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1.
Infect Genet Evol ; 79: 104166, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31883457

RESUMO

The HTLV-1 is the first human retrovirus and is associated with several clinical syndromes, however, the pathogenesis of these clinical manifestations is still not fully understood. Furthermore, there are few complete genomes publicly available, about 0.12 complete genomes per 10,000 infected individuals and the databases have a major deficiency of sequences information. This study generated and characterized 31 HTLV-1 complete genomes sequences derived from individuals with Tropical Spastic Paraparesis/HTLV-1-Associated Myelopathy (TSP/HAM), Adult T-cell leukemia/lymphoma (ATL), infective dermatitis associated to HTLV-1 (IDH) and asymptomatic patients. These sequences are associated to clinical and epidemiological information about the patients. The sequencing data generated on Ion Torrent PGM platform were assembled and mapped against the reference HTLV-1 genome. These sequences were genotyped as Cosmopolitan subtype, Transcontinental subgroup. We identified the variants in the coding regions of the genome of the different clinical profiles, however, no statistical relation was detected. This study contributed to increase of HTLV-1 complete genomes in the world. Furthermore, to better investigate the contribution of HTLV-1 mutations for the disease outcome it is necessary to evaluate the interaction of the viral genome and characteristics of the human host.


Assuntos
Dermatite/virologia , Vírus Linfotrópico T Tipo 1 Humano/classificação , Leucemia-Linfoma de Células T do Adulto/virologia , Paraparesia Espástica Tropical/virologia , Sequenciamento Completo do Genoma/métodos , Adolescente , Adulto , Idoso , Criança , Feminino , Variação Genética , Tamanho do Genoma , Genoma Viral , Sequenciamento de Nucleotídeos em Larga Escala , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Adulto Jovem
2.
Rev Soc Bras Med Trop ; 52: e20180486, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31778419

RESUMO

INTRODUCTION: Bowel dysfunction is frequent in patients with spinal cord diseases, but little is known about the prevalence of bowel symptoms in human T-lymphotropic virus-(HTLV-1) infected individuals. The purpose of this study is to determine the frequency of bowel symptoms in HTLV-1 infected individuals and their correlation with the degree of neurologic disease. METHODS: This is a cross-sectional study comparing the frequency of bowel symptoms in HTLV-1-infected individuals* and seronegative donors (controls). Patients answered a questionnaire, the Rome III Criteria was applied, and stool consistency was evaluated by the Bristol Stool Form Scale. The individuals were classified as HTLV-1 carriers, probable HTLV-1 myelopathy and definitive HTLV-1 associated myelopathy or tropical spastic paraparesis (definitive HAM / TSP)**. RESULTS: We studied 72 HTLV-1 infected individuals and 72 controls with equal age and gender distribution. Constipation was the most frequent complaint, occurring in 38 % of HTLV-1 individuals and in 15 % of the controls. In comparison to the seronegative controls, the probability of constipation occurrence was approximately 18 times higher in definitive HAM / TSP patients. Straining, lumpy or hard stools, sensation of anorectal obstruction/blockage, fewer than 3 defecations per week, flatulence, soiling, evacuation pain, and bleeding were also more frequent in the HTLV-1 patients than in the controls. Moreover, bowel symptoms were more frequent in patients with definitive or probable HAM / TSP than in carriers. CONCLUSIONS: Bowel symptoms were more frequent in HTLV-1-infected patients than in seronegative controls and the frequency of bowel symptoms correlated with the severity of neurologic disease.


Assuntos
Infecções por HTLV-I/fisiopatologia , Intestinos/fisiopatologia , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Índice de Gravidade de Doença , Fatores Socioeconômicos
4.
Rev Soc Bras Med Trop ; 52: e20180481, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31166487

RESUMO

INTRODUCTION: Human T-cell lymphotropic virus type 1 (HTLV-1)-associated inflammatory diseases are not well understood; however, their clinical manifestations may be influenced by the host genetic background. METHODS: We genotyped 298 individuals with HTLV-1 and 380 controls for interleukin-10 (IL10) gene variants-rs3024496, rs1800871, rs1800896-and used logistic regression analysis to determine their association with clinical phenotypes. RESULTS: No association with HTLV-1 infection was observed. However, allele A of rs1800896 (1082bp upstream) was associated with protection against neurological impairment, specifically overactive bladder (OR=0.447, 95% CI 0.28-0.70, p=0.001). CONCLUSIONS: Our data suggests that IL10 regulation ameliorates neurological damage in HTLV-1 infections.


