Repetitive dihydroergotamine nasal spray for treatment of refractory headaches:an open-label pilot study

ABSTRACT

Objective: To evaluate the safety and efficacy of a repetitive intranasal (IN) dihydroergotamine (DHE) burst protocol for treatment of refractory headaches.

Research design and methods: Patients with refractory headaches were enrolled in a prospective, open-label, pilot study. Patients were instructed to self-administer IN DHE every 8 hours for 3 days; each IN DHE dose consisted of one 0.5-mg spray in each nostril that was repeated 15 minutes later, for a total of 2.0?mg DHE per dose. Follow-up visits were scheduled approximately 3 weeks later.

Main outcome measures: Efficacy and safety measurements were collected during patient interviews. Primary efficacy measures were the change in headache frequency, duration, and severity (rated from 0 [none] to 5 [extremely severe]) between the initial and follow-up visits. Safety was assessed at the follow-up visits through the occurrence of adverse events (AEs).

Results: Twenty-six patients were enrolled in the study. Follow-up visits were completed by 24 patients whose mean headache frequency at study entry was 6.6 d/wk. The IN DHE burst protocol was associated with significant mean decreases in headache frequency (2.6 d/wk, p < 0.001), duration (5.8 hours, p = 0.03), and severity (1.2 units, p < 0.001) between study entry and the follow-up visit. One patient discontinued IN DHE use early because of an AE (nasal stuffiness); two additional patients each reported one AE (fatigue and increased headache) that was attributed to IN DHE.

Conclusions: The results of this pilot study suggest that the IN DHE burst protocol may be an effective and safe treatment for refractory headaches; interpretation of these results is limited by the open-label, uncontrolled design and the small number of patients. The development of a doubleblind, placebo-controlled study to further evaluate this treatment regimen is warranted.     

Treatments and compositions targeting α-synuclein: a patent review (2010-2016)

Introduction: Abnormal deposition of α-synuclein (ASN) is a hallmark and possible central mechanism of Parkinson’s disease and other synucleinopathies. Their therapy is currently hampered by the lack of early, screening-compatible diagnostic methods and efficient treatments.

Areas covered: Patent applications related to synucleinopathies obtained from Patentscope and Espacenet databases are described against the background of current knowledge regarding the regulatory mechanisms of ASN behavior including alternative splicing, post-translational modifications, molecular interactions, aggregation, degradation, and changes in localization.

Expert opinion: As the central pathological feature and possibly one of root causes in a number of neurodegenerative diseases, deregulation of ASN is a potentially optimal diagnostic and therapeutic target. Changes in total ASN may have diagnostic value, especially if non-invasive /peripheral tissue tests can be developed. Targeting the whole ASN pool for therapeutic purposes may be problematic, however. ASN mutations, truncation, and post-translational modifications have great potential value; therapeutic approaches selective towards aggregated or aggregation-prone ASN forms may lead to more successful and safe treatments. Numerous ASN interactions with signaling pathways, protein degradation and stress mechanisms widen its potential therapeutic significance dramatically. However, significant improvement in the basic knowledge on ASN is necessary to fully exploit these opportunities.     

Hyperimmunized Chickens Produce Neutralizing Antibodies against SARS-CoV-2

The novel severe acute respiratory syndrome (SARS) coronavirus, SARS-CoV-2, is responsible for the global COVID-19 pandemic. Effective interventions are urgently needed to mitigate the effects of COVID-19 and likely require multiple strategies. Egg-extracted antibody therapies are a low-cost and scalable strategy to protect at-risk individuals from SARS-CoV-2 infection. Commercial laying hens were hyperimmunized against the SARS-CoV-2 S1 protein using three different S1 recombinant proteins and three different doses. Sera and egg yolk were collected at three and six weeks after the second immunization for enzyme-linked immunosorbent assay and plaque-reduction neutralization assay to determine antigen-specific antibody titers and neutralizing antibody titers, respectively. In this study we demonstrate that hens hyperimmunized against the SARS-CoV-2 recombinant S1 and receptor binding domain (RBD) proteins produced neutralizing antibodies against SARS-CoV-2. We further demonstrate that antibody production was dependent on the dose and type of antigen administered. Our data suggests that antibodies purified from the egg yolk of hyperimmunized hens can be used as immunoprophylaxis in humans at risk of exposure to SARS-CoV-2.     

TSo联合IFN-γ鼻内免疫小鼠诱导的弓形虫IgA抗体特异性免疫应答

目的研究速殖子超声裂解物(TSo)和IFN-γ鼻内免疫小鼠经口感染弓形虫速殖子后,血清、小肠液和粪便IgA抗体分泌的动态变化。方法将6～7周龄BALB/c小鼠100只随机分为4组,每组25只,分别用10μl缓冲液PBS、20μgTSo、500UIFN-γ和20μgTSo 500UIFN-γ鼻内免疫小鼠。用RH株弓形虫速殖子4×104个/只灌胃攻击,分别于攻击后第7、10、13、16、19天处死小鼠,收集血清、小肠液及粪便,ELISA法测定IgA含量。结果各组血清IgA抗体水平在攻击后第10天达到峰值,TSo IFN-γ组血清IgA抗体含量高于其他各组。小肠液和粪便IgA抗体含量在攻击后第13天达到峰值,在实验期各时点TSo IFN-γ组小肠液和粪便IgA抗体含量高于其他组。小肠液与粪便IgA抗体水平呈正相关。结论TSo或IFN-γ或TSo联合IFN-γ鼻内免疫小鼠可诱导黏膜免疫,产生高水平的弓形虫特异性IgA抗体。TSo联合IFN-γ鼻内免疫优于单独免疫,免疫小鼠肠道产生大量SIgA,发挥抗虫作用。鼻黏膜免疫是一种安全有效的免疫接种途径。     

