Onabotulinumtoxin type A improves lower urinary tract symptoms and quality of life in patients with human T cell lymphotropic virus type 1 associated overactive bladder

ABSTRACT Aim: To evaluate the efficacy of the onabotulinum toxin type A in the treatment of HTLV-1 associated overactive bladder and its impact on quality of life (QoL). Methods: Case series with 10 patients with overactive bladder refractory to conservative treatment with anticholinergic or physical therapy. They received 200Ui of onabotulinumtoxin type A intravesically and were evaluated by overactive bladder symptoms score (OABSS) and King's Health Questionnaire. Results: The mean (SD) of the age was 52 + 14.5 years and 60% were female. All of them had confirmed detrusor overactivity on urodynamic study. Seven patients had HAM/TSP. The median and range of the OABSS was 13 (12-15) before therapy and decreased to 1.0 (0-12) on day 30 and to 03 (0-14) on day 90 (p < 0.0001). There was a significant improvement in 8 of the 9 domains of the King's Health Questionnaire after the intervention. Hematuria, urinary retention and urinary infection were the complications observed in 3 out of 10 patients. The mean time to request retreatment was 465 days. Conclusion: Onabotulinum toxin type A intravesically reduced the OABSS with last long effect and improved the quality of life of HTLV-1 infected patients with severe overactive bladder.

The microbiological signature of human cutaneous leishmaniasis lesions exhibits restricted bacterial diversity compared to healthy skin

Localised cutaneous leishmaniasis (LCL) is the most common form of cutaneous leishmaniasis characterised by single or multiple painless chronic ulcers, which commonly presents with secondary bacterial infection. Previous culture-based studies have found staphylococci, streptococci, and opportunistic pathogenic bacteria in LCL lesions, but there have been no comparisons to normal skin. In addition, this approach has strong bias for determining bacterial composition. The present study tested the hypothesis that bacterial communities in LCL lesions differ from those found on healthy skin (HS). Using a high throughput amplicon sequencing approach, which allows for better populational evaluation due to greater depth coverage and the Quantitative Insights Into Microbial Ecology pipeline, we compared the microbiological signature of LCL lesions with that of contralateral HS from the same individuals.Streptococcus, Staphylococcus,Fusobacterium and other strict or facultative anaerobic bacteria composed the LCL microbiome. Aerobic and facultative anaerobic bacteria found in HS, including environmental bacteria, were significantly decreased in LCL lesions (p < 0.01). This paper presents the first comprehensive microbiome identification from LCL lesions with next generation sequence methodology and shows a marked reduction of bacterial diversity in the lesions.

Association between urinary symptoms and quality of life in HTLV-1 infected subjects without myelopathy

Objective To investigate the relationship between urinary symptoms and quality of life of patients infected with HTLV-1. Materials and Methods This is a cross-sectional study that enrolled individuals with HTLV-1 positive serology from February 2010 to March 2011. Participants were HTLV-1 infected subjects followed in the HTLV-1 clinic of the University Hospital in Salvador, Bahia, Brazil. Patients with HTLV-1 associated myelopathy / tropical spastic paraparesis (HAM/TSP), who had evidence of other neurological diseases, diabetes mellitus or were pregnant were excluded from the study. The questionnaire SF-36 was used to evaluate quality of life and the questionnaire OAB-V8 was used to evaluate urinary symptoms. Results From the 118 individuals evaluated, 50 (42.4%) complained of urinary symptoms and 68 (57.6%) did not. Most participants were females. There was no difference between the groups regarding demographic variables. The group with symptoms showed significantly lower scores in all domains of the SF-36 questionnaire. The domains with greatest differences were vitality and general health state. Conclusions Urinary symptoms negatively influence the quality of life of individuals infected with HTLV-1. .

Citocinas pró-inflamatórias em pacientes com dor neuropática submetidos a tratamento com Tramadol / Proinflammatory cytokines in patients with neuropathic pain treated with Tramadol / Interleucinas proinflamatorias en pacientes con dolor neuropático sometidos a tratamiento con Tramadol

