Dexamethasone loaded bioresorbable films used in medical support devices: structure, degradation, crystallinity and drug release

Bioresorbable polymer films containing dexamethasone (DM) were prepared using a solution processing technique. Investigation of the films focused on cumulative DM release as affected by film morphology (drug location/dispersion in the film) and degradation processes. Two film structures were studied: A-type, a polymer film with large drug crystals located on the film’s surface, and B-type, a polymer film with small drug particles and crystals distributed within the bulk. The effect of the polymer’s degree of crystallinity on the drug release profile was also studied. Prototypical applications of these films are biodegradable medical support devices which combine mechanical support with drug release. In most of our studied systems the drug release profile from the film is determined mainly by both drug location/dispersion in the film and the polymer’s weight loss rate. All release profiles from A-type films exhibited a burst effect of approximately 30%, accompanied by a second release phase at a constant rate, whereas the release profiles from B-type films were determined mainly by the degradation profile of the host polymer, and did not exhibit any burst effect. A high degree of crystallinity is important for the current application, since good mechanical properties are required. This contributes to slower drug release rates, mainly at relatively low weight losses, whereas at high weight losses, where a porous structure is created, the crystallinity almost does not affect the rate of drug release. The shape of the porous structure that develops with degradation also affects the drug release profile from the B-type films.     

A double-blind study on the effect of discontinuation of gold therapy in patients with rheumatoid arthritis

Summary To assess the benefit of further gold treatment of rheumatoid arthritis (RA) patients who had already received more than 6 g of this metal, 24 such patients were included in a double-blind trial. Besides this gold group comprising 11 patients who received gold (Auromyose^®) in the same dosage schedule as before the study, the trial included a placebo group comprising 13 patients who received gold in a suspension diluted 1/100. In either group clinical, laboratory, and radiological data did not differ after 6 and 24 months in relation to the results at entry except for the serum gold concentrations, which were lower in the placebo group. We conclude that discontinuation of the treatment in RA patients who have received more than 6 g gold is not harmful to the patients for at least two years after withdrawal.     

Ouabain enhances release of acetylcholine in the heart evoked by unilateral vagal stimulation

Summary The aim of the study was to elucidate peripheral effects of ouabain on the parasympathetic innervation of the heart, effects that could contribute to the experimentally and clinically well established vagal effect of cardiac glycosides. The experiments were carried out with ouabain concentrations of 3×10^–7 and 10^–6 mol/l, which were considered therapeutic, as they increased force of contraction and did not elicit arrhythmias in incubated chicken atria.In atrial preparations of chickens and guinea-pigs the negative chronotropic and inotropic effects of acetylcholine (ACh) were not altered by 3×10^–7 mol/l ouabain. Resting efflux of ACh from perfused chicken hearts was increased by ouabain from 10 to a maximum of 30 pmol/g min, whereas release of ACh evoked by bilateral vagal stimulation at 3 or 20 Hz for 1 min was unchanged (resting release subtracted). In contrast, release of ACh caused by unilateral vagal stimulation was augmented by ouabain up to 200% of the control. Release by unilateral stimulation (80 pmol/g; 20 Hz) was calculated for each experiment by averaging the releases evoked by consecutive stimulation of the right and left nerves. Ouabain infused for 90 min did not alter the tissue content of ACh (5.5 nmol/g).Within 2 days after unilateral (left) vagal transsection (denervation of cardiac ganglia) the release of ACh evoked by stimulation of the intact nerve (20 Hz) increased from about 80 to 200 pmol/g, whereas the release from the lesioned nerve markedly declined. One day after denervation, ouabain had lost the ability to facilitate the release of ACh evoked by stimulation of the intact nerve, whereas the release by stimulation of the lesioned nerve was still increased.It is concluded that ouabain at therapeutic concentrations increased resting release of ACh but did not influence the mechanism of action potential-evoked release of ACh. The effect of exogenous ACh on sinus node activity was not enhanced by ouabain. The observation that ouabain increased release of ACh caused by unilateral, but not by bilateral vagal stimulation was explained by an increase in the number of activated postganglionic neurons arising from those (contralateral) ganglia that received a subthreshold input from the stimulated vagus nerve.Supported by the Deutsche ForschungsgemeinschaftSome of the results are part of the M.D. theses of M. Feinauer and B. Ullrich     

