A novel pharmacodynamic assay to evaluate the effects of crystallization inhibitors on calcium phosphate crystallization in human plasma.

Cardiovascular calcification (CVC) is a progressive complication of chronic kidney disease and a predictor of CV events and mortality. The use of biomarkers to predict CV risk and activities of potential or current treatment drugs in these patients could have a crucial impact on therapeutic approaches. Our aim was to develop a novel assay for measurement of the rate of calcium phosphate crystallization in human plasma and provide a tool to evaluate the effects of crystallization inhibitors. The efficacy of inhibitors was determined by adding inhibitory compounds (polyphosphates, fetuin-A, sodium thiosulfate or citrate) to control samples. The assay was additionally validated for SNF472, an experimental formulation of phytate being developed for the treatment of calciphylaxis and CVC in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). The method was repeatable and reproducible. The plasma crystallization rate was reduced up to 80% in a concentration-dependent manner following treatment with inhibitors in vitro, among which SNF472 was the most potent. This method appears beneficial in evaluating and discriminating between inhibitory activities of compounds such as polyphosphates on calcium phosphate crystallization, which present a novel therapeutic approach to treat CVC in ESRD patients.

Vitamin C supplementation influences the antioxidant response and nitric oxide handling of erythrocytes and lymphocytes to diving apnea.

OBJECTIVE: We have investigated the influence of vitamin C diet supplementation on the antioxidant response and nitrite levels in lymphocytes and erythrocytes during diving apnea. SUBJECTS: Seven male professional apnea divers participated in a double blind crossover study. Divers were randomly assigned to either vitamin C supplemented or placebo groups. The subjects did not take any other supplements than the ones provided for this study. INTERVENTION: One group was supplemented with vitamin C capsules (1 g per day) for 7 days while the other group took a placebo composed of lactose. The usual dietary habits of participants were assessed using a self-reported 7-days 24-h recall before the day of the study. Blood samples were taken under basal conditions, immediately after diving apnea for 4 h and after 1 h of recovery. RESULTS: Catalase activity increased in erythrocytes (23%) and superoxide dismutase increased in lymphocytes (35%) during the recovery only in the placebo group. Lymphocyte ascorbate levels increased in the supplemented group after diving (85%) and maintained high at recovery. Plasma nitrite levels increased about twofold in both groups during the recovery. Erythrocyte nitrite levels increased after diving (50%) and about twofold during the recovery in the supplemented group. Nitrite levels and iNOS levels in lymphocytes were higher in the placebo group than in the supplemented during the recovery. Erythrocyte carbonyl derivates were unchanged in all situations. CONCLUSIONS: Vitamin C supplementation influenced the antioxidant response and NO handling in erythrocytes and lymphocytes to the oxidative stress induced by hypoxia-reoxygenation.

[Follow-up of children and young adults with differentiated thyroid cancer treated with radioiodine]. / Seguimiento de niños y jóvenes adultos con cáncer diferenciado de tiroides (CDT) tratados con radioyodo.

This is a retrospective study carried out in a group of 30 patients with differentiated thyroid cancer (age at diagnosis equal to or less than twenty years old). The aim of the study is to evaluate outcome after 131I therapy. Patients were classified into three groups on the basis of initial surgery, pathology and scintigraphic results: group I (thyroid extent), group II (locoregional extent), and group III (distant metastatic disease). Clinical parameters, 131I scans, serum thyroglobulin determinations and 131I therapeutic administered doses were evaluated in the follow-up. Some other complementary techniques such as chest X-ray and pulmonary function tests are also described. Scintigraphic absence of thyroid tissue has been observed in 83% of the cases; high thyroglobulin level is still detectable in 34% of the patients as a single evidence of disease, and 21% remain without any abnormal clinical, scintigraphic or analytical findings. Total doses administered have increased in groups I, II and III respectively, and have also been inversely proportional to the extension of lymph node surgery. At present, all the patients are alive and in good general condition. According to the results obtained, we conclude that children and young adults with DTC should undergo periodical 131I therapeutic doses in case of positive scans (once total thyroidectomy has been realized, with or without lymph node resection depending on the extension of disease). In our experience, the use of radioiodine is effective and safe in the follow-up of children and youngs with DTC.

Seguimiento de niños y jóvenes adultos con cáncer diferenciadode tiroides (CDT) tratados con radioyodo / Follow-up of children and young adults with differentiated thyroid cancer treated with radioiodine

Este es un estudio retrospectivo realizado en un grupo de treinta pacientes con carcinoma diferenciado de tiroides (edad al dignóstico igual o menor a veinte años), que tiene como objetivo valorar la respuesta al tratamiento con radioyodo. Los pacientes fueron clasificados en tres grupos según los resultados quirúrgicos, anatomopatológicos y gammagráficos iniciales: grupo I (enfermedad limitada al tiroides), grupo II (enfermedad locorregional), grupo III (afectación metastásica a distancia). En el seguimiento se evaluaron parámetros clínicos, resultados de rastreos gammagráficos con Iodo-131, determinaciones de tiroglobulina sérica y dosis terapeúticas de radioyodo administradas. También se describen otras técnicas complementarias como la radiología de tórax y las pruebas de función respiratoria. Hemos observado una negativización gammagráfica en el 83 por ciento de los casos; un 34 por ciento presenta niveles de tiroglobulina elevados como único hallazgo sugestivo de existencia de enfermedad y un 21 por ciento no presenta hallazgos clínicos, analíticos o gammagráficos patológicos. Las dosis totales de radioyodo administradas han sido crecientes en los grupos I, II y III respectivamente, e inversamente proporcionales a la extensión de la limpieza ganglionar efectuada. En la actualidad todos los pacientes están vivos y presentan un buen estado general.De acuerdo con los resultados obtenidos, concluímos que el manejo adecuado del CDT en este grupo de edad debe incluir rastreos gammagráficos periódicos con 131I y dosis terapeúticas de 131I en caso de rastreos positivos (una vez realizada la tiroidectomía total, con o sin limpieza ganglionar dependiendo de la extensión de la enfermedad). Según nuestra experiencia, el empleo de radioiodo es eficaz y seguro en el seguimiento de niños y jóvenes con CDT. (AU)