JUSTIFICATIVA E OBJETIVOS: As citocinas pró-inflamatórias têm função importante na fisiopatologia das síndromes dolorosas neuropáticas. O objetivo desse estudo foi avaliar os níveis plasmáticos de citocinas pró-inflamatórias antes e após o tratamentocom tramadol em pacientes com hérnia discal e síndrome do túnel do carpo e compará-los com indivíduos normais.MÉTODO: Investigou-se 38 pacientes com dor neuropática por hérnia discal ou síndrome do túnel do carpo. Todos os pacientes foram tratados com tramadol de liberação controlada (100 mg em 12h) durante 10 dias. Realizaram-se coletas de sangue venoso (5 mL), no período matutino, antes do tratamento e no 11º dia e as amostras foram armazenadas até análise (-70ºC). Foram utilizados testes enzimáticos ELISA para dosagem de citocinas plasmáticas (TNF-α, IL-1, IL-6) e receptores sTNF-R1, (R & D Systems). Realizou-se dosagem de citocinas em soro de 10 voluntários sadios. RESULTADOS: A concentração de TNF-α antes (5,8 ± 2,8 pg.mL-1) foi significativamente maior que após o tramadol (4,8 ± 2,1 pg.mL-1; p = 0,04, Teste Mann-Whitney). Não houve diferença significativa de IL-1β, IL-6 e sTNF-R1 antes e após o tratamento. As concentrações plasmáticas de TNF-α (sadios: 1,4 ± 0,5; pacientes com dor: 5,8 ± 2,8 pg.mL-1; p = 0.01) e IL-6 (sadios: 1,2 ± 0,8; pacientes com dor: 3,5 ± 2,6 pg.mL-1; p = 0,01) foram significativamente maiores nos pacientes com dor neuropática que nos voluntários, Teste de Mann-Whitney. CONCLUSÕES: Nos pacientes com hérnia discal e síndrome do túnel do carpo as concentrações plasmáticas de TNF-α e IL-6 foram maiores que em voluntários sadios, não havendo diferença das concentrações de sTNF-R e IL-1β. Houve redução da concentraçãoplasmática de TNF-α após tratamento com tramadol (100 mg em 12h), mas não de IL-6, sTNF-R e IL-1β.

BACKGROUND AND METHODS: Proinflammatory cytokines play an important role in the pathophysiology of neuropathic pain syndromes. The objective of this study was to evaluate plasma levels of proinflammatory cytokines before and after treatment with tramadol in patients with herniated intervertebral disks and carpal tunnel syndrome, and to compare them with normal individuals. METHODS: Thirty-eight patients with neuropathic pain secondary to herniated intervertebral disks or carpal tunnel syndrome participated in this study. All patients were treated with controlled release tramadol (100 mg every 12 hours) for 10 days. Venous blood (5 mL) was collected in the morning, before treatment and on the 11th day, and stored (-70º C) until analysis. ELISA was used to determine the plasma levels of cytokines (TNF-α, IL-1, IL-6) andreceptors sTNF-R1 (R & D Systems). Plasma levels of cytokines of 10 healthy volunteers were also determined. RESULTS: The concentration of TNF-α before (5.8 ± 2.8 pg.mL-1) was significantly higher than after treatment with tramadol (4.8 ± 2.1 pg.mL-1; p = 0.04, Mann-Whitney test). The levels of IL-1β, IL-6, and sTNF-R1 before and after treatment with tramadol showed nosignificant differences. Plasma levels of TNF-α (healthy individuals: 1.4 ± 0.5; pain patients: 5.8 ± 2.8 pg.mL-1; p = 0.01) and IL-6 (healthy individuals: 1.2 ± 0.8; pain patients: 3.5 ± 2.6 pg.mL-1; p = 0.01) were significantly higher in patients with neuropathic pain, Mann-Whitney Test. CONCLUSIONS: In patients with herniated intervertebral disks and carpal tunnel syndrome, plasma levels of TNF-α and IL-6 werehigher than in healthy volunteers, while differences in the concentrations of sTNF-R and IL-1β were not observed. Plasma levels of TNF-α, but not of IL-6, sTNF-R, and IL-1β, decreased after treatment with tramadol (100 mg every 12 hours).

JUSTIFICATIVA Y OBJETIVOS: Las interleucinas proinflamatorias tienen una función importante en la fisiopatología de los síndromes dolorosos neuropáticos. El objetivo de este estudio, fue evaluar los niveles plasmáticos de interleucinas proinflamatorias antes y después del tratamiento con tramadol en pacientes con hernia de disco y síndromedel túnel del carpo, y compararlos con individuos normales. MÉTODO: Se investigaron 38 pacientes con dolor neuropático por hernia de disco o síndrome del túnel del carpo. Todos los pacientes fueron tratados con tramadol de liberación controlada (100 mg en 12h) durante 10 días. Se realizaron muestras de sangre venosa (5 mL), por la mañana, antes del tratamiento y en el 11º día, y las mismas se almacenaron para ser analizadas (-70ºC). Se utilizaron test enzimáticos ELISA para la dosificación de las interleucinas plasmáticas (TNF-α, IL-1, IL-6) y receptores sTNFR1, (R & D Systems). Se realizó la dosificación de interleucinasen suero de 10 voluntarios sanos. RESULTADOS: La concentración de TNF-α antes (5,8 ± 2,8 pg.mL-1) fue significativamente mayor que después del tramadol (4,8 ± 2,1 pg.mL-1; p = 0,04, Test de Mann-Whitney). No hubo diferencia significativa de IL-1β, IL-6 y sTNF-R1 antes y después del tratamiento. Las concentraciones plasmáticas de TNF-α (sanos: 1,4 ± 0,5; pacientes con dolor: 5,8 ± 2,8 pg.mL-1; p = 0.01) y IL-6 (sanos: 1,2 ± 0,8; pacientes con dolor: 3.5 ± 2,6 pg.mL-1; p = 0,01) fueron significativamente mayores en los pacientes con dolor neuropático que en los voluntarios, test de Mann-Whitney. CONCLUSIONES: En los pacientes con hernia discal y síndrome del túnel del carpo, las concentraciones plasmáticas de TNF-α yIL-6, fueron más elevadas que en los voluntarios sanos, no habiendo ninguna diferencia en las concentraciones de sTNF-R y IL-1β...

