ABSTRACT
Schwann cells (SCs) critically maintain the plasticity of the peripheral nervous system. Peripheral nerve injuries and infections stimulate SCs in order to retrieve homeostasis in neural tissues. Previous studies indicate that Mycobacterium leprae (ML) regulates the expression of key factors related to SC identity, suggesting that alterations in cell phenotype may be involved in the pathogenesis of neural damage in leprosy. To better understand whether ML restricts the plasticity of peripheral nerves, the present study sought to determine the expression of Krox-20, Sox-10, c-Jun and p75NTR in SC culture and mice sciatic nerves, both infected by ML Thai-53 strain. Primary SC cultures were stimulated with two different multiplicities of infection (MOI 100:1; MOI 50:1) and assessed after 7 and 14 days. Sciatic nerves of nude mice (NU-Foxn1nu ) infected with ML were evaluated after 6 and 9 months. In vitro results demonstrate downregulation of Krox-20 and Sox-10 along with the increase in p75NTR-immunolabelled cells. Concurrently, sciatic nerves of infected mice showed a significant decrease in Krox-20 and increase in p75NTR. Our results corroborate previous findings on the interference of ML in the expression of factors involved in cell maturation, favouring the maintenance of a non-myelinating phenotype in SCs, with possible implications for the repair of adult peripheral nerves.
Subject(s)
Down-Regulation , Early Growth Response Protein 2/biosynthesis , Leprosy/metabolism , Schwann Cells/metabolism , Sciatic Nerve/metabolism , Animals , Cell Differentiation/physiology , Cells, Cultured , Disease Models, Animal , Leprosy/microbiology , Leprosy/pathology , Mice, Nude , Mycobacterium leprae/isolation & purification , Neuronal Plasticity/physiology , Receptors, Nerve Growth Factor/metabolism , Schwann Cells/microbiology , Schwann Cells/pathology , Sciatic Nerve/microbiology , Sciatic Nerve/pathology , Tissue Culture TechniquesABSTRACT
Schwann cells (SCs) critically maintain the plasticity of the peripheral nervous system. Peripheral nerve injuries and infections stimulate SCs in order to retrieve homeostasis in neural tissues. Previous studies indicate that Mycobacterium leprae (ML) regulates the expression of key factors related to SC identity, suggesting that alterations in cell phenotype may be involved in the pathogenesis of neural damage in leprosy. To better understand whether ML restricts the plasticity of peripheral nerves, the present study sought to determine the expression of Krox20, Sox10, cJun and p75NTR in SC culture and mice sciatic nerves, both infected by ML Thai53 strain. Primary SC cultures were stimulated with two different multiplicities of infection (MOI 100:1; MOI 50:1) and assessed after 7 and 14 days. Sciatic nerves of nude mice (NUFoxn1nu) infected with ML were evaluated after 6 and 9 months. In vitro results demonstrate downregulation of Krox20 and Sox10 along with the increase in p75NTRimmunolabelled cells. Concurrently, sciatic nerves of infected mice showed a significant decrease in Krox20 and increase in p75NTR. Our results corroborate previous findings on the interference of ML in the expression of factors involved in cell maturation, favouring the maintenance of a nonmyelinating phenotype in SCs, with possible implications for the repair of adult peripheral nerves(AU).
Subject(s)
Animals , Mice , Schwann Cells/microbiology , Leprosy/metabolism , Leprosy/microbiology , Mycobacterium leprae/isolation & purification , Peripheral Nerves/microbiology , Schwann Cells/metabolism , In Vitro Techniques , Down-Regulation , Receptors, Nerve Growth Factor/physiology , Early Growth Response Protein 2/biosynthesis , Neuronal Plasticity/physiologyABSTRACT
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).
