Studies of Mucosal Irritation and Cellular Uptake Mechanisms of Xingnaojing Nanoemulsion

Abstract Xingnaojing (XNJ) injection was used to treat pneumonia and stroke in clinic in China, but with poor patient compliance. Xingnaojing nanoemulsion for intranasal delivery was developed to improve it. This article tried to evaluate the mucosal irritation of Xingnaojing nanoemulsion and investigate cellular uptake mechanism of its encapsulated lipophilic drugs. The toad palate model and rat nasal mucosa model were used to study the nasal ciliotoxicity and nasal mucosal irritation of nanoemulsion to evaluate its safety intranasally. The cellular uptake mechanism was studied by Calu-3 cell model. Coumarin 6 was encapsulated in nanoemulsion and the endocytic pathways were studied by cellular uptake experiments after being treated with different inhibitors. In toad palate model, the cilia movement of Xingnaojing nanoemulsion group last for 467.40 ± 39.02 min, which was obviously longer than deoxycholate group (90.60 ± 15.40 min). Studies on rats showed that the damage caused by nanemulsion is capable of being recovered. Nanoemulsion uptake was reduced obviously when cells were treated with wortmannin, and it also decreased about 13% when the temperature reduced from 37ºC to 4ºC. Mucosal irritation caused by nanoemulsion is low and the damage is recoverable. The cellular uptake of Xingnaojing nanoemulsion is energy-dependent, and macropinocytosis was the most important pathway for cellular uptake.

Migraine: A look down the nose.

BACKGROUND: Studies have suggested that contact between opposing mucosal surfaces in the nasal wall and cavity can be a target of the surgical treatment of migraines. Unfortunately, not enough is known about the role of nasal pathology in the pathogenesis of this condition. The co-existence of further rhinological disorders can be an impediment to defining the cause and effect of anatomical variants. The authors compared the MRI scans of migraine- and non-migraine patients (MPs and NMPs, respectively) to determine the prevalence of such mucosal contact points in order to extrapolate whether there is a significant association with migraines. METHODS: Coronal and axial MRI brain scans of 522 patients (412 migraineurs and 110 non-migraineurs) were analysed for the prevalence of anatomical variations of the nasal cavity, e.g. concha bullosa, septal deviations, mucosal swelling and contact points. RESULTS: The results showed no significant difference between MPs and NMPs patients for any of the parameters examined. Moreover, 87% MPs and 79% NMPs had at least one contact point. The most frequent contact point was between the middle turbinate and the septum, observed in 54% of MPs and 45% of NMPs. CONCLUSIONS: Contact points with the nasal mucosa are highly prevalent in both MPs and NMPs. Although a contact point does not cause a migraine in the absence of the disease, the concomitant presence of migraine and contact points can trigger an attack, and therefore, it is necessary to differentiate or exclude a rhinological disorder in these patients.

Mucosa nasal: un nuevo tejido para el diagnóstico biópsico de amiloidosis hereditaria relacionada con transtirretina / Nasal mucosa: A new site for tissue biopsy to diagnose hereditary TTR amyloidosis

Background and objective: We report 2 carriers of the TTRV30M mutation and its plasmatic biochemical marker with clinical symptoms compatible with hereditary TTR amyloidosis. Materials and methods: Based on our previously reported casual finding of amyloid TTR in nasal mucosa (2008), we requested biopsy of this tissue to search for amyloid with Congo red staining and TTR immunohistochemical analysis. Results: The histological diagnosis was achieved by retrospective analysis of surgical sinonasal biopsy in the first patient and prospective biopsy of inferior nasal concha in the second. Large interstitial deposits of ATTR were observed in both cases. Conclusions: We suggest nasal mucosa as a suitable site for tissue biopsy in patients with suspected hereditary TTR amyloidosis (AU)

Antecedentes y objetivo: Presentamos 2 portadores de la mutación TTRV30M y su marcador bioquímico plasmático, con síntomas sugestivos de amiloidosis hereditaria TTR. Material y métodos: Basándonos en el hallazgo casual de amiloide TTR en la mucosa nasal previamente publicado (2008), indicamos la biopsia de este tejido para la búsqueda de amiloide TTR con tinción Rojo Congo y análisis inmunohistoquímico de TTR. Resultados: El diagnóstico histológico se logró en el primer enfermo con análisis retrospectivo de la biopsia de material operatorio sinonasal, y en el segundo con biopsia prospectiva del cornete nasal inferior. En ambos casos se observaron grandes depósitos intersticiales de amiloide de amiloidosis hereditaria relacionada con transtirretina. Conclusiones: Consideramos que la biopsia de la mucosa nasal es idónea para el diagnóstico de pacientes con sospecha de amiloidosis hereditaria TTR (AU)

Nasal polyposis: an overview of differential diagnosis and treatment.

