Expression of the HIF-1α/VEGF pathway is upregulated to protect alveolar bone density reduction in nasal-obstructed rats.

BACKGROUND: Hypoxia and mouth breathing are closely related to maxillofacial bone metabolism and are characteristic of obstructive sleep apnea-hypopnea syndrome (OSAHS). Being key factors in the hypoxia response, hypoxia-inducible factor 1α (HIF-1α) and HIF-responsive gene vascular endothelial growth factor (VEGF) are essential for bone remodeling. This study focuses on the role of the HIF-1α/VEGF pathway in alveolar bone metabolism during OSAHS. MATERIALS AND METHODS: 36 three-week-old male Wistar rats were divided into three groups: twelve control rats, twelve bilateral nasal obstructed (BNO) rats, twelve BNO rats treated with intraperitoneal injection of Dimethyloxalylglycine (DMOG). After two weeks, the microstructure and bone mineral density (BMD) of alveolar bone were evaluated using micro-computed tomography (micro-CT). The expressions of HIF-1α and VEGF in the alveolar bone were then assessed via immunohistochemistry staining, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Alkaline phosphatase (ALP) staining and Alizarin red S staining were performed to evaluate osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs). RESULTS: Significant reductions in alveolar bone density were noted in BNO rats. Bilateral nasal obstruction increased the expressions of HIF-1α and VEGF in alveolar bone. With upregulation of HIF-1α/VEGF via DMOG, alveolar bone density of BNO rats increased. Furthermore, DMOG promoted the osteogenic differentiation of BMSCs by stabilizing the HIF-1α protein and increasing the expression of VEGF. CONCLUSION: Bilateral nasal obstruction changes alveolar bone structure and leads to a reduction in alveolar bone density. Moreover, the expression of the HIF-1α/VEGF signaling pathway increases to protect alveolar bone density reduction in BNO rats.

15-Hydroxyeicosatrienoic acid induces nasal congestion by changing vascular functions in mice.

BACKGROUND: Nasal congestion in allergic rhinitis (AR) is caused by vascular hyperpermeability and vascular relaxation of the nasal mucosa. We previously detected high levels of a lipoxygenation metabolite of dihomogammalinolenic acid, 15-hydroxy-8Z,11Z,13E-eicosatrienoic acid (15-HETrE) in the nasal lavage fluid of AR model mice. Here, we investigated the effects of 15-HETrE on vascular functions associated with nasal congestion. METHODS: We measured 15-HETrE levels in the nasal lavage fluid of ovalbumin-induced AR model mice and nasal discharge of patients with AR. We also assessed nasal congestion and vascular relaxation in mice. Vascular contractility was investigated using isolated mouse aortas. RESULTS: Five ovalbumin challenges increased 15-HETrE levels in AR model mice. 15-HETrE was also detected in patients who exhibiting AR-related symptoms. Intranasal administration of 15-HETrE elicited dyspnea-related behavior and decreased the nasal cavity volume in mice. Miles assay and whole-mount immunostaining revealed that 15-HETrE administration caused vascular hyperpermeability and relaxation of the nasal mucosa. Intravital imaging demonstrated that 15-HETrE relaxed the ear vessels that were precontracted via thromboxane receptor stimulation. Moreover, 15-HETrE dilated the isolated mouse aortas, and this effect was attenuated by K+ channel inhibitors and prostaglandin D2 (DP) and prostacyclin (IP) receptor antagonists. Additionally, vasodilatory effects of 15-HETrE were accompanied by an increase in intracellular cAMP levels. CONCLUSIONS: Our results indicate that 15-HETrE, whose levels are elevated in the nasal cavity upon AR, can be a novel lipid mediator that exacerbates nasal congestion. Moreover, it can stimulate DP and IP receptors and downstream K+ channels to dilate the nasal mucosal vasculature.

