A guide to oral vaccination: Highlighting electrospraying as a promising manufacturing technique toward a successful oral vaccine development

Most vaccines approved by regulatory bodies are administered via intramuscular or subcutaneous injections and have shortcomings, such as the risk of needle-associated blood infections, pain and swelling at the injection site. Orally administered vaccines are of interest, as they elicit both systemic and mucosal immunities, in which mucosal immunity would neutralize the mucosa invading pathogen before the onset of an infection. Hence, oral vaccination can eliminate the injection associated adverse effects and enhance the person's compliance. Conventional approaches to manufacturing oral vaccines, such as coacervation, spray drying, and membrane emulsification, tend to alter the structural proteins in vaccines that result from high temperature, organic and toxic solvents during production. Electrohydrodynamic processes, specifically electrospraying, could solve these challenges, as it also modulates antigen release and has a high loading efficiency. This review will highlight the mucosal immunity and biological basis of the gastrointestinal immune system, different oral vaccine delivery approaches, and the application of electrospraying in vaccines development.     

他克莫司联合308nm准分子激光治疗面部白癜风

目的探讨他克莫司联合308nm准分子激光在面部白癜风治疗中的应用效果。方法选取2017年2月-2019年2月医院84例面部白癜风患者为研究对象,根据入院单双号将受试者进行分组,其中对照组42例患者接受308nm准分子激光治疗,研究组42例患者在对照组的基础上联合他克莫司软膏治疗,比较两组患者治疗后1个月、3个月时的治疗总有效率以及治疗前后白斑面积与皮损区IL-17水平变化。结果研究组患者在治疗后1个月、3个月时的治疗总有效率均显著高于对照组(P<0.05),与治疗前相比,治疗后两组患者白斑面积及皮损区IL-17水平均显著减少,且研究组显著少于对照组(P<0.05)。结论他克莫司联合308nm准分子激光可有效缩小白斑面积,降低皮损区IL-17水平,疗效确切。     

Food-induced contact urticaria syndrome (CUS) in atopic dermatitis: reproducibility of repeated and duplicate testing with a skin provocation test, the skin application food test (SAFT)

IgE-mediated contact urticaria syndrome (CUS) is one of the manifestations of allergy in childhood atopic dermatitis (AD). Allergens such as foods and animal products penetrate the skin easily. They can then cause urticarial reactions in sensitized individuals. A provocation test system for foods, called the skin application food test (SAFT), has been developed. Over more than 5 years, a group of 175 patients with AD was built-up and investigated in a prospective follow-up study with SAFT. SAFT was more frequently positive in AD children aged 6–2 years than in older children. In several children of this population (Group 1), we repeated SAFT within a period of 1 year. In another unrelated group of children (Group 2–1), we compared the results of 'original' SAFT and SAFT using square chambers (Van der Bend) or Silver patches. In the 3rd group (Group 2–2) we compared'original' SAFT with SAFT using big Finn Chambers. The agreement between the tests was high: in Group 1, we observed 88 to 93% concordant scores, and in Group 2, the scores were 96% to 100%. Statistically, the K coefficient ranged from 0.71–0.87 in Group 1, and from 0.83–1.00 in Group 2. SAFT is therefore highly reproducible. Agreement was at least 88% between the scores (the lowest K value observed was at least 0.71).     

Laparoscopic Findings in Senescent Patients with Primary Biliary Cirrhosis

Abstract: Fifty -two patients with primary biliary cirrhosis (PBC), 10 of whom were 65 years or older at the time of diagnosis, were investigated by laparo-scopy. Laparoscopic findings in these 10 patients were evaluated and compared with those in younger patients. The 10 cases were composed of nine females and one male, and two had been diagnosed as having symptomatic PBC with skin itching, while the remaining eight had asymptomatic PBC. Two, seven and one case were in Scheuer's stage I, II and III, respectively, and eight had chronic non-suppurative destructive cholangitis (CNSDC) on liver biopsy specimens. The majority of senescent PBC patients had typical findings of the early stage of PBC on the liver surface; mild undulations in nine and reddish patches in eight. The laparoscopic findings in senescent PBC were relatively mild.     

ONTOGENIC DEVELOPMENT OF GUT-ASSOCIATED LYMPHOID TISSUE IN THE RAT. An Immunohistochemical Study

The development of gut-associated lymphoid tissue (GALT) in the rat was investigated, with special reference to the behavior and ultrastructure of Ia(+) cells during the development of Peyer's patches (PP). At birth, Ia(+) cells were randomly scattered in the lamina propria. From three days, small aggregates of CD4(+), Ia(+), CD5(−) and IL-1(+) cells were observed in the lamina propria. Immunoelectron microscopically, these appeared as mixed populations of dendritic cells, capillary endothelial cells, flbroblast-like spindle cells and lymphocytes. In addition, CD8(+), CD4(–) and IL-1(−) cells were present in the interepithelial space. By seven days, lymphoid follicles were recognizable in the lamina propria, each with an aggregate of IgM-positive small lymphocytes at its center, surrounded by CD4(+) or CD8(+) lymphocytes. Between the 10th and 14th days, these follicles were covered with single-layered, specially differentiated epithelial cells, and structures resembling PP were formed. IgA plasma cells were identified in the lamina propria between the third and the fourth weeks. We speculate that the PP developed from aggregates of Ia(+), IL-1(+) spindle- or dendritic-shaped cells in the lamina propria. The PP were structurally complete by two weeks, although establishment of the characteristic distribution of GALT components evident in the adult took more than six weeks.     

