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Biomedical subjects

A Crema

Publications and source records attributed to A Crema.

At least 37 records · Page 2Linked to original sources
PubMed1990

[Tiaprofenic acid: levels in plasma and upper airway tissues].

Inflammatory processes of the upper airways can be successfully improved by using non steroid anti-inflammatory drugs, alone or in association with antibiotics. Recent clinical reports suggest that tiaprofenic acid (TA) is particularly suited for this purpose. This fact can be explained on the basis of the drug's pharmacokinetics and by the high concentration TA can achieve in the respiratory tract mucous membranes. In order to confirm this hypothesis TA levels were studied in the plasma as well as in tonsillar and turbinal tissue. Patients admitted for tonsillectomy or turbinectomy were given two tablets (600 mg) of TA from one and a half to five hours before surgery. In all cases blood and tissue samples were taken at the same time during surgery and drug levels determined by HPLC. Plasma levels ranged from 12 to 26 to 32.2 microgram/ml; tissue levels ranged from 3.9 to 5.4 to 4.9 micrograms/g, respectively, depending on time of administration. There was no significant difference between tonsillar and turbinal tissue. These results suggest a good penetration of nasal and airway mucosa by TA and are in agreement with the clinical data on the efficacy of TA in dealing with upper airway inflammatory conditions.

Adolescent↗
PubMed1989

Inhibitory effects of calcium channel blockers on intestinal motility in the dog.

Calcium channel blockers are now widely used for the treatment of cardiovascular disorders. However, data concerning their effects on intestinal motility in vivo are still rather fragmentary. Therefore, we evaluated the effects of three prototype calcium channel blockers (nifedipine, verapamil and diltiazem) on intestinal motility in five fasting, conscious dogs fitted with electrodes and strain-gauges along the small bowel. The myoelectric data were analyzed by a recently developed and validated computer program which allows accurate monitoring of intestinal spike activity. The mechanical data were analyzed by calculating a motility index. After recording of at least two migrating motor complexes (control), an i.v. infusion of one of the following calcium channel blockers was maintained for 3 h: 0.29 or 0.87 mumol/kg per h nifedipine, 1.02 or 2.04 mumol/kg per h verapamil and 1.11 or 2.22 mumol/kg per h diltiazem. Nifedipine 0.29 mumol/kg per h significantly reduced (P less than 0.05) spike activity and motility index during phases II and III without disrupting migrating motor complex cycling. The higher dose suppressed migrating motor complex cycling and almost completely abolished both spike and mechanical activities. The two doses of verapamil had effects similar to those of the two doses of nifedipine. Both doses of diltiazem significantly reduced (P less than 0.05) spike activity and motility index during phases II and III without disrupting migrating motor complex cycling. We conclude that all the agents tested, apart from their well known cardiovascular effects, also have a profound inhibitory effect on intestinal motility in vivo, the order of potency being nifedipine greater than verapamil greater than diltiazem. The search for more selective calcium channel blockers for the treatment of intestinal motor disorders with minimal cardiovascular effects is warranted.

Animals↗
PubMed1989

The role of GABAA receptor function in peristaltic activity of the guinea-pig ileum: a comparative study with bicuculline, SR 95531 and picrotoxinin.

1. The peristaltic activity of the guinea-pig ileum was studied in the absence and in the presence of the blockade of GABAA receptors. 2. Bicuculline (1-30 microM), improved at the highest concentrations the efficiency of peristalsis by enhancing the frequency of propulsive contractions and the amount of fluid ejected per unit of time. 3. Neither SR 95531 (0.3-10 microM), a novel GABAA receptor antagonist, which competitively antagonized 3-aminopropane sulphonic acid induced contractions in myenteric plexus-longitudinal muscle preparations (pA2 value: 6.47), nor picrotoxinin (1-30 microM) modified peristaltic parameters or influenced the potentiating effect of bicuculline on peristaltic activity. 4. In myenteric plexus-longitudinal muscle preparations, bicuculline (1-30 microM) enhanced the amplitude of electrically-induced cholinergic contractions without modifying submaximal contractions to applied acetylcholine. SR 95531 and picrotoxinin had no effect on twitch amplitude. In the presence of each of these compounds, bicuculline retained its potentiating effect. 5. The results obtained with SR 95531 and picrotoxinin question the view that GABAA receptors may exert a critical role in intestinal propulsion by modulating the activity of nerve pathways subserving peristalsis. Bicuculline potentiates the peristaltic activity of the ileum probably via a facilitatory effect on enteric cholinergic transmission that is independent of GABAA receptor blockade.

