bcg no tratamento de condiloma acuminado genital recidivante

Introdução: O Papiloma Virus Humano é a doença sexualmente transmissível de maior prevalência. O tratamento do Condiloma Acuminado é um grande desafio devido ao elevado índice de recidiva (30-70%) e à inexistência de medicamento eficaz para sua eliminação. Objetivo: Avaliar a eficácia do tratamento com OncoBCG para portadores de condilomas recidivantes por mais de 2 anos. Pacientes e métodos: Foram incluídos pacientes entre 18 e 60 anos, com história de verrugas genitais há mais de 2 anos, atendidos a partir de 01-08-2011, sendo excluídos os portadores de doenças graves, imunodeficiência ou em uso de imunossupressor. O método foi: iniciar com biopsia(s) da verruga(s) com anestesia local, seguida de eletrocoagulação de todas as verrugas e bases das biopsias, e aplicação de solução com 80 mg de Onco BCG dissolvido em 2 ml de solução salina a 0,9%, em toda área genital, inclusive nas áreas cauterizadas. Cobrir a área com plástico por 2 horas, e, depois lavar com água. As aplicações locais de Onco BCG foram repetidas por 8 semanas consecutivas. No final do segundo mês os casos foram reavaliados. Quando havia recidiva clínica um novo procedimento com o mesmo medicamento era feito, porém com 3 aplicações semanais pelo próprio paciente por 8 semanas. Resultado: Dezesseis pacientes completaram seguimento de 2 anos. O índice de cura foi de 68,75%. Dos 11 pacientes curados, 6 (37,5%) usaram uma série de Onco BCG, dois usaram 2 (12,5%) séries, e 3 (18,75%) usaram 3 séries. Dos 5 pacientes não curados, houve redução de número de cauterizações de 5,5 vezes num período médio de doença de 51,6 meses, para 2,4 vezes de cauterizações, num período médio de acompanhamento de 52,3 meses, após uso de Onco BCG. Os efeitos colaterais com o uso do BCG são insignificantes. Conclusão: BCG tópico é boa opção no tratamento para condilomas resistentes, com mínimo efeito colateral e pode ser usado mesmo nos pacientes PPD negativos. No entanto, esse resultado deve ser confirmado com maior casuística e estudo com grupo controle.Introduction: The Human Papilloma Virus (HPV) is the most prevalent sexually transmissible disease. The treatment of Condyloma Accuminatum is a great challenge because of the high recurrence rate and of the lack of any drug efficient in its elimination. Objective: To assess the efficacy of the treatment with Imuno BCG (Bacillus Calmette-Guérin) for bearers of condylomas recurrent for more than 2 years. Patients and Methods: Patients with age between 18 and 60 years, having a history of more than 2 years of genital warts, were included, attended as from 01-08-2011; bearers of serious diseases, immunodeficiency or users of immune-suppressors, being excluded. The procedure adopted began with a biopsy of the wart(s) with local anesthetic, followed by the electro-coagulation of all the warts and bases of the biopsies, a solution with 80 mg of Imuno BCG dissolved in 2 ml of saline solution 0.9% was applied to all the genital area, including the cauterized areas. The area was covered with plastic for 2 hours and afterwards washed with water. The local application of Imuno BCG was repeated for 8 consecutive weeks. At the end of the second month the cases were re-assessed. When there was clinical recurrence a new procedure with the same drug was undertaken, but with 3 weekly applications made by the patient himself for 8 weeks. Result: Sixteen patients completed 2-year follow-up. The cure rate was of 62.5%. Of the 10 patients cured, 6 (37.5%) used one series of Imuno BCG, 1 (6.25%) used 2 series, and 3 (18.75%) used 3 series. Of the 6 patients who were not cured, there was a reduction in the number of cauterizations from 5.5 times (over an average period of the disease of 51.6 months) to 2.4 cauterizations (over an average follow-up period of 52.3 months) after the use Imuno BCG. The collateral effects of the use of Imuno BCG were insignificant. Conclusion: Topical BCG is a good option for the treatment of recurrent condylomas, with minimal collateral effect. It may be used even on PPD-negative patients. However, this result must be confirmed with larger sample populations and control-group studies

Electrochemical impedimetric biosensor based on a nanostructured polycarbonate substrate

