Advances in the field of intranasal oxytocin research: lessons learned and future directions for clinical research.

Reports on the modulatory role of the neuropeptide oxytocin on social cognition and behavior have steadily increased over the last two decades, stimulating considerable interest in its psychiatric application. Basic and clinical research in humans primarily employs intranasal application protocols. This approach assumes that intranasal administration increases oxytocin levels in the central nervous system via a direct nose-to-brain route, which in turn acts upon centrally-located oxytocin receptors to exert its behavioral effects. However, debates have emerged on whether intranasally administered oxytocin enters the brain via the nose-to-brain route and whether this route leads to functionally relevant increases in central oxytocin levels. In this review we outline recent advances from human and animal research that provide converging evidence for functionally relevant effects of the intranasal oxytocin administration route, suggesting that direct nose-to-brain delivery underlies the behavioral effects of oxytocin on social cognition and behavior. Moreover, advances in previously debated methodological issues, such as pre-registration, reproducibility, statistical power, interpretation of non-significant results, dosage, and sex differences are discussed and integrated with suggestions for the next steps in translating intranasal oxytocin into psychiatric applications.

Advancement of the Infant Air-Jet Dry Powder Inhaler (DPI): Evaluation of Different Positive-Pressure Air Sources and Flow Rates.

PURPOSE: In order to improve the delivery of dry powder aerosol formulations to the lungs of infants, this study implemented an infant air-jet platform and explored the effects of different air sources, flow rates, and pulmonary mechanics on aerosolization performance and aerosol delivery through a preterm nose-throat (NT) in vitro model. METHODS: The infant air-jet platform was actuated with a positive-pressure air source that delivered the aerosol and provided a full inhalation breath. Three different air sources were developed to provide highly controllable positive-pressure air actuations (using actuation volumes of ~10 mL for the preterm model). While providing different flow waveform shapes, the three air sources were calibrated to produce the same flow rate magnitude (Q90: 90th percentile of flow rate). Multiple air-jet DPI designs were coupled with the air sources and evaluated with a model spray-dried excipient enhanced growth formulation. RESULTS: Compared to other designs, the D1-Single air-jet DPI provided improved performance with low variability across all three air sources. With the tested D1-Single air-jet and Timer air source, reducing the flow rate from 4 to 1.7 L/min marginally decreased the aerosol size and significantly increased the lung delivery efficiency above 50% of the loaded dose. These results were not impacted by the presence of downstream pulmonary mechanics (resistance and compliance model). CONCLUSIONS: The selected design was capable of providing an estimated >50% lung delivery efficiency of a model spray-dried formulation and was not influenced by the air source, thereby enabling greater flexibility for platform deployment in different environments.

Formaldehyde-induced hematopoietic stem and progenitor cell toxicity in mouse lung and nose.

Formaldehyde (FA), an economically important and ubiquitous chemical, has been classified as a human carcinogen and myeloid leukemogen. However, the underlying mechanisms of leukemogenesis remain unclear. Unlike many classical leukemogens that damage hematopoietic stem/progenitor cells (HSC/HPC) directly in the bone marrow, FA-as the smallest, most reactive aldehyde-is thought to be incapable of reaching the bone marrow through inhalation exposure. A recent breakthrough study discovered that mouse lung contains functional HSC/HPC that can produce blood cells and travel bi-directionally between the lung and bone marrow, while another early study reported the presence of HSC/HPC in rat nose. Based on these findings, we hypothesized that FA inhalation could induce toxicity in HSC/HPC present in mouse lung and/or nose rather than in the bone marrow. To test this hypothesis, we adapted a commercially available protocol for culturing burst-forming unit-erythroid (BFU-E) and colony-forming unit-granulocyte, macrophage (CFU-GM) colonies from bone marrow and spleen to also enable culture of these colonies from mouse lung and nose, a novel application of this assay. We reported that in vivo exposure to FA at 3 mg/m3 or ex vivo exposure up to 400 µM FA decreased the formation of both colony types from mouse lung and nose as well as from bone marrow and spleen. These findings, to the best of our knowledge, are the first empirically to show that FA exposure can damage mouse pulmonary and olfactory HSC/HPC and provide potential biological plausibility for the induction of leukemia at the sites of entry rather than the bone marrow.

