摘要:

Summary—Any pharmaceutical nasal preparation should respect the physiological function of the mucociliary transport system and should undergo testing to this effect. An experimental protocol has been developed using the guinea pig in order to assess the effects of commercial nasal drop preparations on mucociliary function. The method presented here consists of applyingin vivothe test solution on the nasal respiratory epithelium. After a specified contact time and following rapid sacrifice of the animal, the mucosa is removed; the beating frequency of the cilia is then recordedex vivoby micro‐photo‐oscillography.The method is sensitive to compounds known to diminish mucociliary function as sodium mercurothiolate inhibits ciliary movement of the nasal epitheliumex vivo. This inhibition of ciliary movement is long‐lasting, although reversible.This method can be used to test the action of intranasally administered pharmaceutical preparations on mucociliary function. Commercially available solutions of the nasal vasoconstrictors tymazoline, fenoxazoline or oxymetazoline do not alter ciliary movementex vivoat dose levels equal to or greater than those clinically utilized. ATP significantly enhances nasal ciliary frequency in instances where a low basal rate occurred.Thus, this method can be used for the testing of the maintenance of nasal ciliary function in the presence of compounds and preparations which will be applied into the nostrils. The advantages over previous techniques include a closer approach to the therapeutic utilization and the maintained physiological conditions of the mucosa during drug adminis

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1989.tb00682.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Summary—Cerebral and renal α‐adrenoceptors are implicated in the control of sympathetic activity and of sodium reabsorption respectively. In addition, sodium ions play an important role in the regulation of either α‐adrenoceptor densities and affinities for adrenergic agonists. In the present study, α‐adrenoceptor properties were investigated in genetically predetermined salt‐sensitive and salt‐resistant Dahl and Sabra rats.Cerebral α2‐adrenoceptor densities were higher in salt‐resistant than in salt‐sensitive Dahl and Sabra rats. In contrast, renal α2‐adrenoceptor density was higher in salt‐sensitive than in salt‐resistant rats. No difference in cerebral and renal α1‐adrenoceptor densities was observed between Dahl and Sabra substrains. Noradrenaline content in cerebral and renal cortex were also similar in both these rat substrains.Sodium ions markedly increased cerebral and renal high‐affinity α2‐adrenoceptor densities in salt‐sensitive but not in salt‐resistant rats. Cerebral and renal α1‐adrenoceptor densities were unchanged in salt‐sensitive and salt‐resistant substrains of Dahl and Sabra rats. In addition, sodium ions reduced the affinity of adrenaline for renal α2‐adrenoceptors in salt‐sensitive rats but not in salt‐resistant rats.We can conclude that there exist genetically determined differences in the densities and properties of cerebral and renal α2‐adrenoceptors between salt‐sensitive and salt‐resistant rat strains. Abnormal densities of α2‐adrenoceptors may play a primary role in the role in the development of hypertension in salt‐sensitive animals. These results also suggest an association between absence of sodium regulation of α2‐adrenoceptors and resistance to salt‐induced hypertension. The absence of sodium regulation in salt‐resistant rats may be linked either to a particular receptor conformation or to an abnormal structure of the receptor system. This property may represent a genetically‐mediated change res

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1989.tb00683.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Summary—Strips of human corpus cavernosum were incubated with3H‐noradrenaline and subsequently superfused with physiological salt solution containing desipramine and corticosterone. The electrically (0.66 Hz) evoked tritium overflow was abolished by tetrodotoxin or omission of Ca2+from the superfusion fluid. The α2‐adrenoceptor agonist B‐HT 920 (6‐allyl‐2‐amino‐5, 6, 7, 8–4H‐thiazolo‐5,4‐d‐azepine), inhibited the evoked overflow, whereas the α1‐adrenoceptor agonist, methoxamine, was ineffective. The α2‐adrenoceptor antagonist, rauwolscine, facilitated the evoked tritium overflow. It is concluded that the stimulation‐evoked release of noradrenaline from the sympathetic nerve fibres of the human corpus cavernosum is modulate