Leishmaniose mucosa: aspectos clínicos e epidemiológicos: [revisão] / Mucosal leishmaniasis: epidemiological and clinical aspects: [review]

A leishmaniose tem sido documentada em diversos países, sendo estimada uma prevalência mundial de 12 milhões, com 400.000 casos novos de doença por ano. A leishmaniose tegumentar americana encontra-se situada entre as grandes endemias existentes no Brasil e na América Latina. OBJETIVO: O objetivo deste estudo é complementar o conhecimento sobre leishmaniose mucosa, apresentando a experiência dos Serviços de Imunologia e de Otorrinolaringologia do Hospital Universitário Professor Edgar Santos da Universidade Federal da Bahia. COMENTÁRIOS: A leishmaniose cutânea é a forma mais comum de leishmaniose tegumentar americana, contudo, concomitantemente ou após anos de doença cutânea podem ocorrer lesões mucosas. A leishmaniose mucosa é causada principalmente pela L. braziliensis braziliensis e, apesar de a mucosa nasal ser a área principalmente acometida, lesões podem também ser documentadas nos lábios, boca, na faringe e na laringe. Fatores do parasito, bem como da resposta imune do hospedeiro podem estar envolvidos na patogênese da lesão tissular na leishmaniose mucosa.

Leishmaniasis has been documented in several countries, with an estimated prevalence of 12 million people and an incidence at around 400,000 new cases per year. Leishmaniasis in the New World is one the major endemic diseases in Brazil and Latin America. OBJECTIVE: The aim of this study was to add to the current knowdlegde on mucosal leishmaniasis, bringing the experience of the Imunology and Otolaryngology Departments in the Professor Edgar Santos University Hospital of the Federal University of Bahia. CONCLUSION: Cutaneous leishmaniasis is the most common form of New World Leishmaniasis; mucosal legions may occur simultaneously or after years of disease. Mucosal leishmaniasis is caused mainly by L. braziliensis braziliensis; although the nasal mucosa is the most affected area, lesions may be found on the lips, mouth, pharynx and larynx. In addition to parasite-related factors, the host immune response may be involved in the pathogenicity of lesions in mucosal leishmaniasis.

Urodynamic features of the voiding dysfunction in HTLV-1 infected individuals

OBJECTIVE:To describe urodynamic abnormalities in HTLV-1 infected individuals presenting urinary symptoms and verify if these findings and quality of life (QOL) evaluation correlate with overall neurological impairment. MATERIALS AND METHODS: From January/2001 to May/2004, 324 HTLV-1 seropositive subjects were evaluated to determine the occurrence of urinary symptoms. Urodynamic testing was performed in those who complained of frequency, urgency, or incontinence. They went through a complete clinical, neurological, and urological examination to investigate symptoms and signs of myelopathy. Neurological disability was assessed by Expanded Disability Status Scale (EDSS). RESULTS: From the 324 patients evaluated, 78 underwent the urodynamic testing. Fifty-seven individuals were females (73.1 percent) and age ranged from 23 to 76 years (mean = 48.7 years; SD ± 11.6). Urodynamic testing was abnormal in 63 patients (80.8 percent). The major abnormality was detrusor overactivity (DO), observed in 33 individuals (33/63; 52.4 percent), followed by detrusor-external sphincter dyssynergia (DESD), diagnosed in 15 subjects (15/63; 25.4 percent). HAM/TSP patients had significantly more DESD than the HTLV-I carriers (p = 0.005; OR = 5.5; CI: 1.6 to 19.4). QOL was severely compromised in HAM/TSP patients. CONCLUSIONS: Prominent urodynamic abnormalities were identified in individuals genuinely considered as HTLV-I carriers, suggesting an early compromise of the urinary tract; whereas HAM/TSP patients presented urodynamic findings, which posed a potential risk to the upper urinary tract (dyssynergia). Urodynamic evaluation should be performed in all HTLV-I-infected individuals with voiding complaints.

