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101.
Our group has shown in a phase II clinical trial that pomegranate juice (PJ) increases prostate specific antigen (PSA) doubling time in prostate cancer (CaP) patients with a rising PSA. Ellagitannins (ETs) are the most abundant polyphenols present in PJ and contribute greatly towards its reported biological properties. On consumption, ETs hydrolyze to release ellagic acid (EA), which is then converted by gut microflora to 3,8-dihydroxy-6H-dibenzo[b, d]pyran-6-one (urolithin A, UA) derivatives. Despite the accumulating knowledge of ET metabolism in animals and humans, there is no available data on the pharmacokinetics and tissue disposition of urolithins. Using a standardized ET-enriched pomegranate extract (PE), we sought to further define the metabolism and tissue distribution of ET metabolites. PE and UA (synthesized in our laboratory) were administered to C57BL/6 wild-type male mice, and metabolite levels in plasma and tissues were determined over 24 h. ET metabolites were concentrated at higher levels in mouse prostate, colon, and intestinal tissues as compared to other tissues after administration of PE or UA. We also evaluated the effects of PE on CaP growth in severe combined immunodeficient (SCID) mice injected subcutaneously with human CaP cells (LAPC-4). PE significantly inhibited LAPC-4 xenograft growth in SCID mice as compared to vehicle control. Finally, EA and several synthesized urolithins were shown to inhibit the growth of human CaP cells in vitro. The chemopreventive potential of pomegranate ETs and localization of their bioactive metabolites in mouse prostate tissue suggest that pomegranate may play a role in CaP treatment and chemoprevention. This warrants future human tissue bioavailability studies and further clinical studies in men with CaP.  相似文献   
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Starting from the known bitter-masking flavanones eriodictyol and homoeriodictyol from herba santa some structurally related hydroxybenzoic acid amides of benzylamines were synthesized and evaluated as masking agents toward bitterness of caffeine by sensory methods. The closest structural relatives of homoeriodictyol, the hydroxybenzoic acid vanillylamides 5-9, were the most active and were able to reduce the bitterness of a 500 mg L(-1) caffeine solution by about 30% at a concentration of 100 mg L(-1). 2,4-Dihydroxybenzoic acid vanillylamide 7 showed a clear dose-dependent activity as inhibitor of the bitter taste of caffein between 5 and 500 mg L(-1). Additionally, it was possible to reduce the bitterness of quinine and salicine but not of the bitter peptide N-l-leucyl-l-tryptophan. Combinations of homoeriodictyol and amide 7 showed no synergistic or antagonistic changes in activity. The results for model compound 7 suggested that the hitherto unknown masking mechanism is probably the same for flavanones and the new amides. In the future, the new amides may be alternatives for the expensive flavanones to create flavor solutions to mask bitterness of pharmaceuticals or foodstuffs.  相似文献   
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Europe has a long and distinguished history in veterinary science and education, and it was here that the first professional investigations of pathological conditions in zoo animals took place. However, despite an increasing number of veterinarians working with wildlife, education in zoological and wildlife medicine has only recently become part of formal veterinary training at the undergraduate level. Consequently, current educational opportunities in zoological and wildlife medicine vary widely throughout Europe, both in availability and in composition. The need to establish agreed standards in education across Europe and to foster the mobility of students and teaching staff are reflected by international agreements such as the Bologna Treaty and the ERASMUS-SOCRATES program. Europe is also home to a number of voluntary professional organizations, such as the European Wildlife Disease Association and the European Association of Zoo and Wildlife Veterinarians, that actively promote the inclusion of zoological and wildlife medicine in veterinary education. Zoo and wildlife medicine is currently a veterinary specialization in Europe, but educational opportunities are likely to increase in availability in the future.  相似文献   