Animals↗
PubMed1989

An in vitro study of the relationship between GABA receptor function and propulsive motility in the distal colon of the rabbit.

1. The effects of gamma-aminobutyric acid (GABA), 3-aminopropane sulphonic acid (3-APS) and baclofen on spontaneous, electrically-induced and propulsive motility were investigated in rabbit distal colon. 2. In unstimulated longitudinal (LMPs) and circular muscle strip preparations (CMPs) 3-APS (10-200 microM) and GABA caused a clear-cut relaxation susceptible to desensitization. Baclofen (10-200 microM) caused relaxation in a minority (30%) of preparations. The 3-APS response was sensitive to tetrodotoxin (TTX; 1 microM), SR 95531 (a novel competitive GABAA-receptor antagonist) (10 microM), picrotoxinin (30 microM), and insensitive to hyoscine (1 microM) and to a combination of prazosin (1 microM) and propranolol (1 microM). The baclofen response was antagonized by 5-aminovaleric acid (DAVA, 500 microM), TTX and hyoscine and resistant to GABAA-receptor and adrenoceptor blockade. GABAA-receptors were therefore associated with non-adrenergic non-cholinergic (NANC) inhibitory nerve activation while GABAB-receptors were involved in depression of cholinergic tone of smooth muscle. GABA (10-200 microM) elicited both above mentioned effects. 3. In LMPs, baclofen (10-200 microM) dose-dependently inhibited submaximal responses to both cholinergic and NANC inhibitory nerve stimulation. This effect was resistant to SR 95531 and picrotoxinin and prevented by DAVA and baclofen desensitization. GABA (10-200 microM) mimicked the action of baclofen. GABA inhibitory effects persisted in the presence of GABAA-receptor blockade. 4. In segments of distal colon, GABA and baclofen (1-200 microM), but not 3-APS (1-200 microM), dose-dependently decreased the velocity of propulsion of an intraluminally-distended balloon. This effect was antagonized by DAVA and GABA or baclofen desensitization and resistant to SR 95531 and picrotoxinin. These antagonists per se had no effect on propulsion. In preparations in which propulsion was slowed by hyoscine (1 microM), baclofen caused no consistent further depression of propulsive activity. 5. Our results show that GABAA- and GABAB-receptors are present in rabbit colon. GABAA-receptor stimulation activates NANC inhibitory nerves without apparently affecting propulsion. GABAB-receptors are associated with a reduction of neural (mainly cholinergic) activity subserving muscular tone and peristalsis and appear to be located on both cholinergic and NANC inhibitory nerves. However, the persisting propulsive activity during suppression of GABAA- and GABAB-receptor function suggests that GABA in enteric neurones is not crucial for the neural circuitry subserving colonic peristalsis in this species.

Amino Acids↗
PubMed1989

[3H]acetylcholine release from the guinea-pig distal colon: comparison with ileal [3H]acetylcholine release and effect of adrenoceptor stimulation.

To study cholinergic function in the guinea-pig colon, resting and electrically evoked 3H release after preincubation with [3H] choline has been compared in colonic and ileal myenteric plexus preparations. Fractional spontaneous colonic 3H release was significantly higher than ileal 3H release, while the reverse was true for electrically evoked 3H outflow. Electrically evoked 3H outflow in the colon was linearly related to stimulation frequency (0.2-3 Hz range) and current intensity (300-600 mA range), while 3H outflow per pulse was inversely related to stimulation frequency. Electrically evoked 3H outflow was prevented in Ca2(+)-free solution, indicating that it probably mirrored neuronal exocytotic [3H]acetylcholine release. Both noradrenaline and clonidine concentration-dependently inhibited electrically evoked 3H outflow, clonidine being more potent but less efficacious than noradrenaline. For both noradrenaline and clonidine, the potency and efficacy for inhibition of 3H outflow were close to the values previously reported for the inhibition of electrically evoked endogenous acetylcholine output from colonic preparations. In conclusion, these data indicate that 3H release after incubation with [3H]choline is a valid alternative to measurement of endogenous acetylcholine output to study colonic cholinergic neuronal function in the guinea-pig.