Urinary and sexual manifestations of patients infected by HTLV-I

HTLV-I is considered to be a virus of low morbidity, since the principal diseases associated with this viral infection, HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL), are observed in less than 5 percent of infected individuals. Urinary symptoms are frequent in patients with myelopathy and consist principally of nocturia, frequency, urgency, and urinary incontinence; however, the importance of these dysfunctions and their correlation with myelopathy is still to be fully clarified. This review gives particular emphasis to the high frequency of urinary and sexual complaints not only in patients with myelopathy but also in individuals considered to be HTLV-I carriers. Detrusor overactivity and bladder-sphincter dyssynergia are the most common urodynamic findings. The fact that urinary complaints and urodynamic parameters reported in individuals considered to be carriers are similar to those detected in patients with myelopathy supports the hypothesis that urinary disorders may represent an oligosymptomatic form of HAM/TSP. Erectile dysfunction is frequently observed in HTLV-I-infected patients with or without myelopathy. Urinary tract infections are also highly prevalent in these patients. Despite the lack of an effective treatment for myelopathy, the use of anticholinergic drugs and phosphodiesterase type 5 (PDE5) inhibitors may improve urinary complaints and erectile dysfunction in these patients.

O HTLV-1 é considerado um vírus de baixa morbidade sendo a mielopatia associada ao HTLV-1 (HAM/TSP) e a leucemia / linfoma de células T do adulto (ATL) as principais doenças associadas à infecção viral, observados em menos de 5 por cento dos indivíduos infectados. Manifestações urinárias são freqüentes em pacientes com mielopatia, e representadas principalmente por noctúria, polaciúria, urgência e incontinência urinária, embora a importância destas alterações, e a correlação com a patologia medular não tem sido devidamente estudada. Nesta revisão enfatizamos a elevada freqüência de queixas urinárias e sexuais em pacientes, não apenas os portadores de mielopatias, mas também em indivíduos considerados como portadores assintomáticos do HTLV-I. Hiperatividade detrusora e dissinergia vesico-esfincteriana são as manifestações urodinâmicas mais freqüentes. A documentação de queixas urinárias e os achados urodinâmicos observados em indivíduos considerados portadores assintomáticos são semelhantes aos detectados em pacientes com mielopatia dão suporte à hipótese que alterações urinárias possam representar uma forma oligossintomática da HAM/TSP. Disfunção eréctil é freqüentemente observada em pacientes infectados pelo HTLV-1, com ou sem mielopatia. Infecção do trato urinário também tem elevada prevalência nestes pacientes. A despeito da ausência de um tratamento efetivo da mielopatia, o uso de anticolinérgicos e de inibidores da fosfodiesterase tipo 5 podem melhorar as queixas urinárias e a disfunção eréctil destes pacientes.

Schistosoma mansoni antigen-driven interleukin-10 production in infected asthmatic individuals

Asthmatics infected with Schistosoma mansoni have a less severe course of asthma and an inhibition of the Th2 inflammatory response that seems to be mediated by interleukin (IL-10). The objective of this study was to evaluate the capacity of some S. mansoni antigens to stimulate IL-10 production in vitro by cells of asthmatic infected individuals. Peripheral bloods mononuclear cells were stimulated with the S. mansoni recombinant antigens Sm22.6, Sm14, P24, and PIII antigen. IL-10 was measured in the supernatants of cultures. As the recombinant antigens were cloned in Escherichia coli, we blocked contaminant endotoxin with polymyxin B added to the cultures. We demonstrated that all antigens used drove high production of IL-10 in S. mansoni infected individuals (n = 13, 408 ± 514 and 401 ± 383 pg/ml, 484 ± 245 pg/ml, 579 ± 468 pg/ml, respectively). In asthmatics infected with S. mansoni (n = 21) rP24 induced higher levels of IL-10 (565 ± 377 pg/ml) when compared to PIII, rSm14 and rSm22.6 (184 ± 209 pg/ml; 292 ± 243 pg/ml; 156 ± 247 pg/ml, respectively). Conclusion: the S. mansoni antigens evaluated in this study stimulated IL-10 production by cells from infected individuals and therefore they have the potential to be used as a modulator of the inflammatory response in asthma.

