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Marcus Maurer Werner Aberer Laurence Bouillet Teresa Caballero Vincent Fabien Gisèle Kanny Allen Kaplan Hilary Longhurst Andrea Zanichelli 《PloS one》2013,8(2)
Background
Attacks of hereditary angioedema (HAE) are unpredictable and, if affecting the upper airway, can be lethal. Icatibant is used for physician- or patient self-administered symptomatic treatment of HAE attacks in adults. Its mode of action includes disruption of the bradykinin pathway via blockade of the bradykinin B2 receptor. Early treatment is believed to shorten attack duration and prevent severe outcomes; however, evidence to support these benefits is lacking.Objective
To examine the impact of timing of icatibant administration on the duration and resolution of HAE type I and II attacks.Methods
The Icatibant Outcome Survey is an international, prospective, observational study for patients treated with icatibant. Data on timings and outcomes of icatibant treatment for HAE attacks were collected between July 2009–February 2012. A mixed-model of repeated measures was performed for 426 attacks in 136 HAE type I and II patients.Results
Attack duration was significantly shorter in patients treated <1 hour of attack onset compared with those treated ≥1 hour (6.1 hours versus 16.8 hours [p<0.001]). Similar significant effects were observed for <2 hours versus ≥2 hours (7.2 hours versus 20.2 hours [p<0.001]) and <5 hours versus ≥5 hours (8.0 hours versus 23.5 hours [p<0.001]). Treatment within 1 hour of attack onset also significantly reduced time to attack resolution (5.8 hours versus 8.8 hours [p<0.05]). Self-administrators were more likely to treat early and experience shorter attacks than those treated by a healthcare professional.Conclusion
Early blockade of the bradykinin B2 receptor with icatibant, particularly within the first hour of attack onset, significantly reduced attack duration and time to attack resolution. 相似文献44.
45.
Forest ecosystems need to be sustainably managed, as they are major reservoirs of biodiversity, provide important economic resources and modulate global climate. We have a poor knowledge of populations responsible for key biomass degradation processes in forest soils and the effects of forest harvesting on these populations. Here, we investigated the effects of three timber-harvesting methods, varying in the degree of organic matter removal, on putatively hemicellulolytic bacterial and fungal populations 10 or more years after harvesting and replanting. We used stable-isotope probing to identify populations that incorporated 13C from labeled hemicellulose, analyzing 13C-enriched phospholipid fatty acids, bacterial 16 S rRNA genes and fungal ITS regions. In soil microcosms, we identified 104 bacterial and 52 fungal hemicellulolytic operational taxonomic units (OTUs). Several of these OTUs are affiliated with taxa not previously reported to degrade hemicellulose, including the bacterial genera Methylibium, Pelomonas and Rhodoferax, and the fungal genera Cladosporium, Pseudeurotiaceae, Capronia, Xenopolyscytalum and Venturia. The effect of harvesting on hemicellulolytic populations was evaluated based on in situ bacterial and fungal OTUs. Harvesting treatments had significant but modest long-term effects on relative abundances of hemicellulolytic populations, which differed in strength between two ecozones and between soil layers. For soils incubated in microcosms, prior harvesting treatments did not affect the rate of incorporation of hemicellulose carbon into microbial biomass. In six ecozones across North America, distributions of the bacterial hemicellulolytic OTUs were similar, whereas distributions of fungal ones differed. Our work demonstrates that diverse taxa in soil are hemicellulolytic, many of which are differentially affected by the impact of harvesting on environmental conditions. However, the hemicellulolytic capacity of soil communities appears resilient. 相似文献
46.
Our understanding of the evolutionary history and ecology of cave‐associated species has been driven historically by studies of morphologically adapted cave‐restricted species. Our understanding of the evolutionary history and ecology of nonrestricted cave species, troglophiles, is limited to a few studies, which present differing accounts of troglophiles’ relationship with the cave habitat, and its impact on population dynamics. Here, we used phylogenetics, demographic statistics, and population genetic methods to study lineage divergence, dates of divergence, and population structure in the Cave Salamander, Eurycea lucifuga, across its range. In order to perform these analyses, we sampled 233 individuals from 49 populations, using sequence data from three gene loci as well as genotyping data from 19 newly designed microsatellite markers. We find, as in many other species studied in a phylogeographic context, discordance between patterns inferred from mitochondrial relationships and those inferred by nuclear markers indicating a complicated evolutionary history in this species. Our results suggest Pleistocene‐based divergence among three main lineages within E. lucifuga corresponding to the western, central, and eastern regions of the range, similar to patterns seen in species separated in multiple refugia during climatic shifts. The conflict between mitochondrial and nuclear patterns is consistent with what we would expect from secondary contact between regional populations following expansion from multiple refugia. 相似文献
47.