Subject(s)
Anti-Bacterial Agents/therapeutic use , Leprosy/prevention & control , Post-Exposure Prophylaxis/methods , Clarithromycin/therapeutic use , Fluoroquinolones/therapeutic use , Humans , Leprosy/drug therapy , Leprosy/microbiology , Moxifloxacin , Netherlands , Rifampin/therapeutic useABSTRACT
O Metotrexato (MTX) é um dos principais fármacos para o tratamento da psoríase. Os efeitos adversos mais importantes são alterações hepáticas e hematológicas. Para tanto foram avaliados as informações registradas em 604 prontuários de portadores de psoríase em um hospital dermatológico da cidade de Bauru. O objetivo do estudo foi avaliar se a interrupção do tratamento com Metrotexato foi decorrentes das alterações laboratoriais das transaminases e exames hematológicos de rotina. A gamaglutamilpeptidase foi a mais alterada entre os pacientes, mas sem correlação significativa entre doses-cumulativas para hepatoxicidade e hematotoxicidade. Assim pode-se cogitar que o metotrexate apresentou um perfil toxicológico semelhante aos dados da literatura o pode justificar seu uso no tratamento da psoríase com aceitável margem de segurança nas doses empregadas para esta doença
Methotrexate (MTX) is one of the main drugs for the treatment of psoriasis. The adverse events have been related to liver, kidney and haematological impairment. Therefore were evaluated 604 medical records of these patients in a dermatological hospital at Bauru. The aim of this study was evaluate if the reason to interruption of therapy with methotrexate was indeed increase of transaminases and impairment haematological tests. The Gamaglutamiltranpeptidadse (-GT) was increased among the patients, however was no correlation between cumulative-doses to liver and haematological toxicity. This way can to say that methotrexate has toxicological profile like in the literature and this fact justify the use this drug in treatment of psoriasis
Subject(s)
Humans , Male , Female , Methotrexate/adverse effects , Psoriasis/drug therapy , Retrospective Studies , Methotrexate/pharmacology , Methotrexate/toxicity , Medical RecordsABSTRACT
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).
Subject(s)
Post-Exposure Prophylaxis , Leprosy/prevention & control , Leprosy/therapy , Communicable Disease Control , Leprosy/drug therapyABSTRACT
BACKGROUND: Mycobacterium peregrinum is a rapidly growing mycobacterium (RGM) that rarely causes skin infections. The correct identification of the specific RGM infecting the skin will enhance therapeutic success. OBJECTIVE: To highlight the importance of rapid and precise identification of the Mycobacterium involved in skin infections in order to enhance therapeutic success. METHODS: We describe an RGM skin infection in an immunocompetent patient. RESULTS: Classic methods (biochemical tests and culture) of RGM identification are time-consuming, and the histopathological features are not specific. Some molecular methods are reliable but expensive. The PRAhsp-65 is a simple procedure that is helpful in identifying the specific agent of an RGM. CONCLUSION: Although skin infections caused by M peregrinum are rare, they represent a substantial clinical challenge. Specific and more effective treatment options depend on the development of precise and rapid methods for identifying mycobacterial species.
Subject(s)
Humans , Female , Middle Aged , Skin Diseases, Bacterial/diagnosis , Skin Diseases, Bacterial/microbiology , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium Infections, Nontuberculous/microbiologyABSTRACT
Leishmaniose Tegumentar Americana (LTA) é uma doença infecciosa, causada por protozoários do gênero Leishmania. É uma das doenças infectoparasitárias mais incidentes no mundo. No presente trabalho realizou-se um estudo transversal retrospectivo das características clínicas, epidemiológicas e imunológicas de portadores de Leishmaniose Tegumentar Americana.Foram utilizados prontuários de 34 pacientes com diagnóstico de LTA. A análise estatística foi realizada pelo Teste de Spearman. O sexo masculino foi acometido em 68% e o feminino 32%. A idade variou de 1 a 92 anos. A forma cutânea localizada ocorreu em 79,5%,sendo as úlceras a forma clínica mais comum (56%).Principal área acometida foi face (44%). O tempo para o diagnóstico foi menor que 10 meses em 68% dos indivíduos.Intradermorreação de Montenegro (IDRM) foi realizada em 29 pacientes, com positividade em 89,6% e a imunofluorescência indireta (IFI) em apenas 16 pacientes, sendo positiva em 13. A idade e o tempode evolução da doença apresentaram associação significativa com IDRM. Entretanto não foi observada associação da IFI com a idade do paciente e o tempo de doença, pelo teste de Spearman. O tratamento foi realizado na maioria dos casos com glucantime (71%),seguido de pentamidina (17%). Os resultados evidenciam que os exames sorológicos constituem uma ferramenta auxiliar e a correlação com achados clínicos e histopatológicos são imprescindíveis.