Associação do anticorpo anticitrulina e gravidade da artrite reumatóide / Association of anti-cyclic citrullinated peptide antibody and severe rheumatoid arthritis

OBJETIVOS: Avaliar a associação do anticorpo antipeptídeo citrulinado cíclico (anti-CCP) com distintos parâmetros clínicos, sorológicos e radiológicos. MÉTODOS: Anti-CCP e fator reumatóide (FR) foram pesquisados no soro de 100 pacientes com artrite reumatóide (AR). A atividade da doença foi definida por meio de um índice combinado compreendendo cinco parâmetros: número de juntas inflamadas, número de juntas doloridas, rigidez matinal, escala visual analógica (EVA) de dor e velocidade de hemossedimentação (VHS). A capacidade funcional foi medida pelo índice HAQ (Health Assessment Questionnaire) e a classe funcional foi determinada mediante aplicação dos critérios revisados do American College of Rheumatology (ACR), de 1991. Erosão e pinçamento articular foram graduados pelo índice de Sharp modificado. A análise estatística empregou os testes do Qui-quadrado, Mann Whitney e Kruskal-Wallis. RESULTADOS: Nenhum dos dois anticorpos demonstrou associação significativa com atividade da doença, sexo, idade de início da doença, presença de nódulos subcutâneos e síndrome de Sjõgren. A média de idade foi significativamente menor nos pacientes com AR anti-CCP positivos. A positividade para o FR e anti-CCP foi maior nos pacientes com AR com menos de 50 anos em comparação com os pacientes com mais de 50 anos. A AR de início recente (< 2 anos) não se associou a uma maior prevalência de soropositividade para o anti-CCP e FR. O anti-CCP apresentou uma correlação positiva moderada com o FR. Houve uma correlação direta entre o anti-CCP e a VHS e a proteína C reativa (PCR). Houve também uma correlação direta entre o FR, a VHS e a PCR. A classificação funcional dos critérios revisados do ACR de 1991 não se associou a qualquer dos dois auto-anticorpos. O índice de HAQ não se correlacionou com a atividade da doença, duração da doença, positividade do FR e atividade medida pela PCR, mas associou-se nitidamente à positividade do anti-CCP e à atividade medida pelo...

OBJECTIVE: Evaluate the association of Anti-Cyclic Citrullinated Peptide Antibody (anti-CCP) with distinct clinic, serological and radiological parameters. METHODS: anti-CCP and rheumatoid factor (RF) were determined in the serum of 100 patients with rheumatoid arthritis (RA). Disease activity was defined by means of a combined index with five parameters: number of swollen joints, number of painful joints, morning stiffness, pain visual analogue scale (VAS), and erythrocyte sedimentation rate (ESR). Functional capacity was measured by (Health Assessment Questionnaire) HAQ index and the functional class was ascribed according to American College of Rheumatology criteria (1991). Articular erosion and narrowing were estimated by the modified Sharp's index. Statistical analysis was performed by chi-square, Mann-Whitney, and Kruskal-Wallis tests. A value of less 0.05 was considered significant. RESULTS: None of the two antibodies showed association with disease flare, gender, age in the time of diagnosis, secondary Sjõgren's syndrome or subcutaneous nodules. The mean age was significantly lower in RA patients with positive anti-CCP. The RF and anti-CCP positivity was higher in RA patients below 50 years old than patients above 50 years old. The early RA, up to 2 years of evolution, was not associated with a higher prevalence of anti-CCP and RF reactivity. Anti-CCP showed direct moderate correlation to RF and also direct correlation to ESR and CRP. FR reactivity showed direct correlation to ESR and CRP. Functional class showed no association with neither autoantibodies. HAQ index showed correlation with anti-CCP-positive patients and activity assessed by ESR, but did not show association with disease activity, disease duration, presence of the RF and activity assessed by ESR. Sharp's erosion and narrowing index showed association to presence of anti-CCP, but not with RF positive patients. CONCLUSIONS: Although anti-CCP displays good diagnosis...

Valor diagnóstico do anticorpo antipeptídeo citrulinado cíclico na artrite reumatóide / Diagnostic value of anti-cyclic citrullinated peptide antibody in rheumatoid arthritis

INTRODUÇÃO: a artrite reumatóide (AR) é considerada uma das doenças auto-imunes mais freqüentes, mas um teste viável e específico para seu diagnóstico não está disponível. OBJETIVOS: avaliar a eficiência diagnóstica de um novo teste comercial realizado pela técnica de ELISA (Immunoscan RA; EuroDiagnostica), que detecta o anticorpo antipeptídeo citrulinado cíclico (anti-CCP), para o diagnóstico da AR. MÉTODOS: anticorpo anti-CCP e fator reumatóide (FR) foram pesquisados no soro de 486 pacientes: 100 pacientes com AR e 386 controles, incluindo indivíduos normais, pacientes com outras doenças reumáticas e não-reumáticas, bem como pacientes com doenças infecciosas. Avaliação comparativa do desempenho diagnóstico dos testes foi feita mediante cálculo dos diversos índices diagnósticos e da curva ROC (receiver operator characteristic). A análise estatística foi feita utilizando os testes do qui-quadrado, exato de Fisher e Mann-Whitney. RESULTADOS: ao ponto de corte de 25 UI/ml, o anti-CCP apresentou sensibilidade de 68 por cento (IC 95 por cento, 57,8-76,8 por cento), especificidade de 97,7 por cento (IC 95 por cento, 95,5-98,8 por cento), valor preditivo positivo (VPP) de 88,3 por cento (IC 95 por cento, 78,5-94,2 por cento), valor preditivo negativo (VPN) de 92,2 por cento (IC 95 por cento, 89-94,5 por cento) e razão de verossimilhança (RV) de 29,2 por cento (IC 95 por cento, 15,1-56,4 por cento). Os pacientes com AR anti-CCP positivos apresentavam titulação média igual a 920,7 UI/ml (variação, 70,5- 2000 UI/ml). Pacientes não-reumatóides anti-CCP positivos apresentavam titulação média de 38,7 UI/ml (variação, 29,5-47,4 UI/ml). O desempenho do anti-CCP, avaliado através da curva ROC, foi superior ao do FR. O FR apresentou uma sensibilidade maior (91 por cento) e uma especificidade menor (78,8 por cento) do que o anti-CCP. Quando os dois anticorpos foram usados em conjunto, a especificidade foi de 99,5 por cento. CONCLUSÃO: o anti-CCP foi o...

