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32.
Spinal muscular atrophy (SMA) is the most common genetic disease that causes infant mortality. Its treatment and prevention represent the paradigmatic example of the ethical dilemmas of 21st-century medicine. New therapies (nusinersen and AVXS-101) hold the promise of being able to treat, but not cure, the condition. Alternatively, genomic analysis could identify carriers, and carriers could be offered in vitro fertilization and preimplantation genetic diagnosis. In the future, gene editing could prevent the condition at the embryonic stage. How should these different options be evaluated and compared within a health system? In this paper, we discuss the ethical considerations that bear on the question of how to prioritize the different treatments and preventive options for SMA, at a policy level. We argue that despite the tremendous value of what we call ‘ex-post’ approaches to treating SMA (such as using pharmacological agents or gene therapy), there is a moral imperative to pursue ‘ex-ante’ interventions (such as carrier screening in combination with prenatal testing and preimplantation genetic diagnosis, or gene editing) to reduce the incidence of SMA. There are moral reasons relating to autonomy, beneficence and justice to prioritize ex-ante methods over ex-post methods. 相似文献
33.
Multitargeting involves the application of molecules that are deliberately intended to bind to two or more unrelated cellular targets with high affinity. In epigenetic chemical biology and drug discovery, the rational design of multitargeting agents has evolved to a sophisticated level, and there are now five examples that have reached clinical trials. This review covers recent developments in the field and future prospects. 相似文献
34.
《Bioorganic & medicinal chemistry》2016,24(7):1419-1430
Parkinson’s disease (PD) is a common chronic degenerative disease of the central nervous system. Due to a rapidly aging society worldwide, PD morbidity is on the rise; however, the treatment of PD with conventional drugs carries serious adverse reactions and cannot fix the root cause of PD, the degeneration of dopaminergic neurons, which limits conventional drug usage in clinical practice. In recent years, research on the pathogenesis of PD and its clinical manifestations has led to the discovery of an increasing number of novel targets in PD, including several small molecule targeted compounds. In this paper, we analyze and summarize the most recently published PD literature and review several recently discovered novel targets in PD and their small molecule targeted pharmacologically active agents based on their mechanisms of action and pharmacodynamic profiles. 相似文献
35.
Growth and nutrient concentrations of alfalfa and common bean as influenced by soil acidity 总被引:2,自引:0,他引:2
Growth and nutrient utilization of alfalfa (Medicago sativa L. cv. Arc) and common bean (Phaseolus vulgaris L. cv. Carioca) were studied in an acid soil adjusted to eight levels of soil acidity by lime addition. Application of lime
significantly (P<0.05) increased shoot and root growth for both species. However, common bean was far less sensitive to soil acidity than
alfalfa. Maximum alfalfa growth was obtained at a soil pH of 5.8 and maximum bean growth was achieved at pH 5.0. Root and
shoot growth of both legumes was positively correlated (P<0.01) with soil pH, exchangeable Ca and exchangeable Mg and negatively correlated (P<0.01) with soil exchangeable Al. Common bean had a lower internal P requirement for maximum growth and was more efficient
than alfalfa in taking up Ca and Mg. These characteristics would contribute to the favorable growth of common bean in acid-infertile
soils. 相似文献
36.
Characterization of B and H blood-group active glycosphingolipids from human B erythrocyte membranes
Peter Hanfland 《Chemistry and physics of lipids》1975,15(2):105-124
Two blood group B active glycosphingolipids (B-I and B-II) previously isolated and highly purified from human B erythrocytes [21] were analysed first by degradation with α-D-galactosidase from coffee beans, α-L-fucosidase from bovine kidney and with 0,1 N trichloracetic acid; the native B-glycolipids as well as their degradation products were then investigated by methylation analysis with combined gas chromatography-mass spectrometry, by thin layer chromatography, twodimensional immunodiffusion and by the hemagglutination inhibition technique. Together with the results obtained by mass spectrometry of permethylated glycolipids [26] the following structures were elucidated: α-D-galactopyranosyl-(1 → 3)-[α-L-fucopyranosyl-(1 → 2)]-D-galactopyranosyl-(1 → 4)-N-acetyl-D-glucosaminosyl-(1 → 3)-D-galactopyranosyl-(1 → 4)-D-glucopyranosyl-(1 → 1)-ceramide for the B-I glycosphingolipid and α-D-galactopyranosyl-(1 → 3)-[α-L-fucopyranosyl-(1 → 2)]-D-galactopyranosyl-(1 → 4)-N-acetyl-D-glucosaminosyl-(1 → 3)-D-galactopyranosyl-(1 → 4)-N-acetyl-D-glucosaminosyl-(1 → 3)-D-galactopyranosyl-(1 → 4)-D-glucopyranosyl-(1 → 1)-ceramide for the B-II glycosphingolipid. A H active glycolipid fraction from B erythrocytes further purified by thin layer chromatography was also investigated by methylation analysis. The pattern of its partially methylated alditol acetates was essentially the same as that of the α-galactosidase treated and permethylated B-I glycolipid. It also exhibited strongly precipitating and hemagglutination inhibiting H properties as well as the two α-galactosidase treated B-I and B-II glycosphingolipids. Based upon these data the following tentative structure was proposed: α-L-fucopyranosyl-(1 → 2)-D-galactopyranosyl-(1 → 4)-N-acetyl-D-glucosaminosyl-(1 → 3)-D-galactopyranosyl-(1 → 4)-D-glucopyranosyl-(1 → 1)-ceramide. Gas chromatographic analysis revealed sphingosine and lignoceric, nervonic and behenic acids to be the main components of the ceramide residues of the three glycosphingolipids. From the data presented the H active substance very probably can be regarded as the immediate precursor of the B-I glycosphingolipid from human B erythrocyte membranes. 相似文献
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It is known that the negatively stained preparations of inner mitochondrial membrane display characteristic ∼9 nmF
1 (ATPase) knobs projecting from the matrix surface. Freeze-etch studies have reported the absence of such knobs from the “etched”
surface of the inner mitochondrial membranes. We have demonstrated their presence on the surface of SMP (submitochondrial
particles) prepared by freeze-drying for transmission electron microscopy. This identification has been substantiated by comparison
with the freeze-dried TU particles (trypsin-urea treated SMP) that are devoid ofF
1 (ATPase). It has been suggested that a layer of water molecules is strongly adsorbed to the surface of SMP and does not sublime
during normal freeze-“etching.” 相似文献
40.