小鼠IgG抗体的制备——IgG—SPA菌体免疫法

本文介绍制备小鼠IgG抗体的一种简便方法,即IgG-SPA菌体免疫法。首先制备10％(w/v)Cowan I 株菌体稳定液,按一定比例与正常小鼠血清制备IgG-SPA菌体免疫原。然后以9—12亿/ml菌体免疫原静脉注射于年青健康家兔,数次免疫后,即得兔抗小鼠IgG抗体(RAM-IgG),其血清效价达1:32～1:64(双扩法);其抗体纯度高,与正常小鼠血清只出现一条沉淀线。经鉴定,其血清不含有鼠IgM抗体。本文又把该法与IgG常规乳化佐剂免疫法作了比较。     

北京市1990 — 2003年急性乙型肝炎疫情报告病例的流行病学分析

  目的  分析1992 — 2013年北京市乙肝疫苗免疫计划总成本与成本构成,评价乙肝性肝癌报告发病率指标与乙肝疫苗免疫计划总成本之间的成本效果关系。  方法  对乙肝疫苗免疫总成本及不同类型成本的构成进行成本分析,以乙肝疫苗免疫总成本为成本指标对乙肝性肝癌发病率进行成本效果分析,包括增量成本效果比与边际效果分析。  结果  乙肝疫苗免疫总成本呈现上升趋势,人力成本及比重明显上升,疫苗成本及比重明显下降;随着乙肝疫苗免疫总成本的增长,乙肝性肝癌的发病率呈现出先增长后下降趋势;乙肝性肝癌的发病率效果指标的成本效果比整体呈现增长趋势,多期间增量成本效果比方面,1999 — 2005年这一期间的增量成本效果比较好。  结论  北京市1992 — 2013年乙肝疫苗免疫计划总成本上升,人力成本逐渐占较大比重,符合实际发展;乙肝性肝癌的成本效果较为理想,未来可加大乙肝疫苗免疫计划的投入继续改善。     

An Active-Learning Laboratory on Immunizations

Objective. To implement and evaluate an active-learning laboratory activity to teach pharmacy students about influenza, pneumococcal, and shingles vaccines.Design. The laboratory session was divided into 6 immunization stations: 3 stations on influenza including a pediatrics station, and 1 station each for pneumococcal, shingles, and anaphylaxis.Assessment. Although 118 of 123 (95.9%) students had completed an immunization training certificate prior to attending the laboratory, the average score on a pre-assessment to measure immunization knowledge and confidence was 56%. The post-assessment score was 87.4%. Students’ confidence improved by 18.7% to 51.2% in each of the 5 areas assessed. Most respondents rated the activity overall as good or excellent on a post-activity evaluation.Conclusion. An active-learning approach to teaching immunizations allowed students to gain knowledge in simulated real-world experiences and reinforced key concepts on influenza, pneumococcal, and shingles vaccines.     

Immunogenicity of Recombinant Maltose-binding Protein (MBP)–Gonadotropin Releasing Hormone I (GnRH-I)

A recombinant fusion protein, maltose-binding protein (MBP) – gonadotropin releasing hormone I (GnRH-I), was produced by cloning a gene fragment encoding a tandem repeated GnRH-I hexmer peptide (GnRH-I6) into the pMAL-c4x vector which was subsequently expressed in E. coli TB1. MBP-GnRH-I6 was affinity purified. MBP-GnRH-I6 was verified by SDS-PAGE and Western blot and immunogenicity tested in boars. Injection of the recombinant fusion protein into boars yielded a high-titer antibody specific for GnRH-I. This was followed by serum testosterone and the degeneration of spermatogenesis. These results showed that MBP-GnRH-I6 acted as a strong immunogen and could be a candidate for an immune antifertility vaccine.     

Radioimmunoassay for rat galanin: immunochemical and chromatographic characterization of immunoreactivity in tissue extracts

Galanin is a regulatory peptide with wide distribution in the central and peripheral nervous system and with numerous biological effects. Several radioimmunoassays based on antisera raised against porcine galanin have been used to measure immunoreactivity in rat tissues. However, considerable lack of parallelism has been observed between the porcine standard and rat tissue extracts, which may decrease the reliability of the quantitative data. The purpose of the present study was therefore to raise antibodies against rat galanin and establish a competitive radioimmunoassay for rat galanin. Two antisera, RatGal4 and RatGal5, were characterized in detail. The homogeneity of the immunoreactive material from several tissues was also investigated with column chromatography. At reverse-phase high-pressure liquid chromatography more than 95% of the immunoreactive material from rat CNS eluted as a single peak in the position of synthetic rat galanin, whereas almost half of the immunoreactive material from the intestine eluted in positions different from the synthetic peptide. Extracts of rat brains as well as jejunum diluted in parallel with the standard curve for both antisera. We conclude that measurements of rat galanin based on these antisera are therefore more reliable than those based on antisera raised against porcine galanin.     

重庆市农村留守儿童接种率现状及其监护人预防接种知信行研究

目的：了解重庆农村地区留守／非留守儿童监护人的预防接种知识、态度、行为现状和知识需求情况,探索相应干预模式。方法对3个项目县的1岁组留守／非留守儿童监护人进行问卷调查并查验儿童接种证获取信息,完成有效问卷1441份。结果留守儿童监护人文化水平低于非留守儿童监护人,留守儿童监护人对预防接种知识知晓率与预防接种行为依从性比例低于非留守儿童监护人。村医对基层预防接种工作开展起主要推动作用。结论建议引入同伴教育的宣传方式深入农村留守儿童家庭中开展宣传教育;针对留守儿童预防接种干预工作的重点是调动村级预防接种人员积极性,加强对农村留守儿童预防接种工作的投入与关心。