Can a Pretreatment Visual Analog Scale Predict Treatment Outcome in Allergic Rhinitis?

BACKGROUND: The visual analogue scale (VAS) is a simple and useful tool to assess the severity of allergic rhinitis. Whether a pretreatment VAS score can guide appropriate medication is unclear. OBJECTIVE: The aim of this study was to evaluate whether a pretreatment VAS score could be used to predict therapeutic response. METHODS: A prospective 4-week cohort study involving 101 allergic rhinitis patients was carried out. All patients were treated with triamcinolone acetonide aqueous nasal spray 220 µg once daily for 28 days. The treatment outcomes were evaluated using VAS scores (0-10 cm), total nasal symptoms scores (TNSSs), nasal mucociliary clearance times (NMCCTs), and global symptom controls (GSCs). The minimal clinically important differences (MCIDs) method was used to separate the patients into with and without improvement groups. Receiver operating characteristic curve analysis was performed to evaluate the predictive value of pretreatment VAS scores in relation to MCIDs after treatment. RESULTS: Pretreatment VAS scores showed a positive correlation with pretreatment TNSSs and NMCCTs (ρ = 0.66, p < 0.001 and r = 0.44, p < 0.001, respectively), and a negative correlation with GSCs after treatment (r = -0.53, p < 0.001). The MCID values of TNSSs and NMCCTs were 3.19 and 2.78, respectively. The cutoff value of pretreatment VAS ranged between 6.5 and 7.7 points, with an average value of 7.1. CONCLUSION: A pretreatment VAS score of 7 or higher was associated with an unfavorable treatment outcome, which suggests the potential therapeutic predictive value of VAS scoring.

ORKAMBI-Mediated Rescue of Mucociliary Clearance in Cystic Fibrosis Primary Respiratory Cultures Is Enhanced by Arginine Uptake, Arginase Inhibition, and Promotion of Nitric Oxide Signaling to the Cystic Fibrosis Transmembrane Conductance Regulator Channel.

ORKAMBI, a combination of the corrector, lumacaftor, and the potentiator, ivacaftor, partially rescues the defective processing and anion channel activity conferred by the major cystic fibrosis-causing mutation, F508del, in in vitro studies. Clinically, the improvement in lung function after ORKAMBI treatment is modest and variable, prompting the search for complementary interventions. As our previous work identified a positive effect of arginine-dependent nitric oxide signaling on residual F508del-Cftr function in murine intestinal epithelium, we were prompted to determine whether strategies aimed at increasing arginine would enhance F508del-cystic fibrosis transmembrane conductance regulator (CFTR) channel activity in patient-derived airway epithelia. Now, we show that the addition of arginine together with inhibition of intracellular arginase activity increased cytosolic nitric oxide and enhanced the rescue effect of ORKAMBI on F508del-CFTR-mediated chloride conductance at the cell surface of patient-derived bronchial and nasal epithelial cultures. Interestingly, arginine addition plus arginase inhibition also enhanced ORKAMBI-mediated increases in ciliary beat frequency and mucociliary movement, two in vitro CF phenotypes that are downstream of the channel defect. This work suggests that strategies to manipulate the arginine-nitric oxide pathway in combination with CFTR modulators may lead to improved clinical outcomes. SIGNIFICANCE STATEMENT: These proof-of-concept studies highlight the potential to boost the response to cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators, lumacaftor and ivacaftor, in patient-derived airway tissues expressing the major CF-causing mutant, F508del-CFTR, by enhancing other regulatory pathways. In this case, we observed enhancement of pharmacologically rescued F508del-CFTR by arginine-dependent, nitric oxide signaling through inhibition of endogenous arginase activity.

Use of Nasal Pathology in the Derivation of Inhalation Toxicity Values for Hydrogen Sulfide.

