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71.
Pau Rocas Yolanda Fernández Natalia García-Aranda Laia Foradada Pilar Calvo Pablo Avilés María José Guillén Simó Schwartz Josep Rocas Fernando Albericio Ibane Abasolo 《Nanomedicine : nanotechnology, biology, and medicine》2018,14(2):257-267
Glutathione degradable polyurethane-polyurea nanoparticles (PUUa NP) with a disulfide-rich multiwalled structure and a cyclic RGD peptide as a targeting moiety were synthesized, incorporating a very lipophilic chemotherapeutic drug named Plitidepsin. In vitro studies indicated that encapsulated drug maintained and even improved its cytotoxic activity while in vivo toxicity studies revealed that the maximum tolerated dose (MTD) of Plitidepsin could be increased three-fold after encapsulation. We also found that pharmacokinetic parameters such as maximum concentration (Cmax), area under the curve (AUC) and plasma half-life were significantly improved for Plitidepsin loaded in PUUa NP. Moreover, biodistribution assays in mice showed that RGD-decorated PUUa NP accumulate less in spleen and liver than non-targeted conjugates, suggesting that RGD-decorated nanoparticles avoid sequestration by macrophages from the reticuloendothelial system. Overall, our results indicate that polyurethane-polyurea nanoparticles represent a very valuable nanoplatform for the delivery of lipophilic drugs by improving their toxicological, pharmacokinetic and whole-body biodistribution profiles. 相似文献
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Di Stefano S Casquero E Bustamante R Gualis J Carrascal Y Bustamante J Fulquet E Florez S Echevarria JR Fiz L 《The Tohoku journal of experimental medicine》2007,213(1):63-69
All types of cardiac surgery involve considerable injury to the myocardium. However, it is difficult to differentiate, in the immediate post-operative state, between ischemic alterations associated with the cardiac surgery itself and the pathological alterations of a peri-operative myocardial infarction. The diagnosis of damaged myocardium, classically performed with the enzymatic markers creatine kinase (CK) and its muscle fraction (CK-MB), has become more precise with the option of measuring cardiac troponins T and I. We measured these markers in 58 patients undergoing elective cardiac surgery with extra-corporeal circulation (ECC). The patients included 37 cases undergoing valve surgery, 14 for coronary revascularization, 6 for mixed procedures, and 1 for closure of an inter-atrial communication. The markers were measured in plasma at baseline (at anesthesia initiation), 5 min post-ECC commencement, following aorta de-clamping, during the surgical closure, and 6, 18 and 42 hrs after surgery. All the markers were increased significantly relative to the baseline values. Troponin I, CK and CK-MB values peaked between 6 and 18 hrs after surgery, troponin T between 18 and 42 hrs, and myoglobin at the surgical closure. The values of all markers were higher in patients undergoing coronary surgery compared to those in patients undergoing valve surgery. In the evaluation of myocardial damage after surgery, the measurement of classical markers such as CK and myoglobin remain valid, but other markers such as troponins provide significant additional diagnostic benefit and, thus, need to be included in the routine biochemical measurements for monitoring myocardial damage associated with the surgical procedure. 相似文献
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Mnica de la Cueva‐Reguera David Rodríguez‐Sanz Csar Calvo‐Lobo Silvia Fernndez‐Martínez Beatriz Martínez‐Pascual Yolanda Robledo‐Do‐Nascimento María Blanco‐Morales Carlos Romero‐Morales 《International wound journal》2020,17(5):1453-1461
Perineal trauma (PT) may be considered as a very common injury during the childbirth. The incidence of PT was estimated in 30% to 85%, with 60% to 70% requiring suture. The present study was a prospective, single‐blinded, randomised, clinical trial carried out from January 2015 to January 2016. For this study, 49 secundigravida women diagnosed with gestational oedema were recruited and randomly divided into two groups (A and B). Group A (n = 30) received the conventional treatment plus perineal massage and group B (n = 19) the conventional treatment plus manual lymphatic drainage (MLD). Visual analogue scale (VAS) and King Health's Questionnaire (KHQ) were performed to assess pain intensity and quality of life‐related with urinary incontinence (UI). Pain intensity measurements showed statistically significant differences for a decrease after 30‐weeks (P = .037), after 36‐weeks (P = .000), and at the end of puerperium (P = .014) for MLD with respect to perineal massage group. Moreover, inter‐groups repeated measures ANOVA for the values related statistically significant differences to the interaction of each applied treatment (perineal massage and MLD group, separately) over the pain intensity variable. MLD treatment reduced pain intensity with respect to perineal massage in secundigravida women with gestational oedema from 25‐weeks of gestation to the end of puerperium. 相似文献
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Sandra Sanchez-Roige Victor Baro Leanne Trick Yolanda Pe?a-Oliver David N Stephens Theodora Duka 《Neuropsychopharmacology》2014,39(13):2919-2927
