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Pharmaceutics May 2024The standard multi-dose nasal spray pump features an integrated actuator and nozzle, which inevitably causes a retraction of the nozzle tip during application. The...
The standard multi-dose nasal spray pump features an integrated actuator and nozzle, which inevitably causes a retraction of the nozzle tip during application. The retraction stroke is around 5.5 mm and drastically reduces the nozzle's insertion depth, which further affects the initial nasal spray deposition and subsequent translocation, potentially increasing drug wastes and dosimetry variability. To address this issue, we designed a new spray pump that separated the nozzle from the actuator and connected them with a flexible tube, thereby eliminating nozzle retraction during application. The objective of this study is to test the new device's performance in comparison to the conventional nasal pump in terms of spray generation, plume development, and dosimetry distribution. For both devices, the spray droplet size distribution was measured using a laser diffraction particle analyzer. Plume development was recorded with a high-definition camera. Nasal dosimetry was characterized in two transparent nasal cavity casts (normal and decongested) under two breathing conditions (breath-holding and constant inhalation). The nasal formulation was a 0.25% w/v methyl cellulose aqueous solution with a fluorescent dye. For each test case, the temporospatial spray translocation in the nasal cavity was recorded, and the final delivered doses were quantified in five nasal regions. The results indicate minor differences in droplet size distribution between the two devices. The nasal plume from the new device presents a narrower plume angle. The head orientation, the depth at which the nozzle is inserted into the nostril, and the administration angle play crucial roles in determining the initial deposition of nasal sprays as well as the subsequent translocation of the liquid film/droplets. Quantitative measurements of deposition distributions in the nasal models were augmented with visualization recordings to evaluate the delivery enhancements introduced by the new device. With an extension tube, the modified device produced a lower spray output and delivered lower doses in the front, middle, and back turbinate than the conventional nasal pump. However, sprays from the new device were observed to penetrate deeper into the nasal passages, predominantly through the middle-upper meatus. This resulted in consistently enhanced dosing in the middle-upper turbinate regions while at the cost of higher drug loss to the pharynx.
PubMed: 38794345
DOI: 10.3390/pharmaceutics16050683 -
International Journal of Molecular... May 2024, a zoonotic pathogen that produces a 146-kDa modular toxin (PMT), causes progressive atrophic rhinitis with severe turbinate bone degradation in pigs. However, its...
, a zoonotic pathogen that produces a 146-kDa modular toxin (PMT), causes progressive atrophic rhinitis with severe turbinate bone degradation in pigs. However, its mechanism of cytotoxicity remains unclear. In this study, we expressed PMT, purified it in a prokaryotic expression system, and found that it killed PK15 cells. The host factor CXCL8 was significantly upregulated among the differentially expressed genes in a transcriptome sequencing analysis and qPCR verification. We constructed a CXCL8-knockout cell line with a CRISPR/Cas9 system and found that CXCL8 knockout significantly increased resistance to PMT-induced cell apoptosis. CXCL8 knockout impaired the cleavage efficiency of apoptosis-related proteins, including Caspase3, Caspase8, and PARP1, as demonstrated with Western blot. In conclusion, these findings establish that CXCL8 facilitates PMT-induced PK15 cell death, which involves apoptotic pathways; this observation documents that CXCL8 plays a key role in PMT-induced PK15 cell death.
Topics: Interleukin-8; Animals; Pasteurella multocida; Bacterial Toxins; Apoptosis; Swine; Bacterial Proteins; Cell Line; Caspase 8; Gene Knockout Techniques; CRISPR-Cas Systems
PubMed: 38791369
DOI: 10.3390/ijms25105330 -
Anatomy & Cell Biology May 2024Pneumatisation of the maxillary sinus (MS) is variable. The archived cone-beam computed tomography file of a 54-year-old female was retrospectively evaluated...
Pneumatisation of the maxillary sinus (MS) is variable. The archived cone-beam computed tomography file of a 54-year-old female was retrospectively evaluated anatomically. Nasal or retrobullar recesses of the MSs (NRMS) were found. The MSs were bicameral. NRMSs extended from the postero-lateral chambers of the MSs into the lateral nasal walls. The right NRMS was reached superior to the middle turbinate and the ethmoidal bulla was applied on its anterior side. The left NRMS had two medial pouch-like ends, one beneath the ethmoidal bulla and the other on the anterior side of the basal lamella of the middle turbinate. Additional anatomical findings were the uncinate bulla, infraorbital recesses of the MS, maxillary recess of the sphenoidal sinus, and atypical posterior insertions of the superior nasal turbinates, maxillo-ethmoido-sphenoidal and ethmoido-sphenoidal. The NRMS is a novel finding and could lead to erroneous endoscopic corridors if not documented before the interventions.
PubMed: 38773954
DOI: 10.5115/acb.24.023 -
Regulatory Toxicology and Pharmacology... May 2024Inhalation is a critical route through which substances can exert adverse effects in humans; therefore, it is important to characterize the potential effects that... (Review)
Review
Inhalation is a critical route through which substances can exert adverse effects in humans; therefore, it is important to characterize the potential effects that inhaled substances may have on the human respiratory tract by using fit for purpose, reliable, and human relevant testing tools. In regulatory toxicology testing, rats have primarily been used to assess the effects of inhaled substances as they-being mammals-share similarities in structure and function of the respiratory tract with humans. However, questions about inter-species differences impacting the predictability of human effects have surfaced. Disparities in macroscopic anatomy, microscopic anatomy, or physiology, such as breathing mode (e.g., nose-only versus oronasal breathing), airway structure (e.g., complexity of the nasal turbinates), cell types and location within the respiratory tract, and local metabolism may impact inhalation toxicity testing results. This review shows that these key differences describe uncertainty in the use of rat data to predict human effects and supports an opportunity to harness modern toxicology tools and a detailed understanding of the human respiratory tract to develop testing approaches grounded in human biology. Ultimately, as the regulatory purpose is protecting human health, there is a need for testing approaches based on human biology and mechanisms of toxicity.
PubMed: 38772524
DOI: 10.1016/j.yrtph.2024.105648 -
Ear, Nose, & Throat Journal May 2024A neoplasm was found in the left nasal cavity of a 45-year-old woman during electronic laryngoscopy for reflux pharyngitis. She reported experiencing an occasional...
A neoplasm was found in the left nasal cavity of a 45-year-old woman during electronic laryngoscopy for reflux pharyngitis. She reported experiencing an occasional slight headache in the left parietal region for 1 to 2 years, which she considered a migraine. Electronic laryngoscopy showed a gray, soft, smooth neoplasm in the left nasal meatus, located near the olfactory region blocking the olfactory clef and compressing the left middle turbinate. The neoplasm was resected at endonasal endoscopic surgery. Histological assessments indicated chronic mucus inflammation and cyst formation. This is a rare case because the polyp was large but asymptomatic and originated from nasal septum.
PubMed: 38770963
DOI: 10.1177/01455613241256836 -
Ear, Nose, & Throat Journal May 2024Retiform hemangioendothelioma (RH) is a rare intermediate (locally aggressive) vascular tumor that mostly affects the dermis of the trunk and limbs, but has never been...
Retiform hemangioendothelioma (RH) is a rare intermediate (locally aggressive) vascular tumor that mostly affects the dermis of the trunk and limbs, but has never been reported in the inferior turbinate. A 10-year-old Chinese boy presented with recurrent epistaxis in his left nasal cavity and anemia for more than 2 years. Radiographic and electronic video laryngoscopic images showed an expansile mass in the left inferior turbinate. Endoscopic surgery and electrocautery were performed to resect the tumor beyond the macroscopic border. Histopathologically, the tissues were infiltrated by hyperplastic blood vessels arranged in a retiform pattern, and endothelial cells proliferate significantly in some areas. Immunohistochemistry showed a positive result for CD31, CD34, Fli-1, and ERG. No epistaxis, tumor recurrence, or metastasis was found on reexamination over 18 months after surgery.
PubMed: 38757668
DOI: 10.1177/01455613241253372 -
Ear, Nose, & Throat Journal May 2024This study aimed to investigate the effects of seated, supine, and recumbent postures on nasal resistance in individuals with allergic rhinitis (AR) and healthy...
This study aimed to investigate the effects of seated, supine, and recumbent postures on nasal resistance in individuals with allergic rhinitis (AR) and healthy controls, which has not been investigated in the past. A visual analog scale (VAS) assessed subjective nasal obstruction, while acoustic rhinometry and video endoscopy provided objective measures. Sixty participants, comprising 30 AR patients and 30 healthy controls, were evaluated across 4 postures without decongestion: seated, supine, left recumbent, and right recumbent. In patients with AR, we noted no significant changes in subjective nasal blockage under various postures (all > .18). However, significant reductions of minimal cross-sectional area (mCSA) were found (seated vs supine, = .014; seated vs left recumbent, = .001; seated vs right recumbent, < .001) and significant increases in the inferior turbinate hypertrophy were observed on the dependent side of the nose when in recumbent posture (right nose: seated vs right recumbent, = .013; left nose: seated vs left recumbent, = .003). On the contrary, healthy controls experienced increased subjective nasal obstruction (VAS scores: seated vs supine, < .001; seated vs left recumbent, = .003; seated vs right recumbent, < .001), reductions in mCSA (seated vs supine, = .002; seated vs right or left recumbent, both = .001), and increased inferior turbinate hypertrophy on the dependent side of the nose (right nose: seated vs right recumbent, = .003; left nose: seated vs left recumbent, = .006). Healthy controls reported better nasal patency when shifting from supine or recumbent to more upright or less gravity-dependent seated postures, which was further supported by objective examinations. On the contrary, despite patients with AR not subjectively perceiving increased nasal patency while adopting more upright postures, objective evaluations demonstrated an improvement in their nasal airflow in these less gravity-dependent postures. 4.
PubMed: 38757667
DOI: 10.1177/01455613241254434 -
Cureus Apr 2024Background Nasal obstruction due to inferior turbinate hypertrophy is a common medical complaint among ENT clinic patients, which can significantly affect the patient's...