Assuntos
Infecções por HTLV-I/genética , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único/genética , Bexiga Urinária Hiperativa/genética , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Genótipo , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Bexiga Urinária Hiperativa/etiologia , Adulto Jovem
6.
Rev. Soc. Bras. Med. Trop ; 52: e20180486, 2019. tab
Artigo em Inglês | LILACS | ID: biblio-1057240

RESUMO

Abstract INTRODUCTION: Bowel dysfunction is frequent in patients with spinal cord diseases, but little is known about the prevalence of bowel symptoms in human T-lymphotropic virus-(HTLV-1) infected individuals. The purpose of this study is to determine the frequency of bowel symptoms in HTLV-1 infected individuals and their correlation with the degree of neurologic disease. METHODS: This is a cross-sectional study comparing the frequency of bowel symptoms in HTLV-1-infected individuals* and seronegative donors (controls). Patients answered a questionnaire, the Rome III Criteria was applied, and stool consistency was evaluated by the Bristol Stool Form Scale. The individuals were classified as HTLV-1 carriers, probable HTLV-1 myelopathy and definitive HTLV-1 associated myelopathy or tropical spastic paraparesis (definitive HAM / TSP)**. RESULTS: We studied 72 HTLV-1 infected individuals and 72 controls with equal age and gender distribution. Constipation was the most frequent complaint, occurring in 38 % of HTLV-1 individuals and in 15 % of the controls. In comparison to the seronegative controls, the probability of constipation occurrence was approximately 18 times higher in definitive HAM / TSP patients. Straining, lumpy or hard stools, sensation of anorectal obstruction/blockage, fewer than 3 defecations per week, flatulence, soiling, evacuation pain, and bleeding were also more frequent in the HTLV-1 patients than in the controls. Moreover, bowel symptoms were more frequent in patients with definitive or probable HAM / TSP than in carriers. CONCLUSIONS: Bowel symptoms were more frequent in HTLV-1-infected patients than in seronegative controls and the frequency of bowel symptoms correlated with the severity of neurologic disease.


Assuntos
Humanos , Masculino , Feminino , Adulto , Infecções por HTLV-I/fisiopatologia , Intestinos/fisiopatologia , Fatores Socioeconômicos , Índice de Gravidade de Doença , Estudos de Casos e Controles , Prevalência , Estudos Transversais , Pessoa de Meia-Idade
7.
Rev. Soc. Bras. Med. Trop ; 52: e20180481, 2019. tab
Artigo em Inglês | LILACS | ID: biblio-1041511

RESUMO

Abstract INTRODUCTION Human T-cell lymphotropic virus type 1 (HTLV-1)-associated inflammatory diseases are not well understood; however, their clinical manifestations may be influenced by the host genetic background. METHODS We genotyped 298 individuals with HTLV-1 and 380 controls for interleukin-10 (IL10) gene variants-rs3024496, rs1800871, rs1800896-and used logistic regression analysis to determine their association with clinical phenotypes. RESULTS No association with HTLV-1 infection was observed. However, allele A of rs1800896 (1082bp upstream) was associated with protection against neurological impairment, specifically overactive bladder (OR=0.447, 95% CI 0.28-0.70, p=0.001). CONCLUSIONS Our data suggests that IL10 regulation ameliorates neurological damage in HTLV-1 infections.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Adulto Jovem , Infecções por HTLV-I/genética , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único/genética , Bexiga Urinária Hiperativa/genética , Fenótipo , Vírus Linfotrópico T Tipo 1 Humano , Infecções por HTLV-I/complicações , Estudos de Casos e Controles , Bexiga Urinária Hiperativa/etiologia , Genótipo , Pessoa de Meia-Idade
8.
J Bras Pneumol ; 42(4): 241-247, 2016.
Artigo em Inglês, Português | MEDLINE | ID: mdl-27832230

