14 research outputs found
Increased hepcidin expression in multibacillary leprosy
Iron is essential for all organisms and its availability can control the growth of microorganisms; therefore, we examined the role of iron metabolism in multibacillary (MB) leprosy, focusing on the involvement of hepcidin. Erythrograms, iron metabolism parameters, pro-inflammatory cytokines and urinary hepcidin levels were evaluated in patients with MB and matched control subjects. Hepcidin expression in MB lesions was evaluated by quantitative polymerase chain reaction. The expression of ferroportin and hepcidin was evaluated by immunofluorescence in paucibacillary and MB lesions. Analysis of hepcidin protein levels in urine and of hepcidin mRNA and protein levels in leprosy lesions and skin biopsies from healthy control subjects showed elevated hepcidin levels in MB patients. Decreases in haematologic parameters and total iron binding capacity were observed in patients with MB leprosy. Moreover, interleukin-1 beta, ferritin, soluble transferrin receptor and soluble transferrin receptor/log ferritin index values were increased in leprosy patients. Hepcidin was elevated in lepromatous lesions, whereas ferroportin was more abundant in tuberculoid lesions. In addition, hepcidin and ferroportin were not colocalised in the biopsies from leprosy lesions. Anaemia was not commonly observed in patients with MB; however, the observed changes in haematologic parameters indicating altered iron metabolism appeared to result from a mixture of anaemia of inflammation and iron deficiency. Thus, iron sequestration inside host cells might play a role in leprosy by providing an optimal environment for the bacillus.CNPq [401012/2005-0]CNPqFundacao Paulista contra a HanseniaseFundacao Paulista contra a Hanseniase [095
An enhanced regimen as post-exposure chemoprophylaxis for leprosy:PEP+
The ongoing transmission of Mycobacterium (M.) leprae reflected in a very slow decline in leprosy incidence, forces us to be innovative and conduct cutting-edge research. Single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for contacts of leprosy patients, reduces their risk to develop leprosy by 60%. This is a promising new preventive measure that can be integrated into routine leprosy control programmes, as is being demonstrated in the Leprosy Post-Exposure Programme that is currently ongoing in eight countries.The limited (60%) effectiveness of SDR is likely due to the fact that some contacts have a preclinical infection beyond the early stages for which SDR is not sufficient to prevent the development of clinical signs and symptoms of leprosy. An enhanced regimen, more potent against a higher load of leprosy bacteria, would increase the effectiveness of this preventive measure significantly.The Netherlands Leprosy Relief (NLR) is developing a multi-country study aiming to show that breaking the chain of transmission of M. leprae is possible, evidenced by a dramatic reduction in incidence. In this study the assessment of the effectiveness of an enhanced prophylactic regimen for leprosy is an important component. To define the so called PEP++ regimen for this intervention study, NLR convened an Expert Meeting that was attended by clinical leprologists, public health experts, pharmacologists, dermatologists and microbiologists.The Expert Meeting advised on combinations of available drugs, with known efficacy against leprosy, as well as on the duration of the intake, aiming at a risk reduction of 80-90%. To come to a conclusion the Expert Meeting considered the bactericidal, sterilising and bacteriostatic activity of the potential drugs. The criteria used to determine an optimal enhanced regimen were: effectiveness, safety, acceptability, availability, affordability, feasibility and not inducing drug resistance.The Expert Meeting concluded that the enhanced regimen for the PEP++ study should comprise three standard doses of rifampicin 600 mg (weight adjusted when given to children) plus moxifloxacin 400 mg given at four-weekly intervals. For children and for adults with contraindications for moxifloxacin, moxifloxacin should be replaced by clarithromycin 300 mg (weight adjusted)
Quality of life profile and correlated factors in chronic leg ulcer patients in the mid-west of São Paulo State, Brazil
BACKGROUND: Chronic leg ulcer may have an impact on patients' quality of life.OBJECTIVES:This study aimed to identify the impact of leg ulcers on patient's quality of life using the Dermatology Life Quality Index and to define the main factors correlated with this perception.METHOD:Cross-sectional, non-probabilistic sampling study. We included patients with chronic leg ulcers being treated for at least 3 months. A sociodemographic and clinical survey was conducted to assess the profile of the ulcers. We administered a screening for depressive symptoms and the Dermatology Life Quality Index. We performed a descriptive statistical analysis, chi-square test and Mann-Whitney test for categorical data, Pearson for numeric variables, and multiple regression for categorical data.RESULTS:Forty-one patients were assessed. Their mean age was 61.78 years. Venous ulcers (48.8%) were the most prevalent. Seventy-three percent of the sample perceived no impact/low impact on quality of life in the past week, and 26.8% perceived moderate/high impact. A multiple regression analysis identified the causes of lesion, pain related to the ulcers, time of onset, and severity of the depressive symptoms as the variables that had an influence on quality of life.CONCLUSIONS:The majority of the sample perceived low or no impact of the condition on the quality of the life. The variables etiology of the lesion (p<0.001), pain related to the ulcers (p=0.001), time of onset (p=0.006), and severity of the depressive symptoms (p<0.001) had an influence on the quality of life, suggesting the need for further studies with more robust designs to confirm the causal relationship between these characteristics and quality of life
