ______ Manual de hematologia. Santos, 1989. p.15-35.
5. BEUTLER, E., BALUDA, M.C. Metemoglobin reduction. Studies of the interaction between cell populations and of the role of methylene blue. Blood, v.22, p. 323-33, 1963.
6. BUNN, H. F. Distúrbios da hemoglobina - metemoglobinemia. In: HARRISSON, T.R. Medicina interna. 13. ed. São Paulo: Mc Graw Hill, 1995. v.2., p.1823-1824.
7. CAMPBELL, J.M. , CAMPBELL, J.B. Cálculo baseado no coeficiente de extinção molar de um produto de reação com absorbânc ia. In: ______ Matemática de laboratório -cálculo de enzimas aplicações médicas e biológicas. 3.ed. São Paulo: Roca, 1986. p.214.
8 . CATICHA-ALFONSO, O.S., MAGNA, L.A., BEIGUELMAN, B. NADH - r e d u t a s e d e metemoglobina e reticulocitose. Ciência e Cultura, v.37, p.280-283,1985.
9. CHOURY, D., LEROUX, A. , KAPLAN, J.C. Membrane-bound cytochrome b5 reductase (methemoglobin reductase) in human erythrocytes. J. Clin. Invest., v.67, p.149-51, 1981.
10. COHEN, G., HOCHSTEIN, P. Generation of hydrogen peroxide in erythrocytes by hemolytic agents. Biochemistry, v.3, p.895-900, 1964.
11. CONROY, J.M., BAKER, J.D., MARTIN, W.J. et al. Acquired methemoglobinemia from multiple oxidants. Soot. Med. J., v.86, p.1156-1159, 1993.
12. CREAM, J. J., SCOTT, G.L. Anaemia in dermatitis herpetiformis. The role of Dapsone- induced haemolysis and malabsorption. Brit. J. Derm., v.82, p.333-342, 1970.
13. DODGE, J.T., MITCHELL, C., HANAHAN, D.J. The preparat ion and character ist ics of hemoglobin-free ghost of human erythrocytes. Arch. Biochem. Biophys., v.100, p.119-130, 1963.
14. EDELHOCH, H., HAYAISHI, O., TEPLY, L.J. The preparat ion and properties of a soluble diphosphopyridine nucleotide cythocrome c reductase. J. biol. chem , v.197, p. 97-104, 1952.
15. EVELIN, K.A., MALLOY, H.T. Microdetermination o f o x y h emo g l o b i n , me t h emo g l o b i n a n d sulfhemoglobin in a single sample of blood. J.
biol. chem., v.126, p. 655-662, 1938.
16. FEIG, S.A., NATHAN, D.G., GERALD, P.S. et al. Congenital methemoglobinemia- the result of age-dependent decay of methemoglobin reductase. Blood, v.39, p.407, 1972.
17. FINCH, C. A. Me t h emo g l o b i n emi a a n d sulfhemoglobinemia. The New Engl. J. of Med.v. 239, p.470-478, 1948.
18. HARLEY, J.D. , MAUER, A.M. Studies on the formation of Heins bodies. I. Methemoglobin production and oxyhemoglobin distruction. Blood, v.16, p.1722-35 , 1960.
19. HARLEY, J.D., MAUER, A.M. Studies on the formation of Heins bodies. II. The nature and significance of heins bodies. Blood, v.17, p.418-33, 1961.
20. HEGESH, E., CALMANOVICI, N., AVRON, M. - New method for determining ferrihemoglobin reductase (NADH-Methemoglobin Reductase) in
erythrocytes. J. Lab & Clin. Med.. v. 72, p.339-44, 1968.
21. HENRY, J.B. Hemoglobina. In: TODD, SANFORD, DAVIDSON. Diagnósticos clínicos e conduta terapêutica por exames laboratoriais. 16. ed., São Paulo: Manole, 1982. V.I, p. 946-54.
22. HOFFBRAND, A.V., PETTIT, J.E. Hematologia clínica ilustrada: manual e atlas colorido. São Paulo: Manole, 1991. p.4-7.
