Altered apoptosis in bronchoalveolar lavage lymphocytes after allergen exposure of atopic asthmatic subjects.

The increased number of lymphocytes in airways during an asthmatic response is believed to be the result of increased recruitment of these cells. However, it is possible that a decreased apoptotic rate could also contribute to the increased number. The aim of the present study was to investigate whether allergen airway provocation influences the apoptotic phenotype of lung and peripheral blood lymphocytes (PBL) in subjects with atopic asthma. Bronchoalveolar lavage (BAL) lymphocytes and PBL from 12 asthmatic subjects previously challenged with allergen (n = 7) or saline (n = 5) were exposed to the apoptotic stimulus tributyltin (TBT) in vitro and assayed for apoptosis. Airway allergen provocation resulted in decreased sensitivity of BAL lymphocytes to TBT-induced apoptosis, with 42.2% (range 33.9-62.5%) apoptotic cells before challenge versus 23.5% (range 15.3-42.4%) after challenge, while PBL were unaffected. The increased apoptosis resistance correlated with higher numbers of Bcl-2-expressing lymphocytes. Interestingly, baseline caspase-3-like activity was significantly elevated in viable BAL lymphocytes compared with viable PBL, and was unaltered by allergen exposure. In conclusion, allergen inhalation renders bronchoalveolar lavage lymphocytes more resistant to apoptosis while peripheral blood lymphocytes were not influenced at all, indicating that the apoptotic phenotype of airway lymphocytes may play a role in asthmatic inflammation.     

Peri-sleep-onset cortisol levels in children and adolescents with affective disorders.

BACKGROUND: Changes in the hypothalamic-pituitary-adrenal (HPA) axis, as evidenced by patterns of cortisol secretion, have been of interest in understanding depression and anxiety disorders across the life span. Previous studies of pediatric depression have pointed to the period around sleep onset as a key time point for observing alterations in cortisol secretion associated with affective disorders. Evidence also indicates that pubertal development may influence the expression of HPA dysregulation. We hypothesized that adolescents with depression and youth with anxiety disorders exhibit elevated peri-sleep-onset cortisol. METHODS: Plasma cortisol was sampled every 20 min around sleep onset from children and adolescents with major depressive disorder (n = 116), anxiety disorders (n = 32), or no history of psychiatric disorder (control; n = 76). Sleep onset was determined by polysomnography. Classification of participants as children or adolescents was based on Tanner staging of pubertal maturation. RESULTS: Children with anxiety disorders had higher peri-sleep-onset cortisol than children with depression or control children. Adolescents with depression had marginally higher peri-sleep-onset cortisol than control adolescents and significantly higher peri-sleep-onset cortisol than children with depression. CONCLUSIONS: Depression and anxiety are associated with altered cortisol secretion around sleep onset, and these changes appear to be influenced by pubertal maturation.     

Flerobuterol: a potential antidepressant drug related to β-adrenergic agonists. Experimental profile in mice

The potential antidepressant effect of flerobuterol (dl-(fluoro-2 phenyl)-1 t-butylamino-2 ethanol), a new drug related to beta-adrenoceptor agonists, was evaluated and compared with imipramine and salbutamol using classical psychopharmacological tests in mice. Like imipramine and salbutamol, flerobuterol (0.5-32 mg kg-1, ip) fully prevented apomorphine (16 mg kg-1, sc)- and partly reversed reserpine- and oxotremorine-induced hypothermia. At higher doses (16-32 mg kg-1), flerobuterol enhanced the toxic effects of yohimbine. Unlike imipramine, flerobuterol and salbutamol did not reduce immobility duration in the behavioural despair test. Salbutamol and flerobuterol decreased locomotor activity. Flerobuterol did not induce mydriasis, did not prevent oxotremorine-induced tremors or salivary and lacrimal gland secretion and did not reduce reserpine-induced palpebral ptosis. Propranolol (8 mg kg-1, ip) but not alpha-methyl-paratyrosine (75 mg kg-1, ip) prevented the flerobuterol-induced antagonism of apomorphine-induced hypothermia. Our results suggest that flerobuterol demonstrates potential antidepressant activity, which could be related to beta-adrenoceptor activation in mice.     

Alpha 2-adrenoceptor-mediated inhibition of nerve stimulation-evoked release of neuropeptide Y (NPY)-like immunoreactivity in the pithed guinea-pig

Clonidine (10 micrograms X kg-1) reduced by almost 50% the increase in plasma neuropeptide (NPY)-like immunoreactivity (-LI) induced by preganglionic nerve stimulation at 8 Hz. This effect was reversed by yohimbine (1 mg X kg-1) which caused a three-fold increase of the plasma NPY-LI. Prazosin (1 mg X kg-1) had no such effect. Guanethidine (5 mg X kg-1) reduced the stimulation-evoked increase in plasma NPY-LI. It is concluded that the release of NPY-LI evoked by nerve stimulation from sympathetic nerve terminals is controlled by a presynaptic alpha 2-adrenoceptor-mediated mechanism.     

Effect of nicotine, silver acetate, and ordinary chewing gum in combination with group counselling on smoking cessation.

Four hundred and ninety six smokers participated in a randomised comparison of the effect of silver acetate, nicotine, and ordinary chewing gum on smoking cessation. All were motivated to stop smoking abruptly and all had smoked at least 10 cigarettes a day for at least five years. Side effects and taste acceptability were related to outcome after six months. The participants attended nine meetings over a year, at which lectures, support, and advice about stopping smoking were given. Tobacco abstinence was confirmed by measurement of carbon monoxide in expired air. The chewing gums were used for 12 weeks. After 12 weeks there was a trend towards more abstainers in the nicotine group (59%) than in the silver acetate (50%) and ordinary (45%) chewing gum groups that was not quite significant (p = 0.07). At 26 and 52 weeks the number of cigarette abstainers was similar in the three treatment groups. Subjects in the nicotine chewing gum group had a longer mean time before relapse than those in the silver acetate and ordinary chewing gum groups. Mean success rates for all subjects combined at 12, 26, and 52 weeks were 52.8%, 39.7%, and 23.3%. The side effects of nicotine and silver acetate chewing gum were generally mild and transient, and unimportant except for mouth irritation from silver acetate, which had a negative effect on outcome, and the low taste acceptability of nicotine, which had a strong negative influence on the success rate. The results suggest a short term effect on nicotine chewing gum on smoking cessation, but the abstinence rates after one year were generally disappointing.