The efficacy and immunogenicity of a live transconjugant hybrid strain of <Emphasis Type="Italic">Shigella dysenteriae</Emphasis> type 1 in two animal models

In our earlier studies, we constructed a hybrid strain of Shigella dysenteriae type 1 by introducing a plasmid vector pPR 1347. After introduction of a lipopolysaccharide (LPS) biosynthesis gene, virulent Shigella dysenteriae type 1 strain became avirulent. In our present study, we have evaluated the immune response and protective efficacy of avirulent live transconjugant Shigella hybrid (LTSH) strain against wild type Shigella dysenteriae type 1, after four doses of oral (rabbit) and intranasal (mouse) immunizations. Serum IgG titers showed exponential increase during immunization and peaking on the 28th day and remained at that level till the 35th day in both the rabbit and the mouse models. When tested, serum IgG titers persisted for 63 days in mice and relatively high for 150 days in case of rabbits. Protection studies showed 100% protection against the challenge with wild type Shigella dysenteriae type 1 strain in rabbits and 80% protection in mice. Our results suggested that the LTSH strain could be a useful vaccine candidate strain in the future.     

Regulation of ciliary beat frequency by the nitric oxide signaling pathway in mouse nasal and tracheal epithelial cells

Objectives

Our purpose was to investigate the role of the nitric oxide (NO) signaling pathway in the regulation of ciliary beat frequency (CBF) in mouse nasal and tracheal epithelial cells.

Methods

We studied the effects of the NO donor l-arginine (L-Arg) and specific inhibitors of the NO signaling pathway on CBF of both nasal and tracheal epithelial cells by using high-speed digital microscopy. We also examined eNOS, sGC β, PKG I and acetylated α tubulin expression in native mouse nasal and tracheal epithelium using immunohistochemical methods.

Results

L-Arg significantly increased CBF of cultured nasal and tracheal epithelial cells, and the effects were blocked by pretreatment with N^G-nitro-l-arginine methyl ester (L-NAME), a NOS inhibitor, with LY-83583, a sGC inhibitor, or with KT-5823, a PKG inhibitor. Positive immunostaining for NO signaling molecules including eNOS, sGC β and PKG I was observed in either nasal or tracheal ciliated epithelium.

Conclusion

NO plays a role in regulating CBF of mouse respiratory epithelial cells via a eNOS–NO–sGC β–cGMP–PKG I pathway.     

Prostaglandin E2 receptors in asthma and in chronic rhinosinusitis/nasal polyps with and without aspirin hypersensitivity

Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma frequently coexist and are always present in patients with aspirin exacerbated respiratory disease (AERD). Although the pathogenic mechanisms of this condition are still unknown, AERD may be due, at least in part, to an imbalance in eicosanoid metabolism (increased production of cysteinyl leukotrienes (CysLTs) and reduced biosynthesis of prostaglandin (PG) E₂), possibly increasing and perpetuating the process of inflammation. PGE₂ results from the metabolism of arachidonic acid (AA) by cyclooxygenase (COX) enzymes, and seems to play a central role in homeostasis maintenance and inflammatory response modulation in airways. Therefore, the abnormal regulation of PGE₂ could contribute to the exacerbated processes observed in AERD. PGE₂ exerts its actions through four G-protein-coupled receptors designated E-prostanoid (EP) receptors EP1, EP2, EP3, and EP4. Altered PGE₂ production as well as differential EP receptor expression has been reported in both upper and lower airways of patients with AERD. Since the heterogeneity of these receptors is the key for the multiple biological effects of PGE₂ this review focuses on the studies available to elucidate the importance of these receptors in inflammatory airway diseases.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0100-7) contains supplementary material, which is available to authorized users.     

