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Phosphodiesterase type 5 (PDE5) induces the breakdown of cyclic guanosine monophosphate (cGMP) in smooth muscle cells. Hence, PDE5 inhibitors promote vasodilative effects by enhancing intracellular cGMP levels. Three PDE5 inhibitors, sildenafil, vardenafil, and tadalafil, have been approved for the treatment of "erectile dysfunction" (ED). All three show an excellent effectiveness regarding ED therapy, but differ from one another regarding their pharmacokinetic properties. Recent experimental studies and clinical trials indicate that PDE5 inhibitors are also effective in the treatment of various other diseases such as pulmonary arterial hypertension (PAH), Raynaud's disease, gastrointestinal disorders, and stroke, and furthermore exert cardioprotective effects. This review describes the cardiovascular safety of PDE5 inhibitors and provides an overview of the current literature regarding potential novel indications. 相似文献
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Gabriela Senti Bettina M. Prinz Vavricka Iris Erdmann Mella I. Diaz Richard Markus Stephen J. McCormack John J. Simard Brunello Wüthrich Reto Crameri Nicole Graf P?l Johansen Thomas M. Kündig 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(46):17908-17912
The only causative treatment for IgE-mediated allergies is allergen-specific immunotherapy. However, fewer than 5% of allergy patients receive immunotherapy because of its long duration and risk of allergic side effects. We aimed at enhancing s.c. immunotherapy by direct administration of allergen into s.c. lymph nodes. The objective was to evaluate safety and efficacy compared with conventional s.c. immunotherapy. In a monocentric open-label trial, 165 patients with grass pollen-induced rhinoconjunctivitis were randomized to receive either 54 s.c. injections with pollen extract over 3 years [cumulative allergen dose 4,031,540 standardized quality units (SQ-U)] or 3 intralymphatic injections over 2 months (cumulative allergen dose 3,000 SQ-U). Patients were evaluated after 4 months, 1 year, and 3 years by nasal provocation, skin prick testing, IgE measurements, and symptom scores. Three low-dose intralymphatic allergen administrations increased tolerance to nasal provocation with pollen already within 4 months (P < 0.001). Tolerance was long lasting and equivalent to that achievable after standard s.c. immunotherapy (P = 0.291 after 3 years). Intralymphatic immunotherapy ameliorated hay fever symptoms (P < 0.001), reduced skin prick test reactivity (P < 0.001), decreased specific serum IgE (P < 0.001), caused fewer adverse events than s.c. immunotherapy (P = 0.001), enhanced compliance (P < 0.001), and was less painful than venous puncture (P = 0.018). In conclusion, intralymphatic allergen administration enhanced safety and efficacy of immunotherapy and reduced treatment time from 3 years to 8 weeks. 相似文献
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Escherichia coli 5S RNA binding proteins L18 and L25 interact with 5.8S RNA but not with 5S RNA from yeast ribosomes. 总被引:11,自引:0,他引:11
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P Wrede V A Erdmann 《Proceedings of the National Academy of Sciences of the United States of America》1977,74(7):2706-2709
Reconstitution experiments showed that the two Escherichia coli 5S RNA binding proteins L18 and L25 form a specific complex with yeast 5.8S RNA and not with yeast 5S RNA. The yeast 5.8S RNA-E. coli protein complex was found to exhibit ATPase and GTPase activities that had previously been observed for the E. coli 5S RNA-protein complex. The tetranucleotide UpUpCpG, which is an analog of the tRNA fragment TpsipCpG, interacted strongly with 5S RNA-protein complexes from E. coli and Bacillus stearothermophilus and weakly with yeast 5.8S RNA. UpUpCpG did not bind to E. coli, B. stearothermophilus, or yeast 5S RNA or to the yeast 5.8S RNA-E. coli protein complex. It is suggested that 5.8S RNA evolved from prokaryotic 5S RNA and that the latter two RNAs are related and have similar functions in protein synthesis. 相似文献
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Giovana Dorneles Callegaro Higashi Alacoque Lorenzini Erdmann 《Revista latino-americana de enfermagem》2014,22(2):269-276
Objective
to understand the meanings of the collegiate deliberations attributed by its members on an undergraduate nursing course.Method
Grounded Theory, interviews being held with 30 participants, making up 4 sample groups, between January and June 2012, in a public higher education institution.Result
5 categories emerged, indicating the phenomenon and weaving the paradigmatic model: Understanding the experience of the complex relationships and interactions in the deliberations of collegiate management in nursing: intertwining divergences, convergences, dialogs, collectivities and diversities. This deliberative process presents various meanings involving discussion, and divergent, convergent and complementary positions, through dialog, commitment and negotiation.Conclusion
the deliberations in the collegiate of nursing, intertwining dialogs, collectivities and diversities, mold the complex relational fabrics. 相似文献69.
Inke R. König Christina Loley Jeanette Erdmann Andreas Ziegler 《Genetic epidemiology》2014,38(2):97-103
In current genome‐wide association studies (GWAS), the analysis is usually focused on autosomal variants only, and the sex chromosomes are often neglected. Recently, a number of technical hurdles have been described that add to a reluctance of including chromosome X in a GWAS, including complications in genotype calling, imputation, and selection of test statistics. To overcome this, we provide a “how to” guide for analyzing X chromosomal data within a standard GWAS. Following a general pipeline for GWAS, we highlight the steps in which the X chromosome requires specific attention, and we give tentative advice for each of these. Through this, we show that by selection of sensible algorithms and parameter settings, the inclusion of chromosome X in GWAS is manageable. Closing this gap is expected to further elucidate the genetic background of complex diseases, especially of those with sex‐specific features. 相似文献
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Virus Genes - The emerging occurrence of antibiotic-resistant bacterial pathogens leads to a recollection of bacteriophage as antimicrobial therapeutics. This article presents a short overview of... 相似文献