A double-blind, placebo-controlled, randomized, multicenter study to investigate CHInese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES Study).

UNLABELLED: Rationale Traditional Chinese Medications(TCM) have been reported to have beneficial effects in stroke patients, but were not rigorously evaluated by GCP standards. Aim This study tests the hypothesis that Neuroaid, a TCM widely used in China post-stroke, is superior to placebo in reducing neurological deficit and improving functional outcome in patients with acute cerebral infarction of an intermediate severity. Design This is a multicenter, randomised, double-blind, placebo-controlled study of Neuroaid in ischemic stroke patients with National Institute of Health Stroke Scale(NIHSS) 6-14 treated within 48 h of stroke onset. Neuroaid or placebo is taken (4 capsules) 3 times daily for 3 months. Treatments are assigned using block randomization, stratified for centers, via a central web-randomization system. With a power of 90% and two-sided test of 5% type I error, a sample size is 874. Allowing for a drop-out rate of up to 20%, 1100 individuals should be enrolled in this study. Study Outcomes The primary efficacy endpoint is the modified Rankin Scale(mRS) grades at 3 months. Secondary efficacy endpoints are the NIHSS score at 3 months; difference of NIHSS scores between baseline and 10 days, and between baseline and 3 months; difference of NIHSS sub-scores between baseline and 10 days, and between baseline and 3 months; mRS at 10 days, 1 month, and 3 months; Barthel index at 3 months; Mini Mental State Examination at 10 days and 3 months. Safety outcomes include complete blood count, renal and liver panels, and electrocardiogram. STUDY REGISTRATION: ClinicalTrials.gov identifier: NCT00554723.

Origin and genetic diversity of Western European populations of the potato cyst nematode (Globodera pallida) inferred from mitochondrial sequences and microsatellite loci.

Native to South America, the potato cyst nematode Globodera pallida is one of the principal pests of Andean potato crops and is also an important global pest following its introduction to Europe, Africa, North America, Asia and Oceania. Building on earlier work showing a clear south to north phylogeographic pattern in Peruvian populations, we have been able to identify the origin of Western European populations with high accuracy. They are all derived from a single restricted area in the extreme south of Peru, located between the north shore of the Lake Titicaca and Cusco. Only four cytochrome b haplotypes are found in Western Europe, one of them being also found in some populations of this area of southern Peru. The allelic richness at seven microsatellite loci observed in the Western European populations, although only one-third of that observed in this part of southern Peru, is comparable to the allelic richness observed in the northern region of Peru. This result could be explained by the fact that most of the genetic variability observed at the scale of a field or even of a region is already observed at the scale of a single plant within a field. Thus, even introduction via a single infected potato plant could result in the relatively high genetic variability observed in Western Europe. This finding has important consequences for the control of this pest and the development of quarantine measures.

Inbreeding and population structure of the potato cyst nematode (Globodera pallida) in its native area (Peru).

The dispersal abilities and the population genetic structure of nematodes living in the soil are poorly known. In the present study, we have pursued these issues in the potato cyst nematode Globodera pallida, which parasitizes potato roots and is indigenous to South America. A hierarchical sampling regime was conducted in Peru to investigate gene flow on regional, field and plant scales. Multilocus genotypes of single individuals were obtained using eight polymorphic microsatellites markers. Large heterozygote deficiencies were observed at most loci. The limited active dispersal of larvae from their cyst, which favours mating between (half) siblings, could be responsible for this pattern. Within fields, as well as among fields within regions (even 35 km apart), low F(ST) values suggest extensive gene flow. Among fields within regions, only 1.5-4.4% genetic variability was observed. Passive dispersal of cysts by natural means (wind, running water, or wild animals) or by anthropogenic means (tillage, movement of infected seed tubers) is probably responsible for the results observed. Among regions, high F(ST) values were observed. Thus long-range dispersal (more than 320 km apart) is probably limited by major biogeographical barriers such as the mountains found in the Andean Cordillera. These results provide useful information for the management of resistant varieties, to slow down the emergence and spread of resistance-breaking pathotypes.