Optimized Protocols for <em>Mycobacterium leprae</em> Strain Management: Frozen Stock Preservation and Maintenance in Athymic Nude Mice
An enhanced regimen as post-exposure chemoprophylaxis for leprosy: PEP+
The ongoing transmission of Mycobacterium (M.) leprae reflected in a very slow decline in leprosy incidence, forces us to be innovative and conduct cutting-edge research. Single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for contacts of leprosy patients, reduces their risk to develop leprosy by 60%. This is a promising new preventive measure that can be integrated into routine leprosy control programmes, as is being demonstrated in the Leprosy Post-Exposure Programme that is currently ongoing in eight countries.The limited (60%) effectiveness of SDR is likely due to the fact that some contacts have a preclinical infection beyond the early stages for which SDR is not sufficient to prevent the development of clinical signs and symptoms of leprosy. An enhanced regimen, more potent against a higher load of leprosy bacteria, would increase the effectiveness of this preventive measure significantly.The Netherlands Leprosy Relief (NLR) is developing a multi-country study aiming to show that breaking the chain of transmission of M. leprae is possible, evidenced by a dramatic reduction in incidence. In this study the assessment of the effectiveness of an enhanced prophylactic regimen for leprosy is an important component. To define the so called PEP++ regimen for this intervention study, NLR convened an Expert Meeting that was attended by clinical leprologists, public health experts, pharmacologists, dermatologists and microbiologists.The Expert Meeting advised on combinations of available drugs, with known efficacy against leprosy, as well as on the duration of the intake, aiming at a risk reduction of 80-90%. To come to a conclusion the Expert Meeting considered the bactericidal, sterilising and bacteriostatic activity of the potential drugs. The criteria used to determine an optimal enhanced regimen were: effectiveness, safety, acceptability, availability, affordability, feasibility and not inducing drug resistance.The Expert Meeting concluded that the enhanced regimen for the PEP++ study should comprise three standard doses of rifampicin 600 mg (weight adjusted when given to children) plus moxifloxacin 400 mg given at four-weekly intervals. For children and for adults with contraindications for moxifloxacin, moxifloxacin should be replaced by clarithromycin 300 mg (weight adjusted)
Statins Increase Rifampin Mycobactericidal Effect
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Previous issue date: 2014Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.Instituto Lauro de Souza Lima. Departamento de Biologia. Bauru, SP, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Professor Paulo de Góes. Laboratório de Microbactérias. Rio de Janeiro, RJ, Brasil.Instituto Lauro de Souza Lima. Departamento de Biologia. Bauru, SP, Brasil.Instituto Lauro de Souza Lima. Departamento de Biologia. Bauru, SP, Brasil.Instituto Lauro de Souza Lima. Departamento de Biologia. Bauru, SP, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.Instituto Lauro de Souza Lima. Departamento de Biologia. Bauru, SP, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chgas. Centro de Pesquisa Clínica em HIV/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.niversidade Federal do Rio de Janeiro. Instituto de Microbiologia Professor Paulo de Góes. Laboratório de Microbactérias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.Mycobacterium leprae and Mycobacterium tuberculosis antimicrobial resistance has been followed with great concern during
the last years, while the need for new drugs able to control leprosy and tuberculosis, mainly due to extensively drug-resistant
tuberculosis (XDR-TB), is pressing. Our group recently showed that M. leprae is able to induce lipid body biogenesis and cholesterol
accumulation in macrophages and Schwann cells, facilitating its viability and replication. Considering these previous results,
we investigated the efficacies of two statins on the intracellular viability of mycobacteria within the macrophage, as well as
the effect of atorvastatin on M. leprae infections in BALB/c mice. We observed that intracellular mycobacteria viability decreased
markedly after incubation with both statins, but atorvastatin showed the best inhibitory effect when combined with rifampin.
Using Shepard’s model, we observed with atorvastatin an efficacy in controlling M. leprae and inflammatory infiltrate in
the BALB/c footpad, in a serum cholesterol level-dependent way. We conclude that statins contribute to macrophage-bactericidal
activity against Mycobacterium bovis, M. leprae, and M. tuberculosis. It is likely that the association of statins with the actual
multidrug therapy effectively reduces mycobacterial viability and tissue lesion in leprosy and tuberculosis patients, although
epidemiological studies are still needed for confirmation