PubMed Health⌕ Search

Biomedical subjects

A Crema

Publications and source records attributed to A Crema.

At least 19 recordsLinked to original sources
PubMed2000

[The electrocardiology of atrial fibrillation].

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and it is associated mainly with a significant mortality and morbidity. The purpose of this report is to focus on the major electro-cardiological aspects of AF and to provide some elements useful in the understanding of its pathophysiology. Experimental and clinical studies have shown that AF is maintained by multiple reentrant wavelets within the atrial muscle. It has been estimated that a critical number of wavelets (from 3 to 6) is necessary for perpetuation of AF. The short duration of the atrial effective refractory period (ERP) usually favors the onset of AF. Two different kinds of reentry have been observed during AF: random reentry and leading circle reentry. The presence of an adequate substrate is critical for the beginning of AF. Although this event is possible even in a normal atrium, atrial dilation and/or structural heterogeneity enhance the atrial propensity to develop AF. Even uniform or non-uniform anisotropy is now believed to play an important role in the genesis of AF. Finally, ionic channel disorders, some of which are genetically transmitted, may represent a possible substrate of AF. An important modulating role of the autonomic nervous system in the genesis of AF is universally accepted. In particular, many observations support the hypothesis that patients without heart disease tend to have vagally-mediated AF, whereas patients with structural heart disease tend to have adrenergic-mediated AF. In the presence of an opportunely modulated substrate, a third prerequisite for the triggering of a multiple atrial reentry is the presence of an adequate "trigger" factor. This is represented, in most cases, by ectopic atrial beats, commonly originating in the pulmonary veins. AF may cause atrial changes, either in an electrophysiological behavior and anatomy or both, that may favor its irreversibility and/or its frequent recurrence. Some of these changes are: atrial ERP disease, paradoxical shortening of ERP at a lower rate (inversed rate adaptation), accumulation of glycogen within atrial cells, apoptosis, and cellular dedifferentiation. The ventricular rate during AF has a pivotal role in its pathophysiology. The ERP of the atrioventricular node, the concealed conduction through the atrioventricular node, the autonomic neural balance and the drug's action are the most important factors that regulate ventricular rate during AF. In the presence of an atrioventricular accessory pathway, with fast anterograde conduction, AF is a very dangerous arrhythmia. During AF, aberrant conduction may often be seen, especially after long cycles (Ashman phenomenon). In patients with dilated cardiomyopathy and AF, arrhythmia is not always a secondary phenomenon. In fact, there is current evidence that AF may be the cause of cardiomyopathy.

Atrial Fibrillation↗
PubMed1995

Inhibitory effects of SR 58611A on canine colonic motility: evidence for a role of beta 3-adrenoceptors.

1. In order to clarify whether atypical or beta 3-adrenoceptors can modulate canine colonic motility in vivo, we studied the effects of SR 58611A (a selective agonist for atypical beta-adrenoceptors) alone and after pretreatment with beta-adrenoceptor antagonists on colonic motility in the conscious dog. The gastrocolonic response (postprandial increase in motility) was monitored by means of electrodes and strain-gauge force transducers chronically implanted along the distal colon. In some experiments, heart rate was also measured. The possible role of beta 3-adrenoceptors in mediating the effects of SR 58611A was also tested in vitro in circular muscle strips taken from the canine distal colon. 2. Intravenous infusion of SR 58611A, ritodrine or isoprenaline at doses inducing the same degree of tachycardia inhibited the gastrocolonic response to a different extent, with SR 58611A and ritodrine being more effective than isoprenaline. 3. In a dose-response study, SR 58611A was more potent in inhibiting colonic motility than in inducing tachycardia: the ED35 values for inhibition of colonic motility and induction of tachycardia were 23 and 156 micrograms kg-1, i.v., respectively. 4. The inhibitory effect of SR 58611A 100 micrograms kg-1, i.v., on the gastrocolonic response was reversed by alprenolol (non-selective beta-adrenoceptor antagonist), but resistant to CGP 20712A (beta 1-adrenoceptor antagonist) or ICI 118551 (beta 2-adrenoceptor antagonist). 5. In vitro, SR 58611A concentration-dependently relaxed circular muscle strips, an effect that was competitively antagonized by alprenolol with a pA2 value of 7.1, but resistant to CGP 20712A (100 nM), ICI 118551 (100 nM) or tetrodotoxin (1 microM). 6. The present study provides strong functional evidence for a role of atypical or beta 3-adrenoceptors in the modulation of canine colonic motility both in vivo and in vitro by an inhibitory effect most likely at the smooth muscle level.

