Nasal Space Research Articles

A novel electro-mechanical chewing system for food oral processing research: A comprehensive design approach

This paper presents a comprehensive design approach for an electro-mechanical system for food oral processing research. The bespoke design and prototype of the proposed device is a standalone and compact table top model and can be operated using a customized software interface. The design considered a bi-directional chewing motion to enable nearly similar mandible movement pattern as in human. Food texture profile can be estimated using a load cell with capacity up to 300 N. This design included a section of real shaped teeth assembly consisting of three teeth; and a controlled supply line for multi-point saliva injections. The device is fitted with easily replaceable sensors for in situ measurements of conductivity, pH, and temperature. Operating volume of the device can be kept in equivalence with the volume of human oral and nasal space. The device chamber can be hermetically sealed and temperature controlled. A duct system is fitted to connect the device with external analytical systems, such as electronic nose, for measuring gaseous substance release during experimentation. The system also enables easy retrieval of the processed sample so as to use the masticated samples and processed saliva for subsequent analysis by analytical instruments, such as electronic tongue, to identify released soluble compounds and taste profiles. Moreover, the design emphasized on easy cleaning and maintainability. Based on the proposed design, two working prototypes are developed. It is envisaged that the device will be a novel contribution to the progress in the field of food science, new product development, training to future professionals, and strengthening industry-academic collaborations in foreseeable future.

Cardiovascular safety of dihydroergotamine mesylate delivered by precision olfactory delivery (INP104) for the acute treatment of migraine.

To report the cardiovascular (CV) safety of dihydroergotamine mesylate (DHE) administered by precision olfactory delivery (INP104) from two clinical trials. Although the absolute risk is low, migraine is associated with an increased risk of CV events. DHE is a highly effective acute treatment for migraine, but due to its theoretical risk of promoting arterial vasoconstriction, DHE is contraindicated in patients with CV disease or an unfavorable risk factor profile. The INP104 is a novel drug-device combination product approved for acute treatment of migraine that delivers DHE to the upper nasal space using precision olfactory delivery (POD®). The STOP 101 was a Phase 1 open-label study that assessed the safety, tolerability, and bioavailability of INP104 1.45 mg, intravenous DHE 1.0 mg, and MIGRANAL (nasal DHE) 2.0 mg in healthy participants. The STOP 301 was a pivotal Phase 3, open-label study that assessed the safety, tolerability, and exploratory efficacy of INP104 1.45 mg over 24 and 52 weeks in patients with migraine. In both studies, active or a history of CV disease, as well as significant CV risk factors, were exclusion criteria. In STOP 101, 36 participants received one or more doses of investigational product. Treatment with intravenous DHE, but not INP104 or nasal DHE, resulted in clinically relevant changes from baseline in systolic blood pressure (BP; 11.4 mmHg, 95% confidence interval [CI] 7.9-15.0) and diastolic BP (13.3 mmHg, 95% CI 9.4-17.1) at 5 min post-dose, persisting up to 30 min post-dose for systolic BP (6.3 mmHg; 95% CI 3.0-9.5) and diastolic BP (7.9 mmHg, 95% CI 3.9-11.9). None of the treatments produced any clinically meaningful electrocardiogram (ECG) changes. In STOP 301, 354 patients received one or more doses of INP104. Over 24 weeks, five patients (1.4%) experienced a non-serious, vascular treatment-emergent adverse event (TEAE). Minimal changes were observed for BP and ECG parameters over 24 or 52 weeks. Off-protocol concomitant use of triptans and other ergot derivatives did not result in any TEAEs. In two separate studies, INP104 demonstrated a favorable CV safety profile when used in a study population without CV-related contraindications.