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1989.tb00684.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Summary—A study aimed at investigating the behavioural effects of aztreonam and gentamicin, given separately or in combination, was carried out in mice. Animals were randomly assigned to two test conditions: acute and chronic treatment. Those receiving acute treatment had a single IP injection 60 min before the test. Those receiving chronic treatment had IP injections once daily for 5 successive days prior to the test.Behavioural patterns (ambulation, rearing, grooming and defecation) were assessed using the “open‐field” test. The results indicate that, both after single and multiple dosing, aztreonam (10, 40 and 80 mg/kg IP) and/or gentamicin (10 mg/kg IP) do produce changes in the behaviour of animals. A rate increasing effect for certain behaviours (rearing, grooming and defecation) and a reduction in other behaviours (ambulation) seems t

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1989.tb00685.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Summary—Previous studies on pharmacokinetic parameters of tricyclic antidepressants (TCAs) in rodents have shown different results from those obtained for the same drugs in man. The kinetics of metapramine (META) and its major demethylated metabolites (METs) were studied in the SWISS CD 1 mouse after acute administration in order to establish the pharmacokinetic parameters in plasma and brain. The plasma half‐life (T1/2) was very short (87 min) compared with the half‐life (7 h) in man. The metabolism of META was intensive as was the transfer of META and its metabolites into the brain. The kinetic profiles of the substances were quite similar both in plasma and in brain, namely a bicompartment open model. META was rapidly absorbed (Tmax=10 min) into and quickly eliminated (T1/2=40 min) from the brain.These parameters were used to schedule sampling (blood and brain) at the appropriate time after acute administration of increased doses.The administered doses were significantly correlated to firstly the plasma or brain levels of META, secondly the plasma levels of the main monodemethylated metabolite (MET I), and thirdly the plasma or brain levels of META + METs.Finally, the evolution of plasma and brain levels of the substances was studied after repeated injections (i.e. every 40 min) and confirmed the high affinity of META and its metabolites for the brain re

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1989.tb00686.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Summary—Disopyramide is a group I antiarrhythmic drug which is mainly used for the treatment of ventricular and supraventricular rhythm disturbances. Commonest side effects result from disopyramide's anticholinergic activity. Other side effects such as hypoglycemia have been reported less frequently. We report one observation of disopyramide induced hypoglycemia, and a review of the literature is presented.Including our observation, 14 cases (9 men and 5 women, aged from 41 to 88) have so far been reported. Doses of disopyramide ranged from 200 to 1 200 mg per day, administered from one day to one year. Symptomatology was mainly neurologic (12 patients) and two patients were clinically asymptomatic. The outcome was favorable in all but the 2 patients who died with persistent hypoglycemia after a single dose of 250 mg in one patient and after 400 mg daily during 4 days in the other (without stopping the drug). Renal function was markedly impaired in 9 patients, two of these patients being on a long term dialysis therapy. Blood levels of disopyramide were measured in 7 patients and ranged from 1 to 11.4 ng/ml. In five patients it was in the normal range (1–4 ng/ml). Three patients were rechallenged for disopyramide: hypoglycemia occured in all, without clinical symptoms in two of them. The main risk factors of disopyramide induced hypoglycemia are a preexisting chronic renal failure, advanced age, and malnutrition. In these patients normally non toxic disopyramide blood levels, as defined in normal subjects, seem to be inappropriately high. We suggest that in patients at risk, disopyramide blood levels should be maintained at the lower range of therapeutic level. The recommended daily dose is 400 mg/day. Thus, it appears appropriate not to exceed 2/3 of this dosage, and to be particularly caution when using this drug in patients at r

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1989.tb00687.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Summary—The pharmacokinetics of colchicine were studied after oral administration of three doses (0.5, 1.0 and 1.5 mg) to nine healthy male volunteers according to randomized cross‐over design. Plasma and urine samples were collected during 48 h after ingestion, and assayed for colchicine levels by a specific and highly sensitive radio‐immunoassay. Pharmacokinetic parameters t1/2β, AUC, MRT, CIT/F, CIR, Vd area/F) were calculated by model‐independent methods and compared across doses by multiway analysis of variance. Terminal half‐life (15.5–19.2 h), mean residence time (15.7–20.3 h), oral systemic (32.2–40.3 l/h) and renal (3.9–4.7 l/h) clearances, and oral volume of distribution (11.4–14.9 l/kg) did not differ significantly between doses, whereas the area under the concentration‐time curve was proportional to dose. Our results show that:1within the dose range studied (0.5–1.5 mg), the pharmacokinetics of colchicine are linear;2monitoring colchicine levels up to 48 hours yields much larger estimates of terminal half‐life and volume of distribution than previously reported from co

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1989.tb00688.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1989.tb00689.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1989.tb00690.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY