Evaluation of cerebrospinal fluid alpha-synuclein seed amplification assay in PSP and CBS.

Background: Seed amplification assay (SAA) testing has become an important biomarker in the diagnosis of alpha-synuclein related neurodegenerative disorders. Objectives: To assess the rate of alpha-synuclein SAA positivity in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), and analyse the clinical and pathological features of SAA positive and negative cases. Methods: 106 CSF samples from clinically diagnosed PSP (n=59), CBS (n=37) and indeterminate parkinsonism cases (n=10) were analysed using alpha-synuclein SAA. Results: Three cases (1 PSP, 2 CBS) were Multiple System Atrophy (MSA)-type SAA positive. 5/59 (8.5%) PSP cases were Parkinson's disease (PD)-type SAA positive, and these cases were older and had a shorter disease duration compared with SAA negative cases. In contrast, 9/35 (25.7%) CBS cases were PD-type SAA positive. Conclusions: Our results suggest that PD-type seeds can be detected in PSP and CBS using a CSF alpha-synuclein SAA, and in PSP this may impact on clinical course.

Association between the antioxidant uric acid and depression and antidepressant medication use in 96 989 individuals.

OBJECTIVE: In the last decade, several studies have suggested that depression is accompanied by increased oxidative stress and decreased antioxidant defenses. We tested the hypothesis that high levels of the antioxidant uric acid are associated with lower risk of hospitalization with depression and use of prescription antidepressant medication. METHOD: We examined plasma levels of the antioxidant uric acid in 96 989 individuals from two independent cohort studies. Logistic regression and Cox proportional hazards regression models were multivariable adjusted for age, gender, alcohol, smoking, income, body mass index, C-reactive protein, hemoglobin, triglycerides, cardiovascular disease, diabetes, and intake of meat and vegetables. Results were performed separately in each study and combined in a meta-analysis. RESULTS: In both studies, high uric acid was associated with lower risk of hospitalization as in-patient or out-patient with depression and antidepressant medication use. A doubling in uric acid was associated with an effect estimate of 0.57 (95% CI 0.49-0.65) and 0.77 (0.73-0.81) for hospitalization with depression and antidepressant medication use. The association was consistent across strata of all covariates. Results were attenuated in Cox regression analyses with less statistical power. CONCLUSION: High plasma levels of uric acid were associated with low risk of depression hospitalization and antidepressant medication use.

No relationship between thymidine phosphorylase (TP, PD-ECGF) expression and hypoxia in carcinoma of the cervix.

The expression of hypoxia-regulated genes promotes an aggressive tumour phenotype and is associated with an adverse cancer treatment outcome. Thymidine phosphorylase (TP) levels increase under hypoxia, but the protein has not been studied in association with hypoxia in human tumours. An investigation was made, therefore, of the relationship of tumour TP with hypoxia, the expression of other hypoxia-associated markers and clinical outcome. This retrospective study was carried out in patients with locally advanced cervical carcinoma who underwent radiotherapy. Protein expression was evaluated with immunohistochemistry. Hypoxia was measured using microelectrodes and the level of pimonidazole binding. There was no relationship of TP expression with tumour pO(2) (r=-0.091, P=0.59, n=87) or pimonidazole binding (r=0.13, P=0.45, n=38). There was no relationship between TP and HIF-1alpha, but there was a weak borderline significant relationship with HIF-2alpha expression. There were weak but significant correlations of TP with the expression of VEGF, CA IX and Glut-1. In 119 patients, the presence of TP expression predicted for disease-specific (P=0.032) and metastasis-free (P=0.050) survival. The results suggest that TP is not a surrogate marker of hypoxia, but is linked to the expression of hypoxia-associated genes and has weak prognostic power.