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Synthesis of novel mono and bis nitric oxide donors with high cytocompatibility and release activity
Tanya Sahyoun Caroline Gaucher Yi Zhou Naïm Ouaini Raphaël Schneider Axelle Arrault 《Bioorganic & medicinal chemistry letters》2018,28(20):3329-3332
Four compounds bearing amidoxime functions were synthetized: (1) 2a,b bearing an aromatic amidoxime function, (2) 2c bearing an aliphatic amidoxime function, and (3) 2d bearing aromatic and aliphatic amidoximes functions. The ability of these compounds to release NO was evaluated in vitro using the oxidative metabolism of cytochrome P450 from rat liver microsomes. Results obtained demonstrate that all amidoximes were able to release NO with a highest amount of NO produced by the 2a aromatic amidoxime. Moreover, all amidoximes exhibit cytocompatibility with human aorta smooth muscle cells. Using intracellular S-nitrosothiol formation as a marker of NO bioavailability, compounds 2a–c were demonstrated to deliver a higher amount of NO in the intracellular environment than the reference. Considering that the concentration of the bis-amidoxime 2d was two times lower that than of 2a and 2b, we can assume that 2d is the most potent molecule among the tested compounds for NO release. 相似文献
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Paula Gonçalves Viana Anna Barreto Fernandes Figueiredo Isabella Dib Ferreira Gremião Luisa Helena Monteiro de Miranda Isabela Maria da Silva Antonio Jéssica Sepulveda Boechat Ana Caroline de Sá Machado Manoel Marques Evangelista de Oliveira Sandro Antonio Pereira 《Mycopathologia》2018,183(2):471-478
Sporotrichosis occurs worldwide, and the metropolitan region of Rio de Janeiro, Brazil, is a main endemic area, with a large number of human and animal cases in the last 19 years. This mycosis is more frequently described in cats rather than in dogs. There are a limited number of oral antifungal agents for the treatment of sporotrichosis in animals. In this context, the effectiveness of terbinafine in the treatment of sporotrichosis in humans, as well as the promising results of in vitro susceptibility tests, inspired us to use this drug in the therapy of this mycosis in dogs. We reported for the first time the use of terbinafine in the treatment of two dogs with sporotrichosis caused by Sporothrix brasiliensis. Moreover, we provided an overview of therapeutic features of canine sporotrichosis cases reported since the 1960s. One of the dogs presented the fixed cutaneous form of the disease, while the other patient presented hyperemia of the nasal mucosa and respiratory signs only. Terbinafine showed high antifungal activity in vitro against the canine Sporothrix isolates. The dogs were successfully treated with terbinafine, with remission of all clinical signs initially presented. The current reports indicate that this drug can emerge as a therapeutic option for canine sporotrichosis. 相似文献
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Stephanie Centofanti Siobhan Banks Antonietta Colella Caroline Dingle Lisa Devine Helen Galindo 《Chronobiology international》2018,35(6):853-864
ABSTRACTIntroduction: Two of the most ubiquitous fatigue countermeasures used by shift-working nurses are napping and caffeine. This mixed-methods case study investigated the ways nurses and midwives utilised napping and caffeine countermeasures to cope with shift work, and associated sleep, physical health and psychological health outcomes.Materials and Methods: N = 130 Australian shift-working nurses and midwives (mean age = 44 years, range = 21–67, 115F, 15M) completed the Standard Shiftwork Index. A sub-set of 22 nurses and midwives completed an in-depth interview.Results: Nearly 70% of participants reported napping. Those who napped during night shifts had significantly less total sleep time before (F2,75 = 5.5, p < 0.01) and between days off (F2,82 = 3.9, p < 0.05). By the end of the night shift, average hours of time awake were significantly less for prophylactic and on-shift nappers compared to non-nappers (F2,85 = 97.2, p < 0.001). Since starting shift work, the percentage of high caffeine consumers (>400 mg/day) increased from 15% to 33% of the sample and an average of 4 (SD = 2) caffeinated beverages per day was reported. Increased caffeine consumption was associated with greater sleep disturbance (r = 0.26, p < 0.05), psychological distress (r = 0.37, p < 0.001), abdomen pain (r = 0.27, p < 0.05) and weight gain since starting shift work (r = 0.25, p < 0.05). Interviews confirmed these relationships and revealed that caffeine consumption on night shift was common, whereas napping on night shift was dependent on a number of factors including ability to sleep during the day.Conclusion: This study identified reasons shift workers chose to engage in or abstain from napping and consuming caffeine, and how these strategies related to poor sleep and health outcomes. Further research is required to help develop recommendations for shift workers regarding napping and caffeine consumption as fatigue countermeasures, whilst taking into account the associated hazards of each strategy. 相似文献
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David Castonguay Julien Dufort-Gervais Caroline Ménard Manavi Chatterjee Rémi Quirion Bruno Bontempi Jay S. Schneider Amy F.T. Arnsten Angus C. Nairn Christopher M. Norris Guylaine Ferland Erwan Bézard Pierrette Gaudreau Paul J. Lombroso Jonathan Brouillette 《Current biology : CB》2018,28(7):1079-1089.e4
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