Nasal obstruction during the growth period modulates the Wnt/ß-catenin pathway and brain-derived neurotrophic factor production in association with tyrosine kinase receptor B mRNA reduction in mouse hippocampus.

There is accumulating evidence that nasal obstruction induces high-level brain dysfunction, including memory and learning deficits. We previously demonstrated that unilateral nasal obstruction (UNO) during the growth period increases the expression of brain-derived neurotrophic factor (BDNF). The expression of BDNF is regulated by the Wnt/ß-Catenin pathway, which is linked to neuronal differentiation, proliferation, and maintenance. However, little is known about whether Wnt3a protein expression could be an index for modulations analyses in the Wnt/ß-Catenin pathway caused by UNO during the growth period. This study aimed to investigate the effects of UNO during the growth period on the Wnt/ß-Catenin pathway in the hippocampus using combined behavioural, biochemical, and histological approaches. Male BALB/C mice were randomly divided into the control (CONT; n = 6) and experimental (UNO; n = 6) groups. Blood oxygen saturation (SpO2 ) levels were measured, and a passive avoidance test was performed in mice aged 15 weeks. Brain tissues were subjected to immunohistochemistry, real-time reverse transcription-polymerase chain reaction, and western blot analysis. Compared with control mice, UNO mice had lower SpO2 levels and exhibited memory/learning impairments during behavioural testing. Moreover, Wnt3a protein, BDNF mRNA, and tyrosine kinase receptor B (TrkB) mRNA expression levels were significantly lower in the hippocampus in the UNO group than in the CONT group. Our findings suggested that UNO during the growth period appeared to modulate the hippocampal Wnt/ß-catenin pathway and BDNF production in association with TrkB mRNA reduction, thereby resulting in memory and learning impairments.

Nasal obstruction during adolescence induces memory/learning impairments associated with BDNF/TrkB signaling pathway hypofunction and high corticosterone levels.

The hippocampus is an important brain region involved in memory and learning. Brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), and phospho-p44/p42 mitogen-activated protein kinase (MAPK) are known to contribute to hippocampal memory/learning. The present study aimed to clarify the effects of nasal obstruction during the growth period on memory/learning in an animal model, using combined behavioral, biochemical, and histological approaches. Male BALB/C mice underwent unilateral nasal obstruction (UNO) by cauterization at 8 days of age and were subjected to Y-maze and passive avoidance tests at 15 weeks of age. The serum corticosterone levels were measured using an enzyme-linked immunosorbent assay, and brain tissues were subjected to hematoxylin-eosin staining and histological analysis or homogenization and Western blot analysis. Compared with control mice, UNO mice had lower blood oxygen saturation levels and exhibited apparent memory/learning impairments during behavioral testing. Additionally, the UNO group had higher hippocampal BDNF levels and serum corticosterone levels, lower hippocampal TrkB and phospho-p44/p42 MAPK levels, and reduced neuron numbers relative to controls. Our findings suggest that UNO during adolescence affects the hippocampus and causes memory/learning impairments.

Expression and localization of GPR99 in human nasal mucosa.

OBJECTIVE: The cysteinyl leukotrienes (CysLTs) are lipid mediators that have been implicated in the pathogenesis of allergic rhinitis. Pharmacological studies of CysLTs indicate that two classes of receptors, CysLT1R and CysLT2R exist. CysLT1R is a high affinity LTD4 receptor with lower affinity for LTC4, and a CysLT1R antagonist is currently used to treat asthma and allergic rhinitis. CysLT2R binds to LTC4 and LTD4 with equal affinity. GPR99 (also called GPR80), previously described as an oxoglutarate receptor (OXGR1), has recently emerged as a potential novel receptor with LTE4. The purpose of this study was to determine the expression and localization of GPR99 protein in the human nasal mucosa. METHODS: Human turbinates were obtained after turbinectomy from 12 patients with nasal obstruction refractory to medical therapy. GPR99 protein expression was evaluated by western blotting, and the specific cells expressing GPR99 protein identified by immunostaining using a commercial anti-GPR99 (OXGR1) monoclonal antibody. RESULTS: A 38-kDa band was detected in the western blots of human nasal samples by using the anti-GPR99 monoclonal antibody. We did not find any differences in GPR99 protein levels between allergic and non-allergic nasal mucosa. The immunohistochemical studies revealed that the anti-GPR99 monoclonal antibody mainly labeled vascular smooth muscle cells in the nasal mucosa. CONCLUSION: These immunohistochemical results suggest that GPR99 may play some roles in the vascular response. Further functional studies will be necessary to clarify the biological significance of the GPR99 receptor in nasal vasculature.

