Venous networks in the upper airways of bats: A histological and diceCT study.

Our knowledge of nasal cavity anatomy has grown considerably with the advent of micro-computed tomography (CT). More recently, a technique called diffusible iodine-based contrast-enhanced CT (diceCT) has rendered it possible to study nasal soft tissues. Using diceCT and histology, we aim to (a) explore the utility of these techniques for inferring the presence of venous sinuses that typify respiratory mucosa and (b) inquire whether distribution of vascular mucosa may relate to specialization for derived functions of the nasal cavity (i.e., nasal-emission of echolocation sounds) in bats. Matching histology and diceCT data indicate that diceCT can detect venous sinuses as either darkened, "empty" spaces, or radio-opaque islands when blood cells are present. Thus, we show that diceCT provides reliable information on vascular distribution in the mucosa of the nasal airways. Among the bats studied, a nonecholocating pteropodid (Cynopterus sphinx) and an oral-emitter of echolocation sounds (Eptesicus fuscus) possess venous sinus networks that drain into the sphenopalatine vein rostral to the nasopharynx. In contrast, nasopharyngeal passageways of nasal-emitting hipposiderids are notably packed with venous sinuses. The mucosae of the nasopharyngeal passageways are far less vascular in nasal-emitting phyllostomids, in which vascular mucosae are more widely distributed in the nasal cavity, and in some nectar-feeding species, a particularly large venous sinus is adjacent to the vomeronasal organ. Therefore, we do not find a common pattern of venous sinus distribution associated with nasal emission of sounds in phyllostomids and hipposiderids. Instead, vascular mucosa is more likely critical for air-conditioning and sometimes vomeronasal function in all bats.

Sinonasal mucosal vasculature in yellow nail syndrome and chronic rhinosinusitis with or without polyps.

BACKGROUND: Lymphatic dysfunction is hypothesized to be an underlying factor in the pathophysiology of yellow nail syndrome (YNS) (yellow nails, lymphedema, pleural effusions, and frequently chronic rhinosinusitis [CRS]). It is unclear why some YNS patients develop CRS. We quantified lymphatic and total vasculature of sinonasal mucosa in YNS patients and compared it to controls from CRS patients with (CRSwNP) or without polyps (CRSsNP). METHODS: Immunohistochemistry was performed on archival sinonasal mucosal samples from 5 patients with YNS and 14 controls with antibodies against podoplanin and CD31, markers of lymphatics. Morphometric assessment was performed on digital images using ImageJ software. RESULTS: In YNS, the number of lymphatics/mm2 ranged from 7 to 18/mm2 (controls: 6 to 43/mm2 , p = 0.343), with a mean perimeter between 92 and 201 µm (controls: 42 to 280 µm, p = 0.482). Total vasculature density was higher than lymphatics, ranging between 189 and 1159 vessels/mm2 , average 669 (controls: 139 to 1467/mm2 , average 503, p = 0.257) with smaller average perimeter, 40 to 117 µm, mean 64.8 µm (controls: 42 to 92 µm, mean 65.3 µm, p = 0.965). Lymphatics constituted only a small fragment of the total vasculature, ranging from 1.15% to 4.76%, average 2.34% (controls: 0.81% to 10.58%, average 4.88%, p = 0.156). CRSwNP patients had significantly higher lymphatic density (p = 0.011) and ratio of lymphatics to total vasculature (p = 0.045) than patients with YNS or CRSsNP. CONCLUSION: This is the first histological analysis of sinus mucosa in patients with YNS. Vascular type, density, size, and distribution in the sinonasal mucosa of YNS patients are not statistically significantly different from those of the CRSsNP group. Lymphatic density and ratio to total vasculature is higher in CRSwNP patients.

Recent advances in carrier mediated nose-to-brain delivery of pharmaceutics.