小鼠派氏集合淋巴结T细胞活化和调节性T细胞的分析

目的： 通过对小鼠派氏集合淋巴结（PPs）、肠系膜淋巴结（MLNs）和腹股沟淋巴结（ILNs）的比较性研究，以分析PPs T细胞活化和调节性T细胞的功能特点。 方法： 无菌分离小鼠PPs、MLNs和ILNs，分别制备单个淋巴细胞悬液，运用流式细胞术结合荧光抗体染色技术来检测CD3+T细胞、CD3+CD4+辅助性T细胞和CD4+CD25＋调节性T细胞的比例；用多克隆刺激剂刀豆蛋白A（Con A）、佛波醇酯（PDB）和离子霉素（Ion） 刺激活化淋巴细胞，随后运用流式细胞术结合双色荧光抗体染色技术来检测T细胞早期活化标志CD69的表达水平。 结果： PPs内CD3+T细胞所占比例明显低于MLNs和ILNs，然而CD4+CD25＋调节性T细胞的比例明显高于MLNs和ILNs；在没有加入刺激剂的培养条件下，PPs来源的T细胞CD69的表达水平明显高于MLNs和ILNs来源的T细胞，MLNs来源的T细胞CD69的表达水平明显高于ILNs来源的T细胞；而在加入Con A或者单纯PDB的培养条件下，PPs来源的T细胞却表现出低反应性；在加入PDB＋Ion的培养条件下，3者来源的T细胞CD69的表达水平没有明显差别。 结论： PPs内CD3+T细胞所占比例较低，CD4+CD25＋调节性T细胞的比例较高，这可能是PPs整体T细胞低反应性的原因之一；PPs来源T细胞的高基础活化率可能与其不断接触小肠来源的食物和共生菌抗原有关；PPs来源T细胞选择性地对某些刺激剂表现出低反应性，提示这群细胞处于某种程度的无能状态。上述特征的生物学意义在于避免因为不断接受小肠来源的食物和共生菌抗原的刺激而发生病理性炎症的同时还保留对病原微生物抗原的应答。     

Activation kinetics of Glutamate receptor channels from wild-type Drosophila muscle

Outside-out patches from wild-type Drosophila larval muscle were exposed briefly to L-Glutamate (Glu) using a piezo-driven application system. Glu in concentrations of 0.1 to 30 mM was applied and the responses to repeated applications of a given concentration were averaged. The peak current, î, and the current rise time, t_r, from 0.1 î to 0.9 î were determined from the averages. Half-maximum activation of the channels was reached with ≈ 2 mM Glu. î increased proportional to the power n = 3.5 to n = 5.8 (average of four experiments, n = 4.4) for Glu concentrations between 0.3 and 0.5 mM. t_r increased from ≈ 0.2 ms at 10 mM Glu to a value of ≈ 3.5 ms at 0.2 mM Glu. A linear reaction scheme with five binding steps preceding the channel-opening conformational change is proposed as the kinetic mechanism of channel activation and investigated in computer simulations. A set of rate constants assuming the same affinity for each binding site is found to describe the data better than one assuming positive cooperativity. The results are very similar to those for Glu-gated channels of crayfish and locust muscle, which is evidence for a common kinetic mechanism of these channels.     

HPLC法同时测定复方雌二醇控释贴片中雌／孕激素的含量

目的：建立同时测定复方雌二醇透皮控释巾片中雌二醇（Ｅ２）和炔诺酮醋酸酯（ＮＥＴＡ）含量的反相ＨＰＬＣ法。方法：色谱柱为岛津柱（５μｍ,６．０ｍｍ＊１５０ｍｍ）检测波长为２８０ｍｍ（０－－８．５ｍｉｎ）,２４０ｎｍ（８．５１－－１５ｍｉｎ）;流动相为甲醇－水（７５：２５）。结果：Ｅ２、ＮＥＴＡ线性范围分别为２．０～２０、６．０～６０ｍｇ．Ｌ^-1。平均回收率分别为１０１．０％（ＲＳＤ＝１．６％）、９９     

磷酸川芎嗪缓释透皮贴剂的制备及体外释放度测定

目的制备磷酸川芎嗪缓释透皮贴剂并优化其处方。方法通过正交实验,筛选缓释透皮贴剂的处方组成。结果采用聚丙烯酸树脂EUDRAGITE100为控释骨架和压敏胶材料,1.0%氮酮作为渗透促进剂制备胶粘剂骨架型经皮给药系统,药物从胶粘剂骨架/药物储库(压敏胶层)中恒速释放,体外释放度表明,贴剂的释放符合零级方程。结论所研制的磷酸川芎嗪缓释透皮贴剂具有理想的释药特性。