Loss of vesicular dopamine release precedes tauopathy in degenerative dopaminergic neurons in a Drosophila model expressing human tau.

While a number of genome-wide association studies have identified microtubule-associated protein tau as a strong risk factor for Parkinson's disease (PD), little is known about the mechanism through which human tau can predispose an individual to this disease. Here, we demonstrate that expression of human wild-type tau is sufficient to disrupt the survival of dopaminergic neurons in a Drosophila model. Tau triggers a synaptic pathology visualized by vesicular monoamine transporter-pHGFP that precedes both the age-dependent formation of tau-containing neurofibrillary tangle-like pathology and the progressive loss of DA neurons, thereby recapitulating the pathological hallmarks of PD. Flies overexpressing tau also exhibit progressive impairments of both motor and learning behaviors. Surprisingly, contrary to common belief that hyperphosphorylated tau could aggravate toxicity, DA neuron degeneration is alleviated by expressing the modified, hyperphosphorylated tau(E14). Together, these results show that impairment of VMAT-containing synaptic vesicle, released to synapses before overt tauopathy may be the underlying mechanism of tau-associated PD and suggest that correction or prevention of this deficit may be appropriate targets for early therapeutic intervention

A screen-printed carbon electrode modified with a chitosan-based film for in situ heavy metal ions measurement

SEM images and FTIR data of the working electrode surface showed that Mn+ ions were adsorbed on chitosan (Chit) and crosslinked chitosan-carbon nanotube (Chit-CNT) films. XPS revealed that chelation of Mn+ ions with the –NH2/–OH groups from chitosan, –COOH group from carbon nanotubes, and aqua ligands represents a possible structure of the active Mn+ species in the Chit-based film. The electrochemical behaviors of the Chit-based film modified screen-printed carbon electrode (SPCE) were characterized for individual and simultaneous detection of Cu2+, Pb2+, Hg2+, Zn2+, Cd2+, and As3+ ions. For individual detection, the concentration range was 0.50–3.00 ppm with a detection limit of 0.4 ppm for Cu2+; 1.0–4.0 ppm with a detection limit of 0.5 ppm for Pb2+; 1.0–5.0 ppm with a detection limit of 0.8 ppm for Hg2+. For simultaneous detection, the lab chip sensor was successfully used to determine the concentrations of Pb2+, Cu2+, Hg2+, and As3+ ions simultaneously

High-Frequency Ultrasound Imaging to Evaluate Liver Fibrosis Progression in Rats and Yi Guan Jian Herbal Therapeutic Effects

The animals used in liver fibrosis studies must usually be sacrificed. Ultrasound has been demonstrated to have the ability to diagnose hepatic fibrosis and cirrhosis in experimental small-animal models. However, few studies have used high-frequency ultrasound (HFU, 40 MHz) to monitor changes in the rat liver and other hollow organs longitudinally. In this study, liver fibrosis was induced by administering dimethylnitrosamine (DMN) in SD rats, aged 8 weeks, for three consecutive days per week for up to 4 weeks. A Chinese herbal medicine Yi Guan Jian (YGJ) was orally administered (1.8 g/kg daily) to DMN-induced liver fibrosis rats for 2 weeks. Compared with the normal control rats, rats treated with DMN for either 2 weeks or 4 weeks had significantly lower body weights, liver indexes and elevation of hydroxyproline, GOT, and GPT contents. YGJ herbal treatment remarkably prevented rats from DMN-induced liver fibrosis. The HFU scoring results among the normal controls, 2-week DMN-treated rats, 4-week DMN-treated rats, and combined 2-week YGJ therapy with 4-week DMN-treated rats also reached statistical significance. Thus, HFU is an accurate tool for the longitudinal analysis of liver fibrosis progression in small-animal models, and the YGJ may be useful in reversing the development of hepatic fibrosis

Prevalence and determinants of dietary supplement and non-prescription medicine use by men and women over 53 years old in Taiwan. Results from a population-based cross-sectional survey

This study investigated the prevalence and determinants of the use of dietary supplements and non-prescription medicines by older adults in Taiwan. Methods:  Data are from the 1999 Survey of Health and Living Status of the Elderly in Taiwan. The survey involved a national random sample of 2360 men and 2080 women, 53 years or older. Results:  Overall, 32.4% of elderly men and 42.7% of elderly women used at least one kind of dietary supplement during the past 12 months. Approximately 16% of elderly men and 19% of elderly women used multivitamin and mineral supplements, 10.5 and 22% used calcium, and 10 and 14% used vitamin E, respectively. Conclusions:  The rates of supplement use are generally lower than those observed in the USA but comparable to that in other industrialised countries. Elderly who are females or who are more highly educated or physically more active are more frequent supplement users.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72609/1/j.1741-6612.2006.00183.x.pd

Clinical significance of erythropoietin receptor expression in oral squamous cell carcinoma

BACKGROUND: Hypoxic tumors are refractory to radiation and chemotherapy. High expression of biomarkers related to hypoxia in head and neck cancer is associated with a poorer prognosis. The present study aimed to evaluate the clinicopathological significance of erythropoietin receptor (EPOR) expression in oral squamous cell carcinoma (OSCC). METHODS: The study included 256 patients who underwent primary surgical resection between October 1996 and August 2005 for treatment of OSCC without previous radiotherapy and/or chemotherapy. Clinicopathological information including gender, age, T classification, N classification, and TNM stage was obtained from clinical records and pathology reports. The mRNA and protein expression levels of EPOR in OSCC specimens were evaluated by Q-RT-PCR, Western blotting and immunohistochemistry assays. RESULTS: We found that EPOR were overexpressed in OSCC tissues. The study included 17 women and 239 men with an average age of 50.9 years (range, 26–87 years). The mean follow-up period was 67 months (range, 2–171 months). High EPOR expression was significantly correlated with advanced T classification (p < 0.001), advanced TNM stage (p < 0.001), and positive N classification (p = 0.001). Furthermore, the univariate analysis revealed that patients with high tumor EPOR expression had a lower 5-year overall survival rate (p = 0.0011) and 5-year disease-specific survival rate (p = 0.0017) than patients who had low tumor levels of EPOR. However, the multivariate analysis using Cox’s regression model revealed that only the T and N classifications were independent prognostic factors for the 5-year overall survival and 5-year disease-specific survival rates. CONCLUSIONS: High EPOR expression in OSCC is associated with an aggressive tumor behavior and poorer prognosis in the univariate analysis among patients with OSCC. Thus, EPOR expression may serve as a treatment target for OSCC in the future