Nasotracheal intubation with the aid of nasopharyngeal airway

Introduction & objective: Oral and maxillofacial surgeries commonly require nasotracheal intubation (NTI) to overcome difficulty of work in the oropharyngeal space. Several variables affect intubation difficulty and complications and include tube type or design, topical vasoconstrictors, lubricating the endotracheal tube (ETT), selecting smaller diameter ETT, using urethral catheter to assist NTI, using some catheters etc. We aimed to explore the effectiveness of nasopharyngeal airway (NPA) as a factor facilitating the passage of ETT in the nasopharynx and diminishing trauma and bleeding during NTI. Methodology: One hundred-forty patients undergoing surgery in the oral and maxillofacial area were divided into groups of 70 each; NPA group, in which an NPA was used as an assist device, and non-NPA group with non-NPA use. Before intubation, the more patent nostril was identified, topical nasal vasoconstrictor was used, lubricant jelly applied and thermo softening of the ETT achieved. In NPA group, nasal cavity dilatation was done with an NPA before NTI. The ease of ETT passage and any nasopharyngeal bleeding were assessed by a scale of four grades. Results: About 95.71% patients had easy (grade 0 or 1) passage of ETT in the NPA group compared to 81.43% in the non-NPA group (P < 0.0001, P = 0.006), and the remaining grades also showing significant differences between groups. About 98.57% patients had grade 0 to 1 bleeding (no or traces of blood) in the NPA group, compared to 97.14% in the non-NPA group (P = 0.001) and the remaining grades also showed significant differences between the groups. NPA minimized difficulties in passage of the ETT and complications. Conclusion: Application of nasopharyngeal airway in patients undergoing nasotracheal intubation for general anesthesia proved to be effective in increasing nasal cavity space and minimizing difficulties faced in the passage of the endotracheal tube through the nasal passages and diminishing the resulting complications. Abbreviations: ETT- Endotracheal Tube; NPA- Nasopharyngeal Airway; NTI- Nasotracheal Intubation Keywords: Endotracheal Tube; Lubricating Gel; Maxillofacial; Nasopharyngeal Airway; Nasotracheal Intubation; Surgery, Oral; Surgery Citation: Abd Al-Qader BK, Abdulahad SA, Mohammad HM. Nasotracheal intubation with the aid of nasopharyngeal airway. Anaesth. pain intensive care 2024;28(1):50−54; DOI: 10.35975/apic.v28i1.2263 Received: July 09, 2023; Reviewed: December 10, 2023; Accepted: December 30, 2023

The nasal route, advanced drug delivery systems and evaluation: a review

Abstract Nasal drug delivery is a well-known alternative to oral and parenteral drug delivery systems. Protein, peptides, hormones, and vaccines are the sensitive molecules for the oral route; hence those can be reached via nasal delivery. The nasal way has several advantages: higher permeability, more vasculature, less contact with enzymes due to less nasal space, and no hepatic first-pass metabolism. Therefore, it is a suitable route for sensitive drug molecules. Different applicators can deliver solid, liquid, and semisolid formulations for treating various diseases. The present review considers a brief introduction to the nasal route and problems associated with the nasal course for drug delivery, conventional and novel formulations, their applications, and evaluation parameters. Moreover, some of the marketed formulations for the nasal route of drug delivery systems and patented technologies are tabulated by reviewing the previous and updated literature.

The Pharmacokinetics of Drugs Delivered to the Upper Nasal Space.

Pharmacokinetics (PK) includes how a drug is absorbed, distributed, metabolized and eliminated. The compartment providing this information is usuallythe plasma. This is as close to the tissue of interest that we can get, although biopsies may be obtained to give "tissue levels" of drugs. Ultimately, the goal of PK is to understand how long the drug is actually engaged with the target in the tissue of interest after a dose has been administered. Most drugs at some point in their development will have been administered intravenously (IV), which acts as the standard for 100% bioavailability. By comparing various routes of administration to IV, the percentage of drug delivered to the plasma, on a dose-normalized basis, can be calculated and is referred to as the "absolute bioavailability". As pharmacology has advanced and more drugs have become available, many older products have been reformulated to be given by routes other than those originally intended (often oral). As the drawbacks of oral (or IV) administration have become better appreciated, non-oral, non-IV formulations and methods of administration have become more popular. Nasal administration is one route that has historically been overlooked as an alternative to oral administration-particularly for products needing rapid and non-invasive access to the target tissue-mostly via the blood stream. But attention is now focused on nasal administration for direct access to the brain, as that has the potential to bypass the blood-brain-barrier (BBB), which not even IV administration can always achieve. Assessing PK for these drugs targeting the brain may require serial sampling of the cerebrospinal fluid (CSF), making PK assessments of CNS drugs more invasive and complex, but still possible in future product development. However, we are now seeing more drugs reformulated for nasal delivery to gain faster systemic levels than oral administration (especially in patients with known or suspected gastrointestinal dysmotility), while avoiding the use of needles. For example, in recent years several different formulations and delivery methods for an old drug, dihydroergotamine (DHE), have been developed and these show very different characteristics, suggesting that delivery to different parts of the nose may have very different PK profiles. This review summarizes the systemic PK of different nasal DHE options that have been, or are being, developed and suggests that delivery of drugs to the upper nasal space (UNS) may represent an optimal target. Further research is required to ascertain if this route could also be utilized for direct administration to the CNS (as an attractive alternative to intrathecal delivery) via the olfactory or trigeminal nerves-but already preclinical data (and some human data) suggest this is entirely possible.