Central nervous system (CNS) disorders (e.g., multiple sclerosis, Alzheimer's disease, etc.) represent a growing public health issue, primarily due to the increased life expectancy and the aging population. The treatment of such disorders is notably elaborate and requires the delivery of therapeutics to the brain in appropriate amounts to elicit a pharmacological response. However, despite the major advances both in neuroscience and drug delivery research, the administration of drugs to the CNS still remains elusive. It is commonly accepted that effectiveness-related issues arise due to the inability of parenterally administered macromolecules to cross the Blood-Brain Barrier (BBB) in order to access the CNS, thus impeding their successful delivery to brain tissues. As a result, the direct Nose-to-Brain delivery has emerged as a powerful strategy to circumvent the BBB and deliver drugs to the brain. The present review article attempts to highlight the different experimental and computational approaches pursued so far to attain and enhance the direct delivery of therapeutic agents to the brain and shed some light on the underlying mechanisms involved in the pathogenesis and treatment of neurological disorders.

Assessment of the effectiveness of platelet rich fibrin in the treatment of Schneiderian membrane perforation.

BACKGROUND: The objective of this study is to evaluate the effect of Platelet rich fibrin (PRF) treatment of maxillary sinus membrane perforation on bone formation and new vascular supply and the success of dental implant survival rate. METHODS: The dataset for this retrospective study consists of patients who received sinus augmentation using the lateral wall technique. A total of 16 patients (20 sinuses) the patients without sinus membrane perforation (10 maxiller sinus area with sinus floor augmentation) and with Schneiderian perforation (10 maxiller sinus area repairing with PRF and augmented sinus floor area) were included in this study. The bone height was measured by comparing the preoperative and postoperative dental CBCT scans. Histological sections were evaluated for possible vasculogenesis augmented sinuses area. RESULTS: In both groups, it was observed that the possible vasculogenesis augmented sinuses area increased. Implant survival rates in both groups found that one hundred percent and any bone loss around implants were not observed. An apparent increase in alveolar bone height was observed and measured in CBCT scans. CONCLUSIONS: PRF can be considered as an alternative material for repairing sinus perforations because it is fully autogenous and easy manipulated.

Association of Nasal Mucosal Vascular Alterations, Gastrointestinal Arteriovenous Malformations, and Bleeding in Patients With Continuous-Flow Left Ventricular Assist Devices.

OBJECTIVES: This study sought to determine whether the nasal mucosa can serve as a surrogate for evaluating arteriovenous malformations (AVMs) related gastrointestinal (GI) bleeding in patients supported by continuous-flow left ventricular assist devices (CF LVADs). BACKGROUND: Bleeding from the mucosal surfaces of GI tract, particularly AVMs, is the most common complication of CF LVAD support. The pathophysiology of AVM formation during CF LVAD support is of critical interest yet poorly understood; in large part because of the length and accessibility of the GI tract. Nasal endoscopy is a minimally invasive, bedside test giving access to a mucosal surface possibly representative of the GI tract. METHODS: Eighty subjects (35 with CF LVAD, 30 with heart failure reduced ejection fraction [HFrEF], and 15 controls without heart failure) underwent nasal endoscopy for systematic evaluation of the intranasal mucosa for the presence of hypervascularity (HV). Patient records were reviewed for episodes and etiology of GI bleeding. RESULTS: Nasal HV was present in 63%, 57%, and 20% of the LVAD, HFrEF, and control groups, respectively (p = 0.018). Although the prevalence was similar, the severity of nasal HV was significantly higher in the CF LVAD group compared with the HFrEF group. Of the baseline characteristics in the entire cohort, only a history of heart failure was associated with HV (odds ratio: 4.8; 95% confidence interval: 1.02 to 22.31; p = 0.040) in adjusted logistic regression modeling. HV was strongly associated with GI bleeding in the CF LVAD cohort: the incidence was 32% in subjects with HV compared with 0% in subjects with normal mucosa (p = 0.023). CONCLUSIONS: In this pilot study, HV of the nasal mucosa was associated with GI bleeding in subjects with CF LVADs. Nasal endoscopy has significant potential to further investigation into mechanisms of bleeding and risk stratification during CF LVAD support.

Relative vascular permeability and vascularity across different regions of the rat nasal mucosa: implications for nasal physiology and drug delivery.