Nasal closure for the treatment of epistaxis secondary to hereditary hemorrhagic telangiectasia / Cierre nasal para el tratamiento de la epistaxis secundaria a Telangiectasia Hemorrágica Hereditaria

Hereditary hemorrhagic telangiectasia (HHT), also known by the eponym Osler-Weber-Rendu syndrome, is an autosomal dominant disorder characterised by the presence of multiple arteriovenous malformations (AVMs) affecting multiple organs. Many procedures have been used for epistaxis control in patients with this disorder. The objective of this study was to report the treatment of severe HHT-related epistaxis with the modified Young’s procedure. Materials and methods: We describe the treatment of 4 patients with severe blood-transfusion dependent epistaxis who underwent a modified Young’s procedure in a tertiary hospital. The nasal closure was bilateral and complete in all cases. All patients were followed for 12 months or longer. Results: The procedure was well tolerated and complete cessation of bleeding was achieved in all the patients. Conclusion: Young’s technique is a safe surgical procedure, well tolerated by patients with severe epistaxis and HHT (AU)

La telangiectasia hemorrágica hereditaria (HHT), también conocida por el epónimo síndrome de Osler-Weber-Rendu es un trastorno autosómico dominante caracterizado por la presencia de malformaciones arteriovenosas (MAV) que afectan a múltiplos órganos y sistemas. Un gran número de procedimientos fue utilizado para el control de epistaxis en estos pacientes. El objetivo de este estudio fue reportar el tratamiento de las epistaxis severas relacionadas con HHT con procedimiento de Young modificado. Materiales y métodos: Describimos cuatro pacientes con epistaxis severa, dependientes de transfusiones de sangre, que se sometieron a un procedimiento de Young modificado en un hospital de tercer nivel. El cierre nasal fue bilateral y completo en todos los casos. Se observaron todos los pacientes durante 12 meses o más. Resultados: El procedimiento fue bien tolerado y se logró el cese completo de las hemorragias en todos los pacientes. Conclusión: La cirugía de Young es un procedimiento seguro y bien tolerado por los pacientes con epistaxis severa y HHT (AU)

Effect of curcumin on nasal symptoms and airflow in patients with perennial allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a common disorder that can significantly affect patient quality of life. Previous studies have found that curcumin had anti-inflammatory and antioxidant effects and clinical benefits in cancer and asthma. OBJECTIVE: To determine the efficacy of curcumin in the treatment of AR and to explore the molecular mechanisms involved. METHODS: In a randomized, double-blind study, 241 patients with AR received either placebo or oral curcumin for 2 months. The therapeutic effects of curcumin were evaluated by nasal symptoms and nasal airflow resistance. In addition, the production of interferon γ, interleukin (IL) 4, IL-10, and tumor necrosis factor α from mononuclear cells and IL-8, soluble intercellular adhesion molecule, polyethylene glycol 2, and leukotriene C4 from polymorphonuclear neutrophils were compared before and after curcumin treatment. RESULTS: Curcumin alleviated nasal symptoms (sneezing and rhinorrhea) and nasal congestion through reduction of nasal airflow resistance. Curcumin was found to exert diverse immunomodulatory effects, including suppression of IL-4, IL-8, and tumor necrosis factor α and increased production of IL-10 and soluble intercellular adhesion molecule. However, curcumin did not affect the release of prostaglandin E2 and leukotriene C4 from polymorphonuclear neutrophils. CONCLUSION: This pilot study provides the first evidence of the capability of curcumin of improving nasal airflow and modulating immune response in patients with AR.

