Involvement of nitric oxide (NO) in cough reflex sensitivity between non-sensitized and OVA-sensitized guinea pigs

Background: Exhaled nitric oxide (ENO) is elevated in bronchial asthma patients, and inhaled corticosteroid therapy lowers the elevated ENO levels in such patients. ENO appears to be an inflammatory marker, but its role in the pathophysiology of cough remains unclear. This study aimed to elucidate the relationship between NO and increased cough reflex sensitivity induced by allergic airway reactions.Methods: Cough reflex sensitivity to inhaled capsaicin was observed under NO depletion caused by NO synthase (NOS) inhibitors in non-sensitized and ovalbumin (OVA)-sensitized guinea pigs. The bronchoalveolar lavage fluid (BALF) was analyzed in an NO depletion setting using the inducible NOS (iNOS) inhibitor ONO1714 in OVA-sensitized guinea pigs.Results: NO depletion by the non-selective NOS inhibitor L-NAME suppressed cough reflex sensitivity in non-sensitized guinea pigs and OVA-induced increase in cough reflex sensitivity in sensitized guinea pigs; however, iNOS inhibition caused by ONO1714 partially suppressed the OVA-induced increase in cough reflex sensitivity, but not the normal cough response in non-sensitized guinea pigs. ONO1714 did not change BAL cell components in OVA-sensitized guinea pigs.Conclusions: The results suggest that NO may be involved not only in the normal cough reflex circuit, but also in the OVA-induced increase in cough reflex sensitivity, possibly via a different mechanism of action. Further studies are needed to clarify the precise mechanism. © 2011 Hori et al; licensee BioMed Central Ltd

Effects of macrolides on antigen-induced increases in cough reflex sensitivity in guinea pigs

金沢大学医薬保健研究域医学系Background: Macrolides are antibiotics that have anti-inflammatory activities. Hence, they are used for both acute and chronic inflammatory airway diseases. However, the effects of these agents on allergic airway disorders presenting with an isolated chronic cough, such as non-asthmatic eosinophilic bronchitis and eosinophilic tracheobronchitis with cough hypersensitivity (atopic cough), still remain to be elucidated. Objective: To determine if macrolides are effective in the management of chronic cough caused by eosinophilic airway inflammation. Methods: The cough reflex sensitivity to inhaled capsaicin was measured at 48 h after challenge with an aerosolized antigen in actively sensitized guinea pigs. The 14-, 15- or 16-membered macrolides (erythromycin, azythromycin, or josamycin, respectively) were given intraperitoneally every 12 h after the antigen challenge. Bronchoalveolar lavage and the resection of the tracheal tissue were performed immediately after the measurement of the cough response to capsaicin. Results: The antigen-induced increase in the number of coughs elicited by capsaicin inhalation was significantly reduced by treatments with erythromycin and azythromycin, but not with josamycin. Erythromycin dose-dependently inhibited the increases in the substance P, prostaglandin E2 and leukotriene B4 levels, but not the histamine levels, in the bronchoalveolar lavage fluid. However, erythromycin did not influence the antigen-induced decrease in the neutral endopeptidase (NEP) activity in the tracheal tissue. Conclusions: Both 14- and 15-membered, but not 16-membered, macrolides could reduce the antigen-induced cough reflex hypersensitivity by inhibiting the antigen-induced release of the afferent sensory nerve sensitizers. These macrolides may be therapeutically useful for the treatment of isolated chronic cough based on cough reflex hypersensitivity in allergic airway diseases such as non-asthmatic eosinophilic bronchitis and atopic cough. © 2009 Elsevier Ltd. All rights reserved

Spectral responses of GaAs photodiodes fabiricated by rapid thermal diffusion

The spectral responses of GaAs photodiodes fabricated by rapid thermal diffusion (RTD) of Zn are presented. The authors tried controlling the p+-n junction depth by the heating rate of RTD, without extending the diffusion time. It is found that Zn diffuses from the surface to a deeper position as the heating rate increases. Consequently, the spectral response of photodiodes formed by RTD is strongly dependent on the heating rate of RTD. A large improvement in the short-wavelength response between 400 and 800 nm is observed as the heating rate decreases

International patient preferences for physician attire: results from cross-sectional studies in four countries across three continents.