INTRODUCTION: Rheumatoid arthritis (RA) is one of the most common autoimmune rheumatic diseases, but a specific and reproducible test for its diagnosis is still lacking. OBJECTIVES: To evaluate the diagnostic efficiency of a new commercial ELISA kit in detecting anti-cyclic citrullinated peptide antibodies (anti-CCP) for the diagnosis of RA. METHODS: Anti-CCP antibodies and rheumatoid factor (RF) were determined in the serum of 486 patients: 100 patients with RA and 386 controls, including healthy subjects, patients with other non-rheumatic and rheumatic disease, as well as patients with infections disease. Comparative evaluation of diagnostic performance of anti-CCP and RF was done by calculation the several diagnostic indexes and construction of the ROC (receiver operator characteristic) curve. Statistical analysis included chi-square, Fisher exact, and Mann-Whitney's test. RESULTS: At cutoff of 25 UI/ml, anti-CCP showed sensitivity of 68 percent (95 percent CI, 57,8-76,8 percent), specificity of 97,7 percent (95 percent CI, 95,5-98,8 percent), positive predictive value (VPP) of 88,3 percent (95 percent CI, 78,5-94,2 percent), negative predictive value (VPN) of 92,2 percent (95 percent CI, 89-94,5 percent) and likelihood ratios (LR) of 29,2 percent (95 percent CI, 15,1-56,4 percent). Anti-CCP-positive RA patients had a mean antibody concentration of 920,7 UI/ml (range, 70,5-2000 UI/ml). Anti-CCP-positive non-RA patients had a mean antibody concentration of 38,7 UI/ml (range, 29,5-47, 4 UI/ml). The diagnostic performance of anti-CCP, as estimated by the ROC curve, was superior to that of RF. RF had a higher sensitivity (91 percent) and a lower specificity (78,8 percent) than anti-CCP. When the two antibodies were used together, specificity was 99,5 percent. CONCLUSION: The anti-CCP testing presented the best diagnostic performance for RA and was the most specific test. It may be useful if performance concomitantly with RF in the diagnostic...

Association of cytokines, neurological disability, and disease duration in HAM/TSP patients

OBEJETIVO: Identificar marcadores clínicos e imunológicos associados com a mielopatia associada ao HTLV-I/paraparesia espástica tropical (MAH/PET). MÉTODO: 237 indivíduos infectados pelo HTLV-I foram clinicamente avaliados. Eles foram classificados de acordo com a escala expandida do estado de incapacidade de Kurtzke (EDSS) e escala de incapacidade motora de Osame (OMDS). Níveis de citocinas foram determinados nos indivíduos. RESULTADOS: 37 pacientes tinham MAH/PET. Houve correlação entre os graus de incapacidade pelas escalas. Houve também correlação entre a duração da MAH/PET e o grau da incapacidade pelas escalas. Níveis elevados de IFN-g foram detectados em células mononucleares de sangue periférico (CMSP) não estimuladas de pacientes com MAH/PET quando comparados com indivíduos HTLV-I positivos assintomáticos. CONCLUSÃO: Os dados demonstram a validade das escalas neurológicas para classificar o grau de incapacidade neurológica em portadores do HTLV-I e sugerem o comportamento progressivo da MAH/PET. Este estudo também demonstra que os níveis de IFN-g em sobrenadante de CMSP são marcadores da MAH/PET.