Voiding dysfunction in patients with nasal congestion treated with pseudoephedrine: a prospective study.

BACKGROUND: Pseudoephedrine is a sympathomimetic drug widely used as a nasal decongestant. However, it can cause adverse effects, such as voiding dysfunction. The risk of voiding dysfunction remains uncertain in patients without subjective voiding problems. METHODOLOGY: We prospectively enrolled patients with nasal congestion who required treatment with pseudoephedrine from May to August 2015. All patients denied concomitant subjective voiding problem. The International Prostate Symptom Score (IPSS) questionnaire was used to evaluate voiding function before and 1 week after the pseudoephedrine treatment. The results of the IPSS questionnaire were analyzed as the total (IPSS-T), voiding (IPSS-V), storage (IPSS-S), and quality of life due to urinary symptom scores. RESULTS: We enrolled 131 males with a mean age of 42.0±14.3 years. The IPSS-T, IPSS-V, and IPSS-S scores slightly increased after the medication (IPSS-T increased from 6.49 to 6.77, IPSS-V from 3.33 to 3.53, and IPSS-S from 3.17 to 3.24). The quality of life due to urinary symptom score nonsignificantly decreased from 2.02 to 1.87. We observed that older age and a higher premedication IPSS-V score yielded significant differences (P<0.05) for subclinical voiding dysfunction and unchanged voiding function. In patients aged ≥50 years, the IPSS-T, IPSS-V, and IPSS-S scores significantly increased after the pseudoephedrine treatment (IPSS-T increased from 9.95 to 11.45, IPSS-V from 5.38 to 6.07, and IPSS-S 4.57 to 5.38), whereas the quality of life due to urinary symptom score nonsignificantly decreased from 2.71 to 2.48 (P=0.057). In patients aged <50 years, all scores did not significantly differ. CONCLUSION: Pseudoephedrine treatment for nasal congestion requires extra precautions in males >50 years, even without subjective voiding symptoms.

Values of SP-A protein in the nasal mucosa.

The paranasal sinus epithelium is exposed to the environment and therefore to a variety of biological, chemical and mechanical insults. Surfactant protein A (SP-A) is a 34-36 kD pulmonary surfactant-associated protein that appears to play an important role in mammalian first-line host defence. Recent studies have reported the possibility of local production of SP-A in the extrapulmonary organs and tissues of the human body. However, the presence of SP-A in the human paranasal sinus mucosa is not well known. The purpose of this study was to investigate the expression of SP-A protein in human turbinate mucosa and to compare the expression of SP-A mRNA in normal turbinate mucosa and turbinate mucosa of chronic rhinosinusitis patients. Reverse transcriptase polymerase chain reaction was used to detect SP-A mRNA. Student's t test was used for statistical comparison of the SP-A/GAPDH-mRNA ratio (GAPDH: glycerinaldehyde-3-phosphate dehydrogenase) of cases and controls. We found expression of SP-A mRNA in mucosa lining the inferior turbinates of healthy patients and its up-regulation in mucosa lining the inferior turbinates of patients with chronic rhinosinusitis. These results may provide targets for new therapies for chronic rhinosinusitis.

Nasal nitric oxide is dependent on sinus obstruction in allergic rhinitis.

