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21.
Cristiana Vitale Giuseppe Mercuro Carlotta Castiglioni Alessandra Cornoldi Arianna Tulli Massimo Fini Maurizio Volterrani Giuseppe MC Rosano 《Cardiovascular diabetology》2005,4(1):1-8
Background
Metabolic syndrome is a cluster of common cardiovascular risk factors that includes hypertension and insulin resistance. Hypertension and diabetes mellitus are frequent comorbidities and, like metabolic syndrome, increase the risk of cardiovascular events. Telmisartan, an antihypertensive agent with evidence of partial peroxisome proliferator-activated receptor activity-gamma (PPARγ) activity, may improve insulin sensitivity and lipid profile in patients with metabolic syndrome.Methods
In a double-blind, parallel-group, randomized study, patients with World Health Organization criteria for metabolic syndrome received once-daily doses of telmisartan (80 mg, n = 20) or losartan (50 mg, n = 20) for 3 months. At baseline and end of treatment, fasting and postprandial plasma glucose, insulin sensitivity, glycosylated haemoglobin (HBA1c) and 24-hour mean systolic and diastolic blood pressures were determined.Results
Telmisartan, but not losartan, significantly (p < 0.05) reduced free plasma glucose, free plasma insulin, homeostasis model assessment of insulin resistance and HbAic. Following treatment, plasma glucose and insulin were reduced during the oral glucose tolerance test by telmisartan, but not by losartan. Telmisartan also significantly reduced 24-hour mean systolic blood pressure (p < 0.05) and diastolic blood pressure (p < 0.05) compared with losartan.Conclusion
As well as providing superior 24-hour blood pressure control, telmisartan, unlike losartan, displayed insulin-sensitizing activity, which may be explained by its partial PPARγ activity. 相似文献22.
Chelliah MV Chackalamannil S Xia Y Eagen K Greenlee WJ Ahn HS Agans-Fantuzzi J Boykow G Hsieh Y Bryant M Chan TM Chintala M 《Bioorganic & medicinal chemistry letters》2012,22(7):2544-2549
Discovery of a novel nor-seco himbacine analog as potent thrombin receptor (PAR-1) antagonist is described. Despite low plasma level, these new analogs showed excellent ex vivo efficacy in the monkey platelet aggregation assay. A potent hydroxy metabolite generated in vivo was identified as the agent responsible for the ex vivo efficacy. Following this discovery, the metabolite series was optimized to obtain analogs that showed very good ex vivo efficacy along with excellent pharmacokinetic profile in c. monkey. 相似文献
23.
Yang SW Smotryski J McElroy WT Tan Z Ho G Tulshian D Greenlee WJ Guzzi M Zhang X Mullins D Xiao L Hruza A Chan TM Rindgen D Bleickardt C Hodgson R 《Bioorganic & medicinal chemistry letters》2012,22(1):235-239
A series of pyrazoloquinoline analogs have been synthesized and shown to bind to PDE10 with high affinity. From the SAR study and our lead optimization efforts, compounds 16 and 27 were found to possess potent oral antipsychotic activity in the MK-801 induced hyperactive rat model. 相似文献
24.
Patrick LJM Zeeuwen Jos Boekhorst Ellen H van den Bogaard Heleen D de Koning Peter MC van de Kerkhof Delphine M Saulnier Iris I van Swam Sacha AFT van Hijum Michiel Kleerebezem Joost Schalkwijk Harro M Timmerman 《Genome biology》2012,13(11):R101
Background
Recent advances in sequencing technologies have enabled metagenomic analyses of many human body sites. Several studies have catalogued the composition of bacterial communities of the surface of human skin, mostly under static conditions in healthy volunteers. Skin injury will disturb the cutaneous homeostasis of the host tissue and its commensal microbiota, but the dynamics of this process have not been studied before. Here we analyzed the microbiota of the surface layer and the deeper layers of the stratum corneum of normal skin, and we investigated the dynamics of recolonization of skin microbiota following skin barrier disruption by tape stripping as a model of superficial injury.Results
We observed gender differences in microbiota composition and showed that bacteria are not uniformly distributed in the stratum corneum. Phylogenetic distance analysis was employed to follow microbiota development during recolonization of injured skin. Surprisingly, the developing neo-microbiome at day 14 was more similar to that of the deeper stratum corneum layers than to the initial surface microbiome. In addition, we also observed variation in the host response towards superficial injury as assessed by the induction of antimicrobial protein expression in epidermal keratinocytes.Conclusions
We suggest that the microbiome of the deeper layers, rather than that of the superficial skin layer, may be regarded as the host indigenous microbiome. Characterization of the skin microbiome under dynamic conditions, and the ensuing response of the microbial community and host tissue, will shed further light on the complex interaction between resident bacteria and epidermis. 相似文献25.
