Correlates of sleep and waking in Drosophila melanogaster. (1/46)

Drosophila exhibits a circadian rest-activity cycle, but it is not known whether fly rest constitutes sleep or is mere inactivity. It is shown here that, like mammalian sleep, rest in Drosophila is characterized by an increased arousal threshold and is homeostatically regulated independently of the circadian clock. As in mammals, rest is abundant in young flies, is reduced in older flies, and is modulated by stimulants and hypnotics. Several molecular markers modulated by sleep and waking in mammals are modulated by rest and activity in Drosophila, including cytochrome oxidase C, the endoplasmic reticulum chaperone protein BiP, and enzymes implicated in the catabolism of monoamines. Flies lacking one such enzyme, arylalkylamine N-acetyltransferase, show increased rest after rest deprivation. These results implicate the catabolism of monoamines in the regulation of sleep and waking in the fly and suggest that Drosophila may serve as a model system for the genetic dissection of sleep.  (+info)

Pharmacological blockade of ERG K(+) channels and Ca(2+) influx through store-operated channels exerts opposite effects on intracellular Ca(2+) oscillations in pituitary GH(3) cells. (2/46)

In the present study, the effects on intracellular calcium concentration ([Ca(2+)](i)) oscillations of the blockade of ether-a-go-go-related gene (ERG) K(+) channels and of Ca(2+) influx through store-operated channels (SOC) activated by [Ca(2+)](i) store depletion have been studied in GH(3) cells by means of a combination of single-cell fura-2 microfluorimetry and whole-cell mode of the patch-clamp technique. Nanomolar concentrations (1-30 nM) of the piperidinic second-generation antihistamines terfenadine and astemizole and of the class III antiarrhythmic methanesulfonanilide dofetilide, by blocking ERG K(+) channels, increased the frequency and the amplitude of [Ca(2+)](i) oscillations in resting oscillating GH(3) cells. These compounds also induced the appearance of an oscillatory pattern of [Ca(2+)](i) in a subpopulation of nonoscillating GH(3) cells. The effects of ERG K(+) channel blockade on [Ca(2+)](i) oscillations appeared to be due to the activation of L-type Ca(2+) channels, because they were prevented by 300 nM nimodipine. By contrast, the piperazinic second-generation antihistamine cetirizine (0.01-30 microM), which served as a negative control, failed to affect ERG K(+) channels and did not interfere with [Ca(2+)](i) oscillations in GH(3) cells. Interestingly, micromolar concentrations of terfenadine and astemizole (0.3-30 microM), but not of dofetilide (10-100 microM), produced an inhibition of the spontaneous oscillatory pattern of [Ca(2+)](i) changes. This effect was possibly related to an inhibition of SOC, because these compounds inhibited the increase of [Ca(2+)](i) achieved by extracellular calcium reintroduction after intracellular calcium store depletion with the sarcoplasmic or endoplasmic reticulum calcium ATPase pump inhibitor thapsigargin (10 microM) in an extracellular calcium-free medium. The same inhibitory effect on [Ca(2+)](i) oscillations and SOC was observed with the first-generation antihistamine hydroxyzine (1-30 microM), the more hydrophobic metabolic precursor of cetirizine. Collectively, the results of the present study obtained with compounds that interfere in a different concentration range with ERG K(+) channels or SOC suggest that 1) ERG K(+) channels play a relevant role in controlling the oscillatory pattern of [Ca(2+)](i) in resting GH(3) cells and 2) the inhibition of SOC might induce an opposite effect, i.e., an inhibition of [Ca(2+)](i) oscillations.  (+info)

Effects of anti-allergic drugs on intestinal mastocytosis and worm expulsion of rats infected with Neodiplostomum seoulense. (3/46)

The effects of anti-allergic drugs on intestinal mastocytosis and the expulsion of Neodiplostomum seoulense were observed in Sprague-Dawley rats, after oral infection with 500 metacercariae. The drugs used were hydroxyzine (a histamine receptor H1 blocker), cimetidine (a H2 blocker), cyclosporin-A (a helper T-cell suppressant), and prednisolone (a T- and B-cell suppressant). Infected, but untreated controls, and uninfected controls, were prepared. Worm recovery rate and intestinal mastocytosis were measured on weeks 1, 2, 3, 5, and 7 post-infection. Compared with the infected controls, worm expulsion was significantly (P < 0.05) delayed in hydroxyzine- and cimetidine-treated rats, despite mastocytosis being equally marked in the duodenum of all three groups. In the cyclosporin-A- and prednisolone-treated groups, mastocytosis was suppressed, but worm expulsion was only slightly delayed, without statistical significance. Our results suggest that binding of histamine to its receptors on intestinal smooth muscles is more important in terms of the expulsion of N. seoulense from rats than the levels of histamine alone, or mastocytosis.  (+info)

Inhibition of histamine-induced nasal obstruction by cetirizine in allergic rhinitis. (4/46)

This double-blind randomized crossover placebo-controlled study was designed to assess objectively the nasal antihistamine effect of cetirizine in patients with allergic rhinitis and control subjects. Nasal challenge was performed by nebulization of increasing doubling doses of histamine (0; 0.04 to 1.28 mg/nostril) in six patients with allergic rhinitis and six control subjects on cetirizine (2 x 10 mg daily for 3 days) or placebo. Sneezings were counted and nasal obstruction was assessed by subjective scoring and by objective measurement of nasal airway resistance by posterior rhinomanometry. Histamine induced sneezing and a dose-dependent increase in nasal airway resistance and in perceived sensation of obstruction. Responses were greater in patients with allergic rhinitis compared with controls, although of borderline significance for nasal obstruction. Cetirizine totally abolished sneezing and significantly reduced increase in nasal airway resistance and perceived sensation of nasal obstruction both in normal and rhinitic subjects. Our results demonstrate by an objective measurement the nasal antihistamine effect of cetirizine. We propose this simple provocation test to assess the time-course of the effect of antihistamines and to compare the relative potency of related compounds.  (+info)