Adrenergic beta-Agonists↗
PubMed1994

Effect of food on the bioavailability of pidotimod in healthy volunteers.

Pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) is a dipeptide-like molecule with immunostimulating activity in animals and in men. According to a cross-over randomized study design, 12 healthy volunteers received pidotimod both as 800 mg sachets and 800 mg ampoules after fasting and after a standard meal. The intake of a standard meal before pidotimod administration, either as sachet or as ampoule, reduced the bioavailability of the drug, probably due to an interference at the absorption level. After eating, the time of maximum plasma level was significantly longer than that observed after fasting, while AUC values and the maximum concentration were reduced by 50%. On the contrary, the pharmacokinetics after absorption phase were not influenced by food: as a matter of fact, half-life and MRT did not differ significantly when the drug was taken after fasting or after a standard meal. Finally, the two formulations used in this study resulted bioequivalent.

Adult↗
PubMed1993

Differential effects of antimuscarinic agents on intestinal motility in the conscious dog.

In this study we investigated the effects of antimuscarinics with different selectivity on the intestinal migrating myoelectric complex (MMC) in five fasting, conscious dogs, chronically fitted with electrodes along the small bowel. Furthermore, we evaluated the chronotropic and mydriatic effects to assess the in vivo selectivity of the agents tested. Dose-response studies were performed with the following drugs administered i.v.: atropine, telenzepine (M1 antagonist), AF-DX 116 [11,2-(diethylamino)methyl-1-piperidinyl-acetyl-5,11-dihydro-6H-pyrido-2 ,3b- 1,4-benzodiazepine-6-one (M2 antagonist)] and 4-diphenylacetoxy-N- methylpiperidine methiodide (4-DAMP) (M3 antagonist). All the antimuscarinics tested dose-dependently increased the duration of the MMC period and inhibited spike activity, except low-dose telenzepine (3-10 nmol/kg), which shortened the MMC period and stimulated spike activity. High-dose telenzepine (> 100 nmol/kg) mimicked the inhibitory effect of atropine on the intestine. ED50 values for delay of MMC onset were 87,232, > 10,000 and 129 nmol/kg for atropine, telenzepine, AF-DX 116 and 4-DAMP, respectively. At doses lengthening the MMC period, atropine and 4-DAMP also induced tachycardia and mydriasis. At doses shortening the MMC period, telenzepine had no effect on pupil diameter or heart rate, except at the dose of 10 nmol/kg, which reduced heart rate. Finally, AF-DX 116, at doses inducing marked tachycardia, had a minor intestinal effect and no mydriatic effect. The present data are consistent with the hypothesis that both M1 and M3 receptors are involved in the regulation of the MMC: M1 receptors are probably located on an inhibitory pathway, whereas M3 receptors mediate excitatory stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Motility of rabbit proximal colon. Relevance of cholinergic pathways and role of different muscarinic receptor subtypes.

To better define the physiologic relevance of the cholinergic muscarinic input to the rabbit colon and the role of different muscarinic receptor subtypes, we studied the effects of atropine, telenzepine (MI antagonist) and DF594 (M3 antagonist) on colonic motility in eight conscious rabbits fitted with bipolar electrodes and strain gauges along the proximal colon. In some experiments, the chronotropic and mydriatic effect of the pharmacological agents were also assessed. Two main patterns of spike activity were identified: short spike bursts (SSBs), which were usually stationary, and long spike bursts (LSBs), which were usually propagated. Both myoelectrical patterns were dose-dependently inhibited by atropine (0.06-4 mumol/kg). Atropine, at the doses of 2-4 mumol/kg, abolished both myoelectrical and mechanical activity. Telenzepine (0.008-0.125 mumol/kg) dose-dependently inhibited migrating LSBs without significant effect on SSBs. Higher doses (0.25-0.5 mumol/kg) inhibited both LSBs and SSBs. DF594 (0.06-2 mumol/kg) dose-dependently inhibited both migrating LSBs and SSBs. The three antimuscarinic agents, at doses that inhibited colonic spike activity by approximately 80% (equiactive doses), behaved as follows on heart rate and pupil diameter: atropine induced tachycardia and mydriasis, telenzepine had no effect, and DF594 induced slight mydriasis with no effect on heart rate. We conclude that spontaneous motility in the rabbit proximal colon depends on a muscarinic excitatory input. M3 receptors are involved in the control of both LSBs and SSBs, while M1 receptors play an important role in the regulation of LSBs. The development of selective antimuscarinic drugs, acting on a given motility pattern and with minimal side effects, may offer new perspectives in the treatment of functional bowel motor disorders.

