Assuntos
Produtos Biológicos/efeitos adversos , Leishmania/isolamento & purificação , Leishmaniose/diagnóstico , Programas de Rastreamento/métodos , Psoríase/tratamento farmacológico , Anticorpos Antiprotozoários/isolamento & purificação , Brasil/epidemiologia , Estudos Transversais , DNA de Protozoário/isolamento & purificação , Doenças Endêmicas/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Leishmania/genética , Leishmania/imunologia , Leishmaniose/epidemiologia , Leishmaniose/imunologia , Leishmaniose/parasitologia , Programas de Rastreamento/estatística & dados numéricos , Psoríase/imunologia , Medição de RiscoRESUMO
OBJECTIVES: Superficial swab sampling of American tegumentary leishmaniasis (ATL) lesions shows higher amounts of Leishmania than those from biopsy. Subcutaneous involvement is also important in ATL, but parasite quantification according to lesion depth has not been evaluated. We aim to present the best depth at which sampling should be performed for molecular exams of ATL. METHODS: Patients with a clinical presentation compatible with ATL were allocated to ATL and control groups. Qualitative and quantitative qPCR assays were performed using SYBR Green and primers amplifying the kDNA minicircle of Leishmania spp. in different skin layers, including the epidermis, the superior dermis, the inferior dermis, and the hypodermis. RESULTS: Fifty-nine patients were included in this study, including 40 who had been diagnosed with ATL and 19 controls. The number of parasites was greater in samples of the epidermis and superior dermis (159.1 × 106, range 4.0-781.7, and 75.4 × 106, range 8.0-244.5, mean Leishmania parasite equivalents per µg of tissue DNA, respectively) than those in samples of the inferior dermis and hypodermis (54.6, range 8.0-256.6, and 16.8 × 106, range 8.0-24.1, mean Leishmania parasite equivalents per µg of tissue DNA, respectively). The best diagnostic accuracy was achieved in the superior dermis (77.9%) and was significantly greater than that in the hypodermis (63.3%; p 0.039). CONCLUSIONS: We conclude that superficial sampling can retrieve a greater quantity of parasites. Future studies of the role of transepidermal elimination as a mechanism of host defence in ATL must be performed as there is a considerable quantity of Leishmania kDNA in the epidermis.
Assuntos
DNA de Cinetoplasto/genética , Leishmania/genética , Leishmaniose Cutânea/parasitologia , Reação em Cadeia da Polimerase/métodos , Pele/parasitologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Sepsis induces a severe systemic inflammatory response that may result in multiple organ dysfunction and death. Studies using a protein derived from natural Hevea brasiliensis (rubber tree) latex, denominated Hev b 13, have demonstrated important anti-inflammatory effects, but no data have been published regarding its effects on sepsis. The aim of this study was to investigate the effects of Hev b 13 on the inflammatory response and lung lesions of septal rats. Male Wistar rats were submitted to cecal ligation and puncture (CLP), randomized into groups and treated with subcutaneously administered doses of 0.5/2.0/3.0 mg/Kg of Hev b 13. Next, animals were subdivided into three different points in time (1, 6 and 24 hours after treatments) for collection of blood samples and euthanasia accompanied by organ removal. Total and differential leukocyte counts, cytokine dosage and histological assessment were analyzed. Treatment with Hev b 13 resulted in a significant decline in total and differential leukocytes as well as suppression of TNF-α and IL-6 production, associated with the increase in IL-10 and IL-4 in plasma and lung tissue. Moreover, it reduced morphological and pathological changes found in the lungs, including neutrophil infiltration, edema and alveolar thickening. The present study concluded that Hev b 13 exerts anti-inflammatory effects and attenuates lung lesions in septal rats, showing potential for clinical application.(AU)