Acetylcholine↗
PubMed1989

Effect of beta-casomorphins on intestinal propulsion in the guinea-pig colon.

beta-Casomorphins are a family of opioid peptides originally isolated from beta-casein. In view of a possible physiological significance of these milk-derived compounds, the effects of bovine beta-casomorphin-5 (beta-CM-5), beta-casomorphin-4 (beta-CM-4) and D-Ala2-beta-casomorphin-4-NH2 (D-Ala2-beta-CM-4-NH2) have been investigated on the peristaltic reflex in the guinea-pig isolated colon and compared with morphine. beta-CM-5 and D-Ala2-beta-CM-4-NH2 each dose-dependently inhibited the velocity of propulsion of an intraluminal bolus; beta-CM-4 was ineffective. IC50 values were 0.30, 5.21 and 0.29 microM for morphine, beta-CM-5 and D-Ala2-beta-CM-4-NH2, respectively. The potency ratios vs morphine were 0.06 and 0.96 for beta-CM-5 and D-Ala2-beta-CM-4-NH2, respectively. Blockade of the peristaltic reflex by beta-CM-5 or D-Ala2-beta-CM-4-NH2 was reversed by the opioid antagonist naloxone. D-Ala2-beta-CM-4-NH2 also dose-dependently inhibited resting acetylcholine output (IC50 = 5.69 microM; potency ratio vs morphine: 0.63). In conclusion, certain beta-casomorphins inhibit intestinal propulsion and cholinergic neurotransmission in the guinea-pig colon, probably by acting at opioid receptors.

Acetylcholine↗
PubMed1989

Inhibitory effects of DF 594, a new antispasmodic agent, on intestinal motility in the dog.

DF 594, 11-(N-methylnipecotyl)-6,11-dihydro-5H-pyrido[2,3-b]-1,5-benzod iazepin-5-one hydrochloride, is a new antimuscarinic compound endowed with high affinity for intestinal muscarinic receptors and showing potent inhibitory effects on intestinal motility. This study investigated the intestinal motor effects of DF 594 in fasting, conscious dogs, chronically fitted with electrodes and strain gauges along the small bowel. In a first series of experiments, we assessed the antispasmodic activity of the compound by comparing the ability of intravenous DF 594 or atropine to antagonize the stimulatory effect of bethanechol (100 micrograms/kg s.c.). ED50 values for inhibition of bethanechol-stimulated contractions were 13.9 (8.8-21.8) and 4.0 (1.8-8.7) micrograms/kg for DF 594 and atropine, respectively. In a second series of experiments, we evaluated the effects of intravenous DF 594 and atropine on the migrating motor complex (MMC), monitoring heart rate as well. Similarly to atropine (30-100 micrograms/kg), DF 594 (100-300 micrograms/kg) blocked the further migration of an ongoing MMC and significantly delayed the onset of the following MMC. Unlike atropine, DF 594 had only a minor effect on heart rate at the highest dose tested (300 micrograms/kg). These data indicate that DF 594 is an effective antispasmodic agent at doses lower than those required to interfere with the MMC and is also less likely than atropine to induce cardiac side effects.

Animals↗
PubMed1988

Quantitative analysis of intestinal electrical spike activity by a new computerized method.

We developed a computerized method that allows quantitative analysis of intestinal spike activity. This method was tested for a series of measurements in six fasting conscious dogs, fitted with bipolar electrodes chronically implanted along the small intestine. Data were stored on 8-channel tape recordings and digitized before computer processing. Spike detection was accomplished by means of a discriminant function able to differentiate spikes from non-spikes (e.g. artifacts) on the basis of six parameters. Computer analysis allowed accurate spike recognition (probability of incorrect classification less than 6%). Spike activity during fasting was monitored by calculating, during each phase of the migrating myoelectric complex, the following parameters per unit of time (30 s): number of spikes, percentage of spiked slow waves and number of spikes per spiked slow wave. Results were given both in tabular and graphical form. This method provides a research tool for a better quantitation of intestinal spike activity.

