Development of Stabilizing Formulations of a Trivalent Inactivated Poliovirus Vaccine in a Dried State for Delivery in the Nanopatch™ Microprojection Array

The worldwide switch to inactivated polio vaccines (IPVs) is a key component of the overall strategy to achieve and maintain global polio eradication. To this end, new IPV vaccine delivery systems may enhance patient convenience and compliance. In this work, we examine Nanopatch? (a solid, polymer microprojection array) which offers potential advantages over standard needle/syringe administration including intradermal delivery and reduced antigen doses. Using trivalent IPV (tIPV) and a purpose-built evaporative dry-down system, candidate tIPV formulations were developed to stabilize tIPV during the drying process and on storage. Identifying conditions to minimize tIPV potency losses during rehydration and potency testing was a critical first step. Various classes and types of pharmaceutical excipients (～50 total) were then evaluated to mitigate potency losses (measured through D-antigen ELISAs for IPV1, IPV2, and IPV3) during drying and storage. Various concentrations and combinations of stabilizing additives were optimized in terms of tIPV potency retention, and 2 candidate tIPV formulations containing cyclodextrin and a reducing agent (e.g., glutathione), maintained ≥80% D-antigen potency during drying and subsequent storage for 4 weeks at 4°C, and ≥60% potency for 3 weeks at room temperature with the majority of losses occurring within the first day of storage.     

肥大细胞激活在术后肠梗阻神经免疫机制中的作用

术后肠梗阻(POI)是临床常见并发症,其发病机制复杂,一直是外科临床关注的焦点。除已知的神经反射抑制作用外,随着临床与基础研究的深入,炎性反应在本病发生、发展中的重要作用越来越受到重视,而由于肠操作激活肥大细胞成为炎性反应启动的关键,进一步导致巨噬细胞激活及白细胞聚集,加重肠肌层炎症并且与神经机制相互协同作用,从而不利于胃肠运动功能障碍的恢复。该文就肥大细胞在POI神经免疫机制中的效应与促炎过程的研究状况予以综述。     

Successful one-stage operation for completely obstructive colorectal carcinoma

We describe herein a new and successful method of performing a safe and steady one-stage operation for completely obstructive colorectal carcinoma. First, a long ileus tube is utilized to decompress the dilated proximal bowel preoperatively and irrigate the feces-loaded colon intraoperatively. Following this procedure, a standard resection with radical lymph node dissection is carried out without a diverting colostomy. We performed this procedure successfully in seven patients, none of whom developed any anastomotic leakage.     

Inclusion of an S-nitrosylating agent in the insufflating gas does not alter gastric activity in rats following pneumoperitoneum

Background We have previously shown that mixing the S-nitrosylating agent ethyl nitrite with carbon dioxide can attenuate pneumoperitoneum-induced decreases in splanchnic blood flow, but it was unclear if this agent would alter gastric function. This question was answered using rats by assessing gastric emptying and gastrointestinal transit times following gavage with radioactive chromium. Methods There were five experimental groups: absolute control, anesthesia control, and carbon dioxide alone or with 100 or 300 parts per million ethyl nitrite. The period of insufflation was 1 h, and all animals were euthanized 6.5 h after chromium administration. Results The mean amount of radioactivity remaining in the stomach ranged between 16% and 27% of the total administered; these differences were not statistically significant (p > 0.05). Modest differences in chromium distribution were identified in the gastrointestinal tract, but for all treatments, the peak amount of radioactivity was located in the distal portion. Location of the peak, expressed as a percentage of total tract length, varied between 70% and 85% (p = 0.366). Conclusions This study found no adverse effect of ethyl nitrite on postoperative gastric emptying or gastrointestinal transit time following pneumoperitoneum. The findings support continued assessment of the clinical utility of ethyl nitrite in the setting of laparoscopic surgery.     

Role of VIP1/PACAP receptors in postoperative ileus in rats

1. Vasoactive intestinal polypeptide (VIP) is an inhibitory neurotransmitter in the enteric nervous system. We investigated the role of VIP₁/PACAP receptors in postoperative ileus in rats.
2. Different degrees of inhibition of the gastrointestinal transit, measured by the migration of Evans blue, were achieved by skin incision, laparotomy or laparotomy plus mechanical stimulation of the gut.
3. The transit after skin incision or laparotomy was not altered by the VIP₁/PACAP receptor antagonist Ac-Hisl,D-Phe², K¹⁵, R¹⁶, VIP(3–7), GRF(8–27)-NH₂ nor by the VIP₁/PACAP receptor agonist K¹⁵, R¹⁶, VIP(1–7), GRF(8–27)-NH₂ and the VIP₂/PACAP receptor agonist RO 25-1553 (5 μg kg⁻¹).
4. However, the transit after laparotomy plus mechanical stimulation was significantly enhanced by the VIP₁/PACAP receptor antagonist, whereas it was further inhibited by the VIP₁/PACAP receptor agonist. The combination of the VIP₁/PACAP receptor agonist and antagonist counteracted the effect of both drugs alone. The VIP₂/PACAP receptor agonist did not alter the effect of the VIP₁/PACAP receptor antagonist.
5. The combination of the VIP₁/PACAP receptor antagonist plus the nitric oxide (NO) synthase inhibitor L-nitroarginine had no effect on the transit after laparotomy plus mechanical stimulation, while the transit after skin incision was significantly decreased.
6. These findings suggest the involvement of VIP₁/PACAP receptors, next to NO, in the pathogenesis of postoperative ileus. However, the combination of the VIP₁/PACAP antagonist and the NO synthase inhibitor abolished the beneficial effect of each drug alone, suggesting the need for one of the inhibitory neurotransmitters to enable normal gastrointestinal transit.

     

胎粪性肠梗阻的临床研究

目的 探讨胎粪性肠梗阻的临床特点与治疗.方法 对4例胎粪性肠梗阻患儿的发病病因、临床症状、诊断及治疗进行回顾性分析.结果 4例胎粪性肠梗阻患儿以肠梗阻就诊3例,术前均怀疑为全结肠型无神经节细胞症,以消化道穿孔为首诊症状者1例,术前怀疑为新生儿坏死性小肠结肠炎.3例为新生儿期就诊,1例生后4个月就诊.4例患儿均进行手术治疗,其中2例行肠腔冲洗、末端回肠造瘘术,1例行回盲部狭窄肠管切除肠吻合术,1例行穿孔肠管修补术及腹腔冲洗引流术.3例新生儿患者术中均发现胎类极度黏稠、阻塞回盲部远端肠腔,4例患儿均在术中取病理证实肠壁存在神经节细胞.随访中1例患儿出院1个月后反复发生呼吸道感染、重症肺炎、呼吸衰竭而死亡:1例患儿X线胸片持续存在肺部阴影,但呼吸正常;其他2例患儿生长发育正常.结论 新生儿期便秘患儿在怀疑全结肠型无神经节细胞症的同时,应考虑到本病的可能,术中病理活检对诊断该病十分重要,术后随访应密切注意肺等其他器官系统的相应合并症.