Introduction: American cutaneous leishmaniasis (ACL) is an infectious disease caused by protozoa of the genus Leishmania. World leishmaniasis is an important endemic disease and public health problem in developing countries. Methods: We conducted a retrospective, descriptive and analytical cross-sectional study of 34 patients diagnosed with ACL. Statistical analysis was performed using the nonparametric Spearmans test. Results: The gender involved was male (68%) and female(32%); the age range of 1 to 92 years old. The most common clinical manifestations were localized cutaneous form (79.5%) and the ulcers (56%).The face was main affected area (44%) and the minor time from onset of symptoms to consultation was 10 months (68%) of patients. Montenegro skin test (MST) was performed in 29 patients, being positive in (89.6%) and the indirect immunofluorescence (IIF) in only 16 patients, being positive in 13. The age and the duration of the disease were significantly associated with MST. Conclusions: It was not observed the IFI association with the patients age and disease duration. The treatment was in most cases, meglumine antimoniate (71%), followed Pentamidine (17%). The results demonstrated thatthe serological tests constitute an auxiliary tool andthe correlations with clinical and histopathological findings are essential.
Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Middle Aged , Aged, 80 and over , Young Adult , Leishmaniasis, Cutaneous/diagnosis , Leishmaniasis, Cutaneous/epidemiology , Leishmaniasis, Cutaneous/immunology , Brazil/epidemiology , Retrospective Studies , Fluorescent Antibody Technique, IndirectABSTRACT
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.
Subject(s)
Antitubercular Agents/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Mycobacterium leprae/drug effects , Mycobacterium leprae/pathogenicity , Rifampin/therapeutic use , Animals , Atorvastatin , Cell Line , Drug Synergism , Heptanoic Acids/therapeutic use , Humans , Leprosy/drug therapy , Macrophages/microbiology , Mice , Mice, Inbred BALB C , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/pathogenicity , Pyrroles/therapeutic use , Simvastatin/therapeutic useABSTRACT
Leprosy, caused by Mycobacterium leprae, is an important infectious disease that is still endemic in many countries around the world, including Brazil. There are currently no known methods for growing M. leprae in vitro, presenting a major obstacle in the study of this pathogen in the laboratory. Therefore, the maintenance and growth of M. leprae strains are preferably performed in athymic nude mice (NU-Foxn1(nu)). The laboratory conditions for using mice are readily available, easy to perform, and allow standardization and development of protocols for achieving reproducible results. In the present report, we describe a simple protocol for purification of bacilli from nude mouse footpads using trypsin, which yields a suspension with minimum cell debris and with high bacterial viability index, as determined by fluorescent microscopy. A modification to the standard method for bacillary counting by Ziehl-Neelsen staining and light microscopy is also demonstrated. Additionally, we describe a protocol for freezing and thawing bacillary stocks as an alternative protocol for maintenance and storage of M. leprae strains.
Subject(s)
Bacteriological Techniques/methods , Mycobacterium leprae/cytology , Animals , Disease Models, Animal , Freezing , Leprosy/microbiology , Mice , Mice, Nude , Mycobacterium leprae/growth & development , Mycobacterium leprae/isolation & purification , SuspensionsABSTRACT
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.
Subject(s)
Leg Ulcer/psychology , Quality of Life , Aged , Anthropometry , Brazil , Chronic Disease , Cross-Sectional Studies , Depression/physiopathology , Diagnostic Self Evaluation , Female , Humans , Leg Ulcer/physiopathology , Male , Middle Aged , Pain Measurement , Psychiatric Status Rating Scales , Psychometrics , Severity of Illness Index , Sex Factors , Socioeconomic Factors , Surveys and QuestionnairesABSTRACT
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. .
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Leg Ulcer/psychology , Quality of Life , Anthropometry , Brazil , Chronic Disease , Cross-Sectional Studies , Depression/physiopathology , Diagnostic Self Evaluation , Leg Ulcer/physiopathology , Pain Measurement , Psychiatric Status Rating Scales , Psychometrics , Surveys and Questionnaires , Severity of Illness Index , Sex Factors , Socioeconomic FactorsABSTRACT
We synthesized a series of novel dapsone-thalidomide hybrids (3a-i) by molecular hybridization and evaluated their potential for the treatment of type 2 leprosy reactions. All of the compounds had analgesic properties. Compounds 3c and 3h were the most active antinociceptive compounds and reduced acetic acid-induced abdominal constrictions by 49.8% and 39.1%, respectively. The hybrid compounds also reduced tumor necrosis factor-α levels in lipopolysaccharide-stimulated L929 cells. Compound 3i was the most active compound; at concentrations of 15.62 and 125 µM, compound 3i decreased tumor necrosis factor-α levels by 86.33% and 87.80%, respectively. In nude mice infected with Mycobacterium leprae in vivo, compound 3i did not reduce the number of bacilli compared with controls. Compound 3i did not have mutagenic effects in Salmonella typhimurium strains TA100 and TA102, with or without metabolic activation (S9 mixture). Our results indicate that compound 3i is a novel lead compound for the treatment of type 2 leprosy reactions.