Nasal polyposis is a chronic inflammatory disease of the nasal and paranasal sinus mucosa. Etiology remains unclear, but allergy, asthma, aspirin sensitivity, cystic fibrosis, and infection have been associated with the disease. Clinically, nasal obstruction, anosmia/hyposmia, rhinorrhea, postnasal drainage, headaches, facial pain, and sleep disorders constitute the main symptoms. Intranasal examination reveals bilateral, mobile, grey, smooth and semi translucent polypoid masses that usually originate in the ethmoid sinuses or the middle meatus. Differential diagnosis is important to rule out congenital anomalies, as well as benign or malignant tumors. In the evaluation of nasal polyps, computerized tomography is helpful especially in determining the extent of the disease and in planning the surgical approach. Management of nasal polyposis consists of medical therapy and surgery. Surgical treatment is performed in cases that are refractory to medical therapy. Recurrence of nasal polyps is quite common and medical therapy after surgery is often necessary for avoiding recurrences. This paper aims to summarize the current trends in the diagnosis, management of nasal polyposis and relevant patents.

Preoperative evaluation of chronic rhinosinusitis patients by conventional radiographies, computed tomography and nasal endoscopy.

OBJECTIVES: The aim of this study was to compare the efficacy of conventional radiography (CR), computed tomography (CT) and nasal endoscopy for the preoperative evaluation of chronic rhinosinusitis in patients with persistent complaints despite appropriate medical therapy. PATIENTS AND METHODS: Forty-three patients (26 males, 17 females; mean age 43 years; range 15 to 73 years) were prospectively evaluated. All patients underwent detailed physical examination, CR and coronal high resolution CT of paranasal sinuses. Thirty of them were evaluated with detailed nasal rigid and/or flexible endoscopy as well. The anatomic variations and mucosal changes in paranasal sinuses were noted. The specificity and sensitivity of CR was calculated using CT findings as a reference point. Surgery was performed on two of the other three patients because of obstructive symptoms of middle turbinate. Paradoxal middle turbinate surgery was performed on one patient due to a headache of rhinogenic origin. RESULTS: In our study 40 (93%) of all patients showed mucosal abnormalities on CT. Computed tomography scanning of the patients revealed anatomic variations in 74.4% of the cases. Mucosal pathology was most frequently observed in the anterior ethmoid region (middle meatus). While we found mucosal anomalies in 47.4% of all sinuses using CR, 42.2% of these cases were confirmed with CT. Also, 19.5% of all sinuses evaluated as normal with CR presented pathologic findings on CT. An overall correlation of 75.3% was observed between CR and CT, while diagnostic nasal endoscopy and CT findings were correlated at a rate of 87%. CONCLUSION: (i) While no ipsilateral maxillary or frontal sinus disease was detected when no abnormality in the anterior ethmoid region and infundibulum was observed endoscopically in the presence of mucosal abnormalities similar abnormalities were seen at the same side for maxillary or frontal sinuses. (ii) Anatomic variations of nasal and paranasal sinuses may be considered as etiologic and predisposing factors of chronic rhinosinusitis. (iii) Conventional radiography should not be used as a single diagnostic tool in preoperative evaluation; however, due to its high sensitivity, CR technique may be used alone in the diagnosis and follow-up of maxillary sinus disease. (iv) Nasal endoscopy may reduce unnecessary diagnostic CT scanning procedures.

Decreased olfactory mucus secretion and nasal abnormality in mice lacking type 2 and type 3 IP3 receptors.

Although nasal mucus is thought to play important roles in the mammalian olfactory system, the mechanisms of secretion of it and its physiological roles are poorly understood. Here we show that type 2 and type 3 IP3 receptors (IP3R2 and IP3R3) play critical roles in olfactory mucus secretion. Histological studies showed that IP3R2 and IP3R3 are predominantly expressed in two types of nasal glands, the anterior glands of the nasal septum and the lateral nasal glands (LNG), which contain mucosal proteins secreted to the main olfactory epithelium. We therefore examined LNG acinar cells, and found that acetylcholine-mediated calcium responses and fluid- and protein- secretion in the acinar cells were markedly decreased in IP3R2-R3 double-knockout (KO) mice. We also found nasal inflammation and a decrease in olfactory capacity in IP3R2-R3 KO mice. Despite intact signal transduction in the olfactory epithelium, IP3R2-R3 KO mice exhibited elevated threshold sensitivity to odorants on in vivo imaging of olfactory glomerular responses and behavioral tests. Our findings suggest that IP3R2 and IP3R3 mediate nasal mucus secretion, which is important for the maintenance of nasal tissue as well as the perception of odors.