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The relationship between number of species and area observed has been described using numerous approaches and has been discussed for more than a century. The general objectives of our study were fourfold: (1) to evaluate the behaviour of species–area curves across geographic scales, (2) to determine sample sizes necessary to produce acceptably precise estimates of tree species diversity, (3) to evaluate relationships among estimates of tree species diversity for local to large geographic scales, and (4) to determine whether the proportion of native tree species may be precisely estimated using sample sizes smaller than those necessary to estimate total tree species diversity. Such investigations are necessary to improve biodiversity monitoring at large scales. The analytical approaches included Monte Carlo bootstrap simulations and two geospatial methods and relied on a database populated with data for more than 12,000 national forest inventory plots (NFI) from 16 regional units, 13 European countries and three ecoprovinces of the United States of America (USA). Four primary results were obtained. First, tree species diversity may be precisely estimated using observations for a random subsample of 2,000–4,000 NFI plots. Second, large sample sizes are necessary to estimate tree species diversity for regional units or forest categories, except possibly for boreal forests for which the number of tree species is small. Third, estimates of the proportion of native tree species may be precisely estimated using tree species information for a random sample of approximately 30 NFI plots. Finally, our estimated species–area curves show that the curve shapes and relationships among estimates of tree species diversity at large scales clearly depend on the relative geographic location of the anchor regional unit (a European country or ecoprovince of the USA) relative to the other regional units. None of the well-known models for species–area curves adequately describes our results. The conclusion was that the uncertainties of the estimates reflect the unfavourable state of global biodiversity monitoring of species groups. The total numbers of tree species in our regional units, which cannot be adequately estimated, are small relative to other tree species-rich regions. Consequently, monitoring of tree species diversity is currently a highly uncertain enterprise at large scales.  相似文献   
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To study the evolution of recombination rates in apes, we developed methodology to construct a fine-scale genetic map from high-throughput sequence data from 10 Western chimpanzees, Pan troglodytes verus. Compared to the human genetic map, broad-scale recombination rates tend to be conserved, but with exceptions, particularly in regions of chromosomal rearrangements and around the site of ancestral fusion in human chromosome 2. At fine scales, chimpanzee recombination is dominated by hotspots, which show no overlap with those of humans even though rates are similarly elevated around CpG islands and decreased within genes. The hotspot-specifying protein PRDM9 shows extensive variation among Western chimpanzees, and there is little evidence that any sequence motifs are enriched in hotspots. The contrasting locations of hotspots provide a natural experiment, which demonstrates the impact of recombination on base composition.  相似文献   
109.
OBJECTIVES: To determine associations among infectious pathogens and diarrheal disease in dogs in an animal shelter and demonstrate the use of geographic information systems (GISs) for tracking spatial distributions of diarrheal disease within shelters. SAMPLE POPULATION: Feces from 120 dogs. PROCEDURE: Fresh fecal specimens were screened for bacteria and bacterial toxins via bacteriologic culture and ELISA, parvovirus via ELISA, canine coronavirus via nested polymerase chain reaction assay, protozoal cysts and oocysts via a direct fluorescent antibody technique, and parasite ova and larvae via microscopic examination of direct wet mounts and zinc sulfate centrifugation flotation. RESULTS: Salmonella enterica and Brachyspira spp were not common, whereas other pathogens such as canine coronavirus and Helicobacter spp were common among the dogs that were surveyed. Only intestinal parasites and Campylobacterjejuni infection were significant risk factors for diarrhea by univariate odds ratio analysis. Giardia lamblia was significantly underestimated by fecal flotation, compared with a direct fluorescent antibody technique. Spatial analysis of case specimens by use of GIS indicated that diarrhea was widespread throughout the entire shelter, and spatial statistical analysis revealed no evidence of spatial clustering of case specimens. CONCLUSIONS AND CLINICAL RELEVANCE: This study provided an epidemiologic overview of diarrhea and interacting diarrhea-associated pathogens in a densely housed, highly predisposed shelter population of dogs. Several of the approaches used in this study, such as use of a spatial representation of case specimens and considering multiple etiologies simultaneously, were novel and illustrate an integrated approach to epidemiologic investigations in shelter populations.  相似文献   
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