Delivery of a lactose derivative of endomorphin 1 to the brain via the olfactory epithelial pathway

The rapid and direct delivery of a neuroactive endomorphin 1 derivative to the brain via nasal delivery is reported. A synthetic derivative of the native opioid peptide, endomorphin 1 bearing a lactose unit on the N-terminus of the peptide has been previously reported to exhibit antinoceceptive activity similar to morphine after both intravenous and oral administration. This compound has been administered nasally to rats and appeared in the olfactory bulb within 10 min of administration with negligible levels appearing in the circulating blood or in the rest of the brain. These results indicate that the peptide is absorbed into the brain via the olfactory epithelial pathway suggesting nasal delivery may be a viable alternative route of delivery in clinical applications.     

Vascular control of the pig nasal mucosa: distribution and effect of somatostatin in relation to noradrenaline and neuropeptide Y

By means of immunohistochemistry and radioimmunoassay (RIA), we have investigated the possible occurrence of somatostatin (SOM)-like immunoreactivity (-LI) in the autonomic innervation of the pig nasal mucosa. SOM-immunoreactive (-IR) fibres were present around nasal arteries, arterioles and venous sinusoids. Double-labelling experiments revealed that SOM-LI was co-localized with the noradrenaline (NA) markers tyrosine hydroxylase and dopamine-β-hydroxylase as well as with neuropeptide Y (NPY) in a subpopulation of neurons in the superior cervical sympathetic ganglion and in perivascular nerve terminals. Furthermore, SOM-LI was also present in perivascular fibres containing vasoactive intestinal polypeptide (VIP) and NPY of presumably parasympathetic origin. The parasympathetic fibres that were associated with glands contained peptide histidine isoleucine (PHI), VIP and NPY but not SOM, suggesting that in the nasal mucosa SOM-IR is restricted to perivascular nerves. As revealed by RIA, the content of SOM-LI in biopsies of both nasal mucosa and superior cervical sympathetic ganglion was about 12 pmol/g and the reverse phase HPLC characterisation of SOM-LI shown two separate peaks for SOM-28 and SOM-14.     

IL-17和VEGF在慢性鼻-鼻窦炎患者鼻息肉组织中的表达及相关性研究

目的:探讨慢性鼻-鼻窦炎患者鼻息肉组织中白介素-17(IL-17)、血管内皮生长因子(VEGF)的表达,并分析IL-17、VEGF表达水平的相关性。方法:以我院2015年1月~2017年12月期间收治的慢性鼻-鼻窦炎患者95例为研究对象,按患者有无鼻息肉分为伴鼻息肉(观察1组)49例和不伴鼻息肉(观察2组)46例。另选取同期在我院进行治疗的鼻中隔偏曲患者40例为对照组。所有患者均进行鼻内镜手术治疗,并在术中取其较窄侧的鼻甲黏膜作为检测标本,采用免疫组化SP法检测各组织标本中的IL-17、VEGF的表达水平,并分析IL-17、VEGF表达水平的相关性。结果:观察1组患者IL-17、VEGF的阳性表达率分别为93.88%(46/49)、85.71%(42/49),均高于观察2组患者IL-17、VEGF的阳性表达率[76.09%(35/46)、65.22%(30/46)]以及对照组患者IL-17、VEGF的阳性表达率[5.00%(2/40)、2.50%(1/40)],差异均具有统计学意义(P0.05)。观察1组患者IL-17、VEGF的表达水平分别为(38.92±5.34)个/LP、(33.21±4.87)个/LP,均高于观察2组患者IL-17、VEGF的表达水平[(28.19±4.56)个/LP、(21.28±4.03)个/LP]以及对照组患者IL-17、VEGF的表达水平[(9.31±2.76)个/LP、(7.19±1.95)个/LP],差异均具有统计学意义(P0.05)。经Spearman相关性分析结果显示,观察1组患者、观察2组患者中,IL-17与VEGF的表达水平呈正相关性(P0.05)。结论:慢性鼻-鼻窦炎患者鼻息肉组织中IL-17、VEGF的表达显著升高,且IL-17与VEGF表达水平呈明显的正相关性,表明IL-17、VEGF可能共同参与鼻息肉的发生与发展过程。     