OBJECTIVES/HYPOTHESIS: The aim of this study was to evaluate the associations between nasal nitric oxide and nasal symptoms, sinus opacification, and markers of allergic inflammation in allergic and in nonallergic rhinitis while taking into account the effect of sinus obstruction. STUDY DESIGN: We studied 175 young adult subjects divided into three groups: 1) allergic rhinitis, 2) nonallergic rhinitis, and 3) controls. METHODS: We measured nasal nitric oxide using the breath-holding method and exhaled nitric oxide and scored semiquantitatively nasal computed tomography scans for opacification and obstruction. We also assessed the visual analogue scores of nasal symptoms, eosinophil count, and interleukin-13 mRNA levels in nasal biopsies. RESULTS: The level of nasal nitric oxide correlated with exhaled nitric oxide (r = 0.377, P < .001). In allergic rhinitis, nasal nitric oxide was elevated when compared to the controls, and an inverse correlation existed between the nasal nitric oxide level and sinus ostial obstruction (r = -0.272, P = .013). In nonallergic rhinitis, the level of nasal nitric oxide was similar to that of the controls. In allergic rhinitis, nasal nitric oxide correlated positively with the opacification score (r = 0.250, P = .033) and the nasal eosinophil count (r = 0.293, P = .030) of patients without a marked sinus ostial obstruction. CONCLUSIONS: Sinus ostial obstruction lowers the level of nasal nitric oxide and reduces its value as an indicator of allergic mucosal inflammation. A high nasal nitric oxide level may be a useful marker of eosinophilic inflammation in the nasal cavity and indicate the absence of marked sinus ostial obstruction. LEVEL OF EVIDENCE: 3b.

Thirty minute-exposure to aged cigarette smoke increases nasal congestion in nonsmokers.

The aim of this study was to assess the effects of short exposures to experimentally aged cigarette smoke on the nose and upper airways. This crossover study compared the effects of 30-min exposures to (1) experimentally aged cigarette smoke at 1 mg/m³ particulate matter (PM)/14 ppm carbon monoxide (CO) and (2) conditioned filtered air on urinary metabolites of nicotine and tobacco-specific nitrosamines. Subjective nasal symptoms were assessed by questionnaire, objective nasal congestion was assessed by anterior rhinomanometry and nasal nitric oxide (NO) concentrations were determined. Experimentally aged cigarette smoke is a validated model for secondhand smoke (SHS). Twenty-six healthy nonsmokers (10 normal, 7 atopic/nonrhinitic, 7 atopic rhinitic, 2 nonatopic/rhinitic) were studied. A 30-min exposure to SHS increased nasal resistance in healthy nonsmokers. The rise in nasal resistance was most pronounced in rhinitic subjects. Significant increases were not noted when atopic subjects were considered independent of rhinitis status. Secondhand smoke exposure also elevated subjective nasal symptoms and urinary concentrations of metabolites of nicotine (cotinine and trans-3´-hydroxycotinine) and tobacco-specific nitrosamines [(4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)] in all subgroups of subjects. Exposure-related, subjective nasal symptoms were significantly higher in rhinitic than in normal subjects. Significant changes in nasal NO concentrations were not detected. Data indicate a 30-min exposure to secondhand smoke at 1 mg/m³ PM increases subjective upper respiratory symptoms, increases urinary cotinine and NNAL, and produces objective nasal airflow obstruction in human subjects.

Expression and localization of purinergic P2Y(12) receptor in human nasal mucosa.

