ABSTRACT
Abstract In Portugal, tetrahydrobiopterin (BH4)-responsive patients with phenylketonuria (PKU) are identified using a loading test (LT). Phenylalanine/natural protein (Phe/NP) intake is increased to elevate blood Phe prior to the LT. In a longitudinal retrospective study, the impact of Phe/NP titration post-LT in 58 patients (19.6 + 8.2 years) with PKU during 4 study periods (SPs) was examined. In SP1 (2010-2013), patients were diet treated only; in SP2 (2014), the Phe/NP titration was followed by the LT in SP3 (2015). In SP4 (2016), patients received diet treatment only (n » 49) or BH4 þdiet (n » 9). The median percentage blood Phe within the target range was higher in SP1 versus SP4 (64 [28-85] vs 45 [0-66]; P < .001). Our results suggest that transient Phe/NP titration, associated with a deliberate increase in NP, may adversely affect metabolic control. Controlled studies are necessary to examine the longer term impact of temporary increased NP with BH4 LT in non-BH4-responsive patients.
ABSTRACT
Valioso conhecimento a respeito de esquizofrenia tem sido gerado recentemente para decifrar sua patobiologia e revelar biomarcadores. Entretanto, esforços ainda são necessários, especialmente se levarmos em conta que essa debilitante desordem mental afeta aproximadamente 30 milhões de pessoas ao redor do mundo. Considerando que esquizofrenia é resultado de uma complexa interação entre fatores ambientais, função genética alterada e expressão proteica diferencial sistemática, a proteômica é provavelmente uma ferramenta adequada ao estudo dessa desordem. Aqui sintetizamos os principais achados em estudos proteômicos e posteriores direções a serem tomadas de forma a melhor compreender a bioquímica da esquizofrenia, bem como revelar biomarcadores.
Valuable knowledge about schizophrenia has been recently generated for deciphering its pathobiology and revealing biomarkers. However, efforts are still needed, especially if we take in account that this debilitating mental disorder affects approximately 30 million people worldwide. Considering that schizophrenia is a result of a complex interaction among environmental factors altered gene function and systematic differential protein expression, proteomics is likely to be a suitable tool for studying this disorder. Here we synthetize the main findings by proteomic studies and further directions to be taken in order to better comprehend the biochemistry of schizophrenia as well as reveal biomarkers. In addition, we summarize proteomic methodologies used in such studies
Subject(s)
Diagnosis, Differential , Mass Spectrometry/methods , Schizophrenia/diagnosis , Schizophrenia/metabolism , Biomarkers , Energy Metabolism , Oligodendroglia , ProteomicsABSTRACT
Motor impairment following stroke is a leading cause of disability in adults. Despite advances in motor rehabilitation techniques, many adult stroke survivors never approach full functional recovery. Intriguingly, children exhibit better rehabilitation outcomes when compared to adults suffering from comparable brain injuries, yet the reasons for this remain unclear. A common explanation is that neuroplasticity in adults is substantially limited following stroke, thus constraining the brain's ability to reorganize in response to neurological insult. This explanation, however, does not suffice for there is much evidence suggesting that neuroplasticity in adults is not limited following stroke. We hypothesize that diminished functional recovery in adults is in part due to inhibitory neuronal interactions, such as transcallosal inhibition, that serve to optimize motor performance as the brain matures. Following stroke, these inhibitory interactions pose rigid barriers to recovery by inhibiting activity in the affected regions and hindering recruitment of compensatory pathways. In contrast, children exhibit better rehabilitation outcomes in part because they have not fully developed the inhibitory interactions that impede functional recovery in adults. We suggest that noninvasive brain stimulation can be used in the context of motor rehabilitation following stroke to reduce the effects of existing inhibitory connections, effectively returning the brain to a state that is more amenable to rehabilitation. We conclude by discussing further research to explore this hypothesis and its implications