Nasal pathology can play an important role in the risk assessment process. For example, olfactory neuron loss (ONL) is one of the most sensitive end points seen in subchronic rodent hydrogen sulfide (H2S) studies and has been used by several agencies to derive health-protective toxicity values. Alternative methods that rely on computational fluid dynamics (CFD) models to account for the influence of airflow on H2S-induced ONL have been proposed. The use of CFD models result in toxicity values that are less conservative than those obtained using more traditional methods. These alternative approaches rely on anatomy-based CFD models. Model predictions of H2S delivery (flux) to the olfactory mucosal wall are highly correlated with ONL in rodents. Three major areas of focus for this review include a brief description of nasal anatomy, H2S-induced ONL in rodents, derivation of a chronic inhalation reference concentration for H2S, and the use of CFD models to derive alternative toxicity values for this gas.

Evaluating Effectiveness of Nasal Compression With Tranexamic Acid Compared With Simple Nasal Compression and Merocel Packing: A Randomized Controlled Trial.

STUDY OBJECTIVE: The primary objective of this study is to compare the effectiveness of 3 treatment protocols to stop anterior epistaxis: classic compression, nasal packing, and local application of tranexamic acid. It also aims to determine the frequency of rebleeding after each of these protocols. METHODS: This single-center, prospective, randomized controlled study was conducted with patients who had spontaneous anterior epistaxis. The study compared the effect of 3 treatment options, tranexamic acid with compression but without nasal packing, nasal packing (Merocel), and simple nasal external compression, on the primary outcome of stopping anterior epistaxis bleeding within 15 minutes. RESULTS: Among the 135 patients enrolled, the median age was 60 years (interquartile range 25% to 75%: 48 to 72 years) and 70 patients (51.9%) were women. The success rate in the compression with tranexamic acid group was 91.1% (41 of 45 patients); in the nasal packing group, 93.3% (42 of 45 patients); and in the compression with saline solution group, 71.1% (32 of 45 patients). There was an overall statistically significant difference among the 3 treatment groups but no significant difference in pairwise comparison between the compression with tranexamic acid and nasal packing groups. In regard to no rebleeding within 24 hours, the study found rates of 86.7% in the tranexamic acid group, 74% in the nasal packing group, and 60% in the compression with saline solution group. CONCLUSION: Applying external compression after administering tranexamic acid through the nostrils by atomizer stops bleeding as effectively as anterior nasal packing using Merocel. In addition, the tranexamic acid approach is superior to Merocel in terms of decreasing rebleeding rates.

Reversal of Post-filler Vision Loss and Skin Ischaemia with High-Dose Pulsed Hyaluronidase Injections.

Nose filler injections are very popular in many Asian countries to improve nose shape and projection. However, due to the vascular supply of nose from the ophthalmic artery and its communication with branches of the facial artery in this region, there could be a possibility of ophthalmic complications in case of an accidental intra-arterial injection of filler material. This may cause devastating complications of partial or complete vision loss with or without associated cutaneous ischaemic changes. We present a case report of a patient who developed features of vascular involvement after two ml of HA filler injection in the nasal dorsum, tip and columella. The patient initially developed tell-tale signs of impending skin necrosis in the nasal and forehead skin followed by ptosis, severe pain and progressive vision loss in the right eye until a point where the patient could only perceive light. The patient was managed with multiple doses of hyaluronidase in the involved skin and two doses of retrobulbar injection for vision loss. Significant recovery in the skin and ophthalmic components occurred within 20 days of filler injection. This case demonstrates that recovery of the ischaemic ophthalmic and cutaneous changes secondary to probable intra-arterial injection could be accomplished using combined retrobulbar and periorbital intracutaneous injections of high-dose pulsed hyaluronidase. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Microbial shifts in the swine nasal microbiota in response to parenteral antimicrobial administration.

