Effect of organogel components on in vitro nasal delivery of propranolol hydrochloride

The purpose of this research was to evaluate in vitro transnasal sustained-release ability of sorbitan monostearate (SMS) organogels in isopropyl myristate (IM). Organogels were prepared containing SMS (2.5%–20%) and water (5%–25%) in IM and analyzed microscopically for phase behavior. The effect of Tween surfactants on gel strength and in vitro nasal diffusion of propranolol is reported. The in vitro nasal release retardant effect of SMS and Tween 20 was investigated using factorial design. The microscopic changes in structure of organogel during in vitro nasal diffusion were studied. The water-holding capacity of SMS organogels in IM increased with SMS concentration. The release retardant effect with incorportation of cosurfactant was of the order of Tween 80> Tween 60> Tween 20. Gel strengthening and increased viscosity were evident with increased concentration of SMS and Tween 20. The 3-dimensional network of SMS molecules controls the diffusional drug release. The organogel system on nasal mucosa during diffusion is dynamic in nature and changes continuously with the time of diffusion. The water penetration in the organogel network results in percolation and emulsification of organogel, thus affecting the release. Organogels provided an effective barrier for diffusion of propranolol. The surface epithelium lining and the granular cellular structure of treated nasal mucosa were intact.     

枸橼酸咖啡因联合加温湿化高流量鼻导管通气对呼吸窘迫综合征早产儿神经发育和血清BMP-7、CC16的影响

摘要 目的：观察枸橼酸咖啡因联合加温湿化高流量鼻导管通气（HHHFNC）对呼吸窘迫综合征（RDS）早产儿神经发育和血清骨形态发生蛋白-7（BMP-7）、Clara细胞分泌蛋白（CC16）的影响。方法：纳入2019年3月~2021年3月期间我院新生儿重症监护室收治的RDS早产儿93例,通过随机数字表法将患儿分为对照组[接受鼻持续气道正压通气 (NCPAP)治疗]和实验组（接受枸橼酸咖啡因联合HHHFNC治疗）,例数分别为46例、47例。对比两组患儿无创辅助通气时间、总用氧时间、撤机失败率、血气分析指标、神经发育指标、BMP-7、CC16水平和并发症情况。结果：实验组的无创辅助通气时间、总用氧时间短于对照组,撤机失败率低于对照组（P<0.05）。两组治疗24 h后pH值组间对比无统计学差异（P>0.05）,实验组治疗24 h后血氧分压（PaO₂）高于对照组,二氧化碳分压（PaCO₂）低于对照组（P<0.05）。实验组治疗结束后精神运动发育指数（PDI）、智力发展指数（MDI）高于对照组,血清β-内啡肽（β-EP）水平低于对照组（P<0.05）。实验组治疗结束后血清BMP-7、CC16水平低于对照组（P<0.05）。两组患儿并发症发生率组间对比无统计学差异（P>0.05）。结论：枸橼酸咖啡因联合HHHFNC治疗早产儿RDS可缩短无创辅助通气时间,提高撤机成功率,促进氧合恢复,同时还可改善血清BMP-7、CC16水平,促进患儿神经发育。     

血清嗜酸性粒细胞表达水平与鼻腔鼻窦内翻性乳头状瘤病理的相关性分析

摘要 目的：探讨血清嗜酸性粒细胞（EOS）表达水平与鼻腔鼻窦内翻性乳头状瘤（SNIP）病理的相关性。方法：选取我院2016年1月至2020年1月收治的63例SNIP患者作为研究对象,依照所有患者EOS水平将其分为低EOS组、中EOS组、高EOS组,对比三组患者的临床病理特征,并分析EOS表达水平与SNIP病理的相关性。行手术治疗后将63例患者分为预后不良组与预后良好组,对比两组患者的临床相关指标,并分析EOS表达水平对SNIP的预后预测价值。结果：三组患者临床分期、病理诊断对比差异显著（P＜0.05）;以EOS表达水平进行分级：高水平：＞300个/μL,中水平：100-300个/μL,低水平：＜100个/μL。Spearman相关分析结果显示：性别、年龄、病灶位置与EOS表达水平无明显相关性（P＞0.05）,临床分期、病理诊断与EOS水平呈负相关（P＜0.05）;预后良好组与预后不良组患者PLT水平对比无明显差异（P＞0.05）,预后两组患者L、EOS水平明显高于预后不良组,N、PLR、NLR低于预后不良组（P＜0.05）;logistic回归分析结果表明：NLR、EOS为SNIP的预后独立预测因素（P＜0.05）。结论：SNIP患者的临床分期、病理诊断与EOS表达水平呈负相关,且应用NLR和EOS可对SNIP术后复发情况进行预测,因此,可以考虑应用EOS表达水平对SNIP进行诊断与治疗效果判定。     

AT1 Receptor Blocker Candesartan-induced Attenuation of Brain Injury of Rats Subjected to Chronic Cerebral Hypoperfusion

One of common pathophysiological states associated with central nervous system is chronic cerebral hypoperfusion (CH) that frequently occurs in conditions such as vascular dementia and Alzheimer’s disease. Long term blockage of angiotensin II type 1 (AT₁) receptor provides protection from ischemia induced injury of brain as well as reduction of cerebrovascular inflammation. Examining effect of the blockage on reduced glutathione (GSH), ascorbic acid (AA), and lipid peroxidation were of purpose in the present study. Modeling CH, rats were subjected to permanent occlusion of common carotid arteries bilaterally. AT₁ receptor antagonist, candesartan, was given daily for 14 days after surgery. CH caused a significant increase in lipid peroxidation and decrease in GSH content of cerebral hippocampal tissue with no change in AA level. Candesartan (0.5 mg/kg, oral) not only reduced lipid peroxidation but also restored GSH significantly besides elevating AA and improving histopathological alterations. In conclusion, long term AT₁ receptor blockage may be considered as novel therapeutic approach for protection from damage associated with CH. Underlying mechanism(s) may in part be related to suppressing oxidative stress and preserving brain antioxidant capacity.     

In vivo colonization profile study of Bordetella bronchiseptica in the nasal cavity

Bordetella bronchiseptica chronically infects a wide range of mammals, and resides primarily in the nasal cavity of the infected host. Multiple virulence factors of Bordetella species have been studied in the context of lower respiratory tract infections, but relatively less is known about the bacterial life cycle in the nasal cavity. Evidences were discovered for Bvg intermediate (Bvg(i)) phase expression in vivo and that the major adhesin filamentous hemagglutinin plays a major role in the colonization of B. bronchiseptica in the unciliated olfactory epithelia of the nasal cavity.     

孟鲁司特钠联合左卡巴斯汀鼻喷剂治疗小儿过敏性鼻炎的疗效评价及对血清ECP、EOS及CRP水平的影响

目的:探讨孟鲁司特钠联合左卡巴斯汀鼻喷剂治疗小儿过敏性鼻炎的疗效及对血清嗜酸性粒细胞阳离子蛋白(ECP)、嗜酸性粒细胞(EOS)及C反应蛋白(CRP)水平的影响。方法:选择我院2016年7月～2018年7月收治的151例过敏性鼻炎患儿,按随机数字表法分为69例对照组和82例观察组,对照组采用左卡巴斯汀鼻喷剂治疗,观察组在对照组基础上联合孟鲁司特钠治疗,比较两组临床疗效,治疗前后症状及体征评分,生活质量评分,血清ECP、EOS及CRP、总免疫球蛋白E(TIg E)和特异性免疫球蛋白E(Sig E)水平,和不良反应发生情况。结果:观察组总有效率高于对照组,差异有统计学意义(P0.05)。治疗前,两组症状及体征评分,生活质量评分,血清ECP、EOS及CRP、总免疫球蛋白E(TIg E)和特异性免疫球蛋白E(Sig E)水平比较差异无统计学意义(P0.05);治疗后,两组以上指标均下降,观察组低于对照组,差异均有统计学意义(均P0.05)。两组均有胃肠道反应、口干、头痛发生,组间总不良反应发生率比较无统计学差异(P0.05)。结论:孟鲁司特钠联合左卡巴斯汀鼻喷剂治疗小儿过敏性鼻炎安全有效,能够降低血清ECP、EOS及CRP水平,促进患儿恢复。     

Association between nasal carriage of Staphylococcus aureus and the human complement cascade activator serine protease C1 inhibitor (C1INH) valine vs. methionine polymorphism at amino acid position 480

Staphylococcus aureus produces compounds that interfere with complement deposition. We hypothesized that humans have developed countermeasures to staphylococcal complement evasion and we screened for single nucleotide polymorphisms in the serine protease C1 inhibitor (C1INH) gene at amino acid position 480 (valine vs. methionine) and nasal carriage of S. aureus. In our study cohort, 38 individuals were persistently colonized by S. aureus, whereas 50 were invariably culture-negative. A trend was observed towards an increased prevalence of the Val/Val genotype in noncarriers compared to persistent carriers (OR 0.50, P=0.07). The Val/Val genotype was significantly overrepresented in noncarriers compared to 463 Caucasian blood donors (OR 0.52, P=0.02). These findings suggest that susceptibility to S. aureus nasal carriage is associated with the C1INH V480M polymorphism.     

Computational model of particle deposition in the nasal cavity under steady and dynamic flow

A computational model for flow and particle deposition in a three-dimensional representation of the human nasal cavity is developed. Simulations of steady state and dynamic airflow during inhalation are performed at flow rates of 9–60 l/min. Depositions for particles of size 0.5–20 μm are determined and compared with experimental and simulation results from the literature in terms of deposition efficiencies. The nasal model is validated by comparison with experimental and simulation results from the literature for particle deposition under steady-state flow. The distribution of deposited particles in the nasal cavity is presented in terms of an axial deposition distribution as well as a bivariate axial deposition and particle size distribution. Simulations of dynamic airflow and particle deposition during an inhalation cycle are performed for different nasal cavity outlet pressure variations and different particle injections. The total particle deposition efficiency under dynamic flow is found to depend strongly on the dynamics of airflow as well as the type of particle injection.