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排序方式: 共有1114条查询结果,搜索用时 31 毫秒
71.
Gary Tresadern Jose María Cid Gregor J. Macdonald Juan Antonio Vega Ana Isabel de Lucas Aránzazu García Encarnación Matesanz María Lourdes Linares Daniel Oehlrich Hilde Lavreysen Ilse Biesmans Andrés A. Trabanco 《Bioorganic & medicinal chemistry letters》2010,20(1):175-179
Imidazo[1,2-a]pyridines were identified via their shape and electrostatic similarity as novel positive allosteric modulators of the metabotropic glutamate 2 receptor. The subsequent synthesis and SAR are described. Potent, selective and metabolically stable compounds were found representing a promising avenue for current further studies. 相似文献
72.
The knowledge about cesium metabolism and toxicity is sparse. Oral intake of cesium chloride has been widely promoted on the basis of the hypothesis referred to as “high pH cancer therapy”, a complimentary alternative medicine method for cancer treatment. However, no properly confirmed tumor regression was reported so far in all probability because of neither theoretical nor experimental grounds for this proposal. The aim of the present review was to resume and discuss the material currently available on cesium salts and their applications in medicine. The presence of cesium in the cell does not guarantee high pH of its content, and there is no clinical evidence to support the claims that cancer cells are vulnerable to cesium. Cesium is relatively safe; signs of its mild toxicity are gastrointestinal distress, hypotension, syncope, numbness, or tingling of the lips. Nevertheless, total cesium intakes of 6 g/day have been found to produce severe hypokalemia, hypomagnesemia, prolonged QTc interval, episodes of polymorphic ventricular tachycardia, with or without torsade de pointes, and even acute heart arrest. However, full information on its acute and chronic toxicity is not sufficiently known. Health care providers should be aware of the cardiac complications, as a result of careless cesium usage as alternative medicine. 相似文献
73.
Garza-Ocañas L Ferrer DA Burt J Diaz-Torres LA Ramírez Cabrera M Rodríguez VT Luján Rangel R Romanovicz D Jose-Yacaman M 《Metallomics : integrated biometal science》2010,2(3):204-210
Silver nanocrystals (Ag NCs) hold promising antibiotic and antiviral properties in biological systems. The biodistribution of silver nanostructures injected into animals in vivo is currently unknown, remaining as a fundamental issue for potential therapeutic applications. Here, we injected Ag NCs capped with bovine serum albumin (BSA) in live rats to elucidate their fate in several organs including liver, heart and brain. Very significant accumulations of nanoparticles were confirmed by inductively coupled plasma mass spectroscopy (ICPMS) and transmission electron microscopy (TEM) techniques on the liver and heart. In contrast, the brain tissue did not reveal evidence of particles content. Our results suggest that Ag+ permeated across the blood-brain barrier (BBB), and followed swift clearance from the organ. 相似文献
74.
Katarzyna A. Rejniak Shizhen E. Wang Nicole S. Bryce Hang Chang Bahram Parvin Jerome Jourquin Lourdes Estrada Joe W. Gray Carlos L. Arteaga Alissa M. Weaver Vito Quaranta Alexander R. A. Anderson 《PLoS computational biology》2010,6(8)
Most tumors arise from epithelial tissues, such as mammary glands and lobules, and their initiation is associated with the disruption of a finely defined epithelial architecture. Progression from intraductal to invasive tumors is related to genetic mutations that occur at a subcellular level but manifest themselves as functional and morphological changes at the cellular and tissue scales, respectively. Elevated proliferation and loss of epithelial polarization are the two most noticeable changes in cell phenotypes during this process. As a result, many three-dimensional cultures of tumorigenic clones show highly aberrant morphologies when compared to regular epithelial monolayers enclosing the hollow lumen (acini). In order to shed light on phenotypic changes associated with tumor cells, we applied the bio-mechanical IBCell model of normal epithelial morphogenesis quantitatively matched to data acquired from the non-tumorigenic human mammary cell line, MCF10A. We then used a high-throughput simulation study to reveal how modifications in model parameters influence changes in the simulated architecture. Three parameters have been considered in our study, which define cell sensitivity to proliferative, apoptotic and cell-ECM adhesive cues. By mapping experimental morphologies of four MCF10A-derived cell lines carrying different oncogenic mutations onto the model parameter space, we identified changes in cellular processes potentially underlying structural modifications of these mutants. As a case study, we focused on MCF10A cells expressing an oncogenic mutant HER2-YVMA to quantitatively assess changes in cell doubling time, cell apoptotic rate, and cell sensitivity to ECM accumulation when compared to the parental non-tumorigenic cell line. By mapping in vitro mutant morphologies onto in silico ones we have generated a means of linking the morphological and molecular scales via computational modeling. Thus, IBCell in combination with 3D acini cultures can form a computational/experimental platform for suggesting the relationship between the histopathology of neoplastic lesions and their underlying molecular defects. 相似文献
75.