Background Nasal obstruction due to inferior turbinate hypertrophy is a common medical complaint among ENT clinic patients, which can significantly affect the patient's quality of life, and some are compelled to use topical intranasal decongestants. Conservative management is the first line of treatment; however, surgical reduction of the inferior turbinate becomes necessary if the symptoms persist after three months of treatment. The optimal surgical technique is controversial. High-intensity focused ultrasound (HIFU) is a minimally invasive surgical option that targets tissue volume precisely and minimally impacts surrounding tissue. This study aimed to assess the effectiveness and safety of HIFU in treating patients suffering from nasal obstruction due to inferior turbinate hypertrophy. Methods This prospective study was conducted from February to December 2016. The study lasted over six months. Patients with a history of allergic and non-allergic rhinitis participated in this study. It included 43 patients who had been experiencing chronic nasal obstruction due to bilateral inferior turbinate hypertrophy and had not shown improvement after three months of medical treatment. The patients underwent Ultrasound Volumetric Tissue Reduction (UVTR) surgery using the D & A Ultrasurg device (Diamant Medical Equipment Ltd., Amman, Jordan) under local anesthesia. The effectiveness, safety, and tolerance of HIFU were assessed subjectively for six months using a well-designed questionnaire utilizing a visual analog scale (VAS) and nasal endoscopy after the surgery. Results The study included 43 patients, 22 male and 21 female, aged 13 to 65 years. The study found that 40 (93%) patients showed significant improvement in nasal obstruction within a month of the surgery. However, three (7%) patients continued to experience persistent nasal obstruction even after six months of follow-up. The procedure was well-tolerated, with low rates of complications after surgery and reasonable pain control. During the surgery, 20 (46.5%) patients reported mild pain described as a pressure-like sensation, and 10 out of 43 patients (23%) required paracetamol after the procedure. Four patients (9.3%) had mild bleeding, which was treated with an ultrasound nasal probe without nasal packing. All patients experienced crusting of the nasal cavity during the first week, but no crustation was observed after the first month. There were no reported cases of synechia among the patients. Conclusion This study confirms that HIFU treatment is a reliable and effective treatment for improving short-term nasal obstruction caused by inferior turbinate hypertrophy. The procedure is easily applied and well-tolerated in outpatient clinics.
PubMed: 38756284
DOI: 10.7759/cureus.58348 -
Animals : An Open Access Journal From... Apr 2024Nasopharyngeal myiasis in European roe deer is a pathological condition caused by the larval stages of , a fly from the Oestridae family. These larvae reside in the...
Nasopharyngeal myiasis in European roe deer is a pathological condition caused by the larval stages of , a fly from the Oestridae family. These larvae reside in the host's upper respiratory tract for months, inducing significant tissue damage and clinical symptoms. The lifecycle of is complex, involving three larval stages before maturation into adult flies, with each stage contributing to the progressive pathology observed in the host. Despite their prevalence, the histopathological effects of these larvae in the nasal and nasopharyngeal cavities have been understudied. Our study fills this knowledge gap by providing a detailed histopathological analysis of the affected tissues, using various staining techniques to reveal the extent and nature of the damage caused by these parasitic larvae. This histopathological examination reveals significant alterations within the nasopharyngeal mucosa and nasal cavity, including erythematous changes, mucosal metaplasia, fibrosis, and tissue necrosis. Parasitic cysts and eosinophilic infiltration further characterize the impact of the infestation, compromising not only the mucosal integrity but also potentially the olfactory function of the affected animals. This research is crucial for understanding the impact of myiasis on both the health and olfactory capabilities of roe deer populations and could have significant implications for wildlife management and conservation.
PubMed: 38731301
DOI: 10.3390/ani14091297 -
Cureus Apr 2024Choanal atresia obstructs the nasal passage due to abnormal bony or soft tissue remnants owing to the faulty canalization of the nasal passages during fetal development....
Choanal atresia obstructs the nasal passage due to abnormal bony or soft tissue remnants owing to the faulty canalization of the nasal passages during fetal development. The clinical manifestations are more pronounced in bilateral cases, often presenting immediately after birth with cyanosis turning pink when crying, as newborns are obligatory nasal breathers. This contrasts in unilateral cases, where the condition may present with mild symptoms and be diagnosed later in life. We present a case of a five-year-old male who initially presented with a concern for nasal polyps due to nasal congestion with absent airflow out of the right nostril. On examination of the pharynx and nose, the patient was diagnosed with nasal turbinate hypertrophy, the right more than the left, and was subsequently scheduled for bilateral inferior turbinate reduction, possible adenoidectomy, and nasal endoscopy. Intraoperatively, inspection with nasal endoscopy along with the inability to pass a catheter through the nasopharynx to reach the oropharynx was our indicator of a more severe diagnosis. Here, we report an incidental finding of the right choanal atresia and seek to highlight its importance given this incidental finding.
PubMed: 38707148
DOI: 10.7759/cureus.57669