RESUMO

OBJECTIVE:: To determine whether COPD severity correlates with sputum cell counts, atopy, and asthma. METHODS:: This was a cross-sectional study involving 37 patients with COPD and 22 healthy subjects with normal lung function (controls). Sputum cell counts were determined by microscopy after centrifugation of samples. Skin prick tests were performed, and serum cytokines were determined by ELISA. RESULTS:: Patients were stratified by bronchodilator response: a non-reversible airflow limitation (nonRAL) group comprised 24 patients showing no significant post-bronchodilator change in FEV1; and a partially reversible airflow limitation (partialRAL) group comprised 13 patients showing FEV1 reversibility (post-bronchodilator FEV1 increase ≥ 12%). The proportion of eosinophils in sputum was higher in the partialRAL group than in the nonRAL group (p < 0.01), and there was an inverse correlation between the proportion of eosinophils and FEV1 (p < 0.05). However, none of the patients had a history of asthma and skin prick test results did not differ between the two groups. In the patient sputum samples, neutrophils predominated. Serum levels of TNF, IL-6, IL-8, and RANTES (CCL5) were higher in patients than in controls (p < 0.001) but did not differ between the two patient groups. CONCLUSIONS:: COPD patients with partial FEV1 reversibility appear to have higher sputum eosinophil counts and greater airway hyperresponsiveness than do those with no FEV1 reversibility. However, we found that COPD severity did not correlate with atopy or with the cytokine profile. OBJETIVO:: Determinar se a gravidade da DPOC se correlaciona com a contagem de células no escarro, atopia e asma. MÉTODOS:: Estudo transversal com 37 pacientes com DPOC e 22 indivíduos saudáveis com função pulmonar normal (controles). As contagens de células no escarro foram determinadas por microscopia após a centrifugação das amostras. Foram realizados testes cutâneos de puntura, e as citocinas séricas foram determinadas por ELISA. RESULTADOS:: Os pacientes foram estratificados pela resposta ao broncodilatador: o grupo de limitação ao fluxo aéreo não reversível (LFAnr) envolveu 24 pacientes sem alteração significativa do VEF1 pós-broncodilatador, e o grupo de limitação ao fluxo aéreo parcialmente reversível (LFApr) envolveu 13 pacientes com reversibilidade do VEF1 (aumento do VEF1 pós-broncodilatador ≥ 12%). A proporção de eosinófilos no escarro foi maior no grupo LFApr do que no LFAnr (p < 0,01), e houve uma correlação inversa entre a proporção de eosinófilos e VEF1 (p < 0,05). Entretanto, nenhum dos pacientes apresentou histórico de asma e os resultados dos testes cutâneos não diferiram entre os dois grupos. Nas amostras de escarro dos pacientes, os neutrófilos predominaram. Os níveis séricos de TNF, IL-6, IL-8 e RANTES (CCL5) foram maiores nos pacientes que nos controles (p < 0,001), mas não diferiram entre os dois grupos de pacientes. CONCLUSÕES:: Pacientes com DPOC e reversibilidade parcial do VEF1 parecem apresentar maiores contagens de eosinófilos no escarro e maior hiper-responsividade das vias aéreas que aqueles sem reversibilidade do VEF1. Entretanto, a gravidade da DPOC não se correlacionou com atopia ou perfil das citocinas.


Assuntos
Asma/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Escarro , Idoso , Asma/fisiopatologia , Broncodilatadores/uso terapêutico , Estudos de Casos e Controles , Estudos Transversais , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Valores de Referência , Índice de Gravidade de Doença , Estatísticas não Paramétricas
9.
J. bras. pneumol ; 42(4): 241-247, July-Aug. 2016. tab, graf
Artigo em Inglês | LILACS | ID: lil-794720

RESUMO

ABSTRACT Objective: To determine whether COPD severity correlates with sputum cell counts, atopy, and asthma. Methods: This was a cross-sectional study involving 37 patients with COPD and 22 healthy subjects with normal lung function (controls). Sputum cell counts were determined by microscopy after centrifugation of samples. Skin prick tests were performed, and serum cytokines were determined by ELISA. Results: Patients were stratified by bronchodilator response: a non-reversible airflow limitation (nonRAL) group comprised 24 patients showing no significant post-bronchodilator change in FEV1; and a partially reversible airflow limitation (partialRAL) group comprised 13 patients showing FEV1 reversibility (post-bronchodilator FEV1 increase ≥ 12%). The proportion of eosinophils in sputum was higher in the partialRAL group than in the nonRAL group (p < 0.01), and there was an inverse correlation between the proportion of eosinophils and FEV1 (p < 0.05). However, none of the patients had a history of asthma and skin prick test results did not differ between the two groups. In the patient sputum samples, neutrophils predominated. Serum levels of TNF, IL-6, IL-8, and RANTES (CCL5) were higher in patients than in controls (p < 0.001) but did not differ between the two patient groups. Conclusions: COPD patients with partial FEV1 reversibility appear to have higher sputum eosinophil counts and greater airway hyperresponsiveness than do those with no FEV1 reversibility. However, we found that COPD severity did not correlate with atopy or with the cytokine profile.


