The Eurocine L3 adjuvants with subunit influenza antigens induce protective immunity in mice after intranasal vaccination

The immunogenicity and protective efficacy in mice of intranasally (i.n.) administrated influenza subunit antigens together with lipid-based adjuvants (Eurocine^®) were compared to those of subcutaneous (s.c.) immunisation. Influenza hemagglutination inhibition (HAI) and ELISA IgG titers were similar in the group's vaccinated s.c. and after i.n. vaccination with adjuvants. The virus-specific IgA levels in serum were higher after vaccination i.n. with adjuvant than after s.c immunisation. Virus-specific IgA was measurable in nasal washings only after i.n vaccinations, with and without adjuvants. Thus, i.n. vaccination with the endogenous non-toxic, lipid adjuvants induced equal or stronger antibody responses as compared to s.c. immunisation with the same antigen. We further analysed the protective efficacy against virus challenge in a mouse model. A subunit antigen preparation of the A/New/Caledonia/20/99 strain was used for vaccination of NMRI mice with different combinations of adjuvants. The mice were challenged i.n. with 6.5 tissue culture infectious doses₅₀ of homologous virus and sacrificed 3 days later. Since the virus is not lethal in mice, the protective efficacy was measured by quantitative, real-time PCR on pulmonary tissue, obtained at autopsy. The mice treated with only adjuvant and the group of naïve mice clearly had the highest mean viral RNA copy numbers (19.200 and 11.000, respectively). All vaccinated groups had significantly lower copy numbers, especially the mice that received the L3A i.n. (−median 120; i.n. L3B − median 2.200; and non-adjuvanted s.c. vaccination − median 2.600). Our findings prompt further investigations of the effect of the formulations in ferrets, monkeys and man.     

Intranasal ketamine for the treatment of patients with acute pain in the emergency department

BACKGROUND: Pain in the emergency department (ED) is common but undertreated. The objective of this study was to examine the efficacy and safety of intranasal (IN) ketamine used as an analgesic for patients with acute injury with moderate to severe pain.METHODS: This study was a cross sectional, observational study of patients more than 8 years old experiencing moderate to severe pain [visual analog score (VAS) >50 mm]. The initial dose of IN ketamine was 0.7 mg/kg with an additional dose of 0.3 mg/kg if VAS was more than 50 mm after 15 minutes. Pain scores and vital signs were recorded at 0, 15, 30 and 60 minutes. Side-effects, sedation level and patient's satisfaction were also recorded. The primary outcome was the number of patients achieving ≥ 20 mm reductions in VAS at 15 minutes. Other secondary outcome measures were median reduction in VAS at 15, 30 and 60 minutes, changes of vital signs, adverse events, satisfaction of patients, and need for additional ketamine.RESULTS: Thirty-four patients with a median age of 29.5 years (IQR 17.5-38) were enrolled, and they had an initial median VAS of 80 mm (IQR 67-90). The VAS decreased more than 20 mm at 15 minutes in 27 (80%) patients. The reduction of VAS from baseline to 40 mm (IQR 20-40), 20 mm (IQR 14-20) and 20 mm (IQR 10-20) respectively at 15, 30 and 60 minutes (P<0.001). No critical changes of vital signs were noted and adverse effects were mild and transient.CONCLUSION: This study showed that IN ketamine is an analgesic choice for patients with acute injury in moderate to severe pain in an overcrowded and resource limited ED.     

Different profile and distribution of antigen specific T cells induced by intranasal and intrarectal immunization with rotavirus 2/6-VLP with and without LT-R192G

In this study, we compared both the profile and distribution of antigen specific primed T cells after intrarectal (IR) and intranasal (IN) immunization with rotavirus (RV) 2/6-VLP, alone or in the presence of LT-R192G, in order to highlight the differences between the two routes and the impact of the adjuvant. Adult BALB/c mice were immunized once with 2/6-VLP with or without adjuvant and the T cell response was analyzed in lymphoid tissues after in vitro restimulation with the antigen.     

Analgesic activity of DaChuanXiongFang after intranasal administration and its potential active components in vivo

Ethnopharmacological relevance

DaChuanXiongFang was a well-known formula originated from Jin Dynasty, China. It has been used in both China and Japan to treat migraine. In the present study, the analgesic and sedative efficacy of DaChuanXiongFang ethanol extract (DCXFEE) after intranasal administration was tested and compared with that by intragastric route.

Materials and methods

Three mice experimental models: acetic acid-induced writhing response test, hot-plate latent pain response test and pentobarbital-induced sleep model were used to evaluate DCXFEE activity. To further explore the in vivo potential active components of DCXFEE that contribute to the difference of activity induced by different administration route, ultra performance liquid chromatography–mass spectrometer (UPLC–MS) was utilized to analyze components in rat brain after given DCXFEE (60 mg/kg).

