In order to study antioxidant action on lipid hydroperoxide decomposition, the effects of alpha-tocopherol (TOH) and ascorbyl palmitate on the decomposition rate and reaction sequences of 9- and 13-cis,trans methyl linoleate hydroperoxide (cis,trans ML-OOH) decomposition in hexadecane were studied at 40 degrees C. Decomposition of cis,trans ML-OOH as well as the formation and isomeric configuration of methyl linoleate hydroxy and ketodiene compounds were followed by high-performance liquid chromatographic analysis. TOH effectively inhibited the decomposition of ML-OOH. The decomposition rate was two times slower at 0.2 mM and more than 10 times slower at 2 and 20 mM of TOH. Ascorbyl palmitate (0.2, 2, and 20 mM) slightly accelerated the decomposition of ML-OOH. Both compounds had an effect on the reaction sequences of ML-OOH decomposition. At high levels TOH inhibited the isomerization of cis,trans ML-OOH to trans,trans ML-OOH through peroxyl radicals and increased the formation of hydroxy compounds. Further, the majority of the hydroxy and ketodiene compounds formed had a cis,trans configuration, indicating that cis,trans ML-OOH decomposed through alkoxyl radicals without isomerization. These results suggest that when inhibiting the decomposition of hydroperoxides, TOH can act as a hydrogen atom donor to both peroxyl and alkoxyl radicals. In the presence of ascorbyl palmitate, cis,trans ML-OOH decomposed rapidly but without isomerization. In contrast to TOH, the majority of hydroxy compounds were cis,trans, but the ketodiene compounds were trans,trans isomers. This indicates that ascorbyl palmitate reduced cis,trans ML-OOH to the corresponding hydroxy compounds. However, the simultaneous formation of trans,trans ketodiene compounds suggests that ML-OOH decomposition, similar to the control sample, also occurred in these samples. Thus, under these experimental conditions, the reduction of ML-OOH to more stable hydroxy compounds did not occur to an extent significant enough to inhibit the radical chain reactions of ML-OOH decomposition.

Low striatal DAT function may predispose PD patients to VHs, and the regional distribution of the findings suggests a particular role of the ventral striatum. This is in line with non-PD research that has implicated ventral striatal dysfunction in psychosis.

The reduction in alcohol prices and the concomitant increase in alcohol consumption did not increase the incidence of alcohol-related moderate-to-severe TBI.

Gut microbiota alterations in Parkinson’s disease (PD) have been found in several studies and are suggested to contribute to the pathogenesis of PD. However, previous results could not be adequately adjusted for a potential confounding effect of PD medication and disease duration, as almost all PD participants were already using dopaminergic medication and were included several years after diagnosis. Here, the gut microbiome composition of treatment-naive de novo PD subjects was assessed compared to healthy controls (HC) in two large independent case-control cohorts (n = 136 and 56 PD, n = 85 and 87 HC), using 16S-sequencing of fecal samples. Relevant variables such as technical batches, diet and constipation were assessed for their potential effects. Overall gut microbiome composition differed between PD and HC in both cohorts, suggesting gut microbiome alterations are already present in de novo PD subjects at the time of diagnosis, without the possible confounding effect of dopaminergic medication. Although no differentially abundant taxon could be replicated in both cohorts, multiple short chain fatty acids (SCFA) producing taxa were decreased in PD in both cohorts. In particular, several taxa belonging to the family Lachnospiraceae were decreased in abundance. Fewer taxonomic differences were found compared to previous studies, indicating smaller effect sizes in de novo PD.