Intranasal administration provides a non-invasive drug delivery route that has been proposed to target macromolecules either to the brain via direct extracellular cranial nerve-associated pathways or to the periphery via absorption into the systemic circulation. Delivering drugs to nasal regions that have lower vascular density and/or permeability may allow more drug to access the extracellular cranial nerve-associated pathways and therefore favor delivery to the brain. However, relative vascular permeabilities of the different nasal mucosal sites have not yet been reported. Here, we determined that the relative capillary permeability to hydrophilic macromolecule tracers is significantly greater in nasal respiratory regions than in olfactory regions. Mean capillary density in the nasal mucosa was also approximately 5-fold higher in nasal respiratory regions than in olfactory regions. Applying capillary pore theory and normalization to our permeability data yielded mean pore diameter estimates ranging from 13-17 nm for the nasal respiratory vasculature compared to <10 nm for the vasculature in olfactory regions. The results suggest lymphatic drainage for CNS immune responses may be favored in olfactory regions due to relatively lower clearance to the bloodstream. Lower blood clearance may also provide a reason to target the olfactory area for drug delivery to the brain.

Autofluorescence multiphoton microscopy for visualization of tissue morphology and cellular dynamics in murine and human airways.

The basic understanding of inflammatory airway diseases greatly benefits from imaging the cellular dynamics of immune cells. Current imaging approaches focus on labeling specific cells to follow their dynamics but fail to visualize the surrounding tissue. To overcome this problem, we evaluated autofluorescence multiphoton microscopy for following the motion and interaction of cells in the airways in the context of tissue morphology. Freshly isolated murine tracheae from healthy mice and mice with experimental allergic airway inflammation were examined by autofluorescence multiphoton microscopy. In addition, fluorescently labeled ovalbumin and fluorophore-labeled antibodies were applied to visualize antigen uptake and to identify specific cell populations, respectively. The trachea in living mice was imaged to verify that the ex vivo preparation reflects the in vivo situation. Autofluorescence multiphoton microscopy was also tested to examine human tissue from patients in short-term tissue culture. Using autofluorescence, the epithelium, underlying cells, and fibers of the connective tissue, as well as blood vessels, were identified in isolated tracheae. Similar structures were visualized in living mice and in the human airway tissue. In explanted murine airways, mobile cells were localized within the tissue and we could follow their migration, interactions between individual cells, and their phagocytic activity. During allergic airway inflammation, increased number of eosinophil and neutrophil granulocytes were detected that moved within the connective tissue and immediately below the epithelium without damaging the epithelial cells or connective tissues. Contacts between granulocytes were transient lasting 3 min on average. Unexpectedly, prolonged interactions between granulocytes and antigen-uptaking cells were observed lasting for an average of 13 min. Our results indicate that autofluorescence-based imaging can detect previously unknown immune cell interactions in the airways. The method also holds the potential to be used during diagnostic procedures in humans if integrated into a bronchoscope.

Vein of foramen caecum: imaging findings.

Vein of foramen caecum has been classically described as a vein that connects nasal mucosa to the superior sagittal sinus in classic anatomy textbooks. However, its existence is controversial in literature. Herein, we demonstrated computed tomography and contrast enhanced magnetic resonance imaging findings of a tubular vascular structure extending to nasal mucosa and superior sagittal sinus.

Microvascular remodeling of nasal mucosa in allergic rhinitis induced by an allergen in Sprague-Dawley rats.

This study aimed to observe microvascular changes in the nasal mucosa of Sprague-Dawley (SD) rats with allergic rhinitis (AR) after persistent exposure to an allergen with fluticasone propionate (FP) treatment. Ninety healthy SD rats were randomly distributed into the control group (A, N = 30), the group with continued exposure to an allergen (B, N = 30), and FP treatment group (C, N = 30). The animals of the persistence group were subjected to persistent exposure to an allergen after 7 weeks of modeling of ovalbumin (OVA) provocation in the nasal mucosa for 16 weeks. At the 8th, 12th, and 16th week after OVA provocation, each group was euthanized at each time point: the FP treatment after OVA provocation, and animals of the control group were not stimulated with OVA and were sacrificed at the same time point. The nasal mucosa of 5 animals from each group was analyzed for the expression of vascular endothelial growth factor (VEGF), and another 5 animals were used to make micro vascular corrosion casts for a scanning electron microscope. The results demonstrate that FP has a strong inhibitory effect on angiogenesis in AR. Inhalation of FP had an antiangiogenic effect through inhibition of VEGF expression but does not completely reverse the remodeling of the nasal mucosa in the short term nor does it have complete control over the expression of VEGF mRNA.