This study integrates the techniques of nanoelectroforming, hot-embossing, and electrochemical deposition to develop a disposable, low-cost, and high sensitivity nanostructure biosensor. A modified anodic aluminum oxide barrier-layer surface was used as the template for thin nickel film deposition. After etching the anodic aluminum oxide template off, a three-dimensional mold of the concave nanostructure array was created. The fabricated three-dimensional nickel mold was further used for replica molding of a nanostructure polycarbonate substrate by hot-embossing. A thin gold film was then sputtered onto the polycarbonate substrate to form the electrode, followed by deposition of an orderly and uniform gold nanoparticle layer on the three-dimensional gold electrode using electrochemical deposition. Finally, silver nanoparticles were deposited on the uniformly deposited gold nanoparticles to enhance the conductivity of the sensor. Electrochemical impedance spectroscopy analysis was then used to detect the concentration of the target element. The sensitivity of the proposed scheme on the detection of the dust mite antigen, Der p2, reached 0.1 pg/mL

Bifurcation of Arabidopsis NLR Immune Signaling via Ca2+-Dependent Protein Kinases

Nucleotide-binding domain leucine-rich repeat (NLR) protein complexes sense infections and trigger robust immune responses in plants and humans. Activation of plant NLR resistance (R) proteins by pathogen effectors launches convergent immune responses, including programmed cell death (PCD), reactive oxygen species (ROS) production and transcriptional reprogramming with elusive mechanisms. Functional genomic and biochemical genetic screens identified six closely related Arabidopsis Ca2+-dependent protein kinases (CPKs) in mediating bifurcate immune responses activated by NLR proteins, RPS2 and RPM1. The dynamics of differential CPK1/2 activation by pathogen effectors controls the onset of cell death. Sustained CPK4/5/6/11 activation directly phosphorylates a specific subgroup of WRKY transcription factors, WRKY8/28/48, to synergistically regulate transcriptional reprogramming crucial for NLR-dependent restriction of pathogen growth, whereas CPK1/2/4/11 phosphorylate plasma membrane-resident NADPH oxidases for ROS production. Our studies delineate bifurcation of complex signaling mechanisms downstream of NLR immune sensors mediated by the myriad action of CPKs with distinct substrate specificity and subcellular dynamics

Dynamic Transcript Profiling of Candida Albicans Infection in Zebrafish: a Pathogen-Host Interaction Study

Candida albicans is responsible for a number of life-threatening infections and causes considerable morbidity and mortality in immunocompromised patients. Previous studies of C. albicans pathogenesis have suggested several steps must occur before virulent infection, including early adhesion, invasion, and late tissue damage. However, the mechanism that triggers C. albicans transformation from yeast to hyphae form during infection has yet to be fully elucidated. This study used a systems biology approach to investigate C. albicans infection in zebrafish. The surviving fish were sampled at different post-infection time points to obtain time-lapsed, genome-wide transcriptomic data from both organisms, which were accompanied with in sync histological analyses. Principal component analysis (PCA) was used to analyze the dynamic gene expression profiles of significant variations in both C. albicans and zebrafish. The results categorized C. albicans infection into three progressing phases: adhesion, invasion, and damage. Such findings were highly supported by the corresponding histological analysis. Furthermore, the dynamic interspecies transcript profiling revealed that C. albicans activated its filamentous formation during invasion and the iron scavenging functions during the damage phases, whereas zebrafish ceased its iron homeostasis function following massive hemorrhage during the later stages of infection. This was followed by massive hemorrhaging toward the end stage of infection. Most of the immune related genes were expressed as the infection progressed from invasion to the damage phase. Such global, inter-species evidence of virulence-immune and iron competition dynamics during C. albicans infection could be crucial in understanding control fungal pathogenesis

EBV-encoded small RNA1 and nonresolving inflammation in rheumatoid arthritis

AbstractRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by perpetuated inflammation in multiple joints. To date, there is no cure for RA, and the causal factor for non-resolving inflammation in RA remains unclear. In this study, we initially observed expression of Epstein–Barr virus-encoded small RNA1 (EBER1) in the synovial tissue of all five patients who showed nonresolving RA inflammation. By contrast, EBER1 was detected in the synovial tissue of only one out of seven patients with advanced osteoarthritis (OA; p < 0.01, Fisher’s exact test). To confirm this finding, we conducted a second study on synovial tissue samples taken from 23 patients with nonresolving RA inflammation and 13 patients with OA. All synovial samples from patients with nonresolving inflammation of RA showed positive expression of EBER1 (23/23, 100%), whereas none of the synovial samples from patients with OA showed expression of EBER1 (0/13, 0%; p < 0.001, by Fisher’s exact test). In vitro, transfection of RA synovial fibroblasts with EBER1 induced the production of interleukin-6. Taken together, these data strongly suggest that nonresolving RA inflammation is strongly related to the presence of EBER1, which might be, at least partially, responsible for synovial fibroblast interleukin-6 production