Major life events and risk of Parkinson's disease

Major life events such as divorce, death of a spouse or a child, or long‐term unemployment are stressful to most people and animal models have suggested a link between stress and onset of parkinsonian symptoms. In a large case‐control study based on nationwide registries, we aim to address whether major life events are risk factors for Parkinson's disease. Between 1986 and 2006, we identified 13,695 patients with a (PD) primary diagnosis of PD in the Danish National Hospital Register. Each case was frequency matched by age and gender to five population controls. Information on major life events before onset of PD was ascertained from national registries. Among men, number of life events was associated with risk of Parkinson's disease in an inverse dose‐response manner (P < 0.0001). Compared to no events, three or more events were associated with a 42% lower risk of PD (OR = 0.58; 95 % CI: 0.34–0.99). Life events were not associated with PD in women. In contrast, a higher risk of PD was observed among women who had never been married (1.16; 1.04–1.29) and among men (1.47; 1.18–1.82) and women (1.30; 1.05–1.61) who have never been employees. The lower risk of Parkinson's disease among men who had experienced life events was unexpected but might suggest a general “risk avoidance behavior” in Parkinson's patients. © 2010 Movement Disorder Society     

Phenguignardic acid and guignardic acid, phytotoxic secondary metabolites from Guignardia bidwellii

Bioactivity-guided isolation led to the identification of phenguignardic acid (2), a new phytotoxic secondary metabolite from submerged cultures of grape black rot fungus, Guignardia bidwellii. The compound is structurally related to guignardic acid (1), a dioxolanone moiety-containing metabolite isolated previously from Guignardia species. However, in contrast to guignardic acid, which is presumably synthesized from deamination products of valine and phenylalanine, the biochemical precursor for the biosynthesis of the new phytotoxin appears to be exclusively phenylalanine. Guignardic acid was also found in extracts of cultures from Guignardia bidwellii. The phytotoxic activities of both compounds were assessed in plant assays using either detached vine leaves or intact plants. Antimicrobial and cytotoxic activities of phenguignardic acid were determined.     

Efficacy of a benzocaine lozenge in the treatment of uncomplicated sore throat

Benzocaine lozenges are popular in symptomatic treatment of acute sore throat. The aim of this study was to evaluate if sucking a benzocaine lozenge was superior to a placebo lozenge in patients with pain while swallowing. Volunteers with acute, uncomplicated sore throat received randomly and double-blind either a benzocaine 8 mg or a placebo lozenge. Pain was assessed on a numerical visual rating scale. The primary outcome measure was the sum of the pain intensity differences (SPID) over 2 h. Secondary outcome measures included the number of patients who reported 50% or more of their baseline pain score (responders) and those with worthwhile and complete pain relief, the times to worthwhile/complete pain relief and to pain recurrence and the occurrence of any adverse effects. A predefined interim analysis after including 50 patients revealed the superiority of benzocaine versus placebo in the SPID (p = 0.0086). At this time, a total of 165 patients had been recruited (full analysis set, FAS) and underwent statistical analysis. In the FAS, median SPID had significantly more decreased in patients receiving benzocaine compared to placebo (−12 vs. − 5, p = 0.001). There were significantly more responders and patients with worthwhile pain relief in group benzocaine. The number of patients with complete pain relief was very small. Median time to worthwhile pain relief was 20 min (benzocaine) and >45 min (placebo). Adverse events were not observed. Benzocaine lozenges are superior to placebo lozenges and a useful, well-tolerated treatment option to reduce painful pharyngeal discomfort.     

Imatinib mesylate at therapeutic doses has no impact on folliculogenesis or spermatogenesis in a leukaemic mouse model

Imatinib should be avoided in women planning to become pregnant or during pregnancy, due to a higher risk of congenital malformations. However, it is not known whether imatinib affects future potential for fertility. Here we analysed ovaries and testes from adult mice receiving imatinib, focusing on testicular and ovarian functions. Seven male and 7 female mice were orally treated with 150 mg/kg body weight/day imatinib for two months. No effects on folliculogenesis or spermatogenesis could be observed postmortem by histological examinations, suggesting that, at least in two mouse models of imatinib treatment this tyrosine kinase inhibitor does not reduce fertility.     

HMGB1 is overexpressed in tumor cells and promotes activity of regulatory T cells in patients with head and neck cancer

HMGB1 has gained a prominent role in cancer development and is implicated in tumor escape phenomena. To date, only few data are available on effects of HMGB1 on regulatory T cells (Treg) in cancer patients. This study evaluates the prevalence of HMGB1 and its effects on Treg in patients with head and neck squamous cell carcinoma (HNSCC). Sixty-seven patients with HNSCC and seventeen healthy donors were included in this study. Tumor tissues of patients were analyzed for expression of HMGB1 employing immunofluorescence and qRT-PCR. HMGB1 serum levels were assessed using ELISA. Tumor-infiltration and Treg from peripheral blood were phenotyped with flow cytometry and immunofluorescence microscopy. Migration and suppressive function of Treg upon HMGB1 stimulation was analyzed in chemotaxis assays and CFSE assays. HMGB1 is overexpressed in tumor cells of HNSCC, and serum levels are significantly elevated. Tumor-infiltrating Treg express HMGB1-recognizing receptors, TLR4 and RAGE. HMGB1 is a chemoattractant for Treg and promotes their suppressive function. Our data provide new aspects how the HMGB1 tumor-derived danger signal augments function of Treg in patients with HNSCC.