Subject(s)
Humans , Animals , Mice , Structure-Activity Relationship , Thalidomide/chemistry , Molecular Structure , Cell Line , Dapsone/pharmacology , Dapsone/chemistry , Dose-Response Relationship, Drug , Leprosy/drug therapy , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Mycobacterium leprae/drug effectsABSTRACT
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.
Subject(s)
Humans , Animals , Mice , Pyrroles/therapeutic use , Rifampin/therapeutic use , Cell Line , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Simvastatin/therapeutic use , Drug Synergism , Atorvastatin , Heptanoic Acids/therapeutic use , Leprosy/drug therapy , Macrophages/microbiology , Mice, Inbred BALB C , Mycobacterium leprae/drug effects , Mycobacterium leprae/pathogenicity , Mycobacterium tuberculosis/pathogenicity , Antitubercular Agents/therapeutic useABSTRACT
Leprosy, caused by Mycobacterium leprae, is an important infectious disease that is still endemic in many countries around the world, including Brazil. There are currently no known methods for growing M. leprae in vitro, presenting a major obstacle in the study of this pathogen in the laboratory. Therefore, the maintenance and growth of M. leprae strains are preferably performed in athymic nude mice (NU-Foxn1(nu)). The laboratory conditions for using mice are readily available, easy to perform, and allow standardization and development of protocols for achieving reproducible results. In the present report, we describe a simple protocol for purification of bacilli from nude mouse footpads using trypsin, which yields a suspension with minimum cell debris and with high bacterial viability index, as determined by fluorescent microscopy. A modification to the standard method for bacillary counting by Ziehl-Neelsen staining and light microscopy is also demonstrated. Additionally, we describe a protocol for freezing and thawing bacillary stocks as an alternative protocol for maintenance and storage of M. leprae strains.
Subject(s)
Animals , Mice , Suspensions , Bacteriological Techniques/methods , Disease Models, Animal , Freezing , Leprosy/microbiology , Mice , Mice, Nude , Mycobacterium leprae/isolation & purification , Mycobacterium leprae/cytology , Mycobacterium leprae/growth & developmentABSTRACT
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.
Subject(s)
Humans , Antimicrobial Cationic Peptides/urine , Cytokines/blood , Iron/metabolism , Leprosy, Multibacillary/blood , Leprosy, Multibacillary/urine , Anemia/microbiology , Case-Control Studies , Disease Progression , Fluorescent Antibody Technique , Homeopathy , Inflammation/microbiology , Leprosy, Multibacillary/complications , Polymerase Chain ReactionABSTRACT
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.
Subject(s)
Antimicrobial Cationic Peptides/urine , Cytokines/blood , Iron/metabolism , Leprosy, Multibacillary/blood , Leprosy, Multibacillary/urine , Anemia/microbiology , Case-Control Studies , Disease Progression , Fluorescent Antibody Technique , Hepcidins , Homeopathy , Humans , Inflammation/microbiology , Leprosy, Multibacillary/complications , Polymerase Chain ReactionABSTRACT
Introdução: Os procedimentos cosmiátricos têm aumentado, e com eles, a busca de analgesia eficiente e segura. Os anestésicos tópicos são opção às anestesias infiltrativas, devendo promover analgesia adequada e atuar na pele íntegra, sem induzir efeitos adversos.Objetivo: Comparar os escores de dor entre duas formulações tópicas de lidocaína, em pacientes submetidos à terapia com laser fracionado de CO2.Métodos: Oito pacientes foram submetidos a uma sessão de laser de CO2 fracionado, após a aplicação de formulação industrializada de lidocaína 4% na hemiface direita e formulação magistral de lidocaína 30% associada à tetracaina 7% na hemiface esquerda. A intensidade da dor foi avaliada através da escala visual analógica de dor (EVA) no final do procedimento.Resultados: Os anestésicos tópicos, nas formulações magistral e industrializada, não apresentaram diferença estatisticamente significativa na avaliação dos escores de dor. Conclusões: Os dados sugerem que fórmulas com grande concentração de anestésicos não são mais eficientes em produzir analgesia do que as formulações industrializadas.