26.
Visual illusions are valuable tools for the scientific examination of the mechanisms underlying perception. In the peripheral drift illusion special drift patterns appear to move although they are static. During fixation small involuntary eye movements generate retinal image slips which need to be suppressed for stable perception. Here we show that the peripheral drift illusion reveals the mechanisms of perceptual stabilization associated with these micromovements. In a series of experiments we found that illusory motion was only observed in the peripheral visual field. The strength of illusory motion varied with the degree of micromovements. However, drift patterns presented in the central (but not the peripheral) visual field modulated the strength of illusory peripheral motion. Moreover, although central drift patterns were not perceived as moving, they elicited illusory motion of neutral peripheral patterns. Central drift patterns modulated illusory peripheral motion even when micromovements remained constant. Interestingly, perceptual stabilization was only affected by static drift patterns, but not by real motion signals. Our findings suggest that perceptual instabilities caused by fixational eye movements are corrected by a mechanism that relies on visual rather than extraretinal (proprioceptive or motor) signals, and that drift patterns systematically bias this compensatory mechanism. These mechanisms may be revealed by utilizing static visual patterns that give rise to the peripheral drift illusion, but remain undetected with other patterns. Accordingly, the peripheral drift illusion is of unique value for examining processes of perceptual stabilization. 相似文献
27.
Hubert Josien Thomas Bara Murali Rajagopalan John W. Clader William J. Greenlee Leonard Favreau Lynn A. Hyde Amin A. Nomeir Eric M. Parker Lixin Song Lili Zhang Qi Zhang 《Bioorganic & medicinal chemistry letters》2009,19(21):6032-6037
A new class of 2,6-disubstituted morpholine N-arylsulfonamide γ-secretase inhibitors was designed based on the introduction of a morpholine core in lieu or piperidine in our lead series. This resulted in compounds with improved CYP 3A4 profiles. Several analogs that were active at lowering Aβ levels in Tg CRND8 mice upon oral administration were identified. 相似文献
28.
Bryan R. Helm Scott Payne Joseph P. Rinehart George D. Yocum Julia H. Bowsher Kendra J. Greenlee 《Arthropod Structure & Development》2018,47(5):521-528
Insect metamorphosis involves a complex change in form and function. In this study, we examined the development of the solitary bee, Megachile rotundata, using micro-computed tomography (μCT) and volume analysis. We describe volumetric changes of brain, tracheae, flight muscles, gut, and fat bodies in prepupal, pupal, and adult M. rotundata. We observed that individual organ systems have distinct patterns of developmental progression, which vary in their timing and duration. This has important implications for commercial management of this agriculturally relevant pollinator. 相似文献
29.
30.
Josiah MC Heyman 《The journal of the Royal Anthropological Institute》2000,6(4):635-652
High-scale morality is the study of moral ideas and sentiments deployed in relations that encompass multiple, geographically or socially distant populaces. The envisioning of distant people, their attributed moral personhood, the evaluation of their perceived behaviour, and the rectification of wrongs through the use of powerful organizations are key topics in high-scale morality. High-scale morality differs from existing anthropological approaches that emphasize local ethnography or contrastive moral ideas; it addresses the moralization of issues like world hunger, the drug trade, or international migration. The officers of the US Immigration and Naturalization Service understand and evaluate legal and illegal immigrants, as well as directly enacting moral rectification for the US polity. As they resolve moral dilemmas on their job, they utilize pervasive models for moral thought and action in capitalist, individualist, stratified, and bureaucratized societies. The article finishes by considering directions in which anthropology can contribute to understanding the moral dimension of global issues. 相似文献