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3.
Int J Lepr Other Mycobact Dis ; 63(2): 259-64, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7602221

RESUMO

In these studies we evaluated the activity of low levels of five antimicrobials against Mycobacterium leprae-infected mice when administered singly and in all possible two- and three-drug combinations. Antibiotics studied were: dapsone (D) 0.0001% in the diet, rifampin (R) 20 mg/kg by gavage once monthly, minocycline (M) 0.004% in the diet, clarithromycin (C) 0.001% in the diet, and sparfloxacin (S) 5 mg/kg by gavage five times weekly. Singly each agent was found bacteriostatic (D + R) or partially bactericidal (M, C, and S) but not fully bactericidal. All 10 two-drug regimens were found at least bacteriostatic, 2 being "partially bactericidal" and 4 being "fully bactericidal." Of the 10 three-drug regimens, 9 were found "fully bactericidal" and the other "partially bactericidal." We conclude that combinations of antibiotics active against M. leprae are generally additive in combination.


Assuntos
Anti-Infecciosos/administração & dosagem , Claritromicina/administração & dosagem , Dapsona/administração & dosagem , Fluoroquinolonas , Hanseníase/tratamento farmacológico , Minociclina/administração & dosagem , Quinolonas/administração & dosagem , Rifampina/administração & dosagem , Animais , Quimioterapia Combinada , Feminino , Camundongos , Camundongos Endogâmicos BALB C
6.
Int J Lepr Other Mycobact Dis ; 62(4): 568-73, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7868955

RESUMO

A clinical trial of minocycline in a total of 10 patients with previously untreated lepromatous leprosy was conducted in order to evaluate the efficacy of a single, initial, 200-mg dose and 100 mg twice daily of minocycline for a total duration of up to 3 months. Patients improved remarkably quickly. Although single-dose therapy did not result in a significant killing of Mycobacterium leprae, viable M. leprae were cleared from the dermis regularly by 3 months of twice-daily therapy, a rate similar to that achieved by minocycline 100 mg once daily. Because more side effects were noted herein than previously with 100 mg daily, we recommend that minocycline, when applied, be administered at 100 mg daily to leprosy patients.


Assuntos
Hanseníase Virchowiana/tratamento farmacológico , Minociclina/administração & dosagem , Adolescente , Adulto , Idoso , Animais , Esquema de Medicação , Feminino , Humanos , Hanseníase Dimorfa/tratamento farmacológico , Hanseníase Dimorfa/microbiologia , Hanseníase Virchowiana/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Minociclina/efeitos adversos , Minociclina/uso terapêutico , Mycobacterium leprae/efeitos dos fármacos , Mycobacterium leprae/crescimento & desenvolvimento , Pele/microbiologia
7.
Eur J Clin Microbiol Infect Dis ; 13(11): 942-52, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7698121

RESUMO

Leprosy is a major debilitating infectious disease, primarily of the developing world. In this paper the current status and future prospects of antimicrobial therapy of the severe anergic lepromatous form of the disease are reviewed. Until the last few years only dapsone, rifampicin, clofazimine and ethionamide have had practical application in its therapy, and only rifampicin was bactericidal. Recently, antibiotics from three different classes have been found to be bactericidal in lepromatous patients: a tetracycline (minocycline), a macrolide (clarithromycin), and several fluoroquinolones (including pefloxacin, ofloxacin and sparfloxacin). Against a background of drug resistance and bacterial persistence, recommendations for multidrug therapy and the means to devise rationally based therapy for the future are discussed.


Assuntos
Hansenostáticos/uso terapêutico , Hanseníase Virchowiana/tratamento farmacológico , Animais , Quimioterapia Combinada , Previsões , Humanos , Camundongos , Mycobacterium leprae/fisiologia
8.
Infect Immun ; 62(10): 4250-5, 1994 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7927681

