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1.
《Drug discovery today》2022,27(6):1733-1742
Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action. 相似文献
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[目的]从六经传变角度分析"虚不受补"的内在机理,探索完善临床遇见的"虚不受补"问题。[方法]归纳疾病传变如五脏、六经、表里传变的一般规律,总结各类传变的治疗原则,辨析虚实辨证和补法分类,分析产生"虚不受补"的常见现象,提出正确进补的原则与条件。[结果](1)有外感、肺部邪气重,先解表、宣肺,然后才能进补;(2)肠胃有邪气,不可进补,先泄邪气通腑然后可进补;(3)少阳枢机不利则气机不畅,不可进补,先理气转机方可进补;(4)疾病的治疗有表里虚实之辨,也有标本缓急之别,标本之辨在辨证施治时至关重要。[结论]"虚不受补"大多数时候是进补顺序错误导致,在进补前辨别人体的气血状态,对症施药,则可以缓解甚至消除因为进补不当带来的不舒适。解表、健脾胃、活气血、寓消于补是解决虚不受补问题的重要途径。 相似文献
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Mohammad Raish Ajaz Ahmad Mushtaq Ahmad Ansari Khalid M. Alkharfy Abdul Ahad Altaf Khan Fahad I. Aljenobi Naushad Ali Abdullah M. Al-Mohizea 《Yao wu shi pin fen xi = Journal of food and drug analysis.》2019,27(1)
Dietary supplements and foods can interact with various drugs, leading to possible clinical concerns. This study aimed to investigate the effect of orally administered sinapic acid (SA) on the pharmacokinetics of aripiprazole (APZ) in rats and its possible modulatory effects on hepatic cytochrome P450 (CYP3A2 and CYP2D6) expression in the liver tissues. Single dose and multiple dose parallel groups of wistar rats were categorized into six groups (n = 6 each) which abstained from food for 12 h prior to the experiment, while water was allowed ad libitum. The investigation was carried out for single dose: Group I was treated with normal saline orally for 15 days (normal control). Group II was administered normal saline orally for 15 days and received APZ (3 mg/kg p.o.) on day 15. Group III received SA (20 mg/kg p.o.) for 15 days and received APZ (3 mg/kg p.o.) on day 15. Group IV was treated with SA (20 mg/kg p.o.) for 15 days. For the multiple dose study, Group I was treated with normal saline orally for 15 days (normal control); Group II received APZ (3 mg/kg p.o.) daily for 15 days; Group III was administered with SA (20 mg/kg p.o.) and APZ (3 mg/kg p.o.) for 15 days and Group IV received SA (20 mg/kg p.o.) for 15 days. The group I and IV were kept common in single and multiple dose groups. After last APZ dose, plasma samples were collected and APZ concentrations were determined using an UPLC-MS/MS technique. The pharmacokinetic parameters were calculated using a non-compartmental analysis. The concomitant administration of APZ with SA (as single or multiple dose) resulted in an increase in APZ absorption and a decrease on its systemic clearance. This was associated with a reduction in CYP3A2 and CYP2D6 protein expressions by 33–43% and -71–68% after the single and multiple co-administration, which are two enzymes responsible of the metabolism of APZ. Therefore, a reduction in the metabolic clearance appears to be the mechanism underlying the drug interaction of dietary supplement containing SA with APZ. Therefore, the concomitant administration of SA and APZ should be carefully viewed. Further investigations are required to assess the clinical significance of such observations in humans. 相似文献
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Children with autism spectrum disorder (ASD) demonstrate limited playfulness. Their difficulty engaging in meaningful interaction with others renders playful engagement in social interactions a challenge. Although little direct evidence exists regarding the promotion of these children’s playful engagement, links can be established with many traits cited in play and social interaction studies. This paper presents the results of a conceptual clarification exercise regarding the key behaviours associated with the construct of playful engagement in preschool-aged children with ASD. Behaviours were identified based on hallmark deficits in early social interactions and play of children with ASD. The analysis revealed the following behaviours: positive affect, engagement, imitation, joint attention, initiation of social interaction, social responsiveness, flexibility, child’s laughter in funny situations and giving and reading non-verbal cues. In conclusion, a conceptually coherent stage has been set for exploring the literature regarding interventions to promote the playful engagement of preschool-aged children with ASD. 相似文献
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《Paediatrics & Child Health》2020,30(4):119-123
The aim of this review was to establish the current evidence base regarding parental involvement in decision-making in the NICU. The review question was set as ‘What is known about the process of parental participation in clinical decision-making in the NICU?’ The findings of this critical literature review illustrate the process of decision-making for parents in NICU. The available evidence base was minimal. The parental role in decision-making is variable with current literature suggesting that the informed parental role, allowing parents to make the ultimate decision, is increasingly desired. Despite this there is still a requirement for medical and shared decision-making for some families. Regardless of the role parents assume it is evident that there will always be an array of emotional complexities to follow. Most feelings and emotional responses reported by parents were negative. The literature suggests several reasons for these feelings. A lack of parental knowledge and experience in NICU leading to confusion as to whether the right decision has been made alongside parents having a heightened awareness of the potential for suffering and harm for their baby. There are the added pressures of time and the weight of responsibility. The burden appears to be unequally distributed between parents. Several studies illustrate the transfer of responsibility from the father to mothers. 相似文献