国产重组人促卵泡激素在辅助生殖技术控制性超促排卵的临床应用

目的评价国产重组人促卵泡激素(recombinant human follicle-stimulating hormone,rhFSH)用于辅助生殖技术(assisted reproductive technology,ART)控制性超促排卵(controlled ovarian hyperstimulation,COH)的有效性及安全性。方法本试验采用多中心、随机、双盲、阳性平行对照、非劣效研究方法,于2017年7月至2019年6月间选取6家生殖医学中心纳入卵巢储备正常的不孕女性进行ART的COH治疗。受试者随机分为试验组(国产rhFSH,n=134)和对照组(进口rhFSH,n=133),研究过程中因各种因素排除受试者共8例,试验组7例,对照组1例,最终依照研究方案完成试验的受试者试验组127例,对照组132例。比较两组受试者COH周期中获得的卵母细胞总数、rhFSH用药情况、卵母细胞受精率、优质胚胎数、临床妊娠率、活产率、新生儿情况及不良反应发生率等指标。结果试验组和对照组在COH周期中获得的卵母细胞总数分别为(13.0±5.8)枚和(12.9±5.7)枚,差异无统计学意义(P>0.05);在82例卵胞质内单精子显微注射(intracytoplasmic sperm injection,ICSI)受试者中,试验组(39例)获得MII卵母细胞数[(9.9±3.9)枚]显著高于对照组(43例)[(7.5±3.0)枚,P=0.003];卵母细胞受精率试验组[63.82%(1048/1642)]显著高于对照组[56.19%(958/1705),P<0.001]。rhFSH用药时间和总量、优质胚胎数、临床妊娠率、早产率、活产率、新生儿异常发生率、新生儿体质量、Apgar评分等两组间差异无统计学意义(P均>0.05);治疗期间卵巢过度刺激综合征(ovarian hyperstimulation syndrome,OHSS)和其他不良反应发生率差异无统计学意义(P均>0.05),且均为进口rhFSH已知的不良反应。结论在卵巢储备正常的不孕女性中使用相同卵巢刺激治疗方案,国产rhFSH有效性及安全性与进口rhFSH相当。     

The Effect of Intravenous Magnesium Sulphate as an Adjuvant in the Treatment of Acute Exacerbations of COPD in the Emergency Department: A Double-Blind Randomized Clinical Trial

BackgroundAcute exacerbations of chronic obstructive pulmonary disease (AECOPD) are serious complications that often require immediate intervention in an emergency department (ED). The aim of this study was to investigate the effect of intravenous magnesium sulphate as an adjuvant in the treatment of AECOPD in the ED.MethodsIn a double-blind, randomized clinical trial, a total of 60 patients with AECOPD presenting to the ED of Imam Khomeini Hospital in Sari, Iran, were included. The study was conducted between September 2016 and February 2018. Eligible patients were randomly allocated into two groups of intervention and control. Patients in the intervention and control groups received intravenous infusion of magnesium sulfate (2 gr) or normal saline over 30 minutes, respectively. For all patients, Borgdyspnea score, forced expiratory volume in one second (FEV1) result and clinical variables of interest were evaluated before the beginning of the intervention, and also 45 minutes and 6 hours after the commencement of intervention.ResultsRegardless of time of evaluation, pulse rate (PR), respiratory rate (RR) and Borg score in intervention group was lower than control group. Also, FEV1 and SPO2 were greater in intervention group compared to control group. However, these differences were not statistically significant (between-subject differences or group effect) (p<0.001). The trends of FEV1, SPO2, PR, RR and Borg score were similar between two groups of study (no interaction effect; P>0.05).ConclusionAccording to the results of this study, it seems that using intravenous magnesium sulfate has no significant effect on SPO2, FEV1, RR, and PR of patients with AECOPD who presented to ED.     

颅脑手术中应用硝酸甘油或复合艾司洛尔调控血压效果的比较

目的：比较艾司洛尔复合硝酸甘油（NTG）降压与单纯硝酸甘油降压效果。方法：36例ASA Ⅰ-Ⅱ级颅外择期手术病人分为两组：艾司洛尔复合NTG组18例,单纯NTG组18例,观察并比较两组控制性降压时血气,血液动力学的变化。结果：艾司洛尔能明显加快NTG起效速率,NTG用量减少55．7％,并能抑制单纯NTG控制性降压时反射性心率增快;停止降压后血压平衡上升,RPP值下降;PaO2,BE仅轻度下降,与单纯NTG组比较有显著差异。结论：艾司洛尔复合NTG控制性降压有明显的协同作用。无反跳现象,对动脉血气影响小。     

A phase IIA extension study evaluating the effect of booster vaccination with a fractional dose of RTS,S/AS01E in a controlled human malaria infection challenge