23. HUENNEKENS, F.M., CAFFREY, R.W., BASFORD, R.E., et al. Erythrocyte metabolism. IV. Isolation and properties of methemoglobin reductase. J. Biol. Chem., v.227, p.261-72, 1957.
24. JANDL, J.H., ENGLE, L.K., ALLEN, D.W. Oxidative hemolysis and precipitation of hemoglobin. I. Heinz body anemias as an acceleration of red cell aging. J. Clin. Invest., v.39, p.1818-36, 1960.
25. KITAJIMA, S., YASUKOCHI Y., MINAKAMI, S. Purification and properties of human erythrocyte membrane NADH-cytochrome b5 reductase. Arch. Biochem. Biophys. v.210, p.330-9, 1981.
26. KUMA, F., ISHIZAWA, S., HIRAYAMA, K , NAKAJIMA, H. Studies on methemoglobin redutase. I. Comparative studies of diaphorases f rom normal and methemoglobinemic erythrocytes. J. Biol. Chem., v.247, p.550-5, 1972.
27. KUMA, F., PROUGH, R.A., MASTER, B. S. S. Studies on methemoglobin reductase. Immunochemical similarity of soluble methemoglobin reductase and cytochrome b5 of human erythrocytes with NADH-citochrome b5 reductase and cytochrome b5 of rat liver microsomes. Arch. Biochem. Biophys. v.172, p.600-7, 1976,
28. LEROUX, A., TORLINSKI, L., KAPLAN, J.C. Soluble and microsomal forms of NADH-cytochrome b5 reductase from human placenta: Similarity with
NADH-methemoglobin reductase from human erythrocytes. Biochim. Biophys. Acta, v.481, p.50, 1977.
29. MAGNA L. A. , BEIGUELMAN, B. NADHMethemoglobin reductase and methemoglobinemia among leprosy patients. Int. J. Lepr.. v.52, p.475-81, 1984
30. MATSUKI, T., TAMURA, M., TAKESHITA, M. et al. Age-dependent decay of cytochrome b5 and cytochrome b5 reduc tase in human erythrocytes. Biochem. J., v.194, p.327-30, 1981.
31. MELDOLESI J., CORTE, G., PIETRINI, G. et al. Localization and biosynthesis of NADHcytochrome b5 reductase, an integral membrane protein, in rat liver cells. J. Cell Biol., v.85, p.516-26, 1980.
32. MIHARA, K., SATO, R., SAKAKIBARA, R. et al. Reduced nicotinamide adenine dinucleotide - cytochrome b5 reductase: Location of the hydrophobic, membrane-binding region at the carboxyl-terminal end and the masked amino terminus. Biochemistry, v.17, p.2829-34, 1978.
33. MILLER, A., SMITH, H.C. The intracellular and membrane effects of oxidant agents on normal red cells. Brit. J. Haem., v.19, p.417-28, 1970.
34. MILLS, G.C., RANDALL, H.P. - Hemoglobin catabolism II. The protection of hemoglobin from oxidative breakdown in the intact erythrocyte. J. Biol. Chem., v.232, p.589- 98, 1958.
35. NORDEEN, S.K., LOPES BRAVO, L., SUNDARESAN, T.K. Mise au point - nomble estimatif de cas de lepre dans le monde. Acta Lepr., v.8, p.121-5, 1993.
36. ORGANIZACION MUNDIAL DE LA SALUD. Una guia para el control de la lepra. Madri: Ministerio de Sanidad Y Consumo, 1988..
37. PANIN, G., PERNECHELE, M., GIURIOLI, R. et al. Cytochrome b5 reductase ac t ivi ty in erythrocytes and leukocytes as related to sex and age. Clin. Chem., v.30, p.701-3, 1984.
38. PASSON, P.G., HULTQUIST, D.E. Soluble cytochrome b5 reductase from human erythrocytes. Bioch. Biophys. Acta, v.275, p.62-73, 1972.