Cristóbal-Azkarate J Chavira R Boeck L Rodríguez-Luna E Veà JJ 《American journal of primatology》2007,69(8):866-876
A growing amount of data shows that a preference for passive-nonaggressive over active-aggressive problem solving is associated with higher levels of glucocorticoids (GC). For mantled howlers, the arrival of an adult male in a new group is a potential source of psychological stress for both resident males and females. Resident mantled howler males take an active stand and aggressively repel the entrance of solitary males, while females take a passive-nonaggressive stand. In order to study whether the relationship between coping strategies and the activation of the hypothalamic-pituitary-adrenal (HPA) axis observed in other species applies to the response of resident mantled howlers to the presence of solitary males, we examine the relationship between different group and subpopulation variables and the GC levels measured in feces collected from 10 groups living in six forest fragments, in Los Tuxtlas, Mexico. The results of our study suggest that the resident mantled howler females' passive response to the presence of solitary males is accompanied by the activation of the HPA axis, whereas resident males' aggressive response is not accompanied by any changes in the HPA axis. In contrast, a previous study suggests that resident male howlers respond by increasing their testosterone levels to the presence of solitary males (Cristobal-Azkarate et al., Hormones and Behavior 2006;49 261-267).These different behavioral and hormonal responses coincide with the active and passive coping styles described for other species. The conditions in which howlers live in our study area may be favoring the interaction between solitary and resident howlers, and inducing chronically high GC levels, which in turn could negatively affect the fitness of these subpopulations. 相似文献
76.
Lack of association between common polymorphisms in the 17beta-hydroxysteroid dehydrogenase type V gene (HSD17B5) and precocious pubarche 总被引:1,自引:0,他引:1
Petry CJ Ong KK Wingate DL de Zegher F Ibáñez L Dunger DB 《The Journal of steroid biochemistry and molecular biology》2007,105(1-5):176-180
BACKGROUND: 17beta-Hydroxysteroid dehydrogenase (type V; HSD17B5) is a key enzyme involved in testosterone production in females. A single nucleotide polymorphism (SNP) in the promoter region of its gene was recently found to be associated with polycystic ovary syndrome (PCOS) and its related hyperandrogenaemia. Precocious pubarche (PP) is a clinical entity pointing to adrenal androgen excess from mid-childhood onward and is associated with ovarian androgen excess from puberty onward. It is therefore a strong risk factor for PCOS. METHODS: To investigate associations between this promoter SNP along with three exonic SNPs (one non-synonymous and two synonymous) from the same gene, and PP, a case-control study was performed in 190 girls with PP (84 of which were also tested for functional ovarian hyperandrogenism) from Barcelona, Spain and 71 healthy controls. Clinical features and hormone concentrations relevant to hyperandrogenism were compared by HSD17B5 genotype and haplotype. RESULTS: Neither HSD17B5 genotypes nor haplotype were associated with PP, or subsequent androgen excess in girls from Barcelona (all P>0.05). CONCLUSIONS: HSD17B5 SNPs predicted to have functional effects do not appear to be a risk factor for PP in girls from Barcelona, despite these girls being at high risk of developing androgen excess in adulthood. 相似文献
77.
78.
Baires-Varguez L Cruz-García A Villa-Tanaka L Sánchez-García S Gaitán-Cepeda LA Sánchez-Vargas LO Quindós G Hernández-Rodríguez C 《Revista iberoamericana de micología》2007,24(2):148-151
The objective of this work was to compare the usefulness of a randomly amplified polymorphic DNA (RAPD) assay to that of the ATB ID32C kit (bioMérieux, France) for identification of different species of Candida isolated from clinical specimens. The RAPD-PCR patterns obtained with OPE-18 primer for identification of clinical isolates were consistent, and the different independent assays revealed reproduction of the band patterns. RAPD with the OPE-18 primer is a very specific and sensitive method for identification of Candida glabrata, Candida guilliermondii, Candida tropicalis, Candida pelliculosa, Candida albicans, Candida krusei, and Candida lusitaniae. 相似文献
79.
Fainboim L Cherñavsky A Paladino N Flores AC Arruvito L 《Cytokine & growth factor reviews》2007,18(1-2):143-157
From an immunological point of view, the healthy liver has been usually associated with the phenomenon of tolerance. A microenvironment of regulatory cytokines produced by liver Kuppfer cells and liver sinusoidal endothelial cells has contributed, together with resident dendritic cells, to generate a tolerogenic environment in this tissue. In this review we discussed the intrahepatic responses to different sorts of liver injury, such as hepatotrophic viruses, alcohol or putative self-antigens. In each case we analyzed the impact of different cytokines in the clinical outcome of the different pathological situations. 相似文献
80.
The extracellular concentration of glutamate is highly regulated due to its excitotoxic nature. Failure of glutamate uptake
or reversed activation of its transporters contributes to neurodegeneration related to some pathological conditions. We have
compared the neurotoxicity of the substrate glutamate uptake inhibitor, l-trans-pyrrolidine-2,4-dicarboxylate (PDC), which promotes glutamate release by heteroexchange, with that of DL-threo-beta-benzyloxyaspartate
(DL-TBOA), a non-substrate inhibitor, in cerebellar granule cell cultures. PDC substantially increases the extracellular concentration
of glutamate during 30 min exposure and causes neuronal death at high concentrations, while DL-TBOA neurotoxicity is only
observed after long-term exposure (8–24 h). During mitochondrial inhibition by 3-nitropropionic acid (3-NP), PDC-induced neuronal
death is facilitated, but not that of DL-TBOA. In cultures containing a higher population of astrocytes DL-TBOA-induced increase
in glutamate levels is more pronounced, but neuronal death is only triggered in the presence of 3-NP. Results suggest that
cerebellar granule neurons are more vulnerable to acute transport-mediated glutamate release than to uptake blockade, which
correlates with the extracellular excitatory amino acids levels. 相似文献