Achados audiológicos em crianças com fenilcetonúria Audiologic findings in children with phenylketonuria

OBJETIVO: Investigar a existência de alterações na audição de crianças com fenilcetonúria diagnosticadas e tratadas precocemente e comparar os resultados com os encontrados nas avaliações auditivas de crianças normais de mesma idade. MÉTODOS: Foram realizadas imitanciometria e audiometria tonal e vocal em 63 crianças, sendo 30 no grupo controle, com média de idade de 8,1 anos, e 33 com fenilcetonúria no grupo de estudo, com média de idade de 7,7 anos. O grupo de estudo foi subdividido em 15 crianças com controle adequado da dieta e 18 crianças com controle inadequado da dieta, com médias de idade 8,1 e 7,2, respectivamente. A análise estatística utilizou o Teste t ou ANOVA. RESULTADOS: A audiometria revelou 83,3% de crianças com audição normal no grupo controle e 16,7% de perdas auditivas condutivas uni ou bilaterais. No grupo com fenilcetonúria, 66,7% das crianças apresentaram audição normal e 33,3% com perdas auditivas condutivas. Na imitanciometria, observou-se curvas normais em 91,7% das crianças do grupo controle e em 72,7% das crianças do grupo com fenilcetonúria. Houve diferença na comparação entre grupos para limiares aéreos, reflexos estapedianos, limiares de recepção da fala e índice de reconhecimento de fala. Não foi observada diferença entre os resultados das avaliações auditivas de crianças fenilcetonúricas com dieta adequada e inadequada. CONCLUSÃO: As crianças com fenilcetonúria diagnosticadas e tratadas precocemente apresentaram piores limiares de audibilidade por via aérea, limiares de recepção de fala e índice de reconhecimento de fala evidenciados à audiometria tonal e vocal, quando comparadas com crianças normais.<br>PURPOSE: To investigate the existence of hearing impairments in infants with phenylketonuria with early diagnose and treatment, and to compare the audiological findings with those of their normal peers. METHODS: Vocal and pure-tone audiometry and acoustic immitance tests were conducted in 63 children, 30 from a control group, with mean age of 8.1 years, and 33 from a study group, with phenylketonuria and mean age of 7.7 years. The study group was subdivided according to diet control: 15 subjects had adequate (mean age of 8.1 years) and 18 had inadequate diet control (mean age 7.2 years). Statistical analysis used t-test or ANOVA. RESULTS: Audiometry showed that, in the control group, 83.3% of the subjects had normal hearing, and 16.7% had uni- or bilateral conductive hearing loss. In the study group, 66.7% of the subjects presented normal hearing, and 33.3% had conductive hearing loss. Immitance measures showed normal results in 91.7% of the children from the control group, and in 72.7% of the subjects with phenylketonuria. Differences were found between the groups regarding hearing thresholds, acoustic reflexes, speech reception thresholds, and speech recognition. No differences were observed between the results of phenylketonuria subjects with adequate and inadequate diets. CONCLUSION: Children with phenylketonuria early diagnosed and treated presented worse conductive hearing thresholds, speech reception threshold and speech recognition when compared to their normal peers, as evidenced in pure-tone and vocal audiometry

Metabolismo do cálcio na fenilcetonúria Calcium metabolism in phenilke

A Fenilcetonúria é um erro inato do metabolismo do aminoácido fenilalanina. O tratamento é essencialmente dietético e envolve uma restrição severa no consumo de alimentos contendo aminoácido fenilalanina. Embora a alimentação seja complementada com fórmulas a fim de suprir as necessidades de vitaminas, minerais e aminoácidos essenciais, carências nutricionais ainda ocorrem. Isto se deve, principalmente, à restrição de fontes protéicas, que acarreta deficiência na ingestão de diversos nutrientes, dentre eles o cálcio. O cálcio possui importante relação com a formação mineral óssea. Estudos recentes demonstram que portadores de fenilcetonúria apresentam freqüentemente osteopenia e fraturas, sendo a maior incidência em crianças acima de 8 anos de idade. O rápido aumento da estatura, a dieta deficiente em cálcio e níveis de aminoácido fenilalanina elevados têm sido descritos como os principais fatores para a aquisição de massa óssea inadequada. A suplementação de cálcio em crianças saudáveis mostrou um efeito positivo sobre a aquisição de massa óssea na fase da pré-puberdade. Assim, torna-se relevante compreender a necessidade da suplementação de cálcio em pacientes fenilcetonúria, a fim de favorecer o desenvolvimento ósseo esperado.<br>Phenylketonuria is an inborn error of the metabolism of the amino acid phenylalanine. The treatment is essentially dietetic and involves a severe restriction in the consumption of foods containing aminoacid phenylalanine. Although the diet is complemented with supplements in order to meet the vitamin, mineral and essential amino acid requirements, nutritional deficiencies still occur. This is mainly due to restricting the consumption of protein sources, which results in low intake of several nutrients, including calcium. Calcium is strongly related to bone mineral formation. Recent studies have demonstrated that patients with phenylketonuria often present osteopenia and fractures, the greatest incidence being in children older than 8 years. Rapid growth, a calcium-deficient diet and elevated aminoacid phenylalanine plasma levels have been described as the principal factors responsible for inadequate bone formation. It has been shown that calcium-supplementation in healthy children had a positive effect on bone mass acquisition during prepuberty. Therefore, it is pertinent to understand the need of calcium-supplementation in phenylketonuria in order to promote full bone development

Vitamin B₁₂ as a carrier for targeted platinum delivery: in vitro cytotoxicity and mechanistic studies

It is attractive to use vitamin B₁₂ as a carrier for targeted delivery of cytotoxic agents such as platinum complexes owing to the high demand for vitamin B₁₂ by fast proliferating cells. The basic {B₁₂-CN-Pt(II)} conjugates are recognized by intracellular enzymes and converted to coenzyme B₁₂ in an enzymatic adenosylation assay. The reductive adenosylation of {B₁₂-CN-Pt(II)} conjugates leads to the release of the Pt(II) complexes; thus, {B₁₂-CN-Pt(II)} conjugates can be considered as prodrugs. It is important not only to elucidate the activity of the cisplatin-B₁₂ conjugates, but also to understand the mode of action on a molecular level. Chemical reduction of {B₁₂-CN-Pt(II)} conjugates with cobaltocene yielded cob(II)alamin and induced release of the corresponding Pt(II) species. Kurnakov tests and coordination of 2'-deoxyguanosine or GMP to the released Pt(II) complexes allowed isolation and characterization of Pt(II) complexes as released during enzymatic adenosylation. The biological activity of these Pt(II) complexes was evaluated. Since the cleaved Pt(II) complexes show cytotoxicity, the {B₁₂-CN-Pt(II)} conjugates can be used for specific targeting of cancer cells and therapeutic drug delivery. Preliminary in vitro cytotoxicity studies indicated lower activity (IC(50) between 8 and 88 μM) than found for pure cisplatin. Since active transport and receptor-mediated uptake limits the intracellular {B₁₂-CN-Pt(II)} concentration, comparison with pure cisplatin is of limited use. We could show that the Pt(II) complexes cleaved from B₁₂ exerted a cytotoxicity comparable to that of cisplatin itself. Cytotoxicity studies in vitamin B₁₂ free media showed a dependence on the addition of transcobalamin II for B₁₂-Pt(II) conjugates