39. PETRAGNANI, N., NOGUEIRA, O.C., RAW, I. Methemoglobin reduction through cytochrome b5 reductase. Nature, v.184, p.1651. 1959.
40. RAPAPORT, S.I. Hemoglobinopatias e síndromes talassêmicas. In : ______ Introdução à hematologia. Rio de Janeiro: Harper & Row do Brasil. 1978. p.54-70.
41. Metemoglobinemia . In:________________ Introdução à hematologia. Rio de Janeiro: Harper & Row do Brasil,1978. p.109-10.
42. RASBRIDGE, M.R., SCOTT, G.L. The haemolytic action of dapsone : he efect on red-cell glycolysis . Brit. J. Haemat., v.24, p.169-81, 1973.
43. ROSS, J.D. Deficient activity of DPNH-dependent methemoglobin diaphorase in cord blood erythrocytes. Blood, v.21, p.51-62,1963
44. SCHWARTZ, J.M., JAFFÉ, E. R.Hereditary methemoglobinemia with deficiency of NADHdehydrogenase. In: STANBURY, J.B., WYNGAARDEN, J.B., FREDRICSON, D.S. eds. The metabolic basis of inherited disease. 4. ed.New York: McGraw-Hill, 1978. p.1452-64
45. SCHWARTZ, J.M., PARESS. P.S., ROSS, J.M., DIPILLO, F., RIZEK R. Unstable variant of NADH-methemoglobin reductase in Puerto Ricans with hereditary methemoglobinemia. J. Clin. Invest., v. 51, p.1594-601, 1972.
46. SCHWARTZ, J.M., REISS, A.L., JAFFÉ, E.R. Hereditary methemoglobinemia with deficiency of NADH-cytochrome b5 reductase. In: STANBURY, J.B., WYNGAARDEN, FREDRICSON, D.S., eds. The metabolic basis of inherited disease. New York: McGraw-Hill, 1983. p.1654-65.
47. SCOTT, E.M. The relation of diaphorase of humam erythrocytes to inheritance of methemoglobinemia. I. Clin. Invest., v.39, p.1176-9, 1960.
48. SCOTT, E. M., DUNCAN, I.W. , EKSTRAND, V. T h e reduced pyridine nucleotide dehydrogenases of human erythrocytes. J.Biol. Chem.,v.240, p.481-5, 1965.
49. SCOTT, E.M., GRIFFITH, I.V. The enzymic defect of hereditary methemoglobinemia- diaphorase (Preliminary notes). Biochem. and Biophys. Acta, v.34, p.584-6, 1959.
50. SCOTT, E.M., MCGRAW, J.C. Purification and properties of diphosphopyridine nucleotide diaphorase of human erythrocytes. J. Biol. Chem., v.237, p.249-52, 1962.
51. SIMPSON, I. A. Appendix. Method of sulfone estimations. Int. I. of Leprosy, v.17, p.208-10, 1949.
52. SOCIEDADE BRASILEIRA DE HEMATOLOGIA E HEMOTERAPIA. Enzimopatias eritrocitárias. In _______Manual de Técnicas e Recomendações
Hematológicas. São Paulo: 1975. p.125-23.
53. SPATZ, L., STRITTMATTER, P. A form of reduced nicotinamide adenine dinucleotide-cytochrome b5 reductase containing both the catalytic site
and an additional hydrophobic membranebinding segment. J. Biol. Chem. v.248, p.793-9, 1973.
54. SUGITA, Y., NOMURA, S., YONEYAMA, Y. Purification of reduced pyridine nucleotide dehydrogenase from human erythrocytes and methemoglobin reduction by the enzyme. I. BioL Chem., v.246, p.6072-78. 1971.
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Dalpino D, Diltor LAM, Opromolla VA. Atividade da NADH-redutase de metemoglobina em hemolisado e membranas eritrocitárias de pacientes hansenianos sob tratamento sulfônico. Hansen. Int. [Internet]. 30º de novembro de 1998 [citado 20º de abril de 2024];23(1/2):14-26. Disponível em: https://periodicos.saude.sp.gov.br/hansenologia/article/view/36461
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