Manifestações urinárias e sexuais em pacientes infectados pelo 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% 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% 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

Forecasting temporal dynamics of cutaneous leishmaniasis in Northeast Brazil.

IntroductionCutaneous leishmaniasis (CL) is a vector-borne disease of increasing importance in northeastern Brazil. It is known that sandflies, which spread the causative parasites, have weather-dependent population dynamics. Routinely-gathered weather data may be useful for anticipating disease risk and planning interventions.Methodology/principal findingsWe fit time series models using meteorological covariates to predict CL cases in a rural region of Bahía, Brazil from 1994 to 2004. We used the models to forecast CL cases for the period 2005 to 2008. Models accounting for meteorological predictors reduced mean squared error in one, two, and three month-ahead forecasts by up to 16% relative to forecasts from a null model accounting only for temporal autocorrelation.SignificanceThese outcomes suggest CL risk in northeastern Brazil might be partially dependent on weather. Responses to forecasted CL epidemics may include bolstering clinical capacity and disease surveillance in at-risk areas. Ecological mechanisms by which weather influences CL risk merit future research attention as public health intervention targets

The miRNA 361-3p, a Regulator of GZMB and TNF Is Associated With Therapeutic Failure and Longer Time Healing of Cutaneous Leishmaniasis Caused by L. (viannia) braziliensis

L. (viannia) braziliensis infection causes American Tegumentary Leishmaniasis (ATL), with prolonged time to healing lesions. The potent inflammatory response developed by the host is important to control the parasite burden and infection however an unbalanced immunity may cooperate to the tissue damage observed. The range of mechanisms underlying the pathological responses associated with ATL still needs to be better understood. That includes epigenetic regulation by non-coding MicroRNAs (miRNAs), non-coding sequences around 22 nucleotides that act as post-transcriptional regulators of RNAs encoding proteins. The miRNAs have been associated with diverse parasitic diseases, including leishmaniasis. Here we evaluated miRNAs that targeted genes expressed in cutaneous leishmaniasis lesions (CL) by comparing its expression in both CL and normal skin obtained from the same individual. In addition, we evaluated if the miRNAs expression would be correlated with clinical parameters such as therapeutic failure, healing time as well as lesion size. The miR-361-3p and miR-140-3p were significantly more expressed in CL lesions compared to normal skin samples (p = 0.0001 and p < 0.0001, respectively). In addition, the miR-361-3p was correlated with both, therapeutic failure and healing time of disease (r = 0.6, p = 0.003 and r = 0.5, p = 0.007, respectively). In addition, complementary analysis shown that miR-361-3p is able to identify with good sensitivity (81.2%) and specificity (100%) patients who tend to fail initial treatment with pentavalent antimonial (Sbv). Finally, the survival analysis considering “cure” as the endpoint showed that the higher the expression of miR-361-3p, the longer the healing time of CL. Overall, our data suggest the potential of miR-361-3p as a prognostic biomarker in CL caused by L. braziliensis

Regulação da resposta blastogênica mediada por antígeno anticorpo específico: I - efeito de complexos imunes pré-formados na resposta proliferativa de linfócitos

Estudos prévios em animais de experimentação têm mostrado que complexos imunes formados por antígeno e anticorpo exercem uma influência reguladora na resposta proliferativa de linfócitos. utilizando-se de indivíduos previamente imunizados ou não com Keyhole Limpet Hemocyanin (KLH) o presente trabalho compara a resposta blastogênica induzida pelo antígeno (KLH) com aquela induzida por complexos imunes sob a forma de precipitado constituídos por KLH e IgG anti-KLH. Em cultura de linfócitos de indivíduos previamente imunizados, complexos formados por KLH e IgG anti-KLH induziram in vitro uma resposta proliferativa significantemente maior que o antígeno. Este aumento da bastogênese verificado quando o anticorpo foi acoplado ao antígeno não dependeu da presença de complemento, da quantidade de moléculas do anticorpo no complexo, foi específico com relação ao antígeno pois não houve bastogênese significante em cultura de linfócitos de indivíduos não imunizados, quando estimulados com complexos de KLH e IgG anti-KLH. Linfócitos que não são nem T nem B mas possuem receptor Fc para moléculas de IgG desempenham papel importante na resposta mediado por complexos imunes, haja vista a depleção destes linfócitos reduziu a resposta proliferativa mediada por complexos imunes à observada com o antígeno isoladamente.Previous studies in experimental animals have documented that immune complexes consisting of antigen and antibody exert a regulatory effect in immunological response. Using peripheral blood human lymphocutes from subjects previously immunized with Keyhole Limpet Hemocyanin (KLH), the present study compared the in vitro lymphocyte blastogenesis induced by KLH with that mediated by precipitated immune complexes formed by KLH and IgG anti KLH. The IgG antibody complexed to the antigen consistenly induced a proliferative response significantly higher than that mediated by the antigen alone. The enhancement observed with the immune complexes was neither dependent of the presence of complement or the amount of antibody molecules in the complexes. Depletion of non T, non B lymphocytes with high avidity Fc receptors for molecules of IgG, reduced the blastogenesis response induced by immune complexes to levels observed with the antigen alone. We conclude that these lymphocytes played an important role in the enhancement of lymphocyte blastogenesis mediated by immune complexes, probably by their ability to bind the IgG through Fc receptors