OBJECTIVE The patient-physician relationship impacts patients' experiences and health outcomes. Physician attire is a form of nonverbal communication that influences this relationship. Prior studies examining attire preferences suffered from heterogeneous measurement and limited context. We thus performed a multicentre, cross-sectional study using a standardised survey instrument to compare patient preferences for physician dress in international settings. SETTING 20 hospitals and healthcare practices in Italy, Japan, Switzerland and the USA. PARTICIPANTS Convenience sample of 9171 adult patients receiving care in academic hospitals, general medicine clinics, specialty clinics and ophthalmology practices. PRIMARY AND SECONDARY OUTCOME MEASURES The survey was randomised and included photographs of a male or female physician dressed in assorted forms of attire. The primary outcome measure was attire preference, comprised of composite ratings across five domains: how knowledgeable, trustworthy, caring and approachable the physician appeared, and how comfortable the respondent felt. Secondary outcome measures included variation in preferences by country, physician type and respondent characteristics. RESULTS The highest rated forms of attire differed by country, although each most preferred attire with white coat. Low ratings were conferred on attire extremes (casual and business suit). Preferences were more uniform for certain physician types. For example, among all respondents, scrubs garnered the highest rating for emergency department physicians (44.2%) and surgeons (42.4%). However, attire preferences diverged for primary care and hospital physicians. All types of formal attire were more strongly preferred in the USA than elsewhere. Respondent age influenced preferences in Japan and the USA only. CONCLUSIONS Patients across a myriad of geographies, settings and demographics harbour specific preferences for physician attire. Some preferences are nearly universal, whereas others vary substantially. As a one-size-fits-all dress policy is unlikely to reflect patient desires and expectations, a tailored approach should be sought that attempts to match attire to clinical context

Factors affecting atmospheric 1-, 2-nitropyrenes and 2-nitrofluoranthene in winter at Noto peninsula, a remote background site, Japan

Airborne particulates were collected at a background site (Wajima Air Monitoring Station; WAMS) on the Noto Peninsula, Japan from January 2006 to December 2007. 1-, 2-nitropyrenes (1-, 2-NPs) and 2-nitrofluoranthene (2-NFR), in the particulates were determined with a sensitive HPLC method with chemiluminescence detection. The average concentrations were higher in winter than in summer. A meteorological analysis indicated that the air samples collected in winter were transported mainly from Northeast China over the Japan Sea. Both the concentration ratios of 2-NFR to 1-NP and 1-NP to pyrene were similar to those in Shenyang in Northeast China which located along the air transportation route to WAMS, but not in Kanazawa which near WAMS. These results strongly suggest that most of the atmospheric 1-, 2-NPs and 2-NFR at WAMS in winter were long range transported from Northeast China. © 2014 Elsevier Ltd. All rights reserved

A-ring modified betulinic acid derivatives as potent cancer preventive agents

Ten new 3,4-seco betulinic acid (BA) derivatives were designed and synthesized. Among them, compounds 7–15 exhibited enhanced chemopreventive ability in an in vitro short-term 12-O-tetradecanoylphorbol-13-acetate (TPA) induced Epstein-Barr virus early antigen (EBV-EA) activation assay in Raji cells. Specifically, analogs with a free C-28 carboxylic acid, including 7, 8, 11, and 13, inhibited EBV-EA activation significantly. The most potent compound 8 displayed 100% inhibition at 1 × 103 mol ratio/TPA and 73. 4%, 35. 9%, and 8. 4% inhibition at 5 × 102, 1 × 102, and 1 × 10 mol ratio/TPA, respectively, comparable with curcumin at high concentration and better than curcumin at low concentration. The potent chemopreventive activity of novel seco A-ring BAs (8 and 11) was further confirmed in an in vivo mouse skin carcinogenesis assay