Ten-year experience using a plastic, disposable curette for the diagnosis of primary ciliary dyskinesia.

BACKGROUND: Primary ciliary dyskinesia (PCD) results in impaired mucociliary clearance. Patients with this disorder develop chronic sinopulmonary disease with recurrent sinusitis, otitis media, nasal polyposis, pneumonia, and, ultimately, bronchiectasis. Other associated findings of dysfunctional ciliary activity include situs inversus, dextrocardia, and infertility. OBJECTIVE: To describe our 10-year experience using a small, plastic, disposable curette to perform a screening procedure for cilia function and to collect samples for electron microscopy. METHODS: In the past 10 years, we screened infants and children with severe chronic sinusitis and other chronic recurrent upper respiratory tract problems for PCD by using a plastic, disposable curette to collect tissue samples from the nasal mucosa. Samples were placed in sterile saline and examined under light microscopy for the presence of cilia. Failure to note ciliary movement prompted another examination 1 month later. If no functional cilia were noted at the follow-up examination, a specimen was obtained and sent for electron microscopy. RESULTS: We identified 7 patients with PCD; 2 had situs inversus totalis. Average age at diagnosis was 3 years. The most common symptom at presentation was frequent upper respiratory tract infections with severe otitis media (7 patients) and sinusitis (5 patients). Recurrent pneumonia was present in 6 patients. Dynein arm deficiency was the most common electron microscopic diagnosis. CONCLUSIONS: Evaluating children for PCD by using a plastic, disposable curette is a relatively simple procedure that could be used by allergists in practice. Primary ciliary dyskinesia occurs frequently enough that physicians should consider it as part of the differential diagnosis in evaluating children with recurrent, severe sinopulmonary infections.

Endoscopic evaluation and management of the lacrimal sump syndrome.

Failed dacryocystorhinostomy caused by the presence of residual lacrimal sac has been termed the "lacrimal sump syndrome." Epiphora occurs when tears collect in this residual pouch and lacrimal drainage is delayed. Irrigation into the nose may seem normal. This condition can be easily diagnosed with nasal endoscopy and has a characteristic radiologic appearance. Six patients with failed dacryocystorhinostomy caused by lacrimal sump syndrome were successfully treated with an endoscopic contact Nd:YAG laser technique. Endoscopic dacryocystorhinostomy using the contact Nd:YAG laser is an effective method for treating patients who have persistent epiphora or dacryocystitis after failed dacryocystorhinostomy.

Familial nasal acilia syndrome.

Mucociliary dysfunction can be caused by the absence of cilia or by abnormalities in their ultrastructure. A family in which some members were suffering from respiratory morbidity due to lack of cilia is described.

Development of a standardized proforma for reporting computerized tomographic images of the paranasal sinuses.

The complex regional anatomy of the paranasal sinuses has only recently been elucidated through the use of modern imaging techniques. The advent of computerized tomography in the delineation of sinonasal pathology and anatomic variation has proven invaluable to the otolaryngologist in preoperative planning for functional endoscopic sinus surgery (FESS). Frequently, the radiologic reporting schemes for these studies are not standardized, and in many respects have been found to be inadequate. This study attempts to develop a simple reporting proforma that the head and neck radiologist can routinely use in order to facilitate the presentation of CT scan findings in evaluating sinus, nasal, or upper airway pathology. Over 100 CT sinus reports that had previously been reported were re-read according to this reporting scheme and were analyzed in order to determine whether any significant discrepancies existed. These differences were then classified according to their incidental, minor, and major surgical significance. It is hoped that through the development of a standardized proforma, the complementary relationship between preoperative imaging and endoscopic intervention can be consolidated and further enhanced.

Open tip rhinoplasty.

An open tip rhinoplasty was used to correct moderate to severe secondary cleft lip nasal deformities in 122 patients from January 1986 to January 1988. The results of the surgery on 92 patients who were followed for 1 year or more were evaluated. When the surgery was performed after the age of 3 years, 60% of the patients had a satisfactory result. The pathology of the deformity included 32% with deficiencies of the nasal lining, 35% needed framework support such as a columellar strut, and 45% required correction of columellar deficiencies. Patients using a postoperative nasal stent had a 71% satisfactory result compared with a 37% satisfactory result when the stent was not used. The pathology and techniques to correct the nasal deformity are described.

Short nasal respiratory cilia and impaired mucociliary function.

A 48-year-old man was examined because of anosmia. He was otherwise healthy except for mild arterial hypertension. He had stopped smoking 20 years ago. Previously he had been exposed to sulfuric acid gases for 3 years in his work. Clinical examination revealed no findings to explain his anosmia. The patient was fertile, indicating normal sperm/cilia motility. Nasal mucociliary function was examined by radioactive tracer and found to be markedly and constantly impaired. Ciliary ultrastructure in cross-sections was normal. However, in longitudinal sections the length of the cilia varied from 0.6 microns to 3.9 microns. The mean length of the cilia from the cell membrane to the tip was 2.5 +/- 0.9 microns, in contrast to normal ciliary length of 5-7 microns. These findings represent a new structural defect among the various known ciliary abnormalities.

Cilia-lacking respiratory cells in ciliary aplasia.

This report describes the ultrastructural alterations observed in the nasal and bronchial mucosa of an 11-yr-old male suffering from immotile cilia syndrome (ICS). The morphological features observed in this patient are consistent with a ciliary aplasia. In fact, ciliated cells appeared to be replaced by columnar cells lacking cilia and basal bodies, and bearing on their surface cilium-like projections without any internal axonemal structure. In spite of the absence of basal bodies, centrioles, and kinocilia, these cells unexpectedly showed mature striated roots and centriolar precursor material scattered throughout the apical cytoplasm. These data suggest that control over basal body assembly is distinct from control over striated root formation. The presence of the above-reported structures in cells otherwise presenting many morphological features of normal ciliated cells is discussed on the basis of current knowledge of respiratory cilia biogenesis.

Blind quantitative electron microscopy of cilia from patients with primary ciliary dyskinesia and from normal subjects.

Cilia from the nasal cavity of 27 patients with congenital ciliary dyskinesia (immotile cilia syndrome) and of 15 normal persons were examined by transmission electron microscopy. The patients had on average a significantly higher number of cilia with absent or markedly reduced numbers of outer or inner dynein arms, of cilia with various types of abnormal configuration of the microtubules, except for compound cilia, and of cilia with an abnormally large variation of the beating axis. Compound cilia were equally frequent in patients and controls. The main structural defect in 9 patients was absent or abnormality low number of outer dynein arms in 4 in conjunction with an abnormally large axis variation and in 1 with a markedly reduced number of inner dynein arms also in 1 with supernumerous axonemal microtubules also. In 9 patients the main defects were abnormal configuration of the axonemal microtubules and a large axis variation. Seven of these had eccentrically located central pairs of microtubules and radial spoke defects, 5 in conjunction with abnormally low numbers of inner dynein arms. In one patient there were various types of abnormal configuration of the axonemal microtubules together with absent inner dynein arms, in another cilia with supernumerous microtubules only were present. The only abnormal finding in 1 patient was an extreme variation in the ciliary axes. Completely normal ciliary ultrastructure was found in 8 patients.

The nose in anhidrotic ectodermal dysplasia.

A case is presented of anhidrotic ectodermal dysplasia, of extreme rarity. This is distinguished by disorders in the structures of ectodermal origin. The clinical characteristics--hypohidrosis, hypodontia, hypotrichosis-, and the genetic features--genealogy, karyotype--are examined first. The patient's face appears to be small, due to the combination of frontal bossing, hypodontia, and a depressed nasal dorsum, somewhat resembling the saddle nose of congenital syphilis. The case is studied from various perspectives: clinical, radiological, anatomicopathological and ultrastructural. The study concentrates principally on the anomalies of the nasal cavities, where there is a notable atrophy of the nasal mucosa. This atrophic rhinitis displays all the features of ozaena: severe crusting, fetid green secretion, nasal obstruction, etc.

[The sick cilia syndrome]. / Siek-siliasindroom.

The incidence of bronchiectasis should decrease because of improved immunization, but certain defects would still cause the malady. Fifteen consecutive patients with bronchiectasis were examined for ciliary defects by examining the nasal mucosae with an electron microscope and measuring the clearance of technetium-99m from the lung with a gamma camera. Three patients were found to have defects. Compound cilia, disorganization of the tubular structure, vacuolization and deficient inner dynein arms were observed. In one patient a loss of cell membranes which returned to normal after 4 months, was observed. Ciliary abnormalitites can either be anatomical or physiological and 'sick cilia' should be considered as a cause of bronchiectasis.