PET scan analysis demonstrated the early reduction of cerebral glucose metabolism in Alzheimer disease (AD) patients that can make neurons vulnerable to damage via the alteration of the hexosamine biosynthetic pathway (HBP). Defective HBP leads to flawed protein O-GlcNAcylation coupled, by a mutual inverse relationship, with increased protein phosphorylation on Ser/Thr residues. Altered O-GlcNAcylation of Tau and APP have been reported in AD and is closely related with pathology onset and progression. In addition, type 2 diabetes patients show an altered O-GlcNAcylation/phosphorylation that might represent a link between metabolic defects and AD progression. Our study aimed to decipher the specific protein targets of altered O-GlcNAcylation in brain of 12-month-old 3×Tg-AD mice compared with age-matched non-Tg mice. Hence, we analysed the global O-GlcNAc levels, the levels and activity of OGT and OGA, the enzymes controlling its cycling and protein specific O-GlcNAc levels using a bi-dimensional electrophoresis (2DE) approach. Our data demonstrate the alteration of OGT and OGA activation coupled with the decrease of total O-GlcNAcylation levels. Data from proteomics analysis led to the identification of several proteins with reduced O-GlcNAcylation levels, which belong to key pathways involved in the progression of AD such as neuronal structure, protein degradation and glucose metabolism. In parallel, we analysed the O-GlcNAcylation/phosphorylation ratio of IRS1 and AKT, whose alterations may contribute to insulin resistance and reduced glucose uptake. Our findings may contribute to better understand the role of altered protein O-GlcNAcylation profile in AD, by possibly identifying novel mechanisms of disease progression related to glucose hypometabolism.
Introduction:
Traumatic injuries are the leading cause of death among <40 year olds, a good part of the working age population. Traumatic injuries are also the leading cause of lost productivity, causing more lost working days than cancer or vascular cardiomyopathy.
Materials and Methods:
We retrospectively and statistically analyzed the characteristics of facial fractures treated between June 2010 and December 2016 at the Maxillofacial Adult Surgery Unit, Spedali Civili Brescia, Italy.
Discussion:
Facial fractures are common in polytrauma patients, due to exposure of the cephalic end. The incidence of concomitant facial injuries with major trauma is 15%–24% in England (between Liverpool and London) and up to 34% in Washington, based on a large database of 87,174 patients. High-energy trauma frequently involving multiple traumatic injuries often leads to complex facial fractures, affecting different portions of the splanchnocranium.
Conclusions:
Treatment of facial fractures often focuses on functional or esthetic outcomes, and the outcomes are often substantially worse than those of other trauma treatments. Given the esthetic value of the face, facial trauma often leads to heightened emotional distress.
This study was undertaken to compare the effect of 1 year hemodialysis (HD) or hemodiafiltration (HDF) treatment on peripheral neuropathy. Thus 21 of 42 patients on chronic HD (1–1.3 m2 cuprophane dialyzer, Qb 300 ml/min) were switched to HDF (1.3 m2 polysulfone dialyzer, Qb 400 ml/min, substitution volume 9-13 liters, ultrafiltration rate 60-70 ml/min), while the remaining patients were considered as a control group. Treatment time was scheduled both in HD and HDF to maintain adequate BUN levels in relation to protein catabolic rate. However, HDF provided a significantly greater weekly inulin (MW 5,000) clearance than HD (5.8 ± 1.2 vs. 1.6 ± 0.2 ml/min; p < 0.001). HD and HDF groups were comparable for age, time on dialysis and starting electroneurographic parameters, which were on average within the normal range. After 1 year follow-up, creatinine, hematocrit, calcium, phosphate, PTH, BUN, protein catabolic rate and residual GFR were comparable in the two groups, whereas β2-microglobulin was significantly reduced in HDF patients (29 ± 6.7 vs. 38.8 ± 13.9 mg/l in HD patients, p < 0.01). During the 1-year treatment, electroneurographic parameters did not change in HDF patients, whereas a significant decrease of ulnar motor nerve conduction velocity, ulnar muscle action potential amplitudes, median sensory nerve conduction velocity and peroneal muscle action potential amplitudes was detected in HD patients. We conclude that HDF might prevent the worsening of the electroneurographic indices occurring during chronic HD treatment, as it provides a more effective removal of middle and larger molecules than HD. The use of a more bio-compatible membrane in HDF might further contribute to this favorable effect on uremic neuropathy.
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