The continuous administration of antimicrobials in swine production has been widely criticized with the increase of antimicrobial-resistant bacteria and dysbiosis of the beneficial microbial communities. While an increasing number of studies investigate the effects of antimicrobial administration on swine gastrointestinal microbiota biodiversity, the impact of their use on the composition and diversity of nasal microbial communities has not been widely explored. The objective of this study was to characterize the short-term impact of different parenteral antibiotics administration on the composition and diversity of nasal microbial communities in growing pigs. Five antimicrobial treatment groups, each consisting of four, eight-week old piglets, were administered one of the antimicrobials; Ceftiofur Crystalline free acid (CCFA), Ceftiofur hydrochloride (CHC), Tulathromycin (TUL), Oxytetracycline (OTC), and Procaine Penicillin G (PPG) at label dose and route. Individual deep nasal swabs were collected immediately before antimicrobial administration (control = day 0), and again on days 1, 3, 7, and 14 after dosing. The nasal microbiota across all the samples were dominated by Firmicutes, proteobacteria and Bacteroidetes. While, the predominant bacterial genera were Moraxella, Clostridium and Streptococcus. Linear discriminant analysis, showed a pronounced, antimicrobial-dependent microbial shift in the composition of nasal microbiota and over time from day 0. By day 14, the nasal microbial compositions of the groups receiving CCFA and OTC had returned to a distribution that closely resembled that observed on day 0. In contrast, pigs that received CHC, TUL and PPG appeared to deviate away from the day 0 composition by day 14. Based on our results, it appears that the impact of parenteral antibiotics on the swine nasal microbiota is variable and has a considerable impact in modulating the nasal microbiota structure. Our results will aid in developing alternative strategies for antibiotics to improve swine health and consequently production.

Control of canine idiopathic nasal hyperkeratosis with a natural skin restorative balm: a randomized double-blind placebo-controlled study.

BACKGROUND: Nasal hyperkeratosis may cause discomfort in dogs by predisposing them to fissures and secondary bacterial infection. Approaches to treatment have been described anecdotally; the effectiveness of such therapies remains unproven. HYPOTHESIS/OBJECTIVES: To investigate the efficacy of a balm containing essential oils and essential fatty acids in dogs with idiopathic nasal hyperkeratosis. ANIMALS: Client-owned dogs with noncomplicated nasal hyperkeratosis. METHODS: The study was conducted as a randomized, double-blind, placebo-controlled clinical trial with parallel group design and two month follow-up period. Dogs received daily topical application of a commercial balm product (group DBB) or placebo (aqueous gelling agent with preservatives, group PB). The main outcome variables were lichenification, dryness, suppleness and extent of lesions. Subjective owner satisfaction index score was a secondary variable. Evaluation was performed on days (D)0, 30 and 60. Response to treatment was assessed as the change from baseline to each examination day for each criterion. RESULTS: Forty eight dogs, principally French (26 of 48) and English (seven of 48) bulldogs, were included and 39 completed the study. No major adverse events were reported. On D60, changes from baseline for lichenification, lesion extent, suppleness and total score were -31.2%, -18.3%, -72.8% and -36.8% in group DBB (23 dogs) and -11.9%, 2.3%, -42.1% and -14% in group PB (16 dogs), respectively. The total score was significantly improved on D60 in group DBB compared to PB (Wilcoxon-Mann-Whitney U-test, P = 0.0016). CONCLUSIONS AND CLINICAL IMPORTANCE: The balm proved safe and helpful in managing canine idiopathic noncomplicated nasal hyperkeratosis.

Decolonization in Prevention of Health Care-Associated Infections.

Colonization with health care-associated pathogens such as Staphylococcus aureus, enterococci, Gram-negative organisms, and Clostridium difficile is associated with increased risk of infection. Decolonization is an evidence-based intervention that can be used to prevent health care-associated infections (HAIs). This review evaluates agents used for nasal topical decolonization, topical (e.g., skin) decolonization, oral decolonization, and selective digestive or oropharyngeal decontamination. Although the majority of studies performed to date have focused on S. aureus decolonization, there is increasing interest in how to apply decolonization strategies to reduce infections due to Gram-negative organisms, especially those that are multidrug resistant. Nasal topical decolonization agents reviewed include mupirocin, bacitracin, retapamulin, povidone-iodine, alcohol-based nasal antiseptic, tea tree oil, photodynamic therapy, omiganan pentahydrochloride, and lysostaphin. Mupirocin is still the gold standard agent for S. aureus nasal decolonization, but there is concern about mupirocin resistance, and alternative agents are needed. Of the other nasal decolonization agents, large clinical trials are still needed to evaluate the effectiveness of retapamulin, povidone-iodine, alcohol-based nasal antiseptic, tea tree oil, omiganan pentahydrochloride, and lysostaphin. Given inferior outcomes and increased risk of allergic dermatitis, the use of bacitracin-containing compounds cannot be recommended as a decolonization strategy. Topical decolonization agents reviewed included chlorhexidine gluconate (CHG), hexachlorophane, povidone-iodine, triclosan, and sodium hypochlorite. Of these, CHG is the skin decolonization agent that has the strongest evidence base, and sodium hypochlorite can also be recommended. CHG is associated with prevention of infections due to Gram-positive and Gram-negative organisms as well as Candida. Conversely, triclosan use is discouraged, and topical decolonization with hexachlorophane and povidone-iodine cannot be recommended at this time. There is also evidence to support use of selective digestive decontamination and selective oropharyngeal decontamination, but additional studies are needed to assess resistance to these agents, especially selection for resistance among Gram-negative organisms. The strongest evidence for decolonization is for use among surgical patients as a strategy to prevent surgical site infections.

A single dose of epidermicin NI01 is sufficient to eradicate MRSA from the nares of cotton rats.

Objectives: To investigate the efficacy of a potent novel antimicrobial protein of mass 6 kDa, epidermicin NI01, for eradicating the nasal burden of MRSA in a cotton rat ( Sigmodon hispidus ) model. Methods: MRSA strain ATCC 43300 was used to establish a robust colonization of cotton rat nares. This model was used to evaluate the efficacy of topical 0.04% and 0.2% epidermicin NI01, administered twice daily for 3 days consecutively, and topical 0.8% epidermicin NI01 administered once, for reducing nasal MRSA burden. Control groups remained untreated or were administered vehicle only (0.5% hydroxypropylmethylcellulose) or 2% mupirocin twice daily for 3 days. The experiment was terminated at day 5 and MRSA quantitative counts were determined. Tissues recovered from animals treated with 0.2% epidermicin twice daily for 3 days were examined for histological changes. Results: Mupirocin treatment resulted in a reduction in burden of log 10 (log R) of 2.59 cfu/nares compared with vehicle ( P < 0.0001). Epidermicin NI01 administered once at 0.8% showed excellent efficacy, resulting in a log R of 2.10 cfu/nares ( P = 0.0004), which was equivalent to mupirocin. Epidermicin NI01 administered at 0.2% or 0.04% twice daily for 3 days did not have a significant impact on the tissue burden recovered from the nares. Mild to marked histological abnormalities were noted, but these were determined to be reversible. Conclusion: A single dose of topical epidermicin NI01 was as effective as mupirocin administered twice daily for 3 days in eradication of MRSA from the nares of cotton rats. This justifies further development of epidermicin for this indication.

Numerical Comparison of Nasal Aerosol Administration Systems for Efficient Nose-to-Brain Drug Delivery.

PURPOSE: Nose-to-brain drug administration along the olfactory and trigeminal nerve pathways offers an alternative route for the treatment of central nervous system (CNS) disorders. The characterization of particle deposition remains difficult to achieve in experiments. Alternative numerical approach is applied to identify suitable aerosol particle size with maximized inhaled doses. METHODS: This study numerically compared the drug delivery efficiency in a realistic human nasal cavity between two aerosol drug administration systems targeting the olfactory region: the aerosol mask system and the breath-powered bi-directional system. Steady inhalation and exhalation flow rates were applied to both delivery systems. The discrete phase particle tracking method was employed to capture the aerosol drug transport and deposition behaviours in the nasal cavity. Both overall and regional deposition characteristics were analysed in detail. RESULTS: The results demonstrated the breath-powered drug delivery approach can produce superior olfactory deposition with peaking olfactory deposition fractions for diffusive 1 nm particles and inertial 10 µm. While for particles in the range of 10 nm to 2 µm, no significant olfactory deposition can be found, indicating the therapeutic agents should avoid this size range when targeting the olfactory deposition. CONCLUSIONS: The breath-powered bi-directional aerosol delivery approach shows better drug delivery performance globally and locally, and improved drug administration doses can be achieved in targeted olfactory region.

