Investigation of non-linear Mate1-mediated efflux of trimethoprim in the mouse kidney as the mechanism underlying drug-drug interactions between trimethoprim and organic cations in the kidney

The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with K_i values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with K_m values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CL_R) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CL_R (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CL_R of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates.     

Qigong in the treatment of children with autism spectrum disorder: A systematic review

BackgroundAutism spectrum disorder is a condition that affects all races, ethnic and socioeconomic groups. With a high incidence ratio of one in every 68, it has become one of the most discussed psychiatric disorders. For this reason, the need for investigating novel treatments has been emerging. Qigong, a traditional Chinese mind-body technique, has already proven to be able to reduce symptoms of several physical and psychological illnesses.ObjectiveThe purpose of this systematic review is to examine and categorize the current scientific evidence regarding the efficacy of Qigong on children suffering from autism spectrum disorders.Search strategyA systematic literature search of the electronic scientific databases PubMed, Clinical Trials.gov, BioMed Central, PubMed Central and Google Scholar was performed to identify studies of Qigong in the treatment of children with autism spectrum disorder.Inclusion criteriaThis review included randomized controlled trials, replication studies, retrospective studies and observational follow-up studies of Qigong on children with autism spectrum disorder. Case reports and case series were excluded.Data extraction and analysisTwo researchers independently evaluated the methodological quality of all included studies. Any discrepancies were solved by discussion until consensus was achieved.ResultsOur literature search identified 157 publications, and 10 additional publications from hand search of references. After duplicate removal, 103 records remained. After the title/abstract screening, 19 publications were obtained for detailed evaluation. After detailed evaluation, 10 studies were included. Seven studies were conducted with small children with 2–6 years old employing Qigong massage, and three studies were conducted with older children aged 7–17 years old applying both Qigong massage (one study) and Neigong (two studies).ConclusionStudies demonstrated that Qigong has interesting and promising applicability and effect on children with autism spectrum disorder and should be tested further. Despite the need for more rigorous controlled studies, Qigong seems to be able to decrease severity of individual sensory, behavioural, and language components of autism, and improve self-control, sociability, sensory and cognitive awareness as well as healthy-physical behaviour. Besides positive effect on children and adolescents, benefits seem to extend to parents and caregivers as well. However, quality of methodology seems to be insufficient to state that Qigong is an alternative to common behavioural therapies. We suggest that, until more investigation is performed, Qigong may only be used as a complement, or when behavioural therapies are not accessible.     

Mise à jour des croyances et congruence à l'humeur dans le trouble dépressif

Depressive disorder is characterized by a polymorphic symptomatology associating emotional, cognitive and behavioral disturbances. One of the most specific symptoms is negative beliefs, called congruent to mood. Despite the importance of these beliefs in the development, the maintenance, and the recurrence of depressive episodes, little is known about the processes underlying the generation of depressive beliefs. In this paper, we detail the link between belief updating mechanisms and the genesis of depressive beliefs. We show how depression alters information processing, generating cognitive immunization when processing positive information, affective updating bias related to the valence of belief and prediction error, and difficultie to disengage from negative information. We suggest that disruption of belief-updating mechanisms forms the basis of belief-mood congruence in depression.     

珠海地区NRXN1和NLGN1基因多态性与儿童孤独症的关联性研究

目的 探索珠海地区NRXN1和NLGN1基因多态性与儿童孤独症易感性的关系,为孤独症的防治提供科学依据。方法 采用病例对照的研究方法,选取2011－2016年就诊于珠海市妇幼保健院的123例珠海地区的孤独症患儿和506例健康对照。采用口腔拭子采集口腔上皮细胞以提取DNA,采用Sequenom Mass Array platform分型技术对NRXN1基因上的rs1045881和rs11885824以及NLGN1上的rs9855544进行基因分型。结果 NRXN1基因上的rs1045881和rs11885824以及NLGN1上的rs9855544位点基因型分布在孤独症组和健康对照组比较,差异无统计学意义;但NLGN1基因上的rs9855544与NRXN1基因上的rs11885824存在基因与基因间的交互作用(预测准确率为0.480,交叉验证一致性为10/10,P=0.040)。结论 NRXN1基因上的rs1045881和rs11885824以及NLGN1上的rs9855544位点基因多态性可能与孤独症易感性没有关联,但NLGN1基因上的rs9855544与NRXN1基因上的rs11885824之间的交互作用可能是孤独症易感性的影响因素。     

Quantification of 5-HT1A and 5-HT2A receptor Binding in Depressed Suicide Attempters and Non-Attempters

Objective: To determine serotonin system abnormalities related to major depression or previous suicidal behavior.

Methods: [¹¹C]WAY100635, [¹⁸F]altanserin and positron emission tomography were used to compare 5-HT_1A and 5-HT_2A binding in MDD patients divided into eight past suicide attempters (>4yrs prior to scanning) and eight lifetime non-attempters, and both groups were compared to eight healthy volunteers.

Results: The two receptor types differed in binding pattern across brain regions from each other, but there were no differences in binding between healthy volunteers and the two depressed groups or between depressed suicide attempters and non-attempters. No effects of depression severity or lifetime aggression were observed for either receptor.

Conclusion: Limitations of this study include small sample size and absence of high lethality suicide attempts in the depressed attempter group. No trait-like binding correlations with past suicide attempt or current depression were observed. Given the heterogeneity of nonfatal suicidal behavior, a larger sample study emphasizing higher lethality suicide attempts may find the serotonin biological phenotype seen in suicide decedents.     

lncRNA RP11-86H7.1在川崎病诊断中的临床意义

目的：探讨lncRNA RP11-86H7.1在川崎病（KD）患者血清中的表达及其与临床病理特征及预后的关系。方法：筛选KD特异相关的循环lncRNA，分KD治疗前患儿组、KD治疗后患儿组、普通发热患儿组及健康儿童组，采用qPCR检测各组血清lncRNA RP11-86H7.1相对表达。分析血清lncRNA RP11-86H7.1相对表达与KD临床病理特征间关系；绘制ROC曲线，分析血清lncRNA RP11-86H7.1表达水平对KD的诊断效能。结果：KD急性患儿组血清lncRNA RP11-86H7.1相对表达量高于各对照组（P＜0.05）；年龄和性别比例与低表达组比较差异无统计学意义（P＞0.05）；qPCR发现lncRNA RP11-86H7.1在KD急性期患儿血清中表达水平明显高于KD恢复期、健康儿童及发热儿童组，差异均有统计学意义（P＜0.05）。结论：血清lncRNA RP11-86H7.1在KD患者中表达上调，其可作为KD早期诊断和评估预后的潜在的生物标志物。