Estrogen receptor alpha mediates the proliferative but not the cytotoxic dose-dependent effects of two major phytoestrogens on human breast cancer cells.

Phytoestrogens are a chemically diverse group of compounds made by plants that can have estrogenic effects in animals. Both tumorigenic and antitumorigenic effects have been reported. Although estrogens stimulate the growth of many breast tumors, there is a negative correlation between the incidence of breast cancer and the phytoestrogen-rich diet of certain Asian populations. To begin to resolve this paradox, we have analyzed the estrogenic properties of genistein and quercetin, two flavonoid phytoestrogens particularly abundant in soybeans. Trans-activation experiments with a transfected reporter gene for nuclear estrogen receptors (ER) show strong activation of the endogenous ER alpha by both phytoestrogens in two MCF7 human breast cancer cell lines. This is supported by the observation that the two phytoestrogens induce the down-regulation of ER alpha mRNA and protein levels. Using chimeric proteins consisting of the hormone binding domains of ER alpha and ER beta fused to the Gal4 DNA binding domain, we have established that genistein and quercetin are full estrogenic agonists of both ER isoforms. Ligand binding experiments with purified ER alpha and ER beta confirm that the two phytoestrogens are ER ligands. At concentrations that are sufficient to obtain substantial transcriptional activity, they stimulate the proliferation of two ER alpha-dependent breast cancer cell lines. At high concentrations, such as those reached with a soy-rich diet, genistein and quercetin are strong cytotoxic agents that even kill ER-independent HeLa cells. Thus, the mode of action of phytoestrogens and the balance between being risk or chemopreventive factors for breast cancer may depend on the dietary load.

The anti-estrogen hydroxytamoxifen is a potent antagonist in a novel yeast system.

The budding yeast Saccharomyces cerevisiae has been used extensively as a biological 'test tube' to study the regulation of the human estrogen receptor (ER) alpha. However, anti-estrogens, which are of great importance as therapeutic agents and research tools, fail to antagonize the activation by estrogen in yeast. Here, we have surveyed the antagonistic potential of five different anti-estrogens of diverse chemical nature. While they all act as agonists for wild-type ERalpha, we have established a novel yeast assay system for anti-estrogens, in which at least the commonly used anti-estrogen hydroxytamoxifen is a potent antagonist.

The relationship of physical activity to bone mineral content in postmenopausal women.

The purpose of this study was to compare the bone mineral content (BMC) of two groups of healthy postmenopausal women. The two groups differed on their physical activity profile as established by the Simons-Morton scale. Subjects (33) were French Canadian, resident in the same geographical area and aged between 60 and 75 years. Subject selection criteria were as follows: no history of oestrogen supplements, osteoporosis, premature menopause, no medication related to bone metabolism and exemption from factors predisposing to secondary osteopathy. Subjects were categorized as very active (VA) or sedentary (S) based on their physical activity profile established over a 6-month period. The VA group was composed of 20 women (62.1+/-2.8) and the S group of 13 other females (68.0+/-4.7). Subject intake of calcium, coffee and alcohol was evaluated. BMC of the lumbar spine and wrist were measured by dual and single photon absorptiometry. In order to validate the different physical activity levels, general fitness parameters including functional exercise capacity, abdominal and arm muscle endurance and forearm strength were also measured. A significant difference (p<0.018) was observed between mean values measured at the lumbar spine between the VA group (0.76 g+/-0.09) and the S group (0.65+/-0.12) g hydroxyapatite per cm(2). However no significant difference was found between the VA and the S group for the wrist measure, with mean values of 34.0 unit length (UL)+6.3 and 31.3 UL+/-6.4 respectively. The observations that the subjects of the VA group were only involved in weight-bearing aerobic activities which mainly exert a mechanical load to the axial skeleton and that no difference was observed between both groups for the forearm strength suggest that the positive effect of exercise on BMC is limited only to the bone structure submitted to sufficient mechanical forces.