IntroductionTotal parkinsonian motor symptom severity correlates with presynaptic striatal dopamine function in patients with Parkinson’s disease. There is a lack of studies that have investigated the associations between parkinsonian motor signs and striatal dopaminergic deficiency in patients with parkinsonism of an unknown origin. Identification of specific motor signs associated with the highest likelihood of striatal dopamine deficiency could aid the differential diagnostics of parkinsonian and tremor syndromes.MethodsIn this cross-sectional clinical and imaging study, detailed motor examinations were performed for 221 patients with parkinsonism or tremor of an unknown origin immediately before dopamine transporter (DAT) [I-123]FP-CIT SPECT imaging. Region-of-interest and voxel-based methods were used to investigate striatal DAT deficiency in relation to individual motor signs.ResultsUpper extremity rigidity and facial expression were the only motor signs that differentiated patients with normal and abnormal striatal DAT function. The presence of any upper extremity rigidity showed the highest likelihood of DAT deficiency (OR 4.79, 95% CI 1.56–14.75, P = 0.006) followed by reduced facial expression (OR 2.14, 95% CI 1.14–4.00, P = 0.018). In patients with DAT deficits, reduced facial expression was associated with DAT deficiency specifically in the caudate nucleus, and increased upper extremity rigidity was associated with DAT loss in the dorsal putamen (FWE-corrected P < 0.05).ConclusionsIncreased upper extremity muscle tone and hypomimia are independently associated with a higher likelihood of striatal hypodopaminergic imaging finding. This information can be used as a factor when the clinical need of auxiliary investigations, such as DAT SPECT, is considered for patients with parkinsonism.Electronic supplementary materialThe online version of this article (10.1007/s00415-019-09202-6) contains supplementary material, which is available to authorized users.

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Background The neurophysiological correlates of gastrointestinal symptoms (GISs) in Parkinson's disease (PD) are not well understood. It has been proposed that in patients with a gastrointestinal origin of PD dopaminergic neurodegeneration would be more symmetric. Objectives The aim is to assess the associations between GISs and asymmetry of nigrostriatal dopaminergic neurodegeneration in PD. Methods Ninety PD patients were assessed using motor and GIS scales and 123I‐FP‐CIT SPECT. We calculated the asymmetry index and the predominant side of motor symptoms and dopamine transporter (DAT) imaging defect and assessed their association with GISs. Results There were no significant differences in GISs between symmetric and asymmetric dopaminergic defect. Left predominant defect was related to more GIS and higher constipation scores. Conclusions GISs were associated with left predominant reduction in putaminal DAT binding but not asymmetry per se. It remains open whether left‐sided DAT deficit is related to more pronounced GI involvement or symptom perception in PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

The clinical evaluation of dopamine transporter (DAT) SPECT scans typically relies on visual analysis in combination with an automated semi-quantitative method. The interpretation of the results may be difficult in cases that show disagreement between the two methods on the borderline of abnormality. The frequency and clinical characteristics of such cases are unclear. Automated semi-quantitative analyses and independent visual analyses by two experienced nuclear medicine physicians and four inexperienced raters were performed for 120 patients with clinically uncertain parkinsonism scanned with brain [I-123]FP-CIT SPECT. Agreement was evaluated with kappa statistics. The clinical characteristics of patients who had discrepant findings between the two analysis methods were investigated. The expert raters outperformed nonexperts in terms of agreement between visual and automated analyses (κ = 0.66, 0.72 vs. 0.23-0.54) and between raters (κ = 0.81 vs. 0.44-0.63). Twelve patients showed discrepant findings between the visual and automated analyses. These patients were older compared to other patients (p = 0.023), had 17.6 % lower mean striatal tracer binding compared to normal scans (p = 0.003) and 62.7 % higher compared to abnormal scans (p < 0.001). After a minimum of 4.5 years of clinical follow-up, none of these patients developed neurodegenerative parkinsonism. Clinical DAT SPECT scans show discrepancies between visual and automated analyses in 10 % of cases. The patients with discrepant findings are older, show normal to slightly abnormal tracer binding, and importantly, do not develop neurodegenerative parkinsonism syndromes. Visual analyses by experienced raters are reliable, but the diagnostic accuracy in discrepant cases can be improved by an automated method.