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Biomedical subjects

A Monopoli

Publications and source records attributed to A Monopoli.

67 records · Page 4Linked to original sources
PubMed1989

Left ventricular diastolic filling improvement obtained by intravenous verapamil in mild to moderate essential hypertension: a complex effect.

In order to try and evaluate through what prevailing mechanism verapamil (V) can induce an improvement in left ventricular (LV) diastolic early filling in mild to moderate essential hypertension, 43 properly classified essential hypertensives, aged 41-74 years (mean age 58.1 +/- 10.3), and 20 age-matched normotensives were studied. All subjects underwent both echocardiographic evaluation and 99mTc radionuclide angiocardiography in basal conditions between 8.00 a.m. and noon, after an overnight rest. In essential hypertensives gated equilibrium angiocardiography was repeated 3 and 30 min after i.v. V (0.1-mg/kg bolus, followed by 0.005 mg/kg/min for the period of radionuclide data acquisition). Simultaneously, supine arterial pressure was measured with a cuff manometer. In 36 essential hypertensives a phono-echo evaluation was obtained, both at 3 and 30 min after V, deriving a LV isovolumetric relaxation index (IRTI). Among diastolic early filling indices, we particularly considered the ratio of peak filling rate (PFR) to peak ejection rate (PER) in order to take into account the interaction of systolic performance with LV relaxation and diastolic early filling. Three minutes after V the increase in PFR (from 2.47 +/- 0.5 to 3.04 +/- 0.8 EDV/s, p less than 0.001) and the upwards tendency of PFR/PER were coupled with the enhancement in ejection fraction (from 61.1 +/- 13.3 to 63.9 +/- 13.8%, p less than 0.001) and heart rate (from 70.3 +/- 12.6 to 77.7 +/- 12.2 b/min, p less than 0.001) and with the reduction in mean arterial pressure (from 122 +/- 16 to 107 +/- 14 mm Hg, p less than 0.001), systemic arterial resistance index (from 3,234 +/- 968 to 2,432 +/- 678 dyn s cm-5 m2, p less than 0.001) and end-systolic volume index (from 32.9 +/- 17.1 to 31.5 +/- 18.3 ml/m2, p less than 0.02). On the contrary, 30 min after V, when systolic indices, heart rate, mean arterial pressure and systemic arterial resistance index had returned towards baseline values, PFR/PER showed a persistent improvement when compared with basal values (0.71 +/- 0.12 vs. 0.63 +/- 0.08, p less than 0.005). No changes were observed in LV volumes and IRTI, either at 3 or 30 min. Moreover, also the pulmonary blood volume ratio was unchanged. A weak negative correlation was found between delta % of IRTI and delta % of PFR/PER 30 min after drug administration (r = 0.58, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1989

[Atrial electrophysiologic properties in paroxysmal atrial fibrillation. Study conducted with the stimulation of 5 atrial sites].

Programmed atrial stimulation at five atrial sites was performed to evaluate electrophysiologic atrial properties in 17 control patients (14 M, 3F, mean age 61 +/- 9 years) (Group A) and in 18 patients with paroxysmal atrial fibrillation (13 M, 5 F, mean age 61 +/- 5 years) (Group B) with normal sinus node function. The mean value of the P wave duration was similar in both groups. Programmed atrial stimulation was performed at five atrial sites: high, medium and low lateral wall, and high and low medial wall. We evaluated the following parameters: A) local conduction delay measured at the functional refractory period as the difference between A1-A2 and S1-S2 intervals; B) widening of local electrogram measured at the functional refractory period as the difference between A1-A2 interval measured at the end of each local electrogram and A1-A2 interval measured at the beginning of each local electrogram. We evaluated the mean and the maximum value of the two above-mentioned parameters; C) dispersion of effective refractory period and functional refractory period, determined as the longest minus the shortest refractory period from the range of refractory periods measured in each patient; D) the mean of effective refractory periods and functional refractory periods observed at five atrial sites. Mean and maximum local conduction delay, mean effective and functional refractory periods did not present significant differences in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Antihypertensive effect of spirapril and felodipine during repeated administration to spontaneously hypertensive rats.