Corrosion resistance in artificial perspiration of Cr-based decorative coatings

We aim at developing hexavalent chromium-free coatings for frequently touched decorative parts. Cr(N,O) and multilayered CrN/CrO coatings were deposited by means of reactive magnetron sputtering. All samples presented good adhesion to the substrates enhanced by an epoxy layer designed to enhance PVD coating adhesion. Similar substrates are found in the automotive industry and can be used in appliances where a metallic finish is desired by the consumer. Corrosion behavior was induced, using artificial sweat to simulate long exposure to human touch for 96 h. In potentiodynamic polarization tests, the coatings were revealed to be nobler than the substrate alone. Cr displayed a non-existent passivation region, while gCrN exhibited a quick passivation of the surface and its respective breakdown and several current fluctuations, indicating the occurrence of pitting, which was confirmed by SEM micrography after the corrosion. Regarding EIS results, all films depicted a diminution of impedance modulus (|Z|) after 96 h, which indicates a diminution of corrosion resistance against artificial sweat. Nitride films exhibited the worst anticorrosive features. On the other hand, Cr and CrO exhibited the highest |Z| values. These results are corroborated by low the corrosion rates of both coatings. The equivalent electrical circuit allows us to confirm oxide formation in the outermost layer of the films due to electrolyte/surface interaction, indicating a self-protecting mechanism. Nitride films showed the lowest values and less corrosion resistance, confirming the results obtained in polarization potentiodynamic tests. The coatings developed in this work, namely Cr and CrO, showed a promising corrosion resistance behavior that could endure a lifetime of frequent human touch in various decorative applications either automotive or general appliances.This work was supported by COMPETE 2020 a Portuguese and European Union initiative through the Project POCI-01-0247-FEDER-072607, R&D and production of logos for the automotive industry. This research was sponsored by Norte2020, through European Social Fund (FSE), under the National Doctoral Program in “Surfaces Engineering and Protection”, NORTE-08-5369-FSE-000047. This research is sponsored by national funds through FCT—Fundação para a Ciência e a Tecnologia, under the Ph.D. Research Scholarship with Reference No. 2020.09436.BD. Author Maria José Lima acknowledges FCT for the research contract 2021.00675.CEECIND. This work was supported by the Portuguese Foundation for Science and Technology (FCT) in the framework of Strategic Funding (co-financed via UIDB/00285/2020 and UIDB/04650/2020) and LA/P/0112/2020

Schistosoma mansoni rSm29 Antigen Induces a Regulatory Phenotype on Dendritic Cells and Lymphocytes From Patients With Cutaneous Leishmaniasis

The immune response induced by Schistosma mansoni antigens is able to prevent immune-mediated diseases. Conversely, the inflammatory response in cutaneous leishmaniasis (CL), although responsible for controlling the infection, is also associated with the pathogenesis of disease. The aim of this study was to evaluate the potential of the S. mansoni Sm29 antigen to change certain aspects of the profiles of monocyte derived dendritic cells (MoDCs) and lymphocytes from subjects with CL in vitro. Expression of surface molecules and intracellular cytokines in the MoDCs and lymphocytes as well as the proliferation of Leishmania braziliensis were evaluated by flow cytometry. Levels of cytokines were evaluated in culture supernatants by ELISA. It was observed that stimulation by rSm29 increased the frequency of expression of CD83, CD80, CD86, and IL-10R in MoDCs compared to non-stimulated cultures. Additionally rSm29 decreased the frequency CD4+ and CD8+ T cells expressing CD28 and increased the frequency of CD4+CD25hi and CD4+CTLA-4+ T lymphocytes. Addition of rSm29 to cultures increased IL-10 levels and decreased levels of IL-12p40 and IFN-γ, while not altering TNF levels compared to non-stimulated cultures. This study showed that rSm29 induced a regulatory profile in MoDCs and lymphocytes and thereby regulated the exaggerated inflammation observed in CL. Considering that there are few therapeutic options for leishmaniasis, the use of rSm29 may be an alternative to current treatment and may be an important strategy to reduce the healing time of lesions in patients with CL

Leishmania braziliensis exosomes activate human macrophages to produce proinflammatory mediators

Exosomes, organelles measuring 30-200nm, are secreted by various cell types. Leishmania exosomes consist of many proteins, including heat shock proteins, annexins, Glycoprotein 63, proteins exerting signaling activity and those containing mRNA and miRNA. Studies have demonstrated that Leishmania donovani exosomes downregulate IFN-γ and inhibit the expression of microbicidal molecules, such as TNF and nitric oxide, thus creating a microenvironment favoring parasite proliferation. Despite lacking immunological memory, data in the literature suggest that, following initial stimulation, mononuclear phagocytes may become “trained” to respond more effectively to subsequent stimuli. Here we characterized the effects of macrophage sensitization using L. braziliensis exosomes prior to infection by the same pathogen. Human macrophages were stimulated with L. braziliensis exosomes and then infected with L. braziliensis. Higher levels of IL-1β and IL-6 were detected in cultures sensitized prior to infection compared to unstimulated infected cells. Moreover, stimulation with L. braziliensis exosomes induced macrophage production of IL-1β, IL-6, IL-10 and TNF. Inhibition of exosome secretion by L. braziliensis prior to macrophage infection reduced cytokine production and produced lower infection rates than untreated infected cells. Exosome stimulation also induced the consumption/regulation of NLRP3 inflammasome components in macrophages, while the blockade of NLRP3 resulted in lower levels of IL-6 and IL-1β. Our results suggest that L. braziliensis exosomes stimulate macrophages, leading to an exacerbated inflammatory state that may be NLRP3-dependent

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% 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% 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