RESUMO Objetivo: Determinar se a gravidade da DPOC se correlaciona com a contagem de células no escarro, atopia e asma. Métodos: Estudo transversal com 37 pacientes com DPOC e 22 indivíduos saudáveis com função pulmonar normal (controles). As contagens de células no escarro foram determinadas por microscopia após a centrifugação das amostras. Foram realizados testes cutâneos de puntura, e as citocinas séricas foram determinadas por ELISA. Resultados: Os pacientes foram estratificados pela resposta ao broncodilatador: o grupo de limitação ao fluxo aéreo não reversível (LFAnr) envolveu 24 pacientes sem alteração significativa do VEF1 pós-broncodilatador, e o grupo de limitação ao fluxo aéreo parcialmente reversível (LFApr) envolveu 13 pacientes com reversibilidade do VEF1 (aumento do VEF1 pós-broncodilatador ≥ 12%). A proporção de eosinófilos no escarro foi maior no grupo LFApr do que no LFAnr (p < 0,01), e houve uma correlação inversa entre a proporção de eosinófilos e VEF1 (p < 0,05). Entretanto, nenhum dos pacientes apresentou histórico de asma e os resultados dos testes cutâneos não diferiram entre os dois grupos. Nas amostras de escarro dos pacientes, os neutrófilos predominaram. Os níveis séricos de TNF, IL-6, IL-8 e RANTES (CCL5) foram maiores nos pacientes que nos controles (p < 0,001), mas não diferiram entre os dois grupos de pacientes. Conclusões: Pacientes com DPOC e reversibilidade parcial do VEF1 parecem apresentar maiores contagens de eosinófilos no escarro e maior hiper-responsividade das vias aéreas que aqueles sem reversibilidade do VEF1. Entretanto, a gravidade da DPOC não se correlacionou com atopia ou perfil das citocinas.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Asma/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Escarro , Asma/fisiopatologia , Broncodilatadores/uso terapêutico , Estudos de Casos e Controles , Estudos Transversais , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Volume Expiratório Forçado/fisiologia , Neutrófilos/imunologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Valores de Referência , Índice de Gravidade de Doença , Estatísticas não Paramétricas
10.
Parasit Vectors ; 9(1): 335, 2016 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-27286813

RESUMO

BACKGROUND: American tegumentary leishmaniasis (ATL) in Brazil is mostly caused by Leishmania (Viannia) braziliensis, with known forms of the disease being cutaneous (CL), mucosal (ML) and disseminated (DL) leishmaniasis. The development of the lesion in ATL is related both to the persistence of the Leishmania in the skin and to the parasite-triggered immune and inflammatory responses that ensue lesions. In this context one factor with expected role in the pathogenesis is insulin-like growth factor (IGF)-I with known effects on parasite growth and healing and inflammatory processes. In the present study, we addressed the effect of IGF-I on intracellular amastigote isolates from CL, ML and DL patients within human macrophage and we evaluated the IGF-I and IGF-binding protein-3 (IGFBP3) serum levels in patients presenting different clinical forms and controls from the endemic area. METHODS: We evaluated biological variability in the responses of intracellular amastigotes of Leishmania isolates derived from CL, ML, and DL patients from an area for ATL in response to IGF-I. Intracellular amastigote growth was evaluated using the human macrophage cell line THP-1. Arginase activity in infected cells was evaluated quantifying the generated urea concentration. Serum samples from patients and controls were assayed using chemiluminescent immunometric assay to determine IGF-I and IGFBP3 levels. RESULTS: We observed an increase in intracellular parasitism upon IGF-I stimulus in 62.5 % of isolates from CL, in 85.7 % from ML and only 42.8 % from DL cases. In DL, the basal arginase activity was lower than that of CL. We then evaluated the IGF-I and IGFBP3 serum levels in patients, and we observed significantly lower levels in ML and DL than in CL and control samples. CONCLUSIONS: The data suggest that IGF-I is modulated distinctly in different clinical forms of tegumentary leishmaniasis. IGF-I seemingly exerts effect on parasite growth likely contributing to its persistence in the skin in earlier phase. In addition the decreased IGF-I serum levels may affect the modulation of inflammation and lesion healing in chronic phase. In view of potential role of IGF-I in the pathogenesis of ATL we can speculate on therapeutic procedures taking into account the local IGF-I level.