Sepse induz uma resposta inflamatória sistêmica grave podendo resultar em disfunção de múltiplos órgãos e morte. Pesquisas utilizando uma proteína derivada do látex natural de Hevea brasiliensis (seringueira), denominada Hev b 13 tem demonstrado importantes efeitos anti-inflamatórios, mas nenhum dado foi publicado dos seus efeitos na sepse. O objetivo deste estudo foi investigar os efeitos da Hev b 13 na resposta inflamatória e na lesão pulmonar de ratos com sepse. Ratos machos da linhagem Wistar foram submetidos a ligação e perfuração do ceco (LPC), randomizados em grupos e tratados com as doses 0,5/2,0/3,0 mg/Kg de Hev b 13 subcutâneo. Após subdividiu-se os animais em três pontos diferentes de tempo (1, 6 e 24 horas após os tratamentos) para coleta de amostras sanguíneas e eutanásia com remoção dos órgãos. Contagem total e diferencial de leucócitos, dosagem de citocinas e avaliação histológica foram analisadas. O tratamento com a Hev b 13 resultou em diminuição significativa de leucócitos totais e diferenciais bem como suprimiu a produção de TNF-α e IL-6, associado ao aumento de IL-10 e IL-4 no plasma e tecido pulmonar. Além disso, reduziu as alterações morfológicas e patológicas encontradas nos pulmões, incluindo infiltrado de neutrófilos, edema e espessamento alveolar. Este estudo concluiu que a Hev b 13 tem efeitos anti-inflamatórios e atenua lesões pulmonares em ratos com sepse, apresentando potencialidades para aplicabilidade clínica.(AU)
Assuntos
Animais , Ratos , Hevea , Látex/uso terapêutico , Sepse/terapia , Proteínas Recombinantes/uso terapêutico , Anti-Inflamatórios/farmacologiaRESUMO
Abstract Sepsis induces a severe systemic inflammatory response that may result in multiple organ dysfunction and death. Studies using a protein derived from natural Hevea brasiliensis (rubber tree) latex, denominated Hev b 13, have demonstrated important anti-inflammatory effects, but no data have been published regarding its effects on sepsis. The aim of this study was to investigate the effects of Hev b 13 on the inflammatory response and lung lesions of septal rats. Male Wistar rats were submitted to cecal ligation and puncture (CLP), randomized into groups and treated with subcutaneously administered doses of 0.5/2.0/3.0 mg/Kg of Hev b 13. Next, animals were subdivided into three different points in time (1, 6 and 24 hours after treatments) for collection of blood samples and euthanasia accompanied by organ removal. Total and differential leukocyte counts, cytokine dosage and histological assessment were analyzed. Treatment with Hev b 13 resulted in a significant decline in total and differential leukocytes as well as suppression of TNF-α and IL-6 production, associated with the increase in IL-10 and IL-4 in plasma and lung tissue. Moreover, it reduced morphological and pathological changes found in the lungs, including neutrophil infiltration, edema and alveolar thickening. The present study concluded that Hev b 13 exerts anti-inflammatory effects and attenuates lung lesions in septal rats, showing potential for clinical application.
Resumo Sepse induz uma resposta inflamatória sistêmica grave podendo resultar em disfunção de múltiplos órgãos e morte. Pesquisas utilizando uma proteína derivada do látex natural de Hevea brasiliensis (seringueira), denominada Hev b 13 tem demonstrado importantes efeitos anti-inflamatórios, mas nenhum dado foi publicado dos seus efeitos na sepse. O objetivo deste estudo foi investigar os efeitos da Hev b 13 na resposta inflamatória e na lesão pulmonar de ratos com sepse. Ratos machos da linhagem Wistar foram submetidos a ligação e perfuração do ceco (LPC), randomizados em grupos e tratados com as doses 0,5/2,0/3,0 mg/Kg de Hev b 13 subcutâneo. Após subdividiu-se os animais em três pontos diferentes de tempo (1, 6 e 24 horas após os tratamentos) para coleta de amostras sanguíneas e eutanásia com remoção dos órgãos. Contagem total e diferencial de leucócitos, dosagem de citocinas e avaliação histológica foram analisadas. O tratamento com a Hev b 13 resultou em diminuição significativa de leucócitos totais e diferenciais bem como suprimiu a produção de TNF-α e IL-6, associado ao aumento de IL-10 e IL-4 no plasma e tecido pulmonar. Além disso, reduziu as alterações morfológicas e patológicas encontradas nos pulmões, incluindo infiltrado de neutrófilos, edema e espessamento alveolar. Este estudo concluiu que a Hev b 13 tem efeitos anti-inflamatórios e atenua lesões pulmonares em ratos com sepse, apresentando potencialidades para aplicabilidade clínica.
