Enteric α-synuclein impairs intestinal epithelial barrier through caspase-1-inflammasome signaling in Parkinson's disease before brain pathology.

Bowel inflammation, impaired intestinal epithelial barrier (IEB), and gut dysbiosis could represent early events in Parkinson's disease (PD). This study examined, in a descriptive manner, the correlation among enteric α-synuclein, bowel inflammation, impairments of IEB and alterations of enteric bacteria in a transgenic (Tg) model of PD before brain pathology. Human A53T α-synuclein Tg mice were sacrificed at 3, 6, and 9 months of age to evaluate concomitance of enteric inflammation, IEB impairments, and enteric bacterial metabolite alterations during the early phases of α-synucleinopathy. The molecular mechanisms underlying the interplay between α-synuclein, activation of immune/inflammatory responses and IEB alterations were investigated with in vitro experiments in cell cultures. Tg mice displayed an increase in colonic levels of IL-1ß, TNF, caspase-1 activity and enteric glia activation since 3 months of age. Colonic TLR-2 and zonulin-1 expression were altered in Tg mice as compared with controls. Lipopolysaccharide levels were increased in Tg animals at 3 months, while fecal butyrate and propionate levels were decreased. Co-treatment with lipopolysaccharide and α-synuclein promoted IL-1ß release in the supernatant of THP-1 cells. When applied to Caco-2 cells, the THP-1-derived supernatant decreased zonulin-1 and occludin expression. Such an effect was abrogated when THP-1 cells were incubated with YVAD (caspase-1 inhibitor) or when Caco-2 were incubated with anakinra, while butyrate incubation did not prevent such decrease. Taken together, early enteric α-synuclein accumulation contributes to compromise IEB through the direct activation of canonical caspase-1-dependent inflammasome signaling. These changes could contribute both to bowel symptoms as well as central pathology.

Aging in a relaxor ferroelectric: scaling and memory effects.

A crossover as a function of temperature is found in the zero-field aging properties of the relaxor ferroelectric Pb(Mg(1/3)Nb(2/3))O3. Below a temperature near which nonlinear susceptibility has indicated a suspected phase transition, the time-frequency dependence shows simple scale-independent behavior resembling that for spin glasses. As in spin glasses, high temperature aging is stable as further aging occurs at lower temperature, but not vice versa, indicating hierarchical state arrangement. A more general interpretation of such effects is briefly discussed.

[Linear tomography and the Zonarc TMJ program. Reproducibility of condylar position of TMJ after surgical correction of dysgnathia]. / Lineare Tomographie und Zonarc-TMJ-Programm. Die Reproduzierbarkeit der Kondylusposition des TMJ nach kieferchirurgischer Korrektur von Dysgnathien.

In this clinical study the position of the mandibular condyles of 40 patients treated for malocclusion by surgical splitting of the mandibular ramus alone or combined with Le Fort I osteotomies was studied on lateral linear TMJ tomograms. Linear tomograms of the right and left TMJ with the mandible closed were taken from each patient prior to surgery and 6 months postoperatively. The postoperative changes in condylar position wee assessed in terms of direction and amount. Condylar displacements were found in 89% of the examined joints, most of them were less than 2mm. All types and combinations of displacement occurred, however, general trends in direction depending on the type of treatment could not be established with statistical significance. The type of surgical correction, its direction and amount did not seem to have an effect on the direction and amount of condylar displacement resulting. A comparison of the measured values with data in the literature showed that the amount of condylar displacement was markedly less--this seemed to be attributable to our precise evaluation method and a more sophisticated surgical technique.