Assuntos
Fator de Crescimento Insulin-Like I/metabolismo , Leishmania/efeitos dos fármacos , Leishmaniose Cutânea/parasitologia , Adulto , Idoso , Linhagem Celular , Feminino , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/imunologia , Fator de Crescimento Insulin-Like I/farmacologia , Leishmaniose Cutânea/imunologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
An Bras Dermatol ; 91(6): 743-747, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28099594

RESUMO

BACKGROUND:: Psoriasis is an immune-mediated disease that manifests predominantly in the skin, although systemic involvement may also occur. Although associated comorbidities have long been recognized and despite several studies indicating psoriasis as an independent risk factor for cardiovascular events, little has been done in general medical practice regardind screening. In the United States, less than 50% of clinicians are aware of these recommendations. OBJECTIVE:: To identify the prevalence of these comorbidities in 296 patients followed up at a university dermatology clinic. METHODS:: Systematically investigated comorbidity frequencies were compared with general practitioners' registry frequencies. Clinical features correlated with comorbidities were also investigated. RESULTS:: High prevalences of systematically investigated comorbidities such as hypertension (30%) and dyslipidemia (26.5%) were documented. Conversely, data from general practitioners' records showed that 33% of dyslipidemia cases were undiagnosed and indicated possible underdiagnosis of some comorbidities. Furthermore, an association was found between: the number of comorbidities and psoriasis duration, age and high body mass index an association was found between the number of comorbidities and psoriasis duration, age, high body mass index, waist circumference or waist-to-hip ratio. (p<0.05). CONCLUSION:: Disease duration, age and high body mass index, waist circumference or waist-to-hip ratio are possible criteria for choosing which patients should be screened for comorbidities. Underdiagnosis of comorbidities by general practitioners highlights the need for a multidisciplinary approach in psoriasis management.


Assuntos
Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Hipertensão/epidemiologia , Psoríase/epidemiologia , Adulto , Índice de Massa Corporal , Brasil/epidemiologia , Doenças Cardiovasculares/etiologia , Comorbidade , Estudos Transversais , Diabetes Mellitus/diagnóstico , Dislipidemias/diagnóstico , Feminino , Humanos , Hipertensão/diagnóstico , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , Fumar/efeitos adversos , Estatísticas não Paramétricas , Circunferência da Cintura
12.
Rev Soc Bras Med Trop ; 47(4): 528-32, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25229299

RESUMO

Urinary symptoms occur in 19% of human T-cell lymphotropic virus type 1 (HTLV-1)-infected patients who do not fulfill criteria for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and in almost 100% of HAM/TSP patients. Few studies have evaluated therapies for overactive bladder (OAB) caused by HTLV-1 infection. This case report describes the effect of onabotulinum toxin A on the urinary manifestations of three patients with HAM/TSP and OAB symptoms. The patients were intravesically administered 200 units of Botox®. Their incontinence episodes improved, and their OAB symptoms scores (OABSS) reduced significantly. These data indicate that Botox® should be a treatment option for OAB associated with HTLV-1 infection.


Assuntos
Inibidores da Liberação da Acetilcolina/uso terapêutico , Toxinas Botulínicas Tipo A/uso terapêutico , Paraparesia Espástica Tropical/complicações , Bexiga Urinária Hiperativa/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento , Bexiga Urinária Hiperativa/virologia , Adulto Jovem
13.
Mem. Inst. Oswaldo Cruz ; 109(3): 279-288, 06/2014. tab, graf
Artigo em Inglês | LILACS | ID: lil-711739

RESUMO

American cutaneous leishmaniasis (ACL) is a vector-transmitted infectious disease with an estimated 1.5 million new cases per year. In Brazil, ACL represents a significant public health problem, with approximately 30,000 new reported cases annually, representing an incidence of 18.5 cases per 100,000 inhabitants. Corte de Pedra is in a region endemic for ACL in the state of Bahia (BA), northeastern Brazil, with 500-1,300 patients treated annually. Over the last decade, population and family-based candidate gene studies were conducted in Corte de Pedra, founded on previous knowledge from studies on mice and humans. Notwithstanding limitations related to sample size and power, these studies contribute important genetic biomarkers that identify novel pathways of disease pathogenesis and possible new therapeutic targets. The present paper is a narrative review about ACL immunogenetics in BA, highlighting in particular the interacting roles of the wound healing gene FLI1 with interleukin-6 and genes SMAD2 and SMAD3 of the transforming growth factor beta signalling pathway. This research highlights the need for well-powered genetic and functional studies on Leishmania braziliensis infection as essential to define and validate the role of host genes in determining resistance/susceptibility regarding this disease.