There are well-established links between impulsivity and alcohol use in humans and animal models; however, whether exaggerated impulsivity is a premorbid risk factor or a consequence of alcohol intake remains unclear. In a first approach, human young (18–25 years) social binge and non-binge drinkers were tested for motor impulsivity and attentional abilities in a human version of the Five-Choice Serial Reaction Time Task (Sx-5CSRTT), modeled on the rodent 5CSRTT. Participants completed four variants of the Sx-5CSRT, in addition to being screened for impulsive traits (BIS-11 questionnaire) and impulsive behavior (by means of the Delay Discounting Questionnaire, Two-Choice Impulsivity Paradigm (TCIP), Stop Signal Reaction Time, and Time Estimation Task). Using a second approach, we compared one of these impulsivity measures, 5CSRTT performance, in two inbred strains of mice known to differ in alcohol intake. Compared with non-bingers (NBD; n=22), binge drinkers (BD, n=22) showed robust impairments in attention and premature responding when evaluated under increased attentional load, in addition to presenting deficits in decision making using the TCIP. The best predictors for high binge drinking score were premature responding in the Sx-5CSRTT, trait impulsivity in the BIS-11, and decision making in the TCIP. Alcohol-naïve C57BL/6J (B6) mice (alcohol preferring) were more impulsive in the 5CSRTT than DBA2/J (D2) mice (alcohol averse); the degree of impulsivity correlated with subsequent alcohol consumption. Homologous measures in animal and human studies indicate increased premature responding in young social BD and in the ethanol-preferring B6 strain of mice.Impulsivity has been consistently implicated as both a determinant and a consequence of alcohol abuse. Binge patterns of alcohol consumption, in particular, have been associated with impaired attentional function and executive function (Scaife and Duka, 2009; Townshend and Duka, 2005), and increased impulsive behavior in both humans and rodent models (Bell et al, 2013; Duka et al, 2003; Stephens and Duka, 2008). However, it is unclear whether high levels of impulsivity are a cause or consequence of alcohol intake.Given the prevalence of binge drinking in adolescence (Healey et al, 2014), the first aim of our study was to examine the relationship of binge drinking to measures of waiting impulsivity and attentional abilities in human adolescents (18–25 years old) and in rodents, which consume alcohol. Taking the rodent 5CSRTT (Robbins, 2002) as a model, we developed a novel, iPad-based task (Sussex 5CSRTT; Sx-5CSRTT), to assess both attentional performance and anticipatory behavior in humans. BD were also characterized in four additional measures of impulsivity, based on different operational definitions of the construct. The Stop Signal Task, used to assess ability to inhibit a prepotent response (Logan, 1994), served as an additional measure of ‘motoric impulsivity''. The Delay Discounting Questionnaire measured preference for immediate over-delayed rewards (Petry, 2001) and, combined with the Two-Choice Impulsivity paradigm (Dougherty et al, 2005), provided an index of ‘choice'' impulsivity or decision making; the fourth behavioral measure used was the Time Estimation Task. Although each of these five measures has been used in the clinical context as an index of impulsive behavior, the sensitivity of each task to characterize impulsive phenotype in young social BD, and their relationship to one another has not been explored. We anticipated binge drinking might be differentially associated with different aspects of impulsive behavior, but generally that high binge drinking scores would be associated with high levels of trait and behavioral motor impulsivity and aversion to delay.The role of premorbid impulsivity as a predictor of elevated alcohol intake cannot be easily disentangled in human studies, as impulsivity measures are almost inevitably assessed after a period of alcohol use. Animal models are more powerful tools in this respect as they allow the exclusion of alcohol experience as a potential contributor to impulsivity. Therefore, having established that 5CSRTT waiting impulsivity was associated with human binge drinking, we asked whether waiting impulsivity in alcohol-naïve mice predicted alcohol drinking in two widely used B6 and D2 inbred strains, that also differ in alcohol consumption (Crabbe et al, 1994). We have previously reported (Walker et al, 2011) that prior exposure to high alcohol concentrations over several weeks in adulthood has only transitory effects in increasing impulsivity in B6 mice. We predicted greater impulsivity in the high-ethanol-preferring mice indicating a potential causal relationship between waiting impulsivity and high alcohol consumption.Using homologous measures of impulsivity in mouse and humans, we provide evidence that waiting impulsivity is associated with binge drinking in young adult humans, and predicts alcohol consumption in mice. 相似文献
77.
Jordi Mestre David Collado David Benito-Alifonso Miguel A. Rodríguez M. Isabel Matheu Yolanda Díaz Sergio Castilln Omar Boutureira 《RSC advances》2018,8(53):30076
The preparation of well-defined d-xylo and d-ribo glycosides represents a synthetic challenge due to the limited configurational availability of starting materials and the laborious synthesis of homogeneous 2-deoxy-β-glycosidic linkages, in particular that of the sugar-steroid motif, which represents the “stereoselective determining step” of the overall synthesis. Herein we describe the use of 2-deoxy-2-iodo-glycopyranosyl sulfoxides accessible from widely available d-xylose and d-ribose monosaccharides as privileged glycosyl donors that permit activation at very low temperature. This ensures a precise kinetic control for a complete 1,2-trans stereoselective glycosylation of particularly challenging steroidal aglycones.Highly stereoselective synthesis of challenging steroidal 2-deoxy-β-glycosides with d-xylo and d-ribo configurations enabled by low temperature activation of 2-deoxy-2-iodoglycopyranosyl sulfoxides. 相似文献
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