Yana Sandlers Kelly Mercier Wimal Pathmasiri Jim Carlson Susan McRitchie Susan Sumner Hilary J. Vernon 《PloS one》2016,11(3)
Barth Syndrome is the only known Mendelian disorder of cardiolipin remodeling, with characteristic clinical features of cardiomyopathy, skeletal myopathy, and neutropenia. While the primary biochemical defects of reduced mature cardiolipin and increased monolysocardiolipin are well-described, much of the downstream biochemical dysregulation has not been uncovered, and biomarkers are limited. In order to further expand upon the knowledge of the biochemical abnormalities in Barth Syndrome, we analyzed metabolite profiles in plasma from a cohort of individuals with Barth Syndrome compared to age-matched controls via 1H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. A clear distinction between metabolite profiles of individuals with Barth Syndrome and controls was observed, and was defined by an array of metabolite classes including amino acids and lipids. Pathway analysis of these discriminating metabolites revealed involvement of mitochondrial and extra-mitochondrial biochemical pathways including: insulin regulation of fatty acid metabolism, lipid metabolism, biogenic amine metabolism, amino acid metabolism, endothelial nitric oxide synthase signaling, and tRNA biosynthesis. Taken together, this data indicates broad metabolic dysregulation in Barth Syndrome with wide cellular effects. 相似文献
48.
Hydrogen isotopic differences between C3 and C4 land plant lipids: consequences of compartmentation in C4 photosynthetic chemistry and C3 photorespiration 下载免费PDF全文
Youping Zhou Kliti Grice Hilary Stuart‐Williams Charles H. Hocart Arthur Gessler Graham D. Farquhar 《Plant, cell & environment》2016,39(12):2676-2690
The 2H/1H ratio of carbon‐bound H in biolipids holds potential for probing plant lipid biosynthesis and metabolism. The biochemical mechanism underlying the isotopic differences between lipids from C3 and C4 plants is still poorly understood. GC‐pyrolysis‐IRMS (gas chromatography‐pyrolysis‐isotope ratio mass spectrometry) measurement of the 2H/1H ratio of leaf lipids from controlled and field grown plants indicates that the biochemical isotopic fractionation (ε2Hlipid_biochem) differed between C3 and C4 plants in a pathway‐dependent manner: ε2HC4 > ε2HC3 for the acetogenic pathway, ε2HC4 < ε2HC3 for the mevalonic acid pathway and the 1‐deoxy‐D‐xylulose 5‐phosphate pathway across all species examined. It is proposed that compartmentation of photosynthetic CO2 fixation into C4 mesophyll (M) and bundle sheath (BS) cells and suppression of photorespiration in C4 M and BS cells both result in C4 M chloroplastic pyruvate – the precursor for acetogenic pathway – being more depleted in 2H relative to pyruvate in C3 cells. In addition, compartmentation in C4 plants also results in (i) the transferable H of NADPH being enriched in 2H in C4 M chloroplasts compared with that in C3 chloroplasts for the 1‐deoxy‐D‐xylulose 5‐phosphate pathway pathway and (ii) pyruvate relatively 2H‐enriched being used for the mevalonic acid pathway in the cytosol of BS cells in comparison with that in C3 cells. 相似文献
49.
Meisha Holloway‐Phillips Lucas A. Cernusak Margaret Barbour Xin Song Alexander Cheesman Niels Munksgaard Hilary Stuart‐Williams Graham D. Farquhar 《Plant, cell & environment》2016,39(11):2414-2427
The process of evaporation results in the fractionation of water isotopes such that the lighter 16O isotope preferentially escapes the gas phase leaving the heavier 18O isotope to accumulate at the sites of evaporation. This applies to transpiration from a leaf with the degree of fractionation dependent on a number of environmental and physiological factors that are well understood. Nevertheless, the 18O enrichment of bulk leaf water is often less than that predicted for the sites of evaporation. The advection of less enriched water in the transpiration stream has been suggested to limit the back diffusion of enriched evaporative site water (Péclet effect); however, evidence for this effect has been varied. In sampling across a range of species with different vein densities and saturated water contents, we demonstrate the importance of accounting for the relative ‘pool’ sizes of the vascular and mesophyll water for the interpretation of a Péclet effect. Further, we provide strong evidence for a Péclet signal within the xylem that if unaccounted for can lead to confounding of the estimated enrichment within the mesophyll water. This has important implications for understanding variation in the effective path length of the mesophyll and hence potentially the δ18O of organic matter. 相似文献
50.
Feng Y Zhao H Luderer HF Epple H Faccio R Ross FP Teitelbaum SL Longmore GD 《The Journal of biological chemistry》2007,282(1):39-48
Increasingly a number of proteins important in the regulation of bone osteoclast development have been shown primarily influence osteoclastogenesis under conditions of physiologic or pathologic stress. Why basal osteoclastogenesis is normal and how these proteins regulate stress osteoclastogenic responses, as opposed to basal osteoclastogenesis, is unclear. LIM proteins of the Ajuba/Zyxin family localize to cellular sites of cell adhesion where they contribute to the regulation of cell adhesion and migration, translocate into the nucleus where they can affect cell fate, but are also found in the cytoplasm where their function is largely unknown. We show that one member of this LIM protein family, Limd1, is uniquely up-regulated during osteoclast differentiation and interacts with Traf6, a critical cytosolic regulator of RANK-L-regulated osteoclast development. Limd1 positively affects the capacity of Traf6 to activate AP-1, and Limd1(-/-) osteoclast precursor cells are defective in the activation of AP-1 and thus induction of NFAT2. Limd1(-/-) mice, although having normal basal bone osteoclast numbers and bone density, are resistant to physiological and pathologic osteoclastogenic stimuli. These results implicate Limd1 as a potentially important regulator of osteoclast development under conditions of stress. 相似文献