Assuntos
Animais , Humanos , Camundongos , Doenças Endêmicas , Marcadores Genéticos/genética , Predisposição Genética para Doença/genética , Leishmaniose Cutânea/genética , Brasil/epidemiologia , Leishmaniose Cutânea/epidemiologia
14.
Mem Inst Oswaldo Cruz ; 109(3): 279-88, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24863979

RESUMO

American cutaneous leishmaniasis (ACL) is a vector-transmitted infectious disease with an estimated 1.5 million new cases per year. In Brazil, ACL represents a significant public health problem, with approximately 30,000 new reported cases annually, representing an incidence of 18.5 cases per 100,000 inhabitants. Corte de Pedra is in a region endemic for ACL in the state of Bahia (BA), northeastern Brazil, with 500-1,300 patients treated annually. Over the last decade, population and family-based candidate gene studies were conducted in Corte de Pedra, founded on previous knowledge from studies on mice and humans. Notwithstanding limitations related to sample size and power, these studies contribute important genetic biomarkers that identify novel pathways of disease pathogenesis and possible new therapeutic targets. The present paper is a narrative review about ACL immunogenetics in BA, highlighting in particular the interacting roles of the wound healing gene FLI1 with interleukin-6 and genes SMAD2 and SMAD3 of the transforming growth factor beta signalling pathway. This research highlights the need for well-powered genetic and functional studies on Leishmania braziliensis infection as essential to define and validate the role of host genes in determining resistance/susceptibility regarding this disease.


Assuntos
Doenças Endêmicas , Marcadores Genéticos/genética , Predisposição Genética para Doença/genética , Leishmaniose Cutânea/genética , Animais , Brasil/epidemiologia , Humanos , Leishmaniose Cutânea/epidemiologia , Camundongos
15.
Mem Inst Oswaldo Cruz ; 108(1): 18-22, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23440109

RESUMO

Disseminated leishmaniasis (DL) differs from other clinical forms of the disease due to the presence of many non-ulcerated lesions (papules and nodules) in non-contiguous areas of the body. We describe the histopathology of DL non-ulcerated lesions and the presence of CD4-, CD20-, CD68-, CD31- and von Willebrand factor (vW)-positive cells in the inflamed area. We analysed eighteen biopsies from non-ulcerated lesions and quantified the inflamed areas and the expression of CD4, CD20, CD68, CD31 and vW using Image-Pro software (Media Cybernetics). Diffuse lymphoplasmacytic perivascular infiltrates were found in dermal skin. Inflammation was observed in 3-73% of the total biopsy area and showed a significant linear correlation with the number of vW+ vessels. The most common cells were CD68+ macrophages, CD20+ B-cells and CD4+ T-cells. A significant linear correlation between CD4+ and CD20+ cells and the size of the inflamed area was also found. Our findings show chronic inflammation in all DL non-ulcerated lesions predominantly formed by macrophages, plasmacytes and T and B-cells. As the inflamed area expanded, the number of granulomas and extent of the vascular framework increased. Thus, we demonstrate that vessels may have an important role in the clinical evolution of DL lesions.


Assuntos
Inflamação/imunologia , Leishmaniose Cutânea/imunologia , Adolescente , Adulto , Antígenos CD/imunologia , Antígenos CD20/imunologia , Antígenos de Diferenciação Mielomonocítica/imunologia , Linfócitos B/imunologia , Linfócitos B/patologia , Biópsia , Linfócitos T CD4-Positivos/imunologia , Criança , Pré-Escolar , Doença Crônica , Progressão da Doença , Feminino , Humanos , Inflamação/patologia , Leishmaniose Cutânea/patologia , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Fator de von Willebrand/imunologia
16.
Mem. Inst. Oswaldo Cruz ; 108(1): 18-22, Feb. 2013. ilus, graf, tab
Artigo em Inglês | LILACS | ID: lil-666038

RESUMO

Disseminated leishmaniasis (DL) differs from other clinical forms of the disease due to the presence of many non-ulcerated lesions (papules and nodules) in non-contiguous areas of the body. We describe the histopathology of DL non-ulcerated lesions and the presence of CD4-, CD20-, CD68-, CD31- and von Willebrand factor (vW)-positive cells in the inflamed area. We analysed eighteen biopsies from non-ulcerated lesions and quantified the inflamed areas and the expression of CD4, CD20, CD68, CD31 and vW using Image-Pro software (Media Cybernetics). Diffuse lymphoplasmacytic perivascular infiltrates were found in dermal skin. Inflammation was observed in 3-73% of the total biopsy area and showed a significant linear correlation with the number of vW+ vessels. The most common cells were CD68+ macrophages, CD20+ B-cells and CD4+ T-cells. A significant linear correlation between CD4+ and CD20+ cells and the size of the inflamed area was also found. Our findings show chronic inflammation in all DL non-ulcerated lesions predominantly formed by macrophages, plasmacytes and T and B-cells. As the inflamed area expanded, the number of granulomas and extent of the vascular framework increased. Thus, we demonstrate that vessels may have an important role in the clinical evolution of DL lesions.