Rapid maxillary expansion and its consequences on the nasal and oropharyngeal anatomy and breathing function of children and adolescents: An umbrella review.

To identify, qualify, and summarize the evidence from different systematic reviews about the outcomes of Rapid Maxillary Expansion (RME) on upper airway dimensions and breathing function in young patients. A literature search (from 2000 to December 2022) was conducted through PubMed (MEDLINE), the Cochrane Library, EMBASE, and Dentistry & Oral Science Source. The authors conducted the following umbrella review phases: research question, study selection criteria (systematic reviews involving randomized clinical trials and longitudinal observational designs), data extraction, and critical appraisal (bias risk assessment) of selected articles through the ROBIS tool. The initial search yielded 65 potential references. After screening titles and summaries, and the elimination of duplicated publications, 15 articles were eligible for the evaluation of the full-text document. Finally, 11 systematic reviews (5 combined with meta-analysis) were selected, reporting 132 single studies; 38 of them were unrepeatable. Risk-of-bias assessment showed an average global moderate/high quality among the included studies. There was high heterogeneity between the systematic reviews' (and meta-analyses') methodologies used. The present umbrella review concludes that significant and stable increases in the nasal and oropharyngeal space volumes and a decrease in airway resistance of growing children and adolescents, occur immediately after RME and at 3, 6- and 12-months follow-up.

Outcomes of 60-Degree Nasal Goniotomy for Open Angle Glaucoma.

Sixty-degree nasal sectoral juxtacanalicular space goniotomy with the single-use Espaillat juxtacanalicular space slider device significantly reduced intraocular pressure and the number of required glaucoma hypotensive medications, with sustained reductions over 24 months. This study analyzed the safety and efficacy of the Espaillat juxtacanalicular space slider during minimally invasive 60-degree nasal sectoral goniotomy for mild-to-moderate open angle glaucoma (OAG). This prospective, observational case series performed at a private clinical practice and outpatient surgery center assessed the eyes of patients with mild-to-moderate OAG who underwent phacoemulsification cataract surgery with 60-degree nasal sectoral goniotomy using the Espaillat juxtacanalicular space slider. The same surgeon performed all procedures. Intraocular pressure, intraocular pressure-lowering drugs, and adverse effects were assessed over 24 months, and a regression analysis of intraocular pressure reduction was performed. Success was defined as (1) A reduction in the intraocular pressure of at least 20% for at least 12 months, compared with the baseline value, and (2) a decrease in the number of medications by at least one for at least 12 months. Among 38 eyes, 27 (72%) had moderate glaucoma, and 11 (28%) had mild glaucoma. Postoperatively, intraocular pressure was decreased by 38% at 12 months (mean 13.7±1.7mmHg), 35% at 18 months (mean 14.4±1.8mmHg), and 31% at 24 months (mean 15.2±1.9mmHg). In addition, the number of topical glaucoma medications used decreased from a mean of 1.6 to 0.4 ( P <0.001). The main adverse event was temporary focal corneal edema (29 patients; 76%). Using the Espaillat juxtacanalicular space slider during invasive 60-degree nasal sectoral goniotomy for OAG yielded a significant and sustained reduction in intraocular pressure and reduced the need for glaucoma medications with minimal adverse events.

The Effect of Trans-Sutural Distraction Osteogenesis on Nasal Bone, Nasal Septum, and Nasal Airway in the Treatment for Midfacial Hypoplasia in Growing Patients.