Action Potentials↗
PubMed1992

Effect of calcium channel blockers on postprandial gastrointestinal motility in the dog.

We have compared the ability of nifedipine and lacidipine, a new 1,4-dihydropyridine, to interfere with postprandial gastrointestinal motility. Five conscious dogs, fitted with 8 bipolar electrodes along the gastrointestinal tract, were studied. Gastrointestinal spike activity was evaluated by means of a computer system. Lacidipine (8 micrograms kg-1) was administered as an i.v. bolus immediately followed by a 10 micrograms kg-1 h-1 i.v. infusion for 3 h, starting 30 min before a standard meal. This dose of lacidipine decreased systolic blood pressure by approximately 20%. Nifedipine was used at equihypotensive doses (30 micrograms kg-1 i.v. bolus followed by 300 micrograms kg-1 h-1 i.v. infusion). Lacidipine had no effect on either gastric or intestinal postprandial spike activity. Nifedipine significantly delayed the appearance of the fed pattern and reduced the number of spikes in the small bowel, while it had no effect on gastric spike activity. We conclude that equihypotensive doses of lacidipine and nifedipine differ in their effects on the gastrointestinal tract, lacidipine having a better cardiovascular selectivity profile than nifedipine, and that the sensitivity to nifedipine varies in different parts of the gut.

Animals↗
PubMed1991

Pharmacological activity and safety of trandolapril (RU 44570) in healthy volunteers.

The pharmacological activity and safety of the new angiotensin converting enzyme (ACE) inhibitor trandolapril (RU 44570) has been evaluated in ten healthy male volunteers given 2 mg once daily for seven days. Assessment criteria included evaluation of plasma ACE and renin activity and aldosterone levels in the supine and standing positions, monitoring of blood pressure, heart rate and electrocardiogram, routine blood and urine laboratory tests, and evaluation of adverse effects. Plasma ACE activity (both in the supine and standing positions) was significantly lower after the first dose and was almost completely suppressed after 7 days of treatment. Plasma renin activity with the subjects in both positions was significantly increased at the end of treatment. Plasma aldosterone did not vary significantly, except for an increase in the standing position after 7 days of wash-out. No significant changes occurred in blood pressure, heart rate, electrocardiogram, blood or urine laboratory tests. No adverse effects were reported, in particular, no orthostatic hypotension, cough or episodes of bronchospasm occurred. It is concluded that oral trandolapril 2 mg o.d. is an effective and long-lasting ACE inhibitor with a good safety profile on repeated dosing. Further studies are warranted to investigate its therapeutic application as well as its safety profile after long-term administration.

Adult↗
PubMed1991

Effect of iron succinyl-protein complexes on gastrointestinal motility in the fasting dog.

Studying the gastrointestinal motor effects of iron compounds may help to elucidate the mechanism originating the gastrointestinal side effects of frequently reported during martial therapy. The aims of the present study were: (1) to examine the gastrointestinal motor effects of ferrous sulfate (reference compound) and (2) to compare its effects with those of two iron succinyl-protein complexes (ITF 1096 and ITF 282, an iron-albumin and iron-casein complex, respectively). In 6 fasting, conscious dogs, fitted with 8 bipolar electrodes and 3 strain-gauge force transducers along the gastrointestinal tract, gastrointestinal motor activity was recorded. Ferrous sulfate and iron succinyl-protein complexes were administered by an orogastric tube at two dose levels: the lower and higher dose levels were approximately equivalent to 10 and 30 mg/kg as Fe, respectively. In control experiments, 154 mM NaCl, ITF 211 (succinylated albumin) and ITF 297 (succinylated casein) were used. Administration of 154 mM NaCl did not affect gastrointestinal motility nor did it disrupt migrating motor complex (MMC) cycling. ITF 1096 and ITF 282, only at the higher dose, lengthened the MMC period and increased intestinal, but not gastric spike activity. The effects of ITF 211 and ITF 297 were similar to those of ITF 1096 and ITF 282. Ferrous sulfate, at the lower dose, lengthened the MMC period; the higher dose disrupted MMC cycling and induced intense, irregular spike bursts in the stomach and in the small bowel, accompanied, in 3 out of 6 dogs, by a prolonged tonic contraction of the upper small bowel. Four out of 6 dogs vomited after the higher dose of ferrous sulfate. No vomiting was observed with any of the other treatments. We conclude that ITF 1096 and ITF 282 have a markedly better gastrointestinal tolerability than ferrous sulfate.