Assuntos
Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Inflamação/imunologia , Leishmaniose Cutânea/imunologia , Antígenos CD/imunologia , /imunologia , Antígenos de Diferenciação Mielomonocítica/imunologia , Linfócitos B/imunologia , Linfócitos B/patologia , Biópsia , /imunologia , Doença Crônica , Progressão da Doença , Inflamação/patologia , Leishmaniose Cutânea/patologia , Macrófagos/imunologia , Macrófagos/patologia , Fator de von Willebrand/imunologia
17.
Rev Soc Bras Med Trop ; 45(5): 545-52, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23152334

RESUMO

The human T lymphotropic virus type-1 (HTLV-1) was the first human retrovirus identified. The virus is transmitted through sexual intercourse, blood transfusion, sharing of contaminated needles or syringes and from mother to child, mainly through breastfeeding. In addition to the well-known association between HTLV-1 and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), several diseases and neurologic manifestations have been associated with the virus. This review was conducted through a PubMed search of the terms HTLV-1, immune response and neurological diseases. Emphasis was given to the most recent data regarding pathogenesis and clinical manifestations of HTLV-1 infection. The aim of the review is to analyze the immune response and the variety of neurological manifestations associated to HTLV-1 infection. A total of 102 articles were reviewed. The literature shows that a large percentage of HTLV-1 infected individuals have others neurological symptoms than HAM/TSP. Increased understanding of these numerous others clinical manifestations associated to the virus than adult T cell leukemia/lymphoma (ATLL) and HAM/TSP has challenged the view that HTLV-1 is a low morbidity infection.


Assuntos
Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Paraparesia Espástica Tropical/imunologia , Infecções por HTLV-I/imunologia , Humanos , Paraparesia Espástica Tropical/complicações
18.
Rev. Soc. Bras. Med. Trop ; 45(5): 545-552, Sept.-Oct. 2012. ilus, tab
Artigo em Inglês | LILACS | ID: lil-656206

RESUMO

The human T lymphotropic virus type-1 (HTLV-1) was the first human retrovirus identified. The virus is transmitted through sexual intercourse, blood transfusion, sharing of contaminated needles or syringes and from mother to child, mainly through breastfeeding. In addition to the well-known association between HTLV-1 and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), several diseases and neurologic manifestations have been associated with the virus. This review was conducted through a PubMed search of the terms HTLV-1, immune response and neurological diseases. Emphasis was given to the most recent data regarding pathogenesis and clinical manifestations of HTLV-1 infection. The aim of the review is to analyze the immune response and the variety of neurological manifestations associated to HTLV-1 infection. A total of 102 articles were reviewed. The literature shows that a large percentage of HTLV-1 infected individuals have others neurological symptoms than HAM/TSP. Increased understanding of these numerous others clinical manifestations associated to the virus than adult T cell leukemia/lymphoma (ATLL) and HAM/TSP has challenged the view that HTLV-1 is a low morbidity infection.


O vírus linfotrópico de células T humanas do tipo 1 (HTLV-1) foi o primeiro retrovírus humano identificado. O vírus é transmitido via relação sexual, transfusão de sangue, compartilhamento de agulhas ou seringas contaminadas ou da mãe para o filho, principalmente através da amamentação. Além da conhecida associação entre o HTLV-1 e a mielopatia associada ao HTLV-1 (HAM/TSP), várias doenças e manifestações neurológicas tem sido associadas com o vírus. Esta revisão de literatura foi conduzida através de pesquisa ao banco de dados do PubMed, com os termos HTLV-1, resposta imune e doenças neurológicas. Foram enfatizados os dados mais recentes sobre a patogênese e às manifestações clínicas na infecção pelo HTLV-1. O objetivo dessa revisão é analisar a resposta imune e a variedade de manifestações neurológicas associadas com a infecção pelo HTLV-1. Um total de 102 artigos foi analisado. A literatura mostra que grande porcentagem de indivíduos infectados pelo HTLV-1 apresenta sintomas neurológicos mesmo na ausência de HAM/TSP. Uma maior compreensão das várias manifestações clínicas associadas ao vírus, além da leucemia/linfoma de células T do adulto (ATLL) e HAM/TSP, auxilia a estabelecer que, na realidade, a infecção pelo vírus possui uma morbidade maior do que se pensava.