Action Potentials↗
PubMed1988

Kinetics of the Hb A to Hb C switch and erythropoietin plasma levels in sheep.

The induction of Hb A (alpha 2 beta A2) and Hb C (alpha 2 beta C2) synthesis in three adult sheep has been sequentially analysed, in relation to the reduction of the haematocrit (Ht) and to the changes of erythropoietin (Epo) concentration in plasma. Hb A production is detected in peripheral reticulocytes when the Ht approaches 70% of its initial value in correspondence with the first rise of EPO plasma level, whereas HB C synthesis appears when the Ht is further reduced to about 50%, at an Epo concentration two to three times higher. The assumption that the cell committed to HB C synthesis is close to the erythroid colony-forming unit (CFU-e) progenitor is also discussed.

Anemia↗
PubMed1987

Involvement of substance P in the excitatory action of GABAA agonists on cholinergic neurons in the guinea-pig ileum.

The possible involvement of substance P (SP) in cholinergic contractions induced by GABAA agonists in the guinea-pig ileum was further investigated. Responses evoked by 3-aminopropane sulphonic acid (3-APS) or muscimol consisted of a rapid phasic contraction followed in 70% of preparations by a tonic contraction, usually smaller in amplitude but considerably longer in duration. Phasic and tonic components were sensitive to bicuculline, neurogenic (cholinergic) in nature and susceptible to desensitization. Capsaicin (0.2 microM) pretreatment and SP receptor desensitization caused by 3 different priming SP concentrations (10 nM, 30 nM, 100 nM), depressed both components of the 3-APS-induced response, the magnitude of antagonism being greater for tonic contractions. Similar findings were obtained by using 10 microM (D-Pro4,D-Trp7.9)SP-(4-11), even though the degree of antagonism caused by this SP antagonist was consistently lower. These results indicate that depression of SP receptor function achieved by three different procedures decreases cholinergic contractile responses to GABAA agonists in the guinea-pig ileum. This provides further support for the hypothesis that GABAA receptor activation evokes both direct and indirect stimulation of enteric cholinergic neurons and that SP and/or a related peptide play an important role in mediating the indirect component of the cholinergic response.

Animals↗
PubMed1987

Pharmacokinetic-dynamic study on different oral biperiden formulations in volunteers.

The pharmacodynamic and kinetic profiles of two oral biperiden formulations (tablet with instant-release and sugar-coated tablet with slow-release) were studied in a total of 12 healthy subjects after the administration of a 4 mg dose and compared in part to placebo. Biperiden as slow-release formulation showed much slower absorption than the instant-release tablet; whereas plasma levels peaked as early as 1-2 h after administration of the tablet, with the slow-release formulation a first peak was seen approximately 4.5 h after intake in the majority of the subjects. In some subjects this was followed by a trough, in others by formation of a shoulder at around 0.5 ng/ml. In all subjects a peak of about 1.0 ng/ml was reached after 10-12 h. The instant-release tablet and the slow-release formulation showed comparable bioavailability. Plasma concentrations for the slow-release formulation at 24 h were around 0.5 ng/ml, about twice as high as those for the instant-release formulation. The ratio of peak to 24 h values showed the marked reduction which is characteristic for a slow-release formulation compared with the instant-release tablet. The subjective well-being of the volunteers was not influenced by the slow-release formulation, whereas after the instant-release tablet slight CNS effects (dizziness, drowsiness and fatigue) were reported up to 6 h after ingestion. Furthermore, objectively quantifiable pharmacodynamic ocular parameters (near-point accomodation, pupil size) and the secretion of saliva proved to be less affected by the slow-release formulation than by the instant-release tablet, or not affected at all.

Accommodation, Ocular↗
PubMed1987

Depressant action of oxybutynin on the contractility of intestinal and urinary tract smooth muscle.