Spontaneous neutrophil activation in HTLV-1 infected patients

Human T cell lymphotropic Virus type-1 (HTLV-1) induces lymphocyte activation and proliferation, but little is known about the innate immune response due to HTLV-1 infection. We evaluated the percentage of neutrophils that metabolize Nitroblue tetrazolium (NBT) to formazan in HTLV-1 infected subjects and the association between neutrophil activation and IFN-gamma and TNF-alpha levels. Blood was collected from 35 HTLV-1 carriers, from 8 patients with HAM/TSP (HTLV-1- associated myelopathy); 22 healthy individuals were evaluated for spontaneous and lipopolysaccharide (LPS)-stimulated neutrophil activity (reduction of NBT to formazan). The production of IFN-gamma and TNF-alpha by unstimulated mononuclear cells was determined by ELISA. Spontaneous NBT levels, as well as spontaneous IFN-gamma and TNF-alpha production, were significantly higher (p<0.001) in HTLV-1 infected subjects than in healthy individuals. A trend towards a positive correlation was noted, with increasing percentage of NBT positive neutrophils and levels of IFN-gamma. The high IFN-gamma producing HTLV-1 patient group had significantly greater NBT than healthy controls, 43±24 percent and 17±4.8 percent respectively (p< 0.001), while no significant difference was observed between healthy controls and the low IFN-gamma-producing HTLV-1 patient group (30±20 percent). Spontaneous neutrophil activation is another marker of immune perturbation resulting from HTLV-1 infection. In vivo activation of neutrophils observed in HTLV-1 infected subjects is likely to be the same process that causes spontaneous IFN-gamma production, or it may partially result from direct IFN-gamma stimulation.

Mecanismos de resposta imune às infecções / Immune response mechanisms to infections

O conhecimento dos principais mecanismos de defesa imune contra os diversos agentes infecciosos permite a compreensão da patogênese das doenças infectoparasitárias e das várias estratégias do hospedeiro e do parasita. O sistema imunológico atua numa rede de cooperação, envolvendo a participação de muitos componentes estruturais, moleculares e celulares. Nesse cenário encontra-se o delicado equilíbrio entre a saúde e a doença, em que tanto a deficiência quanto o exagero resultam em dano tecidual. Este artigo explora esses aspectos e algumas abordagens terapêuticas que surgem desse entendimento.

Cytokine profile associated with human chronic schistosomiasis mansoni

This study objective was to evaluate the cytokines associated with early events of hepatic fibrosis in schistosomiasis mansoni. Hepatic fibrosis was classified by ultrasonography in 94 patients. Immunological evaluation was performed by measurement of secreted cytokines (interleukin IL-5, IL-10, IL-13, interferon-gamma, tumor necrosis factor-alpha and transforming growth factors-beta) in peripherl blood mononuclear cells stimulated by Schistosoma mansoni antigens. Significantly, higher levels of IL-5, IL-10 and IL-13 were found in supernatants of SEA-stimulated PBMC from subjects with degree III hepatic fibrosis as compared to patients with degree I or II fibrosis, Significant increases in IL-5 and IL-13 levels were also observed in some of the subjects who remained untreated for one year following initial assessment and developed more serious fibrosis during this period. The data suggests a role for type 2 cytokines in early stages of hepatic fibrosis in human schistosomiasis mansoni.

Schistosoma mansoni infection modulates the immune response against allergic and auto-immune diseases

Chronic Schistosoma mansoni infection leads to a type 2-immune response with increased production of interleukin (IL-10). Evidence indicates chronic exposure to S. mansoni down regulates the type 1 immune response and prevents the onset of Th1-mediated diseases such as multiple sclerosis, diabetes mellitus and Cronh's disease. Furthermore, our own studies have revealed that chronic exposure to S. mansoni also down regulates atopic disease, Th2-mediated diseases. Our studies show an inverse association between the skin prick test reactivity and infection with S. mansoni and show the severity of asthma is reduced in subjects living in an endemic area of S. mansoni. Moreover, we hypothesize the mechanisms involved in the modulation of inflammatory response in atopic individuals, is likely dependent on IL-10 production, an anti-inflammatory cytokine elevated during helminth infections. Patients with asthma and helminth infections produced less IL-5 than patients with asthma without helminth infections, and this down regulation could, in part, be mediated by IL-10. In conclusion, helminthic infections, through induction of regulatory mechanisms, such as IL-10 production, are able to modulate the inflammatory immune response involved in the pathology of auto-immune and allergic disease.

Clinical and immunological consequences of human T cell leukemia virus type-I and Schistosoma mansoni co-infection