BACKGROUND: Extracellular nucleotides such as ATP and UTP are released from essentially all cells, and they interact with cell surface P2 receptors to produce a broad range of physiological responses. P2Y12 receptor is the major platelet receptor that mediates ADP-induced aggregation, P2Y12 receptor inhibitors such as clopidogrel and prasugrel inhibit platelet aggregation, and thus, they are used in the treatment and prevention of coronary artery disease. Recently, studies have focused on the P2Y12 receptor as a receptor for leukotriene E4 (LTE4), because this receptor is required for LTE4-mediated pulmonary inflammation. To establish the presence of P2Y12 receptor in human nasal mucosa, we investigated the expression and the localization of the P2Y12 receptor in human nasal mucosa. METHODS: Human turbinates were obtained by turbinectomy from 12 patients with nasal obstruction refractory to medical therapy. The expression of P2Y12 receptor was evaluated by RT-PCR, western blotting, and immunohistochemical analysis. RESULTS: RT-PCR analysis of total RNA extracted from human nasal turbinate, primary cultured human nasal epithelial cells and nasal vascular endothelial cells demonstrated the expression of P2Y12 receptor mRNA. A band of approximately 55 kDa was detected in human turbinates by western blot analysis using anti-P2Y12 receptor antibody. We could not find any differences between P2Y12 receptor levels in allergic and non-allergic nasal mucosa. An immunohistochemical study revealed that epithelial cells, submucosal glands and vascular endothelial cells showed intense immunoreactivity for the P2Y12 receptor. CONCLUSIONS: The results may have important clinical implications for understanding the role of P2Y12 receptor in upper airway diseases such as allergic rhinitis and non-allergic rhinitis.

Immunohistochemistry in diagnosis of extranasopharyngeal angiofibroma originating from nasal cavity: case presentation and review of the literature.

Angiofibromas are rare vascular tumors which originate predominantly in the nasopharynx and occur typically in male adolescents. Extranasopharyngeal sites such as nasal cavity and paranasal sinuses are less frequent. This review article was undertaken to evaluate the incidence, clinical features and management of extranasopharyngeal angiofibromas originating exclusivelly from nasal cavity structures. Our focus of interest was to evaluate the significance of immunohistochemical analysis in diagnosis of such extremely rare neoplasms. In the PubMed and Google Search, we found only 39 cases of nasal angifibroma, 27 males and 12 females from 1980 to 2012. The most prevalent site of origin was nasal septum, followed by inferior and middle turbinate. The commonest symptoms were nasal obstruction and epistaxis. Nasal angiofibromas are clinically distinct from nasopharyneal angiofibromas and can therefore be misdiagnosed. The differential diagnosis includes other vascular lesions, such as lobular capillary hemangioma and sinonasal-type hemangiopericytoma. Although immunohistochemistry is not necessary for differentiation between angiofibroma and capillary hemangioma, that diagnostic procedure may be helpful in distinction from sinonasal hemangiopericytoma. As an ilustration for immunohistochemical analysis, we presented a case of an elderly woman with tumor arising from the middle turbinate, diagnosed as angiofibroma. The staining was positive for CD34, CD31, factor VIII, vimentin and smooth muscle alpha-actin, and negative for desmin.

Evaluation of C-reactive protein, haptoglobin and cardiac troponin 1 levels in brachycephalic dogs with upper airway obstructive syndrome.

BACKGROUND: Brachycephalic dogs have unique upper respiratory anatomy with abnormal breathing patterns similar to those in humans with obstructive sleep apnea syndrome (OSAS). The objective of this study was to evaluate the correlation between anatomical components, clinical signs and several biomarkers, used to determine systemic inflammation and myocardial damage (C-reactive protein, CRP; Haptoglobin, Hp; cardiac troponin I, cTnI), in dogs with brachycephalic upper airway obstructive syndrome (BAOS). RESULTS: Fifty brachycephalic dogs were included in the study and the following information was studied: signalment, clinical signs, thoracic radiographs, blood work, ECG, components of BAOS, and CRP, Hp and cTnI levels. A high proportion of dogs with BAOS (88%) had gastrointestinal signs. The prevalence of anatomic components of BAOS was: elongated soft palate (100%), stenotic nares (96%), everted laryngeal saccules (32%) and tracheal hypoplasia (29.1%). Increased serum levels of biomarkers were found in a variable proportion of dogs: 14% (7/50) had values of CRP > 20 mg/L, 22.9% (11/48) had values of Hp > 3 g/L and 47.8% (22/46) had levels of cTnI > 0.05 ng/dl. Dogs with everted laryngeal saccules had more severe respiratory signs (p<0.02) and higher values of CRP (p<0.044). No other statistical association between biomarkers levels and severity of clinical signs was found. CONCLUSIONS: According to the low percentage of patients with elevated levels of CRP and Hp, BAOS does not seem to cause an evident systemic inflammatory status. Some degree of myocardial damage may occur in dogs with BAOS that can be detected by cTnI concentration.