Results

DCXFEE showed analgesic efficacy after intranasal administration (15, 30 and 60 mg/kg) in acetic acid-induced writhing response in mice. While after intragastric administration, DCXFEE only showed analgesic efficacy at high dose (60 mg/kg). Moreover, the analgesic potency was weaker after intragastric administration compared with that after intranasal administration at the same dose (60 mg/kg). Similar results were obtained in hot-plate latent pain response test in mice. DCXFEE (60 mg/kg) had no sedative effect after intranasal and intragastric administration. No components originated from DCXFEE were identified in rat brain 15 min after oral administration. One major parent component ligustilide was detected in rat brain after intranasal administration.

Conclusion

These data demonstrate that DCXFEE had faster onset of action as well as better analgesic efficacy after intranasal administration than that after intragastric administration. DCXFEE has no sedative activity on potentiation of pentobarbital-induced sleep in mice given by both routes. Ligustilide might represents the potential major bioactive component of DCXFEE after intranasal administration and contribute to its analgesic activity in vivo.     

Bilateral central serous chorioretinopathy caused by intranasal corticosteroids: a case report and review of the literature

The relationship between systemic corticosteroids and central serous chorioretinopathy (CSCR) has been well established; however, there also appears to be an association with intranasal corticosteroids. A search of the English literature revealed only three reported cases of CSCR linked to intranasal corticosteroid use, and in each, clinical improvement was observed after cessation of the steroid agent. We present an additional case of bilateral CSCR resulting from intranasal corticosteroid use and review the literature regarding this uncommon side effect. Otolaryngologists, as frequent prescribers of these medications, should be aware of their myriad side effects, including ophthalmologic conditions such as CSCR.     

The role of Toll-like receptor 4 in eliciting acquired immune responses against nontypeable Haemophilus influenzae following intranasal immunization with outer membrane protein

Objective

Acute otitis media (AOM) is one of the most common infectious diseases in children. Nontypeable Haemophilus influenzae (NTHi) is considered a major pathogen in AOM. Current treatment options depend mainly on the use of antibiotics, thus developing vaccines to prevent this disease is an urgent goal for public health. Outer membrane proteins (OMPs) are promising candidate targets for vaccination against NTHi.

Methods

We used C3H/HeJ (Toll-like receptor 4 [TLR4]-mutant) mice, which arose spontaneously and have a non-functional TLR4 protein, and normal wild-type (WT) C3H/HeN mice. These mice were immunized intranasally with OMP from NTHi to investigate the mechanism of acquired immunity via TLR4. We examined the kinetics of mucosal and systemic antibody secretion and the migration of antibody producing lymphocytes to the mucosa in both strains during the course of intranasal immunization.

Results

The mucosal and systemic immune responses against OMP from NTHi were elicited in both TLR4-mutant and WT mice. However, the mucosal IgA, and systemic IgG, and Th1 immune responses in WT mice were stronger than those in TLR4-mutant mice.

Conclusions

TLR4 plays an important role in relation to Th1 function for optimal development of the acquired immune responses to OMP administered intranasally. The variety of immune responses via TLR4 expression needs to be taken into consideration of individual vaccinations to prevent AOM.     

Age-related changes in intranasal air conditioning in the elderly

Objectives/Hypothesis: Elderly patients frequently complain about the feeling of a dry nose and recurrent crusting probably due to age‐related degenerative effects of the nasal mucosa. Data on intranasal air conditioning in elderly patients are missing. The aim of the study was to compare intranasal heating and humidification of respiratory air in elderly subjects and a younger control group. Additionally, rhinomanometrical and rhinometrical data were examined. Study Design: The study was conceived as randomized, prospective study. Methods: Forty study subjects (median age, 70 years; range, 61–84) and 40 control subjects (median age, 27 years; range, 20–40) were included in the study. In vivo air temperature and humidity values were simultaneously measured at defined intranasal sites. Active anterior rhinomanometry and acoustic rhinometry also were performed in every subject. Results: In the study group, the median end‐inspiratory air temperature (°C)/absolute humidity (g/m³) values were 24.0°C/13.8 g/m³ within the nasal valve region and 24.3°C/14.7 g/m³ anterior to the head of the middle turbinate. In the control group, the corresponding values were 27.0°C/15.5 g/m³ and 26.7°C/17.0 g/m³. Temperature and humidity values were significantly lower in the study group (P < .05). The minimal cross‐sectional areas and volumes were significantly higher in the study group (P < .05). Conclusions: Nasal complaints in elderly patients are a consequence of lower intranasal air temperature and humidity values combined with relatively enlarged nasal cavities due to involution atrophy of the nasal mucosa.     