Assuntos
Animais , Masculino , Ratos , Proteínas de Plantas/farmacologia , Antígenos de Plantas/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/metabolismo , Pneumopatias/metabolismo , Proteínas de Plantas/administração & dosagem , Distribuição Aleatória , Citocinas/imunologia , Citocinas/metabolismo , Citocinas/sangue , Ratos Wistar , Sepse/metabolismo , Modelos Animais de Doenças , Antígenos de Plantas/administração & dosagem , Pneumopatias/imunologiaRESUMO
Sepsis induces a severe systemic inflammatory response that may result in multiple organ dysfunction and death. Studies using a protein derived from natural Hevea brasiliensis (rubber tree) latex, denominated Hev b 13, have demonstrated important anti-inflammatory effects, but no data have been published regarding its effects on sepsis. The aim of this study was to investigate the effects of Hev b 13 on the inflammatory response and lung lesions of septal rats. Male Wistar rats were submitted to cecal ligation and puncture (CLP), randomized into groups and treated with subcutaneously administered doses of 0.5/2.0/3.0 mg/Kg of Hev b 13. Next, animals were subdivided into three different points in time (1, 6 and 24 hours after treatments) for collection of blood samples and euthanasia accompanied by organ removal. Total and differential leukocyte counts, cytokine dosage and histological assessment were analyzed. Treatment with Hev b 13 resulted in a significant decline in total and differential leukocytes as well as suppression of TNF-α and IL-6 production, associated with the increase in IL-10 and IL-4 in plasma and lung tissue. Moreover, it reduced morphological and pathological changes found in the lungs, including neutrophil infiltration, edema and alveolar thickening. The present study concluded that Hev b 13 exerts anti-inflammatory effects and attenuates lung lesions in septal rats, showing potential for clinical application.
Assuntos
Antígenos de Plantas/farmacologia , Pneumopatias/metabolismo , Pulmão , Proteínas de Plantas/farmacologia , Sepse/metabolismo , Síndrome de Resposta Inflamatória Sistêmica/metabolismo , Animais , Antígenos de Plantas/administração & dosagem , Citocinas/sangue , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/metabolismo , Pneumopatias/imunologia , Masculino , Proteínas de Plantas/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Wistar , Sepse/imunologia , Síndrome de Resposta Inflamatória Sistêmica/imunologiaRESUMO
INTRODUCTION: Williams-Beuren syndrome (WBS) is a genetic condition caused by a microscopic deletion in the chromosome band 7q11.23. Individuals with WBS may present with congenital cardiovascular defects, neurodevelopmental disturbances and structural abnormalities of the urinary tract. Lower urinary tract symptoms (LUTS) seem to be frequent in this population, but studies on this topic are scarce and based on small case series. OBJECTIVE: To systematically evaluate the prevalence of lower urinary tract symptoms (LUTS) and the acquisition of bladder control in a large population with WBS. STUDY DESIGN: A cross-sectional study evaluating 87 consecutive patients with WBS; there were 41 girls and 46 boys. Genetic studies confirmed WBS in all patients. Subjects were clinically evaluated with: a history of LUTS obtained from the parents and child, a structured questionnaire of LUTS, a 3-day urinary frequency-volume chart, a quality of life question regarding LUTS, and physical examination. A history regarding the acquisition of bladder control was directly evaluated from the parents. RESULTS: Mean age of patients was 9.0 ± 4.2 years, ranging from 3 to 19 years. Based on the symptoms questionnaire and the frequency-volume chart, 70 patients (80.5%) were symptomatic. The most common symptom was urgency, affecting 61 (70.1%) patients, followed by increased urinary frequency in 60 (68.9%) patients, and urge-incontinence in 53 (60.9%), as shown in Summary Fig. More than half of the children reported nocturnal enuresis, including 61% of the girls and 52% of the boys. Twenty-three patients (25.6%) had a history of urinary tract infections. The mean age for acquisition of dryness during the day was 4.4 ± 1.9 years. Parents of 61 patients (70.1%) acknowledged that LUTS had a significant impact on the quality of life of their children. DISCUSSION: A high prevalence of LUTS was confirmed with a significant negative impact on quality of life in a large population of children and adolescents with WBS. It was shown for the first time that the achievement of daytime bladder control is delayed in children with WBS. Although LUTS are not recognized as one of the leading features of the syndrome, it is believed that it should be considered as a significant characteristic of the clinical diagnosis of WBS. CONCLUSIONS: LUTS are highly prevalent in children and adolescents with WBS and have a significant negative impact on patient's quality of life.