The potential role of prostaglandin D2 in nasal congestion observed in a guinea pig model of allergic rhinitis.

BACKGROUND: Allergic rhinitis is the most common allergic disease, displaying the typical nasal symptom of congestion. Prostaglandin D(2) (PGD(2)), a chemical mediator released in large amounts by mast cells upon allergic stimulation in humans, is known to be involved in nasal congestion. However, the mechanism by which this congestion occurs remains unclear. METHODS: The effect of PGD(2) on the nasal airflow in guinea pigs was measured using a noninvasive approach that avoided any anesthetic effect. Isometric tension of isolated nasal mucosa and the nasal vascular corrosion resin cast technique were used to clarify the area of nasal mucosal vessels affected by PGD(2), and to examine the mechanism of PGD(2)-induced nasal congestion. Moreover, the involvement of second messengers in PGD(2)-induced mucosal relaxation was investigated. RESULTS: PGD(2) induced an increase in intranasal pressure in a guinea pig model of rhinitis. Additionally, sinusoidal microvessel dilatation appeared around the septum using the vascular corrosion resin cast technique in the nasal mucosa. Moreover, relaxation of the nasal mucosa following stimulation of the prostanoid DP-1 receptor was associated with cAMP levels in the tissue. CONCLUSIONS: PGD(2)-induced nasal congestion is caused by direct dilatation of the sinusoid vessels through the increase of cAMP levels in the nasal mucosa, demonstrating that the mechanism of PGD(2)-induced nasal congestion is different from other chemical mediators. Consequently, antagonists for the prostanoid DP-1 receptor would be an alternative approach for the relief of nasal congestion. Alternatively, the combined administration with antagonists for other mediators involved in nasal congestion may also be a valuable therapy for allergic rhinitis.

Perceived stress, common health complaints and diurnal patterns of cortisol secretion in young, otherwise healthy individuals.

Research has frequently linked perceived stress with changes in subjective and objective measures of ill health; however, additional assessment should consider the physiological mechanisms mediating these effects. This study investigated whether differential patterns of cortisol secretion might partially mediate perceived stress related disparities in common health complaints in young, otherwise healthy individuals. To capture the kinds of health complaints commonly reported in this population, the Pennebaker Inventory of Limbic Languidness (PILL) was selected. To capture important parameters of the diurnal profile, cortisol was sampled at waking, 30 minutes post waking, 1200 h and 2200 h on three consecutive weekdays. Results revealed flatter diurnal cortisol slopes and elevated mean diurnal output (characterised by HPA hyperactivity in the evening) for participants in the higher stress group. Participants that reported higher perceived levels of stress also reported experiencing common health complaints with markedly greater frequency; however, these disparities were abolished when mean diurnal output of cortisol was statistically controlled. While dysregulation of basal HPA activity has been implicated in the aetiologies of chronic illness, findings reported here implicated hypersecretion of cortisol as one physiological pathway, partially mediating perceived stress related disparities in the kinds of common health complaints that typically affect young, otherwise healthy individuals.

Role of hematopoietic prostaglandin D synthase in biphasic nasal obstruction in guinea pig model of experimental allergic rhinitis.