Comparative pulmonary toxicity of inhaled metalworking fluids in rats and mice.

Metalworking fluids (MWFs) are complex formulations designed for effective lubricating, cooling, and cleaning tools and parts during machining operations. Adverse health effects such as respiratory symptoms, dermatitis, and cancer have been reported in workers exposed to MWFs. Several constituents of MWFs have been implicated in toxicity and have been removed from the formulations over the years. However, animal studies with newer MWFs demonstrate that they continue to pose a health risk. This investigation examines the hypothesis that unrecognized health hazards exist in currently marketed MWF formulations that are presumed to be safe based on hazard assessments of individual ingredients. In vivo 13-week inhalation studies were designed to characterize and compare the potential toxicity of four MWFs: Trim VX, Cimstar 3800, Trim SC210, and Syntilo 1023. Male and female Wistar Han rats or Fischer 344N/Tac rats and B6C3F1/N mice were exposed to MWFs via whole-body inhalation at concentrations of 0, 25, 50, 100, 200, or 400 mg/m3 for 13 weeks, after which, survival, body and organ weights, hematology and clinical chemistry, histopathology, and genotoxicity were assessed following exposure. Although high concentrations were used, survival was not affected and toxicity was primarily within the respiratory tract of male and female rats and mice. Minor variances in toxicity were attributed to differences among species as well as in the chemical components of each MWF. Pulmonary fibrosis was present only in rats and mice exposed to Trim VX. These data confirm that newer MWFs have the potential to cause respiratory toxicity in workers who are repeatedly exposed via inhalation.

Toxicological assessment of a prototype e-cigaret device and three flavor formulations: a 90-day inhalation study in rats.

A prototype electronic cigaret device and three formulations were evaluated in a 90-day rat inhalation study followed by a 42-day recovery period. Animals were randomly assigned to groups for exposure to low-, mid- and high-dose levels of aerosols composed of vehicle (glycerin and propylene glycol mixture); vehicle and 2.0% nicotine; or vehicle, 2.0% nicotine and flavor mixture. Daily targeted aerosol total particulate matter (TPM) doses of 3.2, 9.6 and 32.0 mg/kg/day were achieved by exposure to 1 mg/L aerosol for 16, 48 and 160 min, respectively. Pre-study evaluations included indirect ophthalmoscopy, virology and bacteriological screening. Body weights, clinical observations and food consumption were monitored weekly. Plasma nicotine and cotinine and carboxyhemoglobin levels were measured at days 28 and 90. After days 28, 56 and 90, lung function measurements were obtained. Biological endpoints after 90-day exposure and 42-day recovery period included clinical pathology, urinalysis, bronchoalveolar fluid (BALF) analysis, necropsy and histopathology. Treatment-related effects following 90 days of exposure included changes in body weight, food consumption and respiratory rate. Dose-related decreases in thymus and spleen weights, and increased BALF lactate dehydrogenase, total protein, alveolar macrophages, neutrophils and lung weights were observed. Histopathology evaluations revealed sporadic increases in nasal section 1-4 epithelial hyperplasia and vacuolization. Following the recovery period, effects in the nose and BALF were persistent while other effects were resolved. The no observed effect level based upon body weight decreases is considered to be the mid-dose level for each formulation, equivalent to a daily TPM exposure dose of approximately 9.6 mg/kg/day.

Carcinogenicity and chronic toxicity of hydrazine monohydrate in rats and mice by two-year drinking water treatment.