The purposes of this study were to analyze the effect of trans-sutural distraction osteogenesis (TSDO) on nasal bone, nasal septum, and nasal airway in the treatment of midfacial hypoplasia. A total of 29 growing patients with midfacial hypoplasia who underwent TSDO by a single surgeon were enrolled. The 3-dimensional measurement of nasal bone and nasal septum changes was performed using computed tomography (CT) images obtained preoperatively (T0) and postoperatively (T1). One patient was selected to establish 3-dimensional finite element models to simulate the characteristics of nasal airflow field before and after traction. After traction, the nasal bone moved forward significantly (P<0.01). The septal deviation angle was lower than that before traction (14.43±4.70 versus 16.86 ±4.59 degrees) (P<0.01). The length of the anterior and posterior margin of the vomer increased by 21.4% (P<0.01) and 27.6% (P<0.01), respectively, after TSDO. The length of the posterior margin of the perpendicular plate of ethmoid increased (P<0.05). The length of the posterior inferior and the posterior superior margin of the nasal septum cartilage increased (P<0.01) after traction. The cross-sectional area of nasal airway on the deviated side of nasal septum increased by 23.0% after traction (P<0.05). The analysis of nasal airflow field showed that the pressure and velocity of nasal airflow and the nasal resistance decreased. In conclusion, TSDO can promote the growth of the midface, especially nasal septum, and increase the nasal space. Furthermore, TSDO is conductive to improve nasal septum deviation and decrease nasal airway resistance.

The Upper Nasal Space: Option for Systemic Drug Delivery, Mucosal Vaccines and "Nose-to-Brain".

Sino-nasal disease is appropriately treated with topical treatment, where the nasal mucosa acts as a barrier to systemic absorption. Non-invasive nasal delivery of drugs has produced some small molecule products with good bioavailability. With the recent COVID pandemic and the need for nasal mucosal immunity becoming more appreciated, more interest has become focused on the nasal cavity for vaccine delivery. In parallel, it has been recognized that drug delivery to different parts of the nose can have different results and for "nose-to-brain" delivery, deposition on the olfactory epithelium of the upper nasal space is desirable. Here the non-motile cilia and reduced mucociliary clearance lead to longer residence time that permits enhanced absorption, either into the systemic circulation or directly into the CNS. Many of the developments in nasal delivery have been to add bioadhesives and absorption/permeation enhancers, creating more complicated formulations and development pathways, but other projects have shown that the delivery device itself may allow more differential targeting of the upper nasal space without these additions and that could allow faster and more efficient programs to bring a wider range of drugs-and vaccines-to market.

INP104: a drug evaluation of a nonoral product for the acute treatment of migraine.

Migraine is a highly prevalent, disabling neurological disorder that is also associated with gastrointestinal symptoms, autonomic dysfunctionand allodynia. Despite the availability of multiple acute agents for migraine, an unmet need remains for effective, well-tolerated drugs that are nonoral and noninvasive. Here, we provide a drug evaluation of INP104, a novel drug-device combination product of dihydroergotamine (DHE) mesylate -a molecule with a long history of efficacy familiar to headache specialists -which is delivered to the difficult-to-reach upper nasal space where it is rapidly and consistently absorbed via Precision Olfactory Delivery (POD®). In clinical trials, INP104 exhibited favorable pharmacokinetics, a well-tolerated safety profile, and rapid symptom relief, highlighting its potential as a suitable acute therapy for migraine.

Study on static parameters of internal nasal valve in 3-dimensional model of nasal cavity space

Objective: To identify the internal nasal valve (INV) and to evaluate its key parameters in the established 3D models of nasal cavity space via Mimics from CT images, in order to provide evidence for quantitative diagnosis of nasal valve compromise. Methods: A total of 32 Han adults without nasal diseases who underwent maxillofacial CT test in Shanghai Ninth People's Hospital from January 2015 to December 2018 were retrospectively recruited, including 16 males and 16 females, with the age ranged from 20 to 80 years (50% age<50 years old). Maxillofacial CT images were used to create 3D model of nasal cavity space. The INV was identified and the following parameters were measured: the angle between the INV and the nasal bone (θINV-B), unilateral cross-sectional area of the INV (AINV-R, AINV-L), total cross-sectional area of the INV (AINV), unilateral height of the INV (HINV-R, HINV-L), unilateral nasal valve angle (αINV-R, αINV-L), and the sum of nasal valve angle (αINV). The AINV in our study was compared with the results of the previously adopted planes (PlaneC, perpendicular to the hard palate and PlaneB, plane perpendicular to the nasal bone). The parameters above were compared among genders, age and race groups. SPSS 26 and GraphPad Prism 9 software were used for statistical analysis and mapping of data. Results: The AINV in our study was (214.87±52.94) mm², which was significantly less than that of PlaneC (254.97±47.80) mm² and PlaneB (226.07±57.36) mm². The measured parameters were as follows: θINV-B was (82.07±7.06)°; AINV-R was (112.66±31.39) mm²; AINV-L was (102.21±27.14) mm²; AINV was (214.87±52.94) mm²; HINV-R was (24.87±4.62) mm; HINV-L was (24.35±4.86) mm; αINV-R was (20.48±2.99)°; αINV-L was (19.65±3.82)°; αINV was (40.13±6.24)°. The AINV-R was larger than AINV-L (t=2.33, P<0.05); The HINV, AINV-R, AINV-L and AINV of males were more than those of females (t value was 5.77, 3.21, 2.91 and 3.52, respectively, all P<0.01). The AINV of the young group (<50 years) was larger than that of the old group (t=2.83, P<0.01); The θINV-B was different between the Han people and the Caucasian (t=2.92,P<0.01). The αINV of the Han people was larger than that of Caucasians (Z=-6.92, P<0.01), but the HINV was smaller (Z=-3.89, P<0.01). Conclusion: The AINV carried out in 3D models of nasal cavity space is significantly smaller than that obtained by the previous methods of CT evaluation. INV static parameters differ among genders, age and race groups.

