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.     

A cross-sectional survey of patients' beliefs about stress and their help-seeking behaviour

BACKGROUND: Stress has become an increasingly common presentation in general practice. This may relate to an increase in stress in people's lives or a change in the meaning of stress and its conceptualisation as a legitimate problem for the GP. AIM: To explore patients' beliefs about stress, their association with help-seeking behaviour, and to examine differences by ethnic group. DESIGN OF STUDY: Cross-sectional survey of general practice patients attending to see their GP. SETTING: An inner-city London practice. METHOD: Consecutive general practice patients completed a questionnaire, which involved rating a series of symptoms for the extent to which they were associated with stress and describing their help-seeking behaviour. In total, 548 patients completed the questionnaire. Most patients described themselves as black Caribbean (n = 163), black African (n = 48), or white British (n = 187). RESULTS: The symptoms most frequently associated with stress were sleeping problems, feeling depressed, feeling panicky, having high blood pressure and feeling anxious; feeling ashamed, experiencing indigestion, having diarrhoea, feeling hot or cold, and suffering from constipation were least commonly associated to stress. This model of stress did not vary by ethnic group. Ethnic group differences were found for the association between the model of stress and help-seeking behaviour. Although white British patients consistently reported that the more a symptom was seen as indicative of stress, the more likely they would be to visit the doctor for that symptom, this association was not found for either black Caribbean or black African patients. CONCLUSIONS: The belief that stress-related symptoms are a legitimate problem for the GP is not universal and varies according to ethnic group. Stress is used by different patients in different ways and offers a variable pathway to the doctor.     

Is herpes zoster a marker for occult or subsequent malignancy?

BACKGROUND: It has been suggested that herpes zoster may be a marker for occult malignancy. AIM: To examine the emergence of a subsequent cancer diagnosis in patients with and without herpes zoster. DESIGN OF STUDY: Retrospective cohort study. SETTING: Results were based on the database of Intego, an ongoing Belgian general practice-based morbidity registry, covering 37 general practitioners and including about 311 000 patient years between the years 1994 and 2000. METHOD: Survival analysis comparing the emergence of malignancy in patients with and without herpes zoster. RESULTS: The number of patients below the age of 65 years with herpes zoster, cancer or both was too low to draw any sensible conclusions. Above the age of 65 years we identified a significant increase of cancer emergence in the whole group and in females (hazard ratio = 2.65, 95% confidence interval = 1.43 to 4.90), but not in males. No difference could be identified in the first year after the herpes zoster infection. CONCLUSION: Our results do not justify extensive testing for cancer in herpes zoster patients. The association we identified, however, leaves open a number of questions with respect to the physiopathology behind it.     

Targeted routine asthma care in general practice using telephone triage

BACKGROUND: There is a high non-attendance rate for traditional clinic-based routine asthma care in general practice. Alternative methods of providing routine asthma care need to be examined. AIM: To examine the cost and effectiveness of targeted routine asthma care in general practice using telephone triage, compared to usual clinic care. DESIGN OF STUDY: An open randomised controlled trial. SETTING: A single semi-rural practice in the southwest of England. METHOD: Adult patients with asthma were randomised to receive either their routine asthma care in the surgery or care by telephone triage. Asthma control parameters, health status and NHS resource utilisation were measured over the 12-month study period. RESULTS: One hundred and ninety-four patients were randomised and 35% per cent more patients (n = 84 versus n = 62) received more than one consultation in the telephone group. Asthma control as measured by the asthma control questionnaire (ACQ) was similar in the clinic and telephone groups: mean change in ACQ = -0.11 (95% CI = -0.32 to 0.11) versus -0.18 (95% CI = -0.38 to 0.02). Mean NHS costs were 210 pounds sterling per patient per year in the telephone group compared to 334 pounds sterling in the clinic group (P-value of bootstrapped difference = 0.071). CONCLUSION: Targeted routine asthma care by telephone triage of adult asthmatics can lead to more asthma patients being reviewed, at less cost per patient and without loss of asthma control compared to usual routine care in the surgery.     

Multiple Autoantigen Mimotopes of Infectious Agents Induce Autoimmune Arthritis and Uveitis in Lewis Rats

We found multimolecular antigenic mimicry of arthritogenic autoantigens and peptides from several other “self” or foreign antigens sharing amino acid sequence homologies. Many of these new mimotopes induced arthritis and/or uveitis upon immunization in Lewis rats, indicating a role for multiple antigens in the initiation of a certain autoimmune disease.     

Relationship between transmitter release and presynaptic calcium influx when calcium enters through discrete channels.

We have used a three-dimensional diffusion model of calcium entering the presynaptic nerve terminal through discrete channels to simulate experiments relating transmitter release to presynaptic calcium current. The relationship will be less than linear, or will curve downward, if calcium channels are well separated. It will resemble a power-law function with exponent less than the cooperativity of calcium action if channels are clustered closer together. Large presynaptic depolarizations elicit more release than small depolarizations admitting the same calcium influx. This occurs because large pulses open more channels near each other, with the result that the calcium concentration near release sites is greater, due to overlap of calcium diffusing from adjacent channels.     

Scanning electron microscopic study of degeneration and regeneration in the olfactory epithelium after axotomy

Summary The olfactory epithelium of the adult hamster (Mesocricetus auratus) was examined with the scanning electron microscope following olfactory nerve axotomy. Axotomy results in retrograde degeneration of mature olfactory neurons. Maximum degeneration was observed around day 4. During the degeneration period the epithelium consists primarily of supporting and basal cells. Microvillar columnar supporting cells were observed to have fine cellular processes extending from their lateral border to neighbouring cells. Supporting cells extended to the basal lamina where they terminated in foot-like processes of variable shapes (club, splay and hook). Basal cells which gave rise to new replacement olfactory neurons were observed near the basal lamina. They had a rough cellular surface covered with small granules and fine cellular extensions. Bowman's gland duct cells extended unbranched through the epithelium where they formed funnel duct openings covered with microvilli. During early recovery periods (5–30 days) the number of olfactory neurons in the lower epithelium region increased. We observed olfactory neurons with developing axon and dendritic processes. Specialized growth cone structures were seen at the tips. Olfactory neuron growth cones were elongated or club-shaped and had a ruffled membrane surface. Several thin filopodia extended from the growth cone and made contact with adjacent cells. At late recovery periods (35–120 days) there was a marked increase in the number of olfactory neurons within the middle and lower epithelium regions. Numerous dendritic processes extended to the epithelial surface and terminated in knob-like ciliated structures. Olfactory axons passed basally, forming small intra-epithelial bundles that penetrated the basal lamina then fasciculated into larger bundles within the lamina propria.This study provides detailed three-dimensional observations of the olfactory epithelium following neuron injury, and describes neural degenerative changes, replacement of olfactory neurons, development and maturation. In addition, we describe the structure and basal attachment of supporting cells and their glial-like relation with olfactory neurons.