[show abstract][hide abstract] ABSTRACT: It has recently been suggested that regular treatment with racemic beta(2)-adrenoceptor agonists might result in bronchial hyperresponsiveness (BHR) to a range of spasmogens, and this might be due to adverse effects of the distomer.
We sought to determine whether BHR induced by means of continuous exposure to racemic and S-albuterol was mediated by sensory nerves.
Naive or ovalbumin-sensitized guinea pigs were treated for 10 days with RS-, R-, or S-albuterol (1 mg.kg(-1).d(-1)) through subcutaneously implanted minipumps. Lung function was then determined in response to a number of spasmogens and assessed on the basis of an increase in total airway resistance. A separate group of animals were chronically treated with capsaicin (80 mg/kg) before the albuterol treatment.
Treatment with RS- or S-albuterol increased airway responsiveness to bradykinin, leukotriene C(4), and capsaicin in naive guinea pigs (P <.05) and to histamine and ovalbumin in immunized guinea pigs (P <.05). Chronic treatment with capsaicin prevented the development of RS- and S-albuterol-induced BHR in these models. The bronchodilator efficacy of acute intravenously administered RS-albuterol was unaffected in RS-, R-, or S-albuterol-treated guinea pigs compared with in vehicle-treated animals.
We have provided evidence demonstrating that continuous exposure to RS- and S-albuterol increases bronchial responsiveness to a range of stimuli, an effect not attributed to beta-adrenoceptor occupancy or desensitization. Furthermore, capsaicin-sensitive sensory nerves mediate the development of BHR, at least in part.
Journal of Allergy and Clinical Immunology 10/2002; 110(3):388-94.
[show abstract][hide abstract] ABSTRACT: We sought to characterise a refined rat model of respiratory infection with P. aeruginosa over an acute time course and test the antibiotic ciprofloxacin.
Agar beads were prepared ± SPAN(®)80. Rats were inoculated with sterile agar beads or those containing 10(5) colony forming units (cfu) P. aeruginosa via intra-tracheal dosing. Bacterial load and inflammatory parameters were measured.
Differing concentrations of SPAN(®) 80 modified median agar bead diameter and reduced particle size distribution. Beads prepared with 0.01% v/v SPAN(®)80 were evaluated in vivo. A stable lung infection up to 7 days post infection was achieved and induced BALF neutrophilia 2 and 5 days post infection. Ciprofloxacin (50mg/kg) significantly attenuated infection without affecting the inflammatory parameters measured.
SPAN(®) 80 can control the particle size and lung distribution of agar beads and P. aeruginosa-embedded beads prepared with 0.01%v/v SPAN(®)80 can induce infection and inflammation over 7 days.
Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 01/2011; 10(3):166-74.