21 research outputs found
State of the art of immunoassay methods for B-type natriuretic peptides: An update
The aim of this review article is to give an update on the state of the art of the immunoassay
methods for the measurement of B-type natriuretic peptide (BNP) and its related peptides.
Using chromatographic procedures, several studies reported an increasing number of
circulating peptides related to BNP in human plasma of patients with heart failure. These
peptides may have reduced or even no biological activity. Furthermore, other studies have
suggested that, using immunoassays that are considered specific for BNP, the precursor of the
peptide hormone, proBNP, constitutes a major portion of the peptide measured in plasma of
patients with heart failure. Because BNP immunoassay methods show large (up to 50%)
systematic differences in values, the use of identical decision values for all immunoassay
methods, as suggested by the most recent international guidelines, seems unreasonable. Since
proBNP significantly cross-reacts with all commercial immunoassay methods considered
specific for BNP, manufacturers should test and clearly declare the degree of cross-reactivity of
glycosylated and non-glycosylated proBNP in their BNP immunoassay methods. Clinicians
should take into account that there are large systematic differences between methods when
they compare results from different laboratories that use different BNP immunoassays. On the
other hand, clinical laboratories should take part in external quality assessment (EQA) programs
to evaluate the bias of their method in comparison to other BNP methods. Finally, the authors
believe that the development of more specific methods for the active peptide, BNP1–32, should
reduce the systematic differences between methods and result in better harmonization of
results
Elevated glucose and oligomeric β-amyloid disrupt synapses via a common pathway of aberrant protein S-nitrosylation
Metabolic syndrome (MetS) and Type 2 diabetes mellitus (T2DM) increase risk for Alzheimer's disease (AD). The molecular mechanism for this association remains poorly defined. Here we report in human and rodent tissues that elevated glucose, as found in MetS/T2DM, and oligomeric β-amyloid (Aβ) peptide, thought to be a key mediator of AD, coordinately increase neuronal Ca(2+) and nitric oxide (NO) in an NMDA receptor-dependent manner. The increase in NO results in S-nitrosylation of insulin-degrading enzyme (IDE) and dynamin-related protein 1 (Drp1), thus inhibiting insulin and Aβ catabolism as well as hyperactivating mitochondrial fission machinery. Consequent elevation in Aβ levels and compromise in mitochondrial bioenergetics result in dysfunctional synaptic plasticity and synapse loss in cortical and hippocampal neurons. The NMDA receptor antagonist memantine attenuates these effects. Our studies show that redox-mediated posttranslational modification of brain proteins link Aβ and hyperglycaemia to cognitive dysfunction in MetS/T2DM and AD