Toward the optimal dose metric in continuous renal replacement therapy

Purpose: There is no consensus on the optimal method to measure delivered dialysis dose in patients with acute kidney injury (AKI). The use of direct dialysate-side quantification of dose in preference to the use of formal blood-based urea kinetic modeling and simplified blood urea nitrogen (BUN) methods has been recommended for dose assessment in critically-ill patients with AKI. We evaluate six different blood-side and dialysate-side methods for dose quantification. Methods: We examined data from 52 critically-ill patients with AKI requiring dialysis. All patients were treated with pre-dilution CWHDF and regional citrate anticoagulation. Delivered dose was calculated using blood-side and dialysis-side kinetics. Filter function was assessed during the entire course of therapy by calculating BUN to dialysis fluid urea nitrogen (FUN) ratios q/12 hours. Results: Median daily treatment time was 1,413 min (1,260-1,440). The median observed effluent volume per treatment was 2,355 mL/h (2,060-2,863) (p<0.001). Urea mass removal rate was 13.0 +/- 7.6 mg/min. Both EKR (r(2)=0.250; p<0.001) and K-D (r(2)=0.409; p<0.001) showed a good correlation with actual solute removal. EKR and K-D presented a decline in their values that was related to the decrease in filter function assessed by the FUN/BUN ratio. Conclusions: Effluent rate (ml/kg/h) can only empirically provide an estimated of dose in CRRT. For clinical practice, we recommend that the delivered dose should be measured and expressed as K-D. EKR also constitutes a good method for dose comparisons over time and across modalities.

Convergent evolution of [D-Leucine1] microcystin-LR in taxonomically disparate cyanobacteria

Abstract Background Many important toxins and antibiotics are produced by non-ribosomal biosynthetic pathways. Microcystins are a chemically diverse family of potent peptide toxins and the end-products of a hybrid NRPS and PKS secondary metabolic pathway. They are produced by a variety of cyanobacteria and are responsible for the poisoning of humans as well as the deaths of wild and domestic animals around the world. The chemical diversity of the microcystin family is attributed to a number of genetic events that have resulted in the diversification of the pathway for microcystin assembly. Results Here, we show that independent evolutionary events affecting the substrate specificity of the microcystin biosynthetic pathway have resulted in convergence on a rare [D-Leu1] microcystin-LR chemical variant. We detected this rare microcystin variant from strains of the distantly related genera Microcystis, Nostoc, and Phormidium. Phylogenetic analysis performed using sequences of the catalytic domains within the mcy gene cluster demonstrated a clear recombination pattern in the adenylation domain phylogenetic tree. We found evidence for conversion of the gene encoding the McyA2 adenylation domain in strains of the genera Nostoc and Phormidium. However, point mutations affecting the substrate-binding sequence motifs of the McyA2 adenylation domain were associated with the change in substrate specificity in two strains of Microcystis. In addition to the main [D-Leu1] microcystin-LR variant, these two strains produced a new microcystin that was identified as [Met1] microcystin-LR. Conclusions Phylogenetic analysis demonstrated that both point mutations and gene conversion result in functional mcy gene clusters that produce the same rare [D-Leu1] variant of microcystin in strains of the genera Microcystis, Nostoc, and Phormidium. Engineering pathways to produce recombinant non-ribosomal peptides could provide new natural products or increase the activity of known compounds. Our results suggest that the replacement of entire adenylation domains could be a more successful strategy to obtain higher specificity in the modification of the non-ribosomal peptides than point mutations.

Mudanças no consumo alimentar e atividade física de escolares de Florianópolis, SC, 2002 - 2007

OBJETIVO: Avaliar a mudança em cinco anos do consumo alimentar e nível de atividade física em escolares. MÉTODOS: Estudo com amostra representativa (n = 4.168) de escolares de sete a dez anos de idade de Florianópolis, SC. Medidas do consumo alimentar e atividade física foram realizadas em dois estudos de base escolar em 2002 (n = 2.936; 51% meninos; idade média = 8,5 anos) e 2007 (n = 1.232; 50,7% meninos; idade média = 8,6 anos), utilizando questionários ilustrados. O teste do qui-quadrado foi utilizado para avaliar a mudança no consumo de oito alimentos/grupos de alimentos, no atendimento às recomendações do Guia Alimentar para a População Brasileira e no nível de atividade física (avaliado segundo os terços de distribuição do escore e o tipo de deslocamento para a escola). As análises foram realizadas segundo a rede de ensino. RESULTADOS: Houve redução da proporção de crianças que relatou o consumo de frutas, verduras e legumes, feijão, carnes, guloseimas, pizza, batata frita e refrigerantes. Maior proporção de escolares da rede privada atendeu às recomendações de restrição de consumo de refrigerantes, pizzas e batata frita, e de maior consumo de frutas, verduras e legumes, em ambos os estudos. Por outro lado, maior proporção de escolares da rede pública atendeu às recomendações para o consumo de carnes em 2007. Os valores medianos do escore de atividade física diminuíram em 2007. Em ambos os anos escolares da rede privada foram mais ativos. A proporção de escolares que se deslocou ativamente para a escola reduziu de 49% para 41% (p < 0,01). CONCLUSÕES: Houve redução no consumo de alimentos marcadores de dieta saudável (feijão, carnes/peixes, frutas, legumes e verduras) e de alimentos de alta densidade energética e baixo valor nutricional (refrigerantes, guloseimas e pizza/batatas fritas). Também houve decréscimo da proporção de escolares que relataram deslocamento ativo para a escola.