ELEVATED PHENYLACETIC ACID LEVELS DO NOT CORRELATE WITH ADVERSE EVENTS IN PATIENTS WITH UREA CYCLE DISORDERS OR HEPATIC ENCEPHALOPATHY AND CAN BE PREDICTED BASED ON THE PLASMA PAA TO PAGN RATIO

Background Phenylacetic acid (PAA) is the active moiety in sodium phenylbutyrate (NaPBA) and glycerol phenylbutyrate (GPB, HPN-100), both are approved for treatment of urea cycle disorders (UCDs) - rare genetic disorders characterized by hyperammonemia. PAA is conjugated with glutamine in the liver to form phenylacetyleglutamine (PAGN), which is excreted in urine. PAA plasma levels ≥500 μg/dL have been reported to be associated with reversible neurological adverse events (AEs) in cancer patients receiving PAA intravenously. Therefore, we have investigated the relationship between PAA levels and neurological AEs in patients treated with these PAA pro-drugs as well as approaches to identifying patients most likely to experience high PAA levels. Methods The relationship between nervous system AEs, PAA levels and the ratio of plasma PAA to PAGN were examined in 4683 blood samples taken serially from: [1] healthy adults [2], UCD patients ≥2 months of age, and [3] patients with cirrhosis and hepatic encephalopathy (HE). The plasma ratio of PAA to PAGN was analyzed with respect to its utility in identifying patients at risk of high PAA values. Results Only 0.2% (11) of 4683 samples exceeded 500 ug/ml. There was no relationship between neurological AEs and PAA levels in UCD or HE patients, but transient AEs including headache and nausea that correlated with PAA levels were observed in healthy adults. Irrespective of population, a curvilinear relationship was observed between PAA levels and the plasma PAA:PAGN ratio, and a ratio > 2.5 (both in μg/mL) in a random blood draw identified patients at risk for PAA levels > 500 μg/ml. Conclusions The presence of a relationship between PAA levels and reversible AEs in healthy adults but not in UCD or HE patients may reflect intrinsic differences among the populations and/or metabolic adaptation with continued dosing. The plasma PAA:PAGN ratio is a functional measure of the rate of PAA metabolism and represents a useful dosing biomarker

Capacidade combinatória de genótipos de milho para tolerância ao encharcamento do solo Combining the ability of maize genotypes for flooding tolerance

No sul do Brasil, a cultura do milho pode ser uma alternativa de cultivo para áreas de várzea; entretanto, o desenvolvimento de genótipos tolerantes ao encharcamento é condição fundamental para viabilizar economicamente esta opção. O objetivo do presente trabalho foi determinar a capacidade geral e específica de combinação e os efeitos recíprocos para tolerância ao encharcamento do solo de genótipos de milho. A análise foi baseada em um cruzamento dialélico envolvendo quatro linhagens: duas tolerantes ao encharcamento do solo (CT954280 e CT954330) e duas sensíveis (CT966200 e CT966208). O trabalho experimental foi realizado durante os anos de 2000 e 2001 em casa de vegetação localizada na Embrapa Clima Temperado, Pelotas, RS. As variáveis analisadas foram matéria seca da raiz, matéria seca da parte aérea, estatura de planta, comprimento de raiz e conteúdo de clorofila na folha. Os resultados demonstraram a existência de variabilidade genética entre os genótipos estudados, sendo que ambos os efeitos aditivos e não aditivos foram de importância na determinação da herança da tolerância ao encharcamento em milho. A escolha do genitor feminino é fundamental para a obtenção de híbridos tolerantes, uma vez que o efeito materno observado foi elevado. Dentre os dois genótipos tolerantes analisados, a linhagem CT954330 foi a que apresentou a maior CGC e pode ser indicada como genitor preferencial em cruzamentos que visem incrementar a tolerância ao encharcamento.<br>In southern Brazil, corn could be an alternative for cultivation in flooded areas. However, the development of genotypes tolerant to flooding is fundamental to make this option economically feasible. The objective of this paper was to determine the general and specific combining ability and reciprocal effect for flooding tolerance in corn genotypes. The analysis was based on a diallel cross among four inbreds: two flooding tolerant (CT954280 and CT954330) and two sensitive inbreds (CT966200 and CT966208). The experiment was conducted in 2000 and 2001 under greenhouse conditions at Embrapa Clima Temperado, Pelotas, RS. Root dry matter, plant dry matter, plant high, root length, and leaf chlorophyll content were measured. Genetic variability among the inbreds was detected. Both additive and non-additive effects were important in the determination of the inheritance of flooding tolerance in corn. The correct choice of the female parent is fundamental for tolerant hybrids production, since maternal effects were relevant. Among the analyzed genotypes, the inbred CT954330 presented the highest GCA and may be indicated as a preferential progenitor in crossings that aim to increase flooding tolerance