11C-Methionine PET/CT and 18F-FDG PET/CT in the Evaluation of Adult Alveolar Rhabdomyosarcoma.

A 70-year-old man with a tumor in the nasal and paranasal space, was pathologically diagnosed with an alveolar rhabdomyosarcoma, with right cervical lymph node metastasis. Magnetic resonance imaging revealed a primary tumor in the nasal and paranasal sinuses, with associated intracranial infiltration. 11C-methionine positron emission tomography/computed tomography (PET/CT) revealed increased uptake in the primary tumor and right cervical lymph node metastasis. 18F-fluorodeoxyglucose PET/CT also revealed increased uptake in the primary tumor and right cervical lymph node. However, the physiological brain uptake overlapped with the primary tumor uptake. Our case suggests the usefulness of 11C-methionine PET/CT for accurately assessing the extent of alveolar rhabdomyosarcoma, especially in cases with intracranial infiltration or those approximating the brain.

Traumatic Posterior Chamber Intraocular Lens Dislocation into the Subconjunctival Space

Purpose: Here we report a case of posterior chamber intraocular lens (IOL) dislocation into the subconjunctival space (pesudophacocele) following ocular trauma.Case summary: A 66-year-old male presented with ocular pain and decreased vision in the right eye following trauma with a metallic rod. The patient had a history of trabeculectomy, glaucoma drainage device implantation, transscleral cyclophotocoagulation, and cataract surgery for uveitic glaucoma and a cataract in the right eye. On examination, vision was hand movement, the intraocular pressure was 3 mmHg, and subconjunctival hemorrhage and hyphema were observed. After the resolution of hemorrhage, uveal tissue prolapse was seen nasally behind the corneal limbus and the IOL was found to be dislocated into the nasal subconjunctival space. There were no changes in the filtering bleb and tube compared to the pre-trauma status. The IOL was removed through a conjunctival incision because the patient refused any active treatment.Conclusions: Pesudophacocele developed in a patient who had a history of glaucoma and cataract surgery in the injured eye. The IOL could not be assessed immediately after the trauma because of subconjunctival hemorrhage and hyphema. When the status of IOL is unclear or suspected to be dislocated after trauma, the possibility of pseudophacocele should be considered, in addition to the dislocation into the vitreous cavity.

Sino-nasal and pharyngeal mass- Immunohistochemistry cuts the gordian knot

Sinonasal and pharyngeal mass lesion of Extraskeletal Ewing sarcomas (EEWSs) are extremely rare. Herein we present a case of EEWSs of ethmoid sinus extending into nasal and pharyngeal spaces mimicking as angiofibroma clinically. Histopathological examination in conjunction with immunohistochemistry puzzled out the diagnostic dilemma.

Effects of jaw movement in bimaxillary orthognathic surgery on the upper airway: Computational fluid dynamics analysis.