RESUMO

In this study, we evaluated vaccination with a number of purified, as well as recombinant, Mycobacterium leprae proteins for protective efficacy in mice. BALB/c mice were immunized intradermally with various native somatic (purified) or recombinant M. leprae proteins and their synthetic polypeptides emulsified in Freund's incomplete adjuvant. The protective efficacy of these preparations was assessed by enumeration of bacilli in the footpads of mice challenged with viable M. leprae 1 to 2 months following immunization. Protection was afforded by the purified and recombinant 10-kDa M. leprae cytoplasmic heat shock protein, the recombinant cell wall-associated 65-kDa M. leprae heat shock protein, and to a lesser extent, the purified 28-kDa M. leprae cytoplasmic protein (superoxide dismutase). Vaccination with either the purified or recombinant 35-kDa M. leprae cell membrane protein, the synthetic 27-amino-acid N-terminal peptide of the 10-kDa protein, the recombinant 18-kDa M. leprae protein, or the purified 22-kDa cell membrane protein was ineffective. When the interval between immunization and challenge was increased to 6 months, the purified 10-kDa M. leprae protein and the recombinant 65-kDa M. leprae protein lost vaccine efficacy, while a sodium dodecyl sulfate-soluble protein fraction of the M. leprae cell wall (soluble proteins), as had been found previously, continued to protect, suggesting that multiple M. leprae protein epitopes are critical for solid vaccine protection.


Assuntos
Proteínas de Bactérias/imunologia , Vacinas Bacterianas/imunologia , Mycobacterium leprae/imunologia , Animais , Feminino , Pé/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Peso Molecular , Mycobacterium leprae/crescimento & desenvolvimento , Vacinação , Vacinas Sintéticas/imunologia
9.
Lepr Rev ; 65(3): 175-80, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8942148

RESUMO

It had previously been discovered that intradermal mouse vaccination with a protein fraction of Mycobacterium leprae (called soluble proteins) in Freund's incomplete adjuvant (FIA) resulted in consistent and long-lived protection against M. leprae multiplication from subsequent viable footpad challenges. In this study certain density-gradient subfractions of this soluble protein, but not others, in FIA afforded vaccine protection. The results of this study suggest which M. leprae proteins may be involved in protective immunity, particularly 1-3 kD, 10 kD, 65 kD, and those of higher molecular weight.


Assuntos
Proteínas de Bactérias/imunologia , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/imunologia , Hanseníase/imunologia , Mycobacterium leprae/imunologia , Vacinação , Animais , Proteínas de Bactérias/administração & dosagem , Modelos Animais de Doenças , Injeções Intradérmicas , Hanseníase/prevenção & controle , Camundongos
12.
Int J Lepr Other Mycobact Dis ; 61(3): 398-405, 1993 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8228438

RESUMO

To test whether Mycobacterium leprae-immune T cells can confer protection against infection with leprosy bacilli, severe combined immunodeficient (SCID) mice were reconstituted with a BALB/c-derived, M. leprae-responsive, T-cell line. Flow cytometric analysis of spleen and peripheral blood cells confirmed reconstitution with T cells. In vitro lymphokine production and the proliferation of spleen cells from the reconstituted animals established that the donor cells had maintained their functional activity for the duration of the study (275 days). The transfer of immune T cells 24 hr before foot pad infection with leprosy bacilli resulted in a profound reduction in M. leprae multiplication, as compared to the nonreconstituted SCID mice. The yield of acid-fast bacilli in the foot pads of SCID mice reconstituted with the M. leprae-immune T cells also was significantly lower than that found in naive BALB/c mice, and at levels previously found only in BALB/c mice that had been immunized effectively. These experiments demonstrate that M. leprae-immune T cells home effectively and control M. leprae infection in SCID mice.


Assuntos
Imunoterapia Adotiva , Hanseníase/prevenção & controle , Mycobacterium leprae/imunologia , Linfócitos T/imunologia , Animais , Antígenos CD4/análise , Antígenos CD8/análise , Linhagem Celular , Feminino , Citometria de Fluxo , Interferon gama/biossíntese , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Mycobacterium leprae/crescimento & desenvolvimento , Organismos Livres de Patógenos Específicos , Baço/citologia
14.
Antimicrob Agents Chemother ; 36(11): 2544-7, 1992 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1336951

RESUMO

Previously, pefloxacin and ofloxacin were found to be active against Mycobacterium leprae in vitro, in experimental animals, and in clinical trials of lepromatous leprosy patients. In this study, we compared certain more recently developed fluoroquinolones (lomefloxacin, PD 124816, WIN 57273, temafloxacin, and sparfloxacin) with pefloxacin and ofloxacin in M. leprae-infected mice at doses of 50, 150, and 300 mg/kg given five times weekly. All seven of the fluoroquinolones studies were active against M. leprae; temafloxacin and sparfloxacin were the most active, being fully bactericidal at all three dosage schedules. Additionally, sparfloxacin was found to be fully bactericidal at 15 and 30 mg/kg given five times weekly.


