Clinical features of Parkinson's disease (PD) patients with LRRK2 mutations (PD
) resemble those of idiopathic PD (PD
). Similar to PD
, reports on CSF levels of alpha-synuclein, amyloid-beta
, ...total-tau and phosphorylated-tau seem conflicting 1. Correspondingly, histopathology in PD
is remarkably variable, including typical Lewy-body pathology with alpha-synuclein aggregation but also tau aggregation or nigral degeneration without distinctive histopathology. However, longitudinal CSF biomarker profiles during lifetime along with post-mortem histopathology are missing. This article is protected by copyright. All rights reserved.
Recent studies have provided evidence that uric acid (UA), a natural antioxidant, may play a role in the development and progression of Parkinsons disease (PD) and of dementia. In this clinical study ...we were therefore interested in the role of UA in Lewy body disorders (LBD), which includes Parkinsons disease (PD) and a common form of neurodegenerative dementias, dementia with Lewy bodies (DLB). Ninety-five LBD patients (55 non-demented PD patients, PDND; 20 PD patients with dementia, PDD; and 20 DLB patients) and 76 controls underwent clinical and biochemical analyses including, from a subcohort, cerebrospinal fluid (CSF) analyses, and analysis of three single nucleotide polymorphisms (SNPs) known to be associated with altered serum UA levels. We confirmed previous findings of lowered serum UA levels in LBD patients compared to controls. In CSF, UA levels were significantly higher in PDND patients (median 0.7 mg/dl) compared only to demented LBD patients (0.4 mg/dl; p = 0.03), but not to controls (0.5 mg/dl; p = 0.12). CSF UA levels correlated positively with CSF A42 levels. This correlation was highest in controls ( = 0.67), intermediate in PDND ( = 0.49), but not observable in demented LBD patients ( = 0.10). These findings suggest an involvement of serum UA in LBD occurrence, and an involvement of CSF UA in cognitive decline in LBD, possibly through the A pathway. SNP rs1165205 (SLC17A3) was weakly associated with altered CSF UA levels. Taken together, our results provide first evidence for disease-relevant but potentially distinct roles of UA in the blood and CSF compartment, respectively, in LBD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Lewy body disease, defined by the occurrence of -synuclein aggregates as fibrils in Lewy bodies and Lewy neurites, is associated with increased probabilities for both co-occurrence of dementia, and ...co-occurrence of Alzheimer's disease (AD)-like pathology, in particular amyloid- (A) plaques and lowered cerebrospinal fluid (CSF) A42 levels. Not surprisingly, in patients with Lewy body disease patients, there is a strong association between dementia and A pathology. Neprilysin (NEP) is an A-degrading protein found at presynaptic terminals and in body fluids. Reduced CSF NEP activity levels have been shown to occur in early AD, suggesting that altered CSF NEP activity levels may also be associated with dementia and lowered CSF A42 levels in Lewy body disease. Hypothesizing a relation between CSF NEP activity and dementia in Lewy body disease, we determined CSF and serum NEP activity, and A42 levels of 41 demented Lewy body disease patients, 38 non-demented Lewy body disease patients, and of 23 elderly controls. Demented Lewy body disease patients had lowered CSF NEP activity levels (0.3 pmol/min*ml, 0.281.5), compared to both non-demented Lewy body disease subjects (8.5 pmol/min*ml, 0.287.2; p=0.004) and controls (21.5 pmol/ml*min, 0.15413.4; p=0.02). In addition, CSF NEP activity levels correlated positively with CSF A42 levels (Rho=0.28, p=0.008) which was not explained by the presence or absence of ApoE4. Serum NEP activity levels were not significantly different between the groups. We conclude that, in Lewy body disease, CSF NEP activity levels are associated with dementia, probably via the A pathway.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background Mutations in the gene coding for glucocerebrosidase (GBA), which metabolizes glucosylceramide (a monohexosylceramide) into glucose and ceramide, is the most common genetic risk factor for ...sporadic Parkinson's disease (PD). GBA mutation carriers are more likely to have an earlier age of onset and to develop cognitive impairment and dementia. We hypothesized that plasma levels of lipids involved in ceramide metabolism would also be altered in PD non-GBA mutation carriers and associated with worse cognition. Methods Plasma ceramide, monohexosylceramide, and lactosylceramide levels in 26 cognitively normal PD patients, 26 PD patients with cognitive impairment or dementia, and 5 cognitively normal non-PD controls were determined by LC/ESI/MS/MS. Results Levels of all lipid species were higher in PD patients versus controls. Among PD patients, levels of ceramide C16:0, C18:0, C20:0, C22:0, and C24:1 and monohexosylceramide C16:0, C20:0 and C24:0 species were higher (all P<0.05) in those with versus without cognitive impairment. Conclusion These results suggest that plasma ceramide and monohexosylceramide metabolism is altered in PD non-GBA mutation carriers and that higher levels are associated with worse cognition. Additional studies with larger sample sizes, including cognitively normal controls, are needed to confirm these findings.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In recent years, the use of carbon fibers (CFs) in various sectors of industry has been increasing. Despite the similarity of CF degradation products to other toxicologically relevant materials such ...as asbestos fibers and carbon nanotubes, a detailed toxicological evaluation of this class of material has yet to be performed. In this work, we exposed advanced air-liquid interface cell culture models of the human lung to CF. To simulate different stresses applied to CF throughout their life cycle, they were either mechanically (mCF) or thermo-mechanically pre-treated (tmCF). Different aspects of inhalation toxicity as well as their possible time-dependency were monitored. mCFs were found to induce a moderate inflammatory response, whereas tmCF elicited stronger inflammatory as well as apoptotic effects. Furthermore, thermal treatment changed the surface properties of the CF resulting in a presumed adhesion of the cells to the fiber fragments and subsequent cell loss. Triple-cultures encompassing epithelial, macrophage, and fibroblast cells stood out with an exceptionally high inflammatory response. Only a weak genotoxic effect was detected in the form of DNA strand breaks in mono- and co-cultures, with triple-cultures presenting a possible secondary genotoxicity. This work establishes CF fragments as a potentially harmful material and emphasizes the necessity of further toxicological assessment of existing and upcoming advanced CF-containing materials.
Cranioplasty following decompressive craniectomy is of low surgical complexity, so much so that it has become the “beginners” cranial case. However, these “simple” procedures may have high ...complication rates. Identification of specific risk factors would allow targeted intervention to lower the complication rates. The aim of this study was to assess the rate of complications and to evaluate potential risk factors. We conducted a review of all patients who underwent cranioplasty in our center following decompressive craniectomy for stroke or brain trauma between 2009 and 2016. One hundred fifty-two patients were identified. Fifty-three percent were male. Mean age was 48 (range 11–78). Median time from craniectomy until cranioplasty was 102 days (range 14–378
)
. The overall rate of complications, such as postoperative bleeding, seizures, postoperative infection, and hydrocephalus, was 30%. The mortality rate was 1%. None of the following potential risk factors was associated with significantly increased risk of periprocedural complications: gender (
p
= 0.34), age (
p
= 0.39), cause of initial surgery (
p
= 0.08), duration of surgery (
p
= 0.59), time of surgery (0.24), surgical experience (
p
= 0.17), and time from craniectomy until cranioplasty (
p
= 0.27). The 30-day complication rate following cranioplasty is high, but serious permanent deficits from these complications were rare. We found no clear predictor for these 30-day complications, which renders its prevention difficult.
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