Assuntos
Sintomas do Trato Urinário Inferior/epidemiologia , Sintomas do Trato Urinário Inferior/etiologia , Qualidade de Vida , Inquéritos e Questionários , Síndrome de Williams/complicações , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Sintomas do Trato Urinário Inferior/fisiopatologia , Masculino , Noctúria/epidemiologia , Noctúria/etiologia , Noctúria/fisiopatologia , Prevalência , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Incontinência Urinária/epidemiologia , Incontinência Urinária/etiologia , Incontinência Urinária/fisiopatologia , Urodinâmica , Síndrome de Williams/diagnósticoRESUMO
Leishmania (L.) amazonensis (La) and L. (V.) braziliensis (Lb) are responsible for a large clinical and immunopathological spectrum in human disease; while La may be responsible for anergic disease, Lb infection leads to cellular hypersensitivity. To better understand the dichotomy in the immune response caused by these Leishmania species, we evaluated subsets of dendritic cells (DCs) and T lymphocyte in draining lymph nodes during the course of La and Lb infection in BALB/c mice. Our results demonstrated a high involvement of DCs in La infection, which was characterized by the greater accumulation of Langerhans cells (LCs); conversely, Lb infection led to an increase in dermal DCs (dDCs) throughout the infection. Considering the T lymphocyte response, an increase of effector, activated, and memory CD4(+) T-cells was observed in Lb infection. Interleukin- (IL-) 4- and IL-10-producing CD4(+)and CD8(+) T-cells were present in both La and Lb infection; however, interferon- (IFN-) γ-producing CD4(+)and CD8(+) T-cells were detected only in Lb infection. The results suggest that during Lb infection, the dDCs were the predominant subset of DCs that in turn was associated with the development of Th1 immune response; in contrast La infection was associated with a preferential accumulation of LCs and total blockage of the development of Th1 immune response.
Assuntos
Células Dendríticas/metabolismo , Leishmania braziliensis/patogenicidade , Leishmania/patogenicidade , Linfonodos/metabolismo , Animais , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Células Dendríticas/imunologia , Citometria de Fluxo , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-4/metabolismo , Leishmania/imunologia , Leishmania braziliensis/imunologia , Linfonodos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: The recurrence of American cutaneous leishmaniasis (ACL) in patients experiencing a long-term cure is often called leishmaniasis recidiva cutis (LRC). LRC is considered an unusual form of ACL. OBJECTIVE: This study aims to estimate the incidence of LRC in ACL patients evaluated at a tertiary dermatologic centre in Midwestern Brazil. We also aim to evaluate the association between various treatment regimens and the development of LRC using multivariate analysis in a case-control study. METHODS: We performed a 17-year epidemiological study using data from patients treated at our dermatologic centre from July 1994 to December 2011. A retrospective analysis was then performed to estimate risk and protective factors related to clinical presentation. We also assessed the influence of treatment regimens in the development of LRC. RESULTS: The incidence of LRC among ACL patients was 1.34%. The analysis included 105 patients; 82 patients (78%) were in the control group, and 23 patients (22%) were in the LRC case group. The data analysis indicated that the standard treatment N-methylglucamine antimoniate (N-MA) reduced the development of LRC in bivariate (odds ratio (OR) = 0.34; 95% CI = 0.13-0.91) and multivariate analyses (OR = 0.16; 95% CI = 0.03-0.86; P = 0.03). However, no differences in LRC incidence were observed when the standard treatment N-MA and alternative drugs, such as pentamidine and amphotericin B, were considered (OR = 0.47; 95% CI = 0.16-1.35) CONCLUSION: We conclude that the standard treatment N-MA, as proposed by the Brazilian Ministry of Health, is effective in the prevention of LRC. Although other drugs have shown promising results in LRC, more scientific evidence is needed to assess their efficacy compared with N-MA.
Assuntos
Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/epidemiologia , Meglumina/uso terapêutico , Compostos Organometálicos/uso terapêutico , Tripanossomicidas/uso terapêutico , Adolescente , Adulto , Anfotericina B/uso terapêutico , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Antimoniato de Meglumina , Pessoa de Meia-Idade , Pentamidina/uso terapêutico , Recidiva , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Adulto JovemRESUMO
Leishmania (Viannia) braziliensis causes cutaneous and mucosal leishmaniasis in several countries in Latin America. In mammals, the parasites live as amastigotes, interacting with host immune cells and stimulating cytokine production that will drive the type of the specific immune responses. Generation of Th17 lymphocytes is associated with tissue destruction and depends on IL-1ß, IL-6, TGF-ß and IL-23 production, whereas IL-10 and TGF-ß are associated with tissue protection. Here, we evaluate whether amastigotes stimulate peripheral blood mononuclear cells (PBMCs) from healthy donors to produce the major cytokines responsible for the generation of Th17. Seven L. (V.) braziliensis isolates from patients with different clinical forms of leishmaniasis were expanded in interferon-γ knockout mice to obtain amastigotes and in culture to get promastigotes. The parasites were used to stimulate PBMCs from healthy donors, and cytokine production was evaluated by ELISA or qPCR. Amastigotes and promastigotes induced IL-10 production in PBMCs; however, only amastigotes induced IL-1ß, IL-6 and TGF-ß. These data demonstrate for the first time that L. (V.) braziliensis amastigotes directly stimulate production of a unique pattern of cytokines that could contribute to the generation of Th17.