Maxillomandibular repositioning in orthognathic surgeries has both morphologic and functional effects. These surgeries are thought to change the pharyngeal space and cause obstructive sleep apnoea syndrome, however. The primary purpose of this study is to evaluate the effects of jaw movement in bimaxillary orthognathic surgery on airway function and to identify the morphometric factors that can predict postoperative airway function. The subjects were 11 males and 12 females who had undergone orthognathic surgeries of the maxilla and mandible. The results of cephalometric analysis, cross-sectional area of the pharynx (CSA), pharyngeal volume and computational fluid dynamics (CFD) were compared. The CSA of the nasal (CSA1), total volume and total nasal volume decreased after surgery with statistical significance. Velocity at the oropharyngeal space (V2) increased after surgery with statistical significance. V2, CSA of the oropharyngeal space (CSA2) and PV were correlated with the horizontal posterior movement of point B, point Menton and overjet. V2 and CSA2 were correlated with SNB before and after surgery in all 46 analyses. Changes in pharyngeal airflow were more affected by pressure drop in the pharyngeal space (ΔPp) than by pressure drop in the nasal space (ΔPn). The relationship between the actual amount of change in the cephalometric reference point and the airway function is evident. CFD may thus be very useful as morphological analysis in preoperative treatment decision making.

Why the Wittenberg anatomist and scientist Konrad Victor Schneider (1614-1680) is also important for pneumologists

The Wittenberg physician Konrad Victor Schneider (1614-1680) was the first to prove that mucus is not formed in the brain, nor is it secreted into the nasal cavity via the ethmoid bone. He recognised that there is no open anatomical connection between the brain and the nasal air space. Schneider discovered the sinonasal mucosa as the production site of mucus and thus refuted the hypothesis of cerebral mucus production and secretion by Hippocrates, Galen and Vesal. The nasal mucosa was named "membrana Schneideria" in honour of Schneider.

Delivery of Dihydroergotamine Mesylate to the Upper Nasal Space for the Acute Treatment of Migraine: Technology in Action.

Oral tablets account for the majority of medications used to acutely treat migraine, but relief can be limited by their rates of dissolution and absorption. The nose is an attractive alternative route of drug delivery since it provides patient convenience of at-home use, gastrointestinal (GI) avoidance, and rapid absorption of drugs into systemic circulation because of its large surface area. However, the site of drug deposition within the nasal cavity should be considered since it can influence drug absorption. Traditional nasal devices have been shown to target drug delivery to the lower nasal space where epithelium is not best-suited for drug absorption and where there is an increased likelihood of drug clearance due to nasal drip, swallowing, or mucociliary clearance, potentially resulting in variable absorption and suboptimal efficacy. Alternatively, the upper nasal space (UNS) offers a permeable, richly vascularized epithelium with a decreased likelihood of drug loss or clearance due to the anatomy of this area. Traditional nasal pumps deposit <5% of active drug into the UNS because of the nasal cavity's complex architecture. A new technology, Precision Olfactory Delivery (POD®), is a handheld, manually actuated, propellant-powered, administration device that delivers drug specifically to the UNS. A dihydroergotamine (DHE) mesylate product, INP104, utilizes POD technology to deliver drug to the UNS for the acute treatment of migraine. Results from clinical studies of INP104 demonstrate a favorable pharmacokinetic profile, consistent and predictable dosing, rapid systemic levels known to be effective (similar to other DHE mesylate clinical programs), safety and tolerability on the upper nasal mucosa, and high patient acceptance. POD technology may have the potential to overcome the limitations of traditional nasal delivery systems, while utilizing the nasal delivery benefits of GI tract avoidance, rapid onset, patient convenience, and ease of use.

Evaluation of the effects of duloxetine treatment on anterior segment parameters by optical coherence tomography.

To evaluate the effects of Duloxetine on anterior segment parameters and intraocular pressure (IOP) in open angle eyes. 38 eyes of 38 patients with fibromyalgia who had open or wide open angles according to the Shaffer classification. Anterior segment optic coherence tomography was performed before and after (month 3) Duloxetine treatment. IOP, central corneal thickness (CCT), corneal endothelial cell density (CECD) and anterior chamber depth (ACD) were also recorded and evaluated. No statistically significant difference was determined in IOP, CCT and CECD (p > 0.05). However, a statistically significant decrease was determined in both the temporal and nasal anterior chamber angle, angle opening distance, nasal trabecular-iris space area and ACD values between the baseline and month 3 (p < 0.001). We think that the short term use of Duloxetine does not lead to clinically significant changes despite their statistically significant effects on the anterior chamber parameters.