Interference of cetirizine with the late eosinophil accumulation induced by either PAF or compound 48/80. (5/46)

1. The effect of topical or systemic treatment with the histamine H1-receptor antagonist, cetirizine, on the rat pleural eosinophil accumulation induced by PAF or compound 48/80 was investigated. The number of pleural resident eosinophils increased 6 h after the intrathoracic (i.t.) injection of PAF (1 microgram/cavity), peaked within 24 h and persisted significantly augmented for at least 96 h. Compound 48/80 (25 micrograms/cavity) also produced a long lasting pleural eosinophilia but this was first noted only 24 h after stimulation. 2. Intraperitoneal pretreatment with cetirizine inhibited eosinophilia induced by either PAF (ED50 = 19 mg kg-1) or compound 48/80 (ED50 = 14 mg kg-1) whereas meclizine, another histamine H1-receptor antagonist, was inactive. 3. Administered locally, cetirizine (5 and 15 micrograms/cavity) also dose-dependently inhibited both PAF- and compound 48/80-induced eosinophilia, providing evidence that its inhibitory effect is not due to any action upon circulating eosinophils. Consistent with this result, incubation of isolated peritoneal eosinophils with cetirizine failed to modify in vitro eosinophil migration caused by PAF. 4. Since the late eosinophilia induced by PAF may depend on the synthesis of a transferable protein mediator, cetirizine was administered to donor or recipient rats in order to determine whether it interferes with the generation or with the expression of this protein. We showed that only the treatment of recipient rats abolished the transfer of the eosinophilotactic activity, indicating that cetirizine does not modify the generation but inhibits the expression of this activity. 5. Our findings indicate that cetirizine is able to inhibit eosinophil accumulation by acting locally. The mechanism is neither related to its recognized ability to antagonize histamine H,-receptors nor to a direct action upon circulating eosinophils.  (+info)


The effect of some centrally-active and other drugs on the transmission of single nerve impulses through the isolated superior cervical ganglion preparation of the rabbit has been studied by recording both preganglionic and postganglionic action potentials. Block of conduction in the axon could be distinguished from block of the synaptic mechanism. The drugs did not appear to exert any one characteristic form of blocking action. A continuous spectrum of drug action linked an agent such as meprobamate which acted predominantly on the synapse to benactyzine which acted mainly by blocking axonal conduction. The drugs have been divided into three groups. Group I: hexamethonium, meprobamate, paraldehyde, amylobarbitone, methylpentynol and azacyclonal; these acted relatively selectively at the ganglion. Group II: N714C (the cis-isomer of chlorprothixene), prochlorperazine, methylpentynol carbamate, pipradrol, promethazine, perphenazine and procaine; the action of these drugs on the ganglion could be accounted for entirely in terms of their axonal depressant action. Group III: chlorprothixene, promazine, N720 (dihydrochlorprothixene), chlorpromazine, hydroxyzine and benactyzine; these drugs also blocked axonal conduction but in addition they appeared to exert a "facilitating" action at the ganglionic synapse. The actions of adrenaline, adrenochrome, iproniazid, ergotoxine, mescaline and lysergic acid diethylamide on transmission were also studied. The implications of the modifications of ganglionic transmission produced by these drugs is discussed.  (+info)

A randomized, controlled, crossover trial of oral midazolam and hydroxyzine for pediatric dental sedation. (7/46)

The effectiveness of oral midazolam in pediatric dentistry is controversial. This randomized, controlled, crossover, double blind clinical trial was conducted in order to study the effect of midazolam, used either alone or in association with hydroxyzine, during child dental treatment. Thirty seven dental sedation sessions were carried out on 11 ASA I uncooperative children less than five years-old. In each appointment children were randomly assigned to groups: P - placebo, M - midazolam (1.0 mg/kg), or MH - midazolam (0.75 mg/kg) plus hydroxyzine (2.0 mg/kg). Vital signs (blood pressure, breathing rate, pulse and oxygen saturation) and behavior parameters (consciousness, crying, movement, overall behavior) were evaluated every 15 minutes. Friedman and Wilcoxon statistical tests were used to compare groups and different moments in the same group. Normal values of vital signs were usually registered. Heart rate increased in groups P and M as the session went on. Group M presented less crying and movement at the first 15 minutes of treatment. Group MH caused more drowsiness at the beginning of the session. Overall behavior was better in group M than in groups P or MH. Group M produced effective sedation in 77% of the cases, and group MH did so in 30.8%. It was concluded that midazolam was effective and safe, and its association with hydroxyzine did not lead to additional advantages in pediatric dental sedation.  (+info)

Hydroxyzine-induced supraventricular tachycardia in a nine-year-old child. (8/46)

Hydroxyzine is a first generation antihistamine widely used in the paediatric population for a variety of conditions. A nine-year-old girl presented with supraventricular tachycardia while on clinical doses of hydroxyzine for pruritus. On arrival at the hospital, she was diaphoretic, with cool peripheries, poor peripheral pulses and a heart rate of 250/minute. There was a history of three palpitation episodes with chest tightness during the five months she was taking hydroxyzine. The supraventricular tachycardia eventually reverted to sinus rhythm with intravenous verapamil. Relevant cardiac examination and investigations had not shown any cardiac abnormalities. After discontinuing hydroxyzine, she had no further episodes of supraventricular tachycardia. To our knowledge, this is the first report of hydroxyzine induced-supraventricular tachycardia in the medical literature.  (+info)