99 research outputs found
Early Energy Deficit in Huntington Disease: Identification of a Plasma Biomarker Traceable during Disease Progression
Huntington disease (HD) is a fatal neurodegenerative disorder, with no effective treatment. The pathogenic mechanisms underlying HD have not been elucidated, but weight loss, associated with chorea and cognitive decline, is a characteristic feature of the disease that is accessible to investigation. We, therefore, performed a multiparametric study exploring body weight and the mechanisms of its loss in 32 presymptomatic carriers and HD patients in the early stages of the disease, compared to 21 controls. We combined this study with a multivariate statistical analysis of plasma components quantified by proton nuclear magnetic resonance (1H NMR) spectroscopy. We report evidence of an early hypermetabolic state in HD. Weight loss was observed in the HD group even in presymptomatic carriers, although their caloric intake was higher than that of controls. Inflammatory processes and primary hormonal dysfunction were excluded. 1H NMR spectroscopy on plasma did, however, distinguish HD patients at different stages of the disease and presymptomatic carriers from controls. This distinction was attributable to low levels of the branched chain amino acids (BCAA), valine, leucine and isoleucine. BCAA levels were correlated with weight loss and, importantly, with disease progression and abnormal triplet repeat expansion size in the HD1 gene. Levels of IGF1, which is regulated by BCAA, were also significantly lower in the HD group. Therefore, early weight loss in HD is associated with a systemic metabolic defect, and BCAA levels may be used as a biomarker, indicative of disease onset and early progression. The decreased plasma levels of BCAA may correspond to a critical need for Krebs cycle energy substrates in the brain that increased metabolism in the periphery is trying to provide
Brief Report: High Frequency of Biochemical Markers for Mitochondrial Dysfunction in Autism: No Association with the Mitochondrial Aspartate/Glutamate Carrier SLC25A12 Gene
A new MRI rating scale for progressive supranuclear palsy and multiple system atrophy: validity and reliability
AIM
To evaluate a standardised MRI acquisition protocol and a new image rating scale for disease severity in patients with progressive supranuclear palsy (PSP) and multiple systems atrophy (MSA) in a large multicentre study.
METHODS
The MRI protocol consisted of two-dimensional sagittal and axial T1, axial PD, and axial and coronal T2 weighted acquisitions. The 32 item ordinal scale evaluated abnormalities within the basal ganglia and posterior fossa, blind to diagnosis. Among 760 patients in the study population (PSP = 362, MSA = 398), 627 had per protocol images (PSP = 297, MSA = 330). Intra-rater (n = 60) and inter-rater (n = 555) reliability were assessed through Cohen's statistic, and scale structure through principal component analysis (PCA) (n = 441). Internal consistency and reliability were checked. Discriminant and predictive validity of extracted factors and total scores were tested for disease severity as per clinical diagnosis.
RESULTS
Intra-rater and inter-rater reliability were acceptable for 25 (78%) of the items scored (≥ 0.41). PCA revealed four meaningful clusters of covarying parameters (factor (F) F1: brainstem and cerebellum; F2: midbrain; F3: putamen; F4: other basal ganglia) with good to excellent internal consistency (Cronbach α 0.75-0.93) and moderate to excellent reliability (intraclass coefficient: F1: 0.92; F2: 0.79; F3: 0.71; F4: 0.49). The total score significantly discriminated for disease severity or diagnosis; factorial scores differentially discriminated for disease severity according to diagnosis (PSP: F1-F2; MSA: F2-F3). The total score was significantly related to survival in PSP (p<0.0007) or MSA (p<0.0005), indicating good predictive validity.
CONCLUSIONS
The scale is suitable for use in the context of multicentre studies and can reliably and consistently measure MRI abnormalities in PSP and MSA. Clinical Trial Registration Number The study protocol was filed in the open clinical trial registry (http://www.clinicaltrials.gov) with ID No NCT00211224
Rhizosphere properties of rice genotypes as influenced by anoxia and availability of zinc and iron
Reliability and day-to-day variability of peak fat oxidation during treadmill ergometry
Effects of temperature in juvenile seabass (Dicentrarchus labrax L.) biomarker responses and behaviour: implications for environmental monitoring
The effects of temperature on European seabass
(Dicentrarchus labrax L.) juveniles were investigated using
a 30-day bioassay carried out at 18 and 25 °C in laboratory
conditions. A multiparameter approach was applied including
fish swimming velocity and several biochemical parameters
involved in important physiological functions. Fish exposed for
four weeks to 25 °C showed a decreased swimming capacity,
concomitant with increased oxidative stress (increased catalase
and glutathione peroxidase activities) and damage (increased
lipid peroxidation levels), increased activity of an enzyme
involved in energy production through the aerobic pathway
(isocitrate dehydrogenase) and increased activities of brain and
muscle cholinesterases (neurotransmission) compared to fish
kept at 18 °C. Globally, these findings indicate that basic
functions, essential for juvenile seabass surviving and well
performing in the wild, such as predation, predator avoidance,
neurofunction and ability to face chemical stress may be compromised
with increasing water temperature. This may be of
particular concern if D. labrax recruitment phase in northwest
European estuaries and coastal areas happens gradually inmore
warm environments as a consequence of global warming.
Considering that the selected endpoints are generally applied
in monitoring studies with different species, these findings also
highlight the need of more research, including interdisciplinary
and multiparameter approaches, on the impacts of temperature
on marine species, and stress the importance of considering
scenarios of temperature increase in environmental monitoring
and in marine ecological risk assessment
Evaluation of the interference due to haemoglobin, bilirubin and lipids on Immulite 2500 assays: a practical approach
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