硫代硫酸钠治疗慢性肾脏病患者血管钙化临床应用进展

近年来,慢性肾脏病(CKD)作为世界范围内主要的公共卫生问题受到越来越多的关注。慢性肾脏病矿物质和骨异常(CKD-MBD)是由于CKD的矿物质及骨代谢异常综合征所致,严重地影响了CKD患者的生存率和生活质量。血管钙化是CKD-MBD的临床表现之一,其包括:动脉内膜钙化、中膜钙化、心脏瓣膜钙化和钙化防御。     

Multiparametric classification of sub‐acute ischemic stroke recovery with ultrafast diffusion, 23Na,and MPIO‐labeled stem cell MRI at 21.1 T

MRI leverages multiple modes of contrast to characterize stroke. High‐magnetic‐field systems enhance the performance of these MRI measurements. Previously, we have demonstrated that individually sodium and stem cell tracking metrics are enhanced at ultrahigh field in a rat model of stroke, and we have developed robust single‐scan diffusion‐weighted imaging approaches that utilize spatiotemporal encoding (SPEN) of the apparent diffusion coefficient (ADC) for these challenging field strengths. Here, we performed a multiparametric study of middle cerebral artery occlusion (MCAO) biomarker evolution focusing on comparison of these MRI biomarkers for stroke assessment during sub‐acute recovery in rat MCAO models at 21.1 T. T₂‐weighted MRI was used as the benchmark for identification of the ischemic lesion over the course of the study. The number of MPIO‐induced voids measured by gradient‐recalled echo, the SPEN measurement of ADC, and ²³Na MRI values were determined in the ischemic area and contralateral hemisphere, and relative performances for stroke classification were compared by receiver operator characteristic analysis. These measurements were associated with unique time‐dependent trajectories during stroke recovery that changed the sensitivity and specificity for stroke monitoring during its evolution. Advantages and limitations of these contrasts, and the use of ultrahigh field for multiparametric stroke assessment, are discussed.     

Assessing the variability of 23Na MRI in skeletal muscle tissue: Reproducibility and repeatability of tissue sodium concentration measurements in the lower leg at 3 T

The goal of this study was to evaluate the reproducibility and repeatability of tissue sodium concentration (TSC) measurements using ²³Na MRI in skeletal muscle tissue. ²³Na MRI was performed at 3 T on the right lower leg of eight healthy volunteers (aged 28 ± 4 years). The examinations were repeated at the same site after ~ 22 weeks to assess the variability over a medium‐term period. Additionally, they were scanned at a second site shortly before or shortly after the first visit (within 3 weeks) to evaluate the inter‐site reproducibility. Moreover, we analysed the effect of B₀ correction on the variability. Coefficients of variations (CVs) from mean TSC values as well as Bland–Altman plots were used to assess intra‐site repeatability and inter‐site reproducibility. In phantom measurements, the B₀ correction improved the quantitative accuracy. We observed differences of up to 4.9 mmol/L between the first and second visit and a difference of up to 3.7 mmol/L between the two different sites. The CV for the medium‐term repeatability was 15% and the reproducibility CV was 9%. The Bland–Altman plots indicated high agreement between the visits in all muscle regions. The systematic bias of ?0.68 mmol/L between site X and Y (P = 0.03) was slightly reduced to ?0.64 mmol/L after B₀ correction (P = 0.04). This work shows that TSC measurements in healthy skeletal muscle tissue can be performed with good repeatability and reproducibility, which is of importance for future longitudinal or multicentre studies.     

Evaluation of the effectiveness of Er: YAG laser and calcium sodium phosphosilicate (Novamine) prophylaxis paste on remineralization of incipient enamel lesions in primary teeth: An in-vitro study

AimThe aim of this study was to evaluate the potential remineralization effect of Novamine and Er:YAG laser on artificial enamel lesions in primary teeth.Materials and methodsIn this in vitro study, 30 sound buccal and lingual surfaces of human primary canines were randomly divided (6 per group) into 5 groups (Novamine, Laser, Novamine+ Laser, Positive control, and a negative control). Remineralization agents were applied for 1 min to teeth using a rubber cup after creating artificially demineralised lesions. EDX analysis was performed to evaluate the Ca/P ratio and take Scanning electron microscope images.ResultsData were analyzed using Kruskal Wallis analysis. Ca/P ratio was higher in all 4 groups than the negative control group, and higher in Novamine+ Laser group than the positive control group with a statistically significant difference between groups. Overall Ca/P ratio was found to be highest in the Novamine group followed by the laser then positive control group. There were no significant differences between groups regard to Ca/P Ratios.ConclusionBased on these result Er:YAG laser combined with Novamine was provided the greatest contribution to remineralization process of primary teeth.     

An evaluation of sodium oxybate as a treatment option for narcolepsy

Introduction: Narcolepsy is a lifelong central nervous system (CNS) disorder characterized by excessive daytime sleepiness, cataplexy, disturbed nocturnal sleep, hypnagogic hallucinations, and sleep paralysis. Treatment is symptomatic and challenging. Current therapies with wake promoting agents, stimulants, and antidepressants improve symptoms but residual sleepiness or cataplexy may persist. Drug tolerance may develop. Adverse drug effects limit therapy. In the United States, sodium oxybate has been approved to treat daytime sleepiness and cataplexy in adults with narcolepsy since 2002. In 2018, it was approved for children ages 7–17 years with cataplexy with narcolepsy.

Areas covered: This drug review includes an overview of narcolepsy, current pharmacotherapy, drug chemistry, pharmacodynamics, pharmacokinetics, and metabolism of sodium oxybate. Published results from 11 randomized control trials are reviewed. Databases searched included PubMed, Google Scholar, Lexi-Comp, Scopus, Science, and Ovid.

Expert opinion: Sodium oxybate is an effective therapy for excessive daytime sleepiness and cataplexy in adults and children ages 7–17 years. It is also an effective therapy for disrupted nocturnal sleep. Sodium oxybate improves narcolepsy symptoms and enhances quality of life in narcolepsy patients.     

Structural adaption of axons during de‐ and remyelination in the Cuprizone mouse model

Multiple Sclerosis is an autoimmune disorder causing neurodegeneration mostly in young adults. Thereby, myelin is lost in the inflammatory lesions leaving unmyelinated axons at a high risk to degenerate. Oligodendrocyte precursor cells maintain their regenerative capacity into adulthood and are able to remyelinate axons if they are properly activated and differentiate. Neuronal activity influences the success of myelination indicating a close interplay between neurons and oligodendroglia. The myelination profile determines the distribution of voltage‐gated ion channels along the axon. Here, we analyze the distribution of the sodium channel subunit Nav1.6 and the ultrastructure of axons after cuprizone‐induced demyelination in transgenic mice expressing GFP in oligodendroglial cells. Using this mouse model, we found an increased number of GFP‐expressing oligodendroglial cells compared to untreated mice. Analyzing the axons, we found an increase in the number of nodes of Ranvier in mice that had received cuprizone. Furthermore, we found an enhanced portion of unmyelinated axons showing vesicles in the cytoplasm. These vesicles were labeled with VGlut1, indicating that they are involved in axonal signaling. Our results highlight the flexibility of axons towards changes in the glial compartment and depict the structural changes they undergo upon myelin removal. These findings might be considered if searching for new neuroprotective therapies that aim at blocking neuronal activity in order to avoid interfering with the process of remyelination.     

Proteases and their inhibitors as prognostic factors for high-grade serous ovarian cancer

Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance.     

多沙唑嗪联合双氯芬酸钠治疗前列腺电切术后膀胱痉挛的安全性和有效性

目的：观察多沙唑嗪联合双氯芬酸钠治疗前列腺电切术（TURP）后膀胱痉挛（BS）的安全性和有效性。方法：以2017年1月-2018年1月某院经TURP治疗的良性前列腺增生患者126例作为研究对象，采用随机数表法，将126例患者分为观察组和对照组，每组63例。对照组于TURP术后口服甲磺酸多沙唑嗪缓释片进行治疗，观察组口服甲磺酸多沙唑嗪片联合双氯芬酸钠栓肛塞进行治疗。比较2组BS时间和次数、视觉模拟评分量表（VAS）评分、汉密尔顿抑郁量表（HAMD）评分、汉密尔顿焦虑量表（HAMA）评分、膀胱冲洗液变淡时间、导管留置时间、术后住院天数和不良反应的发生率。结果：观察组BS发生频率、BS持续时间和VAS评分均较对照组高，差异有显著性（P<0.05）。观察组HAMD评分和HAMA评分均高于对照组，差异有显著性（P<0.05）。2组膀胱冲洗液变淡时间、导管留置时间和术后住院天数的比较无显著差异（P>0.05）。126例患者均成功完成手术，术后服用期间未见任何药物相关不良反应。结论：多沙唑嗪联合双氯芬酸钠治疗TURP术后BS安全和有效。     

Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.     

An evaluation of rectal artesunate for the pre-hospital management of severe malaria

ABSTRACT

Introduction

Severe falciparum malaria stills accounts for around half a million childhood deaths per year in sub-Saharan Africa. Prompt treatment of sick children close to home starting with artesunate given rectally by appropriately trained people can be lifesaving.