Animals↗
PubMed1991

Physiopharmacology of the peristaltic reflex: an update.

The peristaltic reflex is one of the simplest models which can be used to study the function of enteric neurons by recording intestinal motor activity. Peristalsis consists of a coordinated, aborally propagating motor activity which requires the functional integrity of receptor pathways, excitatory and inhibitory neural pathways and neuromuscular junctions. Luminal distension elicits polarized responses: an ascending excitatory response (ascending contraction) and a descending inhibitory response (descending relaxation). The present paper reviews the most recent acquisitions on the neural pathways and neurotransmitters involved in the regulation of the peristaltic reflex.

Humans↗
PubMed1991

Effect of single doses of rufloxacin on the disposition of theophylline and caffeine after single administration.

Several reports indicate that quinolone antibiotics affect the pharmacokinetics of theophylline and caffeine. This study investigated the effects of one single oral dose of rufloxacin, a new quinolone antibacterial, on the pharmacokinetics of theophylline and caffeine, given as single oral doses. Twelve healthy male volunteers were randomly given one of the following treatments: treatment T: 300 mg theophylline; treatment T + R: 300 mg theophylline followed by 400 mg rufloxacin after 30 min; treatment C: 200 mg caffeine; treatment C + R: 200 mg caffeine followed by 400 mg rufloxacin after 30 min. Blood samples for determination of xanthine plasma levels were taken immediately before and 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours after xanthine administration. Urine were collected before treatment and at 0-6, 6-12, 12-24 and 24-48 h intervals. There were no significant differences in the pharmacokinetic parameters or in urinary excretion after administration of either theophylline or caffeine when combined with rufloxacin. Sleep disturbances were reported by two subjects after both treatment T + R and C + R, and by four subjects after treatment T + R. The results of this study indicate that there is no significant pharmacokinetic interaction between a single oral dose of rufloxacin and single doses of theophylline and caffeine.

4-Quinolones↗
PubMed1990

Pharmacokinetics of the total triterpenic fraction of Centella asiatica after single and multiple administrations to healthy volunteers. A new assay for asiatic acid.

A new HPLC assay method was used to investigate the pharmacokinetics of asiatic acid after oral administration of the total triterpenic fraction of Centella asiatica in single doses (30 or 60 mg) and after a 7-day treatment (30 or 60 mg twice daily). Twelve healthy volunteers received each treatment following a randomized cross-over design with trials separated by a 3-week interval. The time of peak plasma concentration was not affected by dosage difference or by treatment scheme. Differences in peak plasma concentration and area under the concentration vs. time curve from 0 to 24 h (AUC0-24) calculated after 30 or 60 mg administration (single dose) were accounted for by the different dose regimen. However, after chronic treatment with both 30 and 60 mg, peak plasma concentrations, AUC0-24 and half-life were significantly higher than those observed after the corresponding single dose administration. This phenomenon could be explained by a metabolic interaction between asiatic acid and asiaticoside, which is transformed into asiatic acid in vivo.

Administration, Oral↗
PubMed1990

Effects of a new 1,4-dihydropyridine, lacidipine, on gastrointestinal motility and other gastrointestinal functions.

Lacidipine is a new 1,4-dihydropyridine calcium entry blocker endowed with slow onset of action and potent and long-lasting antihypertensive activity. This study investigated the effect of lacidipine on some gastrointestinal functions, mainly gastrointestinal motility, in rats and dogs. In fasting conscious dogs chronically fitted with electrodes and strain gauges along the small bowel, lacidipine (12 micrograms/kg i.v. bolus or 10 micrograms/kg/h for 3 h) did not modify the migrating motor complex pattern or intestinal spike activity. In the rat, lacidipine proved less active (ED 50 greater than 100 mg/kg p.o.) than nitrendipine (ED 50 = 31 mg/kg p.o.) in inhibiting gastric emptying of a liquid meal, whereas the opposite was true after a solid meal (ED 50 = 10.9 and 35.0 mg/kg p.o., respectively). Lacidipine inhibited fecal pellet output at lower doses (ED 50 = 14.8 mg/kg p.o.) than nitrendipine (ED 50 = 40.1 mg/kg p.o.). On histamine-induced gastric acid secretion, the effect of 100 micrograms/kg i.v. lacidipine was moderate (maximum inhibition 45%). The gastrointestinal effects displayed by lacidipine appear at doses at least 5 and 50 times as high as those affecting blood pressure after intravenous and oral administration, respectively. Thus, lacidipine is unlikely to cause noteworthy unwanted effects on the gastrointestinal tract.

Animals↗