内镜揭盖术与唇齿沟径路切除术治疗鼻前庭囊肿患者的疗效及对炎性因子的影响

目的:研究内镜揭盖术(ER)与唇齿沟径路切除术(LSPR)治疗鼻前庭囊肿(NVC)患者的临床疗效及对炎性因子的影响。方法:选择2015年7月至2017年6月来我院就诊的NVC患者106例,依据随机数字表法分别纳入ER组(53例)及LSPR组(53例)。ER组行ER治疗,LSPR组行唇齿沟径路切除术。观察两组术中出血量、手术时间、术后创口愈合时间、术后24 h疼痛评分及上皮化时间,两组术前、术后7 d白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)、C-反应蛋白(CRP)水平,两组术后并发症及复发情况。结果:ER组术中出血量、手术时间、术后创口愈合时间、术后24h疼痛评分及上皮化时间等手术指标均低于LSPR组,差异有统计学意义(P0.05);术后7 d,两组IL-6、IL-8、TNF-α及CRP水平均低于治疗前,且ER组低于LSPR组,差异有统计学意义(P0.05);ER组术后并发症发生率7.55%、术后复发率3.77%,均低于LSPR组的22.64%、20.75%,差异均有统计学意义(P0.05)。结论:与LSPR相比较,ER治疗NVC创伤小,恢复快,可有效降低术后炎性因子水平,术后并发症及复发率低,值得临床应用。     

84 例基于三脚架结构改建的鼻尖综合整形术的临床总结

目的:总结基于鼻翼软骨三脚架结构的改建技术在鼻尖综合整形术中的应用经验。方法:从2012年09月到2015年02月间,共84例求美者在我院进行初次鼻尖综合整形术。3例为男性,81例为女性。年龄20-45岁,平均年龄31.7岁。其中鼻头肥大伴鼻背低平65例,行鼻翼软骨缝合+鼻翼软骨切除+鼻假体+自体软骨帽状移植术;鼻头肥大、鼻背低平伴鼻小柱短小19例,行自体软骨鼻小柱支撑+鼻翼软骨切除+鼻翼软骨缝合+鼻假体植入+自体软骨帽状移植术。结果:84例求美者术后随访1个月-2年,除1例病例鼻头过于肥大,鼻尖形态改善不明显以外,其余求美者鼻额角及鼻尖角度及均较术前有明显改善,鼻小柱短小组的鼻小柱长度也较术前有明显改善。所有病例切口瘢痕均不明显,无明显并发症出现。结论:针对不同鼻翼软骨发育条件下的病人,个性化的应用鼻翼软骨三脚架结构改建的鼻尖综合整形术具有较好的临床效果,须根据不同病人特点选用。     

The secretory activity of rat nasal glands and the effect of cholinergic drugs

Summary The secretory behaviour of rat nasal glands, under normal conditions and after the application of cholinergic drugs, has been studied using morphological and radiobiochemical techniques.Autoradiography and electrophoresis provide evidence for the selective incorporation of ³H-arginine into the glycoprotein containing fraction of the nasal glandular secretion. Radiobiochemical experiments show that labelled arginine is rapidly incorporated into the acinar cells of unstimulated glands, although it takes approximately 4 h before the labelled secretory proteins leave the cells. The secretion of proteins is stimulated by the parasympathetic agonist pilocarpine, whose main action is to promote discharge. Histological sections show a depletion of secretory granules after pilocarpine treatment. The cholinergic antagonist atropine inhibits the secretion; the acinar cells are completely filled with secretory granules following this treatment. The time course of the events following atropine administration suggests that there is no feed-back system controlling glycoprotein synthesis.The techniques employed here therefore appear to be useful for studying the effects of drugs that interfere with the secretory activity of the nasal glands.