BackgroundWe previously demonstrated that RTS,S/AS01_B and RTS,S/AS01_E vaccination regimens including at least one delayed fractional dose can protect against Plasmodium falciparum malaria in a controlled human malaria infection (CHMI) model, and showed inferiority of a two-dose versus three-dose regimen. In this follow-on trial, we evaluated whether fractional booster vaccination extended or induced protection in previously protected (P-Fx) or non-protected (NP-Fx) participants.Methods49 participants (P-Fx: 25; NP-Fx: 24) received a fractional (1/5th dose-volume) RTS,S/AS01_E booster 12 months post-primary regimen. They underwent P. falciparum CHMI three weeks later and were then followed for six months for safety and immunogenicity.ResultsOverall vaccine efficacy against re-challenge was 53% (95% CI: 37–65%), and similar for P-Fx (52% [95% CI: 28–68%]) and NP-Fx (54% [95% CI: 29–70%]). Efficacy appeared unaffected by primary regimen or previous protection status. Anti-CS (repeat region) antibody geometric mean concentrations (GMCs) increased post-booster vaccination. GMCs were maintained over time in primary three-dose groups but declined in the two-dose group. Protection after re-challenge was associated with higher anti-CS antibody responses. The booster was well-tolerated.ConclusionsA fractional RTS,S/AS01_E booster given one year after completion of a primary two- or three-dose RTS,S/AS01 delayed fractional dose regimen can extend or induce protection against CHMI.Clinical Trial Registration: NCT03824236.A video linked to this article can be found on the Research Data as well as Figshare https://figshare.com/s/ee025150f9d1ac739361     

影响大鼠主动脉肾上腺髓质素和肾上腺升压素释放的因素

用放射免疫法测定离体大鼠主动脉孵育或灌流介质中肾上腺髓质系（ＡＭ）和肾上腺升压素（ＡＴ）,发现：①～１００ｎｍｏｌ／Ｌ ＡＩＩ和ＥＴ－１呈剂量依赖性增加ＡＭ的释放率;１和１０ｎｍｏｌ／Ｌ ＡＩＩ和ＥＴ－１对ＡＴ的释放无明显的影响,１００ｎｍｏｌ／Ｌ ＡＩＩ和ＥＴ－１则增加ＡＴ释放率;这六组的ＡＭ／ＡＴ比值均增大;②１０ｎｍｏｌ／Ｌ肾上腺素增加ＡＭ和ＡＴ的释放率,１０ｎｍｏｌ／Ｌ ＣＧＲＰ则降低两者     

聚乳酸酮洛芬微球的制备及其体外释放度

制备了生物可降解的材料聚乳酸,用粘度法测定其分子量,并选用Ａ、Ｂ、Ｃ三种不同分子量的聚乳酸为药物的载体,制备了酮洛芬微球（ＡＳ,ＢＳ,ＣＳ）,测定其粒径和体外溶出速率。结果表明催化剂四苯基锡用量增加,所得的聚乳酸分子量增加,而制备酮洛芬微球的聚乳酸分子量越大,其微球粒径越大,溶出速率越小。     

Creative versus repetitive dance therapies to reduce the impact of fibromyalgia and pain: A systematic review and meta-analysis

Background and purposePhysical exercise is one of the most effective interventions to reduce fibromyalgia symptoms. Previous studies have reported benefits of dance-based intervention on the fibromyalgia impact, health-related quality of life and pain, regardless the interventions were based on creative- or repetitive dance. This study aimed to compare the effectiveness of creative and repetitive dance interventions.MethodsPRISMA guidelines were followed in this systematic review. The Cochrane Library, PubMed, Trip, Google Scholar, Web of Science (WOS), Embase and Scopus databases were selected to identify potential articles. Studies were included if they met the following inclusion criteria: to be a clinical trial or a randomized controlled trial, include people with fibromyalgia, have a comparison group and evaluate the impact of the disease, pain or quality of life. Fifteen articles fulfilled the inclusion criteria. The methodological quality of the studies was assessed using the Cochrane Collaboration's tool.ResultsDance-based interventions significantly reduced fibromyalgia impact (standardized mean difference = −0.69), pain (standardized mean difference = −0.70 and increased quality of life (standardized mean difference = 0.43) of people with fibromyalgia. The effectiveness of dance interventions is increased when a creative component is added, since it can lead to higher improvements in pain, impact of the disease and improving quality of life.ConclusionDance-based interventions are significantly effective in reducing the impact of fibromyalgia, pain as well as increasing health-related quality of life. Subgroup analyses suggest that creative dance-based interventions could be more effective than repetitive dance-based interventions to reduce pain and fibromyalgia impact. However, results must be taken with caution due to the large heterogeneity and the small number of articles.