The carcinogenicity and chronic toxicity of hydrazine monohydrate was examined by administrating hydrazine monohydrate in drinking water to groups of 50 F344/DuCrj rats and 50 Crj:BDF1 mice of both sexes for two years. The drinking water concentration of hydrazine monohydrate was 0, 20, 40 or 80 ppm (wt/wt) for male and female rats and male mice; and 0, 40, 80 or 160 ppm for female mice. Survival rates of each group of males and females rats and mice were similar to the respective controls, except female rats administered 80 ppm. Two-year administration of hydrazine monohydrate produced an increase in the incidences of hepatocellular adenomas and carcinomas in rats of both sexes along with hepatic foci. In mice, the incidences of hepatocellular adenomas and carcinomas were increased in females, and significantly increased incidences of hepatocellular adenomas in females administered 160 ppm were observed. Thus, hydrazine monohydrate is carcinogenic in two species, rats and mice. Additionally, non-neoplastic renal lesions in rats and mice and non-neoplastic nasal lesions in mice were observed.

Swelling of Erectile Nasal Tissue Induced by Human Sexual Pheromone.

Most chemically mediated sexual communication in humans remains uncharacterized. Yet the study of sexual communication is decisive for understanding sexual behavior and evolutive mechanisms in our species. Here we provide the evidence to consider 4,16-androstadien-3-one (AND) as a man's sexual pheromone. Our experiment provides support for the physiological effect of AND on nasal airway resistance (Rna) in women, as assessed by anterior rhinomanometry. We found that AND administration increased the area of turbinate during the ovulatory phase, resulting in an increase of Rna. Thus, we discovered that minute amounts of AND, acting through neuroendocrine brain control, regulate Rna and consequently affect the sexual physiology and behavior. Fascinatingly, this finding provides the evidence of the preservation of chemosexual communication in humans, which it has been largely neglected due to its unconscious perception and concealed nature. Therefore, chemical communication is a plesiomorphic evolutive phenomenon in humans.

Assessing the safety and efficacy of drugs used in preparing the nose for diagnostic and therapeutic procedures: a systematic review.

BACKGROUND: Local anaesthetics and vasoconstrictors are essential for pain control and to aid intra-operative haemostasis in nasal procedures. They also improve access, and reduce discomfort when performing nasal endoscopy. There are no clear guidelines on preparing the nose despite evermore diagnostic and therapeutic procedures utilising the nose as a point of access. OBJECTIVE OF REVIEW: This review aims to identify nasal preparations used in diagnostic and therapeutic nasal procedures and to examine their safety and efficacy. TYPE OF REVIEW: Systematic review. SEARCH STRATEGY: A search was carried out using PubMed, MEDLINE, Ovid EMBASE, the Cochrane library and references from the included articles. EVALUATION METHOD: The inclusion criteria included: full-text English language articles with regard to nasal preparation for surgery. Case reports, systematic reviews, meta-analysis, double-blind placebo controlled randomised trials (RCTs) and case series were included. RESULTS: A total of 53 articles were retrieved: 13 articles on nasal preparation for operative procedures, six on functional endoscopic sinus surgery and 22 on nasendoscopy as well as six case reports. Cocaine was the most widely used topical preparation for operative procedures but was associated with more side-effects; thus, topical tetracaine and levobupivacaine infiltration are alternatives with equivalent efficacy but reduced adverse effects. All articles reviewed for functional endoscopic sinus surgery used a mixture containing lidocaine, adrenaline or both. Flexible nasendoscopy causes minimal patient discomfort and preparation is only recommended in selected patients, in contrast to rigid nasendoscopy which requires preparation. CONCLUSION: For operative procedures, such as septorhinoplasty, a single agent tetracaine or levobupivicaine provides an improved surgical field. In functional endoscopic sinus surgery, lidocaine-adrenaline preparations have resulted in significantly better surgical and patient outcomes. There is little evidence to support the routine use of pre-procedural nasal preparation for flexible nasendoscopy. Those undergoing rigid endoscopy conversely always require the use of a vasoconstrictor and local anaesthetic. Pre-procedure assessment of patients is recommended, with agents being reserved for those with low pain thresholds, high anxiety and small nasal apertures presenting resistance to the insertion of the endoscope.