The Pharmacokinetics of Drug Delivery to the Upper Nasal Space: A Review of INP105 Development

Nasal drug delivery presents a potential opportunity for achieving rapid, extensive drug absorption via a nonoral route by 1) avoiding degradation within the gastrointestinal tract and first-pass metabolism in the liver and 2) facilitating faster onset via rapid absorption into the bloodstream. However, the site of drug deposition within the nasal cavity may impact drug pharmacokinetics. Precision Olfactory Delivery (POD®) by Impel Pharmaceuticals Inc. is a new technology that provides handheld, manually actuated, propellant-powered drug delivery to the upper nasal space for rapid and efficient absorption. Rapid onset of effect can be a major advantage in many clinical applications where quick and effective administration is needed (eg, alleviating agitation in emergency settings or reducing debilitating migraine symptoms). Here, we review the pharmacokinetic profile of INP105, which is being developed to deliver olanzapine (OLZ) by POD to treat agitation in patients with autism. Because formulation can play a large role in the pharmacokinetic profile of a nasally administered drug, we provide a comprehensive review of both published and previously unpublished preclinical data outlining how the INP105 formulation was developed and optimized for study in humans. Multiple formulation carriers and excipients were tested to find a stable INP105 formulation with a desirable nasal absorption profile. Because the nasal architecture in nonhuman primates (NHPs) is similar to humans, the pharmacokinetics and tolerability of an INP105 combination product (NHP-INP105) using a clinical formulation combined with a device specifically designed for NHPs has been investigated in preclinical NHP studies, providing translational data for human studies and the pathway for testing novel products and formulations. The pharmacokinetics and tolerability of INP105 were then evaluated in an early clinical study in humans, demonstrating favorable pharmacokinetic and pharmacodynamic profiles. In this review, we aim to illustrate how delivery of therapeutics to the upper nasal space using POD, such as with agents like INP105, has the potential to optimize nasal delivery and unlock the potential of delivery-limited drugs to provide patients with rapid onset of effect, ease of use, and convenience.

Endoscopic Findings in Adults with Nasal Obstruction: A case series study

Background: The obstruction of the nasal is known as the most distinct disturbing complain of nasal disease and nasal sinus. The nasal obstruction could either be found unilateral (in one nasal cavity), bilateral (in both cavities), intermittent, progressive or persistent. The rhino-scopy (anterior and posterior) provides limited information when compared to nasal endoscopy. In certain cases, the structure which lies under the sight line and the posterior rhino-scopy is not possible. Furthermore, the early diagnosis of many unpleasant lesions will be very difficult unless using nasal endoscopy. Objectives: This study was designed to identify the real & precise causes of nasal obstruction in adults & properly evaluate the condition of nasal cavity ,post nasal space and nasal mucosa by direct vision through nasal endoscopy. and evaluate the value of naso endoscopy in diagnosis of the cause of nasal obstruction. Methods: This study was conducted to analyze noses related to 75 patients with nasal obstruction who underwent clinical and endoscopic nasal examination for the period from May 2014 to April 2015 in Mosul namely; Al-jumhoori Teaching hospital. Results: This case series study included 75 patients complaining from nasal obstruction The study include 43 male patients (57.3%), and 32 female patients (42.6%) with a M:F ratio of (1.3:1). The patients’ ages ranged between 15-70 years of age whose mean age was 42.5 years. endoscopic findings for adults patients with nasal obstruction in our study were: congested nasal mucosa 40 (53.3%) patients, septal deviation 26 (34.6%) patients, inferior turbinate hypertrophy 18 (24.0%) patients, pale swollen mucosa with watery nasal secretion 14 (18.6%) patients, bilateral nasal polyposis 10 (13.3%), post nasal drip 10 (13.3%), crustation 8 (10.6%), mucopurulent discharge from middle meatus & congested mucosa 7 patients (9.3%), adenoid hypertrophy 5 patients (6.6%), no abnormal findings 4 patients (5.3%), bluish tinged mucosa with watery nasal secretion 3 patients (4.0%). Conclusion: Nasal endoscopy includes evaluating the passages of the nasal cavity and the nasal sinus, and post nasal space using a magnified high-quality view and serves as an objective diagnostic tool in the evaluating of nasal mucosa, sinonasal anatomy, nasal cavity, and post nasal space pathology. In this study, nasal endoscopy is recommended in cases where patients complain of obstruction in the nasal specifically when anterior and posterior rhino-scopic examinations do not succeed in diagnosing causes of nasal obstruction