Assuntos
Anti-Infecciosos/farmacologia , Fluoroquinolonas , Hanseníase/tratamento farmacológico , Mycobacterium leprae , Animais , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Pefloxacina/farmacologia , Quinolonas/farmacologia
16.
Mol Cell Probes ; 6(5): 401-10, 1992 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1474978

RESUMO

An improved protocol for PCR analysis of Mycobacterium leprae-infected tissues, based on enzymatic lysis, has been developed and used to demonstrate the feasibility of using PCR for detecting M. leprae in routine skin biopsies taken from leprosy patients throughout the clinical spectrum. Of 92 multibacillary patients tested, 99% were PCR-positive using gel electrophoresis or DNA hybridization to detect the amplified product. Similar analysis of paucibacillary patients, in which only one of 27 biopsies had demonstrable AFB microscopically, gave a positivity rate of 74%. No PCR signals were demonstrated from skin biopsies from seven patients with non-leprosy dermatoses and one AIDS patient with a disseminated atypical mycobacteriosis. Evaluation of leprosy patients with antileprosy drug therapy prior to biopsy demonstrated that PCR signals were either greatly diminished or absent after 2 months of continuous antibiotic therapy. PCR was also able to detect the presence of M. leprae in tissues of patients receiving antibacterial therapy when patients were suspected of harbouring drug-resistant M. leprae.


Assuntos
Clofazimina/uso terapêutico , Dapsona/uso terapêutico , Hanseníase/microbiologia , Mycobacterium leprae/isolamento & purificação , Reação em Cadeia da Polimerase , Rifampina/uso terapêutico , Pele/microbiologia , Antibacterianos , Biópsia , Sondas de DNA , DNA Bacteriano/genética , Quimioterapia Combinada/uso terapêutico , Eletroforese em Gel de Ágar , Estudos de Viabilidade , Humanos , Hanseníase/tratamento farmacológico , Mycobacterium leprae/genética , Hibridização de Ácido Nucleico , Sensibilidade e Especificidade , Pele/patologia
18.
Infect Immun ; 60(5): 1840-4, 1992 May.
Artigo em Inglês | MEDLINE | ID: mdl-1563772

RESUMO

Groups of BALB/c mice were vaccinated intradermally with either Freund's incomplete adjuvant (FIA) alone, 10(7) heat-killed Mycobacterium leprae organisms in FIA, or a number of fractions of M. leprae containing soluble and/or cell wall components. At 1, 3, 6, 9, and 12 months later, vaccinated mice were challenged in the right hind footpad with 5,000 live M. leprae organisms, and vaccine protection was assessed 6 to 8 months later, at the peak of M. leprae multiplication in the negative control (FIA alone), by the two-sample rank-sum test. In these studies, a cell wall fraction rich in peptidoglycan was consistently ineffective. Both heat-killed M. leprae and a fraction containing cell wall and fixed proteins generally protected when the interval between vaccination and challenge was 1 or 3 months but not subsequently. On the other hand, soluble proteins of M. leprae alone or in combination (with cell wall fractions) consistently (14 of 14 instances) afforded highly significant protection (P less than or equal to 0.01) at all challenge intervals up to 1 year after vaccination. These results suggest that the soluble protein fraction of M. leprae offers promise for a vaccine against leprosy.


Assuntos
Proteínas de Bactérias/imunologia , Hanseníase/prevenção & controle , Mycobacterium leprae/imunologia , Animais , Vacinas Bacterianas/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Vacinação
20.
Ann Otol Rhinol Laryngol ; 101(3): 261-4, 1992 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1543336

RESUMO

Nasal involvement in lepromatous leprosy is universal and occurs early in the course of the disease. Nasal symptoms include obstruction, crusting, bleeding, and hyposmia. Traditional therapy with dapsone, rifampin, and clofazimine is limited by its cost and toxicity. Minocycline hydrochloride, a tetracycline antibiotic with limited side effects, is promising as a new treatment for leprosy. A case is presented that highlights the clinical presentation, diagnosis, and treatment of lepromatous leprosy.


Assuntos
Hanseníase Virchowiana/tratamento farmacológico , Minociclina/uso terapêutico , Adulto , Dapsona/uso terapêutico , Quimioterapia Combinada , Humanos , Hanseníase Virchowiana/complicações , Hanseníase Virchowiana/diagnóstico , Masculino , Doenças Nasais/etiologia , Rifampina/uso terapêutico
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