Human T cell leukemia virus type-I (HTLV-I) infection is associated with spontaneous T cell activation and uncontrolled lymphocyte proliferation. An exacerbated type-1 immune response with production of pro-inflammatory cytokines (interferon-gamma and tumor necrosis factor-alpha) is significantly higher in patients with myelopathy associated to HTLV-I than in HTLV-I asymptomatic carriers. In contrast with HTLV-I, a chronic Schistosoma mansoni infection is associated with a type-2 immune response with high levels of interleukin (IL-4, IL-5, and IL-10) and low levels of IFN-gamma. In this study, clinical and immunological consequences of the HTLV-I and S. mansoni infection were evaluated. The immune response in patients with schistosomiasis co-infected with HTLV-I showed low levels of IL-5 (p < 0.05) in peripheral blood mononuclear cells cultures stimulated with S. mansoni antigen (SWAP) and decreased SWAP-specific IgE levels when compared with patients with only schistosomiasis (p < 0.05). Liver fibrosis was mild in all HTLV-I co-infected patients. Immunological response was also compared in individuals who had only HTLV-I infection with those who were co-infected with HTLV-I and helminths (S. mansoni and Strongyloides stercoralis). In patients HTLV-I positive co-infected with helminths the IFN-gamma levels were lower than in individuals who had only HTLV-I. Moreover, there were fewer cells expressing IFN-gamma and more cells expressing IL-10 in individuals co-infected with HTLV-I and helminths. These dates indicate that HTLV-I infection decrease type 2-response and IgE synthesis and are inversely associated with the development of liver fibrosis. Moreover, helminths may protect HTLV-I infected patients to produce large quantities of pro-inflammatory cytokines such as IFN-gamma.

Avaliaçäo da resposta imune celular em pacientes com candidíase recorrente / Evaluation of cellular immune response in patients with recurrent candidiasis

A candidíase recorrente cutânea ou mucosa é caracterizada pela ocorrência de, no mínimo, 4 episódios de candidíase no período de um ano. Näo säo conhecidos os fatores que levam à recorrência desta infecçäo. O presente estudo avaliou a resposta linfoproliferativa e a produçäo de IFN-g de pacientes com candidíase recorrente. Os índices de estimulaçäo da resposta linfoproliferativa em culturas de células de pacientes com candidíase recorrente estimuladas com antígeno de Candida albicans, PPD e TT foram respectivamente de 6±8, 17±20 e 65±30. A adiçäo de anticorpo monoclonal anti-IL-10 às culturas de células de 6 pacientes aumentou a resposta linfoproliferativa de 735±415 para 4143±1746 cpm. A produçäo de IFN-g em culturas de células estimuladas com antígeno de Candida, foi 162±345pg/ml. Pacientes com candidíase recorrente apresentam uma deficiência na resposta linfoproliferativa e na produçäo de IFN-g, podendo a resposta imune celular ao antígeno de Candida ser restaurada parcialmente através da neutralizaçäo da IL-10 in vitro

Imunopatogênese da infecção pelo HTLV-1: influência sobre a resposta imune tipo 2 / Immunopathogenesis of HTLV-1 infection: influence upon type 2 immune response

Objetivo: Revisar a imunopatogênese da infecçãopelo HTLV-1 e sua influência sobre a modulação daresposta imune tipo 2.Métodos: A revisão foi feita a partir de estudosidentificados em base de dados MedLine e Lilacs noperíodo de 1980 a 2003.Resultados: O HTLV-1 é um retrovírus que altera funcionalmente células importantes do sistema imunológico. A resposta imune antiviral e suas conseqüências moduladoras são reguladas principalmente através do gene viral tax. O HTLV-1 tem tropismo por linfócitos T CD4+ e CD8+, promove a proliferação espontânea destas células e elevada produção de IFN. Na infecção pelo HTLV-1, a polarização Th1 da resposta imune reduz a produção de IL4, IgE e a reatividade cutânea imediata. As doenças alérgicas e parasitárias caracterizam-se por manifestações imunológicas predominantemente do tipo 2 com elevação de IL4 e ativação de mastócitos e eosinófilos. Indivíduos infectados com o vírus HTLV-1 por apresentarem forte resposta imune do tipo 1 são mais susceptíveis a infestações por helmintos mas podem atenuar as manifestações alérgicas. Conclusão: A resposta imune contra o HTLV-1 com elevada produção de IFNé ineficaz para a eliminação do vírus, mas promove alteração suficiente para supressão da resposta imune tipo 2.Rev. bras. alerg. imunopatol. 2003; 26(4):159-167retrovírus, alergia, citocinas, modulação Th1/Th2.

Eficácia dos antidepressivos para dor crônica / Effectiveness of antidepressants for chronic pain

Há evidências de que os antidepressivos tricíclicos säo eficazes para dor neuropática. Entretanto,os efeitos colaterais limitam seu uso. Os inibidores seletivos da recaptaçäo de serotonina e os atípicos causam menos efeitos colaterais. Para avaliar o efeito analgésico dessas medicaçöes foi feita pesquisa (Medline, Cinhah, ,PsycLIT and Cochrane Library) de estudos em lingua inglesa de 1966 a 2000. As medicaçöes avaliadas foram : trazodona, nefazodona, paroxetina, citalopram, sertralina, fluoxetina e venlafaxina. Os estudos säo insuficientes para estabeleceer eficácia dos antidepressivos ISRS e atípicos para alívio da dor.(au)