Assuntos
Humanos , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Paraparesia Espástica Tropical/imunologia , Infecções por HTLV-I/imunologia , Paraparesia Espástica Tropical/complicações
20.
Rev. bras. reumatol ; 46(5): 315-322, set.-out. 2006. graf, tab
Artigo em Português | LILACS | ID: lil-442417

RESUMO

INTRODUÇÃO: o HTLV-1 é um retrovírus humano associado à leucemia de células T do adulto e à mielopatia associada ao HTLV-1 ou paraparesia espástica tropical, que tem sido implicado também no desenvolvimento de auto-imunidade. OBJETIVO: o objetivo deste estudo foi determinar a freqüência de doenças reumáticas auto-imunes em pacientes infectados pelo HTLV-1. PACIENTES E MÉTODOS: foram incluídos nesse estudo 137 indivíduos infectados pelo HTLV-1 atendidos no Ambulatório Multidisciplinar do Serviço de Imunologia do Hospital Universitário Professor Edgard Santos (HUPES) da Universidade Federal da Bahia (UFBA), no período de janeiro de 2003 a maio de 2004. Os pacientes responderam a um questionário geral relacionado a manifestações reumatológicas e questionários específicos para confirmação dos critérios diagnósticos de artrite reumatóide (AR), lúpus eritematoso sistêmico (LES), síndrome de Sjõgren e polimiosite. Adicionalmente, todos eles foram submetidos a exames clínicos específicos e avaliação complementar. RESUTADOS: 24 pacientes tiveram o diagnóstico de síndrome de Sjõgren (SS) provável (17,5 por cento), 18 pacientes (13,1 por cento) de AR, uma paciente teve diagnóstico de LES e uma de doença mista do tecido conjuntivo (0,7 por cento, respectivamente). Suspeita de artropatia relacionada ao vírus foi encontrada em 22 pacientes (16,1 por cento). Síndrome de Sjõgren e AR foram mais freqüentes nos pacientes com mielopatia (33,3 e 25,9 por cento, respectivamente) do que nos portadores assintomáticos (13,6 e 10 por cento, respectivamente). Artropatia relacionada ao HTLV-1 ocorreu com freqüência semelhante em ambos os grupos. CONCLUSÃO: foi observado neste trabalho alta prevalência de síndrome de Sjõgren e de AR entre os indivíduos infectados pelo HTLV-1, principalmente naqueles com mielopatia. Diante desses resultados, que reforçam os dados da literatura, deve-se estar atento para a ocorrência de doenças reumáticas auto-imunes nesses pacientes.


INTRODUCTION: the HTLV-1 is a human retrovirus associated with adult T-cell leukaemia (ATL) and with HTLV-1- associated myelopathy or tropical spastic paraparesis, which has also been implicated in the development of autoimmunity. OBJECTIVE: the aim of this study was to determine the frequency of autoimmune rheumatic diseases in patients infected with HTLV-1. PATIENTS AND METHODS: it was included 137 individuals infected with HTLV-1 from the Multidisciplinary Ambulatory of Immunology Service, HUPES-UFBA, Salvador (BA), from January 2003 to May 2004. All participants answered to a general questionnaire regarding rheumathological manifestations and specific questionnaires to confirm the diagnose criteria of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), SjõgrenÆs syndrome (SS) and polymyositis. Additionally, they were submitted to specific clinical exams, besides complementary evaluations. RESULTS: 24 patients had diagnose of probable SjõgrenÆs syndrome (17.5 percent), 18 patients (13.1 percent) had RA, one patient had diagnose of SLE (0.7 percent) and another of mixed connective tissue disease (0.7 percent, respectively). HTLV-1-associated arthropathy (HAAP) was suspected in 22 individuals (16.1 percent). SjõgrenÆs syndrome and RA were more frequent in patients with myelopathy (33.3 and 25.9 percent, respectively) than in asymptomatic carriers (13.6 and 10 percent, respectively). The frequency of HTLV-1-associated arthropathy was the same in both groups. CONCLUSION: in this study it was observed a high frequency of SjõgrenÆs syndrome and RA in individuals infected with HTLV-1, mainly in those with myelopathy. Therefore, with this results that support data in the literature, we should call attention to the occurrence of autoimmune rheumatic diseases in these kind of patients.

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