We investigated the role of hematopoietic prostaglandin D synthase (H-PGDS) in biphasic nasal obstruction in allergic rhinitis using a new specific inhibitor, (N-methoxy-N-methyl)-4-(5-benzoylbenzimidazole-2-yl)-3,5-dimethylpyrrole-2-carboxamide hydrochloride (TAS-204). First, we developed a novel guinea pig model of allergic rhinitis. Guinea pigs sensitized to ovalbumin without adjuvant were challenged with intranasal exposure to ovalbumin once a week. After the 3rd antigen challenge, they exhibited biphasic nasal obstruction. Additionally, analysis of nasal lavage fluid revealed an increase in the level of prostaglandin D(2) in both early and late phases. Treatment with oral TAS-204 for 15 days during the period of antigen challenges suppressed increases in nasal airway resistance in both phases. It is noteworthy that the late phase nasal obstruction was almost completely abrogated by inhibiting H-PGDS alone. Eosinophil infiltration in nasal lavage fluid and nasal hyperresponsiveness to histamine was also reduced by TAS-204 administration. These findings suggest that H-PGDS plays a critical role in the development of allergic rhinitis, especially in the induction of late phase nasal obstruction.

Relationship between fractional exhaled nitric oxide and nasal nitric oxide in airways disease.

BACKGROUND: Invasive techniques show evidence of a unified allergic airway. Nitric oxide is measured noninvasively from the lungs (fractional exhaled nitric oxide [FeNO]) and nose (nasal nitric oxide [nNO]). OBJECTIVE: To investigate the relationship between FeNO and nNO in different airway conditions. METHODS: A total of 227 participants were assessed: 41 healthy volunteers (HVs), 33 patients with asthma, 52 patients with allergic rhinitis (AR), 63 with unified airway disease (UAD), and 38 with nasal polyposis (NP). Correlation and multiple linear regression analyses were performed. RESULTS: Geometric means (95% confidence intervals) for FeNO were as follows: 14.7 (12.4-17.5) ppb for HVs, 29.0 (22.5-37.4) ppb for asthma patients, 23.1 (19.0-28.1) for AR patients, 27.2 (23.0-32.4) for UAD patients, and 28.5 (21.5-37.8) for NP patients. For nNO, the values were as follows: 878.1 (807.0-955.6) ppb for HVs, 674.1 (557.4-815.1) for asthma patients, 853.3 (778.8-934.8) ppb for AR patients, 763.4 (694.1-839.5) for UAD patients, and 388.6 (317.9-474.9) for NP patients. The nNO was lower in the NP group than the other groups (P < .001). The nNO and FeNO were correlated in the AR patients (r = 0.56; P < .0001) and HVs (r = 0.44; P = .004) but not significantly in the other groups. Multiple linear regression of the whole cohort demonstrated that after diagnosis, age, sex, and inhaled corticosteroids were taken into account nNO had a significant association with FeNO (P = .02). CONCLUSION: Reduced nNO in NP patients is due to ostiomeatal complex obstruction. FeNO is sensitive to suppression by inhaled corticosteroids. The AR and HV groups have no such confounders; hence, correlation is most evident. Exclusion of confounders reveals a correlation between upper and lower airway inflammation with noninvasive techniques.

Immunohistochemical localization of the bradykinin B1 and B2 receptors in human nasal mucosa.

Bradykinin (BK) has been tobe thought a potent mediator involved in allergic rhinitis because BK was recovered from the nasal lavage fluid of allergic rhinitis patients after allergen provocation and BK receptor antagonists relief nasal allergic symptoms. Two mammalian BK receptor subtypes, B1 and B2, have been defined based on their pharmacological properties. We investigated the localization of these receptors by immunohistochemistry. Human turbinates were obtained after turbinectomy from 12 patients with nasal obstruction refractory to medical therapy. The immunohistochemical study revealed that epithelial cells, submucosal glands, fibroblast, vascular smooth muscle, vascular endothelial cells, and macrophages showed immunoreactivity for both B1 and B2 receptors. The B2 receptor expression was found in peripheral nerve fibers, whereas the B1 expression was not observed in nerves. The results may have an important clinical implication for understanding the differential roles of BK receptor subtypes on upper airway diseases such as allergic rhinitis and nonallergic rhinitis.