Experiments were carried out in-vitro using segments of guinea-pig ileum, taenia caeci, ureter and detrusor. In the ileum, oxybutynin (30, 100 nM) competitively antagonized acetylcholine-induced contractions but did not alter those induced by histamine. Higher concentrations of oxybutynin (up to 10 microM) induced a non-competitive depression of responses to both agonists and caused a parallel shift to the right of the Ca2+-induced contractions in taenia caeci strips bathed in a Ca2+-free, high-K+ medium. In the ureter, oxybutynin (1-10 microM) impaired rhythmic muscular contractions in normal medium and after CaCl2 addition in Ca2+-free medium. Similarly to verapamil (10, 30 microM), oxybutynin (10, 30 microM) depressed both the cholinergic and non-adrenergic, non-cholinergic components of the electrically-induced contractions of detrusor strips. It is concluded that oxybutynin has anticholinergic properties and, at higher concentrations, exerts a direct spasmolytic activity possibly mediated by blockade of the transmembrane Ca2+ fluxes responsible for smooth muscle contraction.

Acetylcholine↗
PubMed1987

Pharmacokinetics of co-trimazine after single and multiple doses.

Plasma and urinary levels of trimethoprim (TMP), sulfadiazine (SDZ) and N4-acetylsulfadiazine (N4-SDZ) were determined after administration of 1 g co-trimazine (equivalent to 180 mg TMP and 820 mg SDZ) (Kombinax) as a single dose and again once daily for 7 days to 6 normal subjects. Both TMP and SDZ were rapidly absorbed from the gastrointestinal tract with peak plasma levels being achieved within 4 h in all subjects. Elimination half-lives ranged from 8 to 13 h for TMP and from 9 to 15 h for SDZ. Approximately 50% of the administered dose of SDZ was recovered in urine within 24 h of the single dose (32% as unchanged drug and 17% as the N4-acetylmetabolite). For TMP, the urinary recovery during the 24 h following the single dose averaged 39%. Mean plasma levels of TMP, SDZ and N4-SDZ at steady state were moderately higher than those observed after a single dose, but no change in absorption or disposition kinetics of these compounds was seen after repeated dosing.

Adult↗
PubMed1986

Inhibitory action of capsaicin on cholinergic responses induced by GABAA agonists in the guinea-pig ileum.

Pretreatment of the guinea-pig ileum with capsaicin resulted consistently in depression of the neurogenic cholinergic contractions induced by the GABAA receptor agonists 3-aminopropane sulphonic acid (3-APS) and muscimol. Since capsaicin acts mainly by releasing and depleting substance P from its stores in intestinal nerves, it is likely that substance P plays a role in the response caused by GABAA-mimetic compounds, On the whole, our results suggest that excitatory responses to 3-APS and muscimol result from both direct and indirect activation of intrinsic intestinal cholinergic neurons innervating smooth muscle cells.

Animals↗
PubMed1986

A re-appraisal of the mode of action of 5-HT in inhibiting GABA-induced cholinergic contractions in the guinea-pig ileum.

In the guinea-pig ileum, pretreatment with 5-hydroxytryptamine (5-HT) (5 microM) for 4-5 min inhibited both 5-HT- and gamma-aminobutyric acid (GABA)-induced cholinergic contractions without consistently altering those induced by electrical field stimulation. Cisapride (1 micron) antagonized 5-HT-induced cholinergic contractions but left those induced by GABA or twitch responses unchanged. These results indicate that the 5-HT action in inhibiting GABA-induced cholinergic responses may arise at the interneuronal level, thus suggesting that GABA may also indirectly activate cholinergic terminal neurons. These findings rule out the possibility of 5-HT acting as an intermediate transmitter in this type of response.

Animals↗
PubMed1986

Pharmacokinetic and pharmacodynamic studies following the intravenous and oral administration of the antiparkinsonian drug biperiden to normal subjects.

The pharmacokinetics and pharmacodynamics (changes in pupil size and salivary flow) of biperiden following a single oral and intravenous dose were investigated in six normal subjects. After the injection plasma concentrations declined biphasically, with half-times of 1.5 h for the rapid phase and 24 h for the terminal phase. Clearance and apparent volume of distribution were high (12 ml X min-1 X kg-1 and 24 l X kg-1 respectively). Absorption was rapid but the systemic availability was incomplete (33%), probably due to first-pass metabolism. Central nervous system (CNS) adverse effects and changes in pupil size were observed after both routes of administration while salivary flow was affected only by the injection.

Administration, Oral↗