Sphenopalatine foramen: endoscopic approach with bony landmarks.

OBJECTIVE: To establish whether nasal bony landmarks on computed tomography could be utilised reliably in endoscopic approaches to the sphenopalatine foramen. METHODS: A prospective analysis of 102 consecutive helical computed tomography scans of the paranasal sinuses was carried out by 2 senior ENT surgeons. Distances from the sphenopalatine foramen to endoscopically palpable bony landmarks were measured. RESULTS: There were a total of 102 patients (45 females and 57 males), with a mean age of 62 years. The mean distance from the posterior fontanelle to the sphenopalatine foramen was 14.1 mm (standard deviation = 2.13). The average vertical distance of the sphenopalatine foramen opening from the bony attachment of the inferior turbinate was 14.13 mm. There were no statistically significant differences between any of these measurements (foramen width p-value = 0.714, distance from fontanelle p-value = 0.43 and distance from inferior turbinate p-value = 0.48). CONCLUSION: Determination of reliable bony landmarks is clinically useful in endoscopic surgery and can aid identification of the sphenopalatine foramen. The inferior turbinate concha and posterior fontanelle may be used as reliable computed tomography landmarks for endoscopic approaches to the sphenopalatine foramen.

Nasal mucosa narrow band imaging in granulomatosis with polyangiitis (Wegener granulomatosis): A preliminary study.

BACKGROUND: Narrow band imaging (NBI) endoscopy is a technique that allows for real-time visualization of mucosal and submucosal vascular patterns. OBJECTIVE: Because granulomatosis with polyangiitis (GPA) (Wegener granulomatosis) is an autoimmune disease defined by vascular inflammation, we examined patients with GPA and with NBI to evaluate whether disease-specific mucosal vascular patterns were present. To the best of our knowledge, the use of NBI endoscopy for assessment of an immune system disease such as GPA has never been previously attempted. METHODS: We conducted a prospective observational study by performing an endoscopic evaluation of upper airways with NBI on patients diagnosed with GPA; on patients with symptoms and signs suggestive for GPA, who were scheduled to undergo nasal biopsy to confirm diagnosis; on patients affected by chronic rhinosinusitis with nasal polyps; and on healthy controls. RESULTS: We enrolled 69 patients. NBI vascular patterns in patients with GPA were consistently and recognizably different from healthy mucosal patterns in 53% of our cases. In patients with GPA, biopsy and NBI results were for the most part comparable, except for three cases. CONCLUSION: Nasal mucosa NBI endoscopy can be considered a promising rapid and noninvasive live imaging technique for nasal mucosa GPA that, based on further study, could become a supplementary diagnostic tool in the complex workup of GPA and vasculitis.

Particle embolization for the treatment of life-threatening epistaxis in a left ventricular assist device patient.

While epistaxis is self-limiting in most cases, patients who are anticoagulated are at increased risk for life-threatening hemorrhage. The management of epistaxis in patients with a left ventricular assist device is further complicated by an increased risk for hemodynamic instability. Here, we detail the successful treatment of massive epistaxis in a left ventricular assist device patient by endovascular particle embolization. We hope to increase awareness in the cardiovascular community of this minimally invasive, potentially life-saving procedure.

First experiences with an individual nasal olive in patients with hereditary haemorrhagic telangiectasia (HHT).

Hereditary haemorrhagic teleangiectasia (HHT) is most notably characterized by vulnerable vascular formations of the nasal superficial mucosa. Epistaxis is one of the most common symptoms of the afflicted patients, with an incidence of more than 90 %. A variable series of treatments have been described, ranging from nasal ointments to the complete surgical occlusion of the nose. The objective of this pilot study is the presentation of first experiences in treating patients suffering from HHT and chronically recurrent epistaxis with an individual nasal olive made from silicone. Eleven patients (six men, five women) aging from 44 to 80 years with known HHT were treated at the ENT department of Homburg/Saar between October 2008 and July 2012 because of nasal bleeding by Nd:YAG laser or argon plasma coagulation. After the surgical treatment, an imprint of the nasal aditus was taken to manufacture an individual custom-made silicone nasal olive. Patients were wearing the nasal olive for 3-8 h a day. Check-ups were made every 6 months. Epistaxis severity score (ESS) was used pre- and post-nasal olive application. The observation period was 12-48 months. The utilization of the silicone nasal olive led to a distinct reduction of epistaxis events. Apart from the nasal olive, our patients needed no further treatment of the nose during the observation period except for a nasal ointment. Insertion and removal of the nasal olive were handled by the patients themselves. The local manipulation in handling the nasal olive caused no epistaxis itself. A significant improvement of the ESS and satisfaction was reported in all patients. Use of an individually manufactured silicone nasal olive is a promising extension to the established treatments of epistaxis in HHT patients. Tolerance towards this treatment by the patients was high due to the low personal burden and encumbrance. The extended use of the presented method in HHT patients may be beneficial. However, a more prolonged observation period is necessary in the future to judge the long-term efficiency of individual nasal olives.

[Blood supply of the pedicle nasal septum mucosa flap of rabbit in experiment].

OBJECTIVE: To explore the blood supply of the pedicle nasal septum mucosa flap of rabbit, in order to supply the theory and experiment basis for making the pedicle nasal septum mucosa flap to repair nasal cavity and skull base defect. METHOD: Twenty rabbits corpses were induced into the experimental subject, and inject 5 ml blue ink into the external carotid artery, then longitudinal cut apart the middle head of rabbit, finally observe the blood supply of the pedicle nasal septum mucosa flap. RESULT: The blood supply of the pedicle nasal septum mucosa flap mostly come from the vessels of extremitas anterior part of nasal septum. CONCLUSION: Keep the he vessels of extremitas anterior part of nasal septum can guarantee the blood supply of mucous membrane, enhance the survival rate of nasal septum mucous membrane.

Evaluation of the effect of nasal dorsal skin cooling on nasal mucosa by acoustic rhinometry.

BACKGROUND: The use of cold nasal packs on the nose and nape of the neck is currently recommended for patients with epistaxis as this is thought to induce reflex nasal vasoconstriction, which decreases the bleeding. There have been a few investigations on the effect of cold compress application to the nose, but none of these focused specifically on nasal cooling of the skin of the nose. METHODS: Acoustic rhinometry was performed to obtain baseline measurements. Nasal dorsal skin was then cooled with two ice packs that were held on the left and right side of the nose for a total of 10 minutes by the subjects. The rhinometry measurements were taken at the time of initial application (baseline), and after 5 and 10 minutes of ice pack application. RESULTS: Comparisons of the first and second minimal cross-sectional area values, and total nasal cavity volume measurements revealed no statistical differences. CONCLUSION: The results of this study indicate that one should be sceptical about the efficiency of cold compress application, which is frequently used in clinical practice in cases with epistaxis.

Heterotopic mucosal engrafting procedure for direct drug delivery to the brain in mice.

Delivery of therapeutics into the brain is impeded by the presence of the blood-brain barrier (BBB) which restricts the passage of polar and high molecular weight compounds from the bloodstream and into brain tissue. Some direct delivery success in humans has been achieved via implantation of transcranial catheters; however this method is highly invasive and associated with numerous complications. A less invasive alternative would be to dose the brain through a surgically implanted, semipermeable membrane such as the nasal mucosa that is used to repair skull base defects following endoscopic transnasal tumor removal surgery in humans. Drug transfer though this membrane would effectively bypass the BBB and diffuse directly into the brain and cerebrospinal fluid. Inspired by this approach, a surgical approach in mice was developed that uses a donor septal mucosal membrane engrafted over an extracranial surgical BBB defect. This model has been shown to effectively allow the passage of high molecular weight compounds into the brain. Since numerous drug candidates are incapable of crossing the BBB, this model is valuable for performing preclinical testing of novel therapies for neurological and psychiatric diseases.