The antihypertensive activity of spirapril given alone or in combination with felodipine was investigated in spontaneously hypertensive rats (SHR) during a 3-week treatment regimen and for one week after drug withdrawal. Systolic blood pressure and heart rate were recorded once a week just before dosing and at varying time intervals up to 6 hr thereafter. Recordings were continued for one week after drug withdrawal. Spirapril alone at 1 and 5 mg/kg p.o. was found to produce dose-related antihypertensive effects throughout the treatment period. Felodipine alone at 5 mg/kg p.o. reduced blood pressure slightly more than did the low dose of spirapril. The combination of spirapril and felodipine induced a marked antihypertensive response which was greater than that observed in rats treated with either drug alone. One week after treatment withdrawal, blood pressure was at initial levels with no evidence of rebound phenomena. No significant heart rate changes were observed in the treated groups, as compared with the controls, except for an increase on the 1st day of treatment in rats given felodipine. These findings indicate that the combination of an angiotensin converting enzyme (ACE) inhibitor with a calcium antagonist leads to an effective control of hypertension over a prolonged period of treatment. Since the combination allows effectiveness with lower doses of ACE inhibitor, it is expected that the antihypertensive efficacy might be associated with a lower liability to untoward effects.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Absence of [3H]SCH 23390 specific binding sites in anterior pituitary: dissociation from effects on prolactin secretion.

We extended a previous study that had shown the selective D1 receptor antagonist SCH 23390, at relatively high doses, to stimulate prolactin (PRL) secretion in the rat and weakly inhibit [3H]spiperone binding to striatum and anterior pituitary (AP) membranes. No specific [3H]SCH 23390 binding sites, up to the micromolar range, were detected in rat AP while specific, saturable [3H]SCH 23390 binding sites (low nanomolar range) were observed in the striatum. In vivo SCH 23390 (1 mg/kg s.c.) induced higher plasma PRL levels, not reversible by the D1 agonist SKF 38393. Similarly the postsynaptic serotonin (5-HT) antagonists metergoline and cyproheptadine did not influence the SCH 23390 effect on PRL. SCH 23390 was also unable to antagonize the decrease of PRL secretion induced by the selective D2 agonist LY 171555. However this latter compound prevented SCH 23390 as well as sulpiride from increasing the PRL concentrations above the control values. These data rule out the possibility that D1 or 5-HT receptors mediate the stimulation of PRL release by SCH 23390. This effect is more likely to be due to a weak indirect interaction with AP-D2 receptors, as indicated by the non-competitive inhibition of [3H]spiperone binding to AP exerted by SCH 23390. Alternatively, non-specific mechanisms triggered by the multiple behavioral changes elicited by such high doses of SCH 23390 may be involved.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1987

Effects of repeated tiapride administration on anterior pituitary dopamine receptors and prolactin release in the rat.

The substituted benzamides tiapride and sulpiride, and the classic neuroleptic haloperidol, were studied in the rat to assess their interaction with the anterior pituitary (AP) dopamine (DA) receptors both in vitro ([3H]spiperone binding) and in vivo prolactin-PRL-release). Tiapride weakly inhibited [3H]spiperone binding in both pituitary and striatal membranes with affinity 5-7 times lower than sulpiride and 400-300 times lower than haloperidol. All three drugs were more potent in displacing [3H]spiperone from striatum than from AP. In vivo, tiapride produced weak and transient stimulation of PRL release reaching a full effect at 2 mg/kg i.p. Similar doses of sulpiride produced longer-lasting effects. Haloperidol was more potent than both benzamides. In prolonged treatments (15 or 60 days), tiapride, given twice daily at 0.5 mg/kg i.p., did not modify [3H]spiperone binding in either AP or striatum, nor did it induce significant changes of basal PRL levels. The challenge with a low threshold dose of TIA (0.2 mg/kg ip) produced similar increases of PRL release in the group either treated with TIA or saline. The data indicate that the benzamides examined have low potency for interaction with DA receptors in pituitary and striatum. In particular, tiapride displayed weaker affinity for AP-DA receptors than the other drugs and induced only slight stimulation of PRL levels. Results from repeated tiapride administration indicate that the drug, at a clinically relevant dose, is unable to modify either kinetic characteristics of DA receptors in the pituitary or plasma PRL levels.

Animals↗
PubMed1987

Antihypertensive activity of a new ACE-inhibitor, SCH 33844, during repeated administration in spontaneously hypertensive rats.

The antihypertensive activity of SCH 33844, a new angiotensin converting enzyme inhibitor, was investigated in conscious spontaneously hypertensive rats during a 3-week treatment regimen and for 1