Estudo de validação das equações de Tanaka e de Kawasaki para estimar a excreção diária de sódio através da coleta da urina casual / Validation study of the Tanaka and Kawasaki equations to estimate the daily sodium excretion by a spot urine sample

RESUMO: Objetivo: Validar as fórmulas de Tanaka e Kawasaki para cálculo do consumo de sal pela relação sódio/creatinina na urina casual. Métodos: Foram estudados 272 adultos (20 - 69 anos, 52,6% de mulheres) com coleta urinária de 24 h e duas coletas casuais no mesmo dia (em jejum - casual 1 - e fora do jejum - casual 2). Antropometria, pressão arterial e coleta de sangue foram obtidos no mesmo dia. A concordância entre o consumo de sal estimado pela urina de 24 h e pela urina casual foi feita por Pearson (r) e Bland & Altman. Resultados: O consumo médio de sal medido pela urina de 24 h foi de 10,4 ± 5,3 g/dia. A correlação entre a excreção de sódio na urina de 24 h e a estimada pela urina casual 1 ou 2, respectivamente, foi apenas moderada, tanto por Tanaka (r = 0,51 e r = 0,55; p < 0,001) como por Kawasaki (r = 0,52 e r = 0,54; p < 0,001). Observa-se subestimação crescente dos valores estimados em relação ao medido com o aumento do consumo de sal pela fórmula de Tanaka e, ao contrário, superestimação ao usar a fórmula de Kawasaki. As fórmulas estimam adequadamente o consumo diário de sal (diferença entre sal medido e estimado de, no máximo, 1 g/dia) somente com consumo entre 9 - 12 g/dia (Tanaka) e 12 - 18 g/dia (Kawasaki). Conclusão: A coleta de urina casual estima adequadamente o consumo de sal apenas nos indivíduos próximos à média populacional.

ABSTRACT: Objective: To validate Tanaka and Kawasaki's formulas to calculate the salt intake by the sodium/creatinine ratio in spot of urine. Methods: Two hundred and seventy two adults (20 - 69 years old; 52.6% women) with 24 h urine collection and two urinary spots collected on the same day (while fasting - spot 1 - or not fasting - spot 2). Anthropometry, blood pressure and fasting blood were measured on the same day. The analysis of agreement between salt consumption measured in the 24 h urine test and urinary spots were determined by the Pearson's correlation (r) and the Bland & Altman method. Results: The mean salt consumption measured by the 24 h sodium excretion was 10.4 ± 5.3 g/day. The correlation between the measured 24 h sodium excretion and the estimation based on spots 1 and 2, respectively, was only moderated according to Tanaka (r = 0.51 and r = 0.55; p < 0.001) and to Kawasaki (r = 0.52 and r = 0.54; p < 0.001). We observed an increasing underestimation of salt consumption by Tanaka to increasing salt consumption and conversely, an overestimation of consumption by the Kawasaki formula. The estimation of salt consumption (difference between measured and calculated salt consumption lower than 1 g/day) was adequate only when the consumption was between 9 - 12 g/day (Tanaka) and 12 - 18 g/day (Kawasaki). Conclusion: Spot urine sampling is adequate to estimate salt consumption only among individuals with an actual consumption near the population mean.

TAPCells, the Chilean dendritic cell vaccine against melanoma and prostate cancer

Here we summarize 10 years of effort in the development of a biomedical innovation with global projections. This innovation consists of a novel method for the production of therapeutic dendritic-like cells called Tumor Antigen Presenting Cells (TAPCells®). TAPCells-based immunotherapy was tested in more than 120 stage III and IV melanoma patients and 20 castration-resistant prostate cancer patients in a series of phase I and I/II clinical trials. TAPCells vaccines induced T cell-mediated memory immune responses that correlated with increased survival in melanoma patients and prolonged prostate-specific antigen doubling time in prostate cancer patients. Importantly, more than 60% of tested patients showed a Delayed Type Hypersensitivity (DTH) reaction against the lysates, indicating the development of anti-tumor immunological memory that correlates with clinical benefits. The in vitro analysis of the lysate mix showed that it contains damage-associated molecular patterns such as HMBG-1 protein which are capable to improve, through Toll-like receptor-4, maturation and antigen cross-presentation of the dendritic cells (DC). In fact, a Toll-like receptor-4 polymorphism correlates with patient clinical outcomes. Moreover, Concholepas concholepas hemocyanin (CCH) used as adjuvant proved to be safe and capable of enhancing the immunological response. Furthermore, we observed that DC vaccination resulted in a three-fold increase of T helper-1 lymphocytes releasing IFN-γ and a two-fold increase of T helper-17 lymphocytes capable of producing IL-17 in DTH+ with respect to DTH- patients. Important steps have been accomplished for TAPCells technology transfer, including patenting, packaging and technology assessment. Altogether, our results indicate that TAPCells vaccines constitute an exceptional Chilean national innovation of international value.

Enhanced anti-tumor effect of a gene gun-delivered DNA vaccine encoding the human papillomavirus type 16 oncoproteins genetically fused to the herpes simplex virus glycoprotein D

Anti-cancer DNA vaccines have attracted growing interest as a simple and non-invasive method for both the treatment and prevention of tumors induced by human papillomaviruses. Nonetheless, the low immunogenicity of parenterally administered vaccines, particularly regarding the activation of cytotoxic CD8+ T cell responses, suggests that further improvements in both vaccine composition and administration routes are still required. In the present study, we report the immune responses and anti-tumor effects of a DNA vaccine (pgD-E7E6E5) expressing three proteins (E7, E6, and E5) of the human papillomavirus type 16 genetically fused to the glycoprotein D of the human herpes simplex virus type 1, which was administered to mice by the intradermal (id) route using a gene gun. A single id dose of pgD-E7E6E5 (2 µg/dose) induced a strong activation of E7-specific interferon-γ (INF-γ)-producing CD8+ T cells and full prophylactic anti-tumor effects in the vaccinated mice. Three vaccine doses inhibited tumor growth in 70 percent of the mice with established tumors. In addition, a single vaccine dose consisting of the co-administration of pgD-E7E6E5 and the vector encoding interleukin-12 or granulocyte-macrophage colony-stimulating factor further enhanced the therapeutic anti-tumor effects and conferred protection to 60 and 50 percent of the vaccinated mice, respectively. In conclusion, id administration of pgD-E7E6E5 significantly enhanced the immunogenicity and anti-tumor effects of the DNA vaccine, representing a promising administration route for future clinical trials.

Vacunación en huéspedes inmunocomprometidos / Vaccine in immunocompromiced host

Los lactantes, niños y adolescentes con inmunodeficiencia primaria o secundaria constituyen una población creciente. La adecuada utilización de las vacunas incluídas en el Calendario Nacional y otras son una valiosa herramienta para la calidad de vida. Debe considerarse simultáneamente la vacunación de los convivientes. La indicación de la vacuna es personalizada. Se revisan las indicaciones en los pacientes con tratamiento prolongado con corticoides; inmundeficiencia primaria (humoral, celular/combinada); inmunodeficiencia secundaria (cáncer, transplante médula ósea/órganos sólidos.)

Liposome encapsulated tumor-associated antigens elicited humoral and cellular immune responses in mice bearing tumor.

Chemically induced tumors in mice provide a system to investigate tumor-associated antigens (TAA). The cell surface glycoprotein antigens on such tumor cells have been identified as suitable targets for immune attack. The induction of immune responses against (TAA) in N-nitrosodiethylamine (DEN) exposed mice has been examined. In order to present antigens to the immune system, the liposome was used as vehicle to deliver the TAA. Liposomal-TAA formulation, elicited both humoral and the cellular immune responses, when administered intramuscularly in DEN-exposed mice. Presence of circulatory antibodies against TAA and the induction of cellular responses in immunized mice were monitored using ELISA and in vitro cell proliferation assay of lymphocytes respectively. Specificity of antibody against TAA in immune sera was analysed using immunoblotting technique. Based on these results, it is proposed that the liposome encapsulated TAA may successfully be used to induce humoral and cellular immune responses against tumor.