Intranasal phenylephrine-surfactant treatment is not beneficial in otitis media with effusion

BACKGROUND: Otitis media is the most common reason for non-well-child visits to the primary care physician. Various treatments are in use to try to ameliorate the pain arising from Eustachian tube (ET) dysfunction. One such treatment is topical phenylephrine spray, despite clinical evidence disputing its use. Previous research by this laboratory has demonstrated the beneficial effect of topical surfactant treatment in reducing ET opening pressure, allowing the tube to open. This study is designed to test the effectiveness of topical phenylephrine, delivered with surfactant, in reducing days of effusion in OME, in an animal model. METHODS: OME was generated by injecting Klebsiella pneumoniae lipopolysaccharide into the right bullae of 28 gerbils. After frank OME resulted, the animals were divided into four groups. Group 1 received no treatment or propellant spray alone (placebo). Group 2 received intranasal surfactant spray once daily. Group 3 received intranasal surfactant-phenylephrine spray once daily. Group 4 received intranasal surfactant-phenylephrine spray twice daily. All animals were evaluated on a daily basis by both otomicroscopy and tympanometry, and treatment was ceased when the ear returned to normal appearance. Evaluations were continued for a total of 30 days. Chi-squared analysis with significance set at .05 was performed. RESULTS: In the untreated and placebo groups, middle ear effusion resolved at 16.25 days by otomicroscopy and 28.26 days by tympanometry. In Group 2 (surfactant alone), effusion resolved at 10.57 days and 15.71 days, respectively. In Group 3 (surfactant-phenylephrine once daily), effusion resolved at 15.67 days and 28.33 days. In Group 4 (surfactant-phenylephrine twice daily), effusion resolved at 18.67 days and 28.33 days. These results were statistically significant. CONCLUSIONS: Intranasal phenylephrine-surfactant treatment is shown to be at least ineffective, and possibly detrimental, in the resolution of OME, in this animal model. The hypothesis is that surfactant potentiates the drying effect of phenylephrine at the ET by allowing it to get to the ET more easily; in addition, the drying effect of phenylephrine prevents full surfactant action. We believe that these results can be extrapolated to humans and that phenylephrine should be avoided in these cases.     

Nasal carriage of Staphylococcus aureus in children with allergic rhinitis and the effect of intranasal fluticasone propionate treatment on carriage status

OBJECTIVE: The aim of this study is to determine the rate of nasal carriage of Staphylococcus aureus (NCSA) in children with allergic rhinitis (AR) and to determine the effect of intranasal fluticasone propionate spray on the NCSA. PATIENTS AND METHODS: Nasal swabs were taken from the children admitted to general pediatrics and pediatric pulmonology clinics. Patients were divided into two groups according to the presence or absence of AR. Diagnosis of AR was based on the patient's symptoms. Nasal swabs were taken from AR patients before and after the treatment with intranasal fluticasone propionate, and from the control group at the beginning and after 2 months. RESULTS: Whole NCSA rate was 17.9%; it was 21.4% for AR patients and 15.9% for control group, respectively (p>0.05). Treatment with intranasal fluticasone propionate spray did not influence NCSA in AR patients. CONCLUSION: It seemed that NCSA was not increased in children with AR and treatment with intranasal fluticasone propionate spray did not change NCSA in AR patients. It is obvious that better understanding of the factors affecting the acquisition and loss of NCSA might increase our knowledge about the relationship between NCSA, allergic airway diseases and their treatments.     

治疗变应性鼻炎对小气道功能的影响

目的　针对伴有小气道功能异常的变应性鼻炎患者,给予正规鼻用糖皮质激素治疗,观察其对小气道功能的影响。方法　筛选具有小气道功能异常的变应性鼻炎患者,给予鼻用糖皮质激素喷鼻治疗12周。治疗前予鼻部症状视觉模拟量表评分及鼻结膜炎相关生活质量问卷评分、肺通气功能检查;治疗后4、8、12周再次评估鼻部症状评分,4、12周时复查肺功能指标,观察肺功能的变化。结果　经过12周治疗,患者主观症状均有显著改善（P <0.01）,肺功能指标：第1秒用力呼气容积占预计值百分比（FEV1pred%）、第1秒用力呼气容积占肺活量比值（FEV1/FVC%）、最大呼气中段流量占预计值百分比（MMEFpred%）、用力呼出75%肺活量的呼气流量占预计值百分比（MEF75pred%）、用力呼出50%肺活量的呼气流量占预计值百分比（MEF50pred%）、用力呼出25%肺活量的呼气流量占预计值百分比（MEF25pred%）均较 治疗前明显提高（P <0.05）,其中代表小气道功能的指标MMEFpred%、MEF75pred%、MEF50pred%的改善具有统计学非常显著性差异（P <0.01）。结论　鼻用糖皮质激素治疗小气道损伤的变应性鼻炎患者可以明显改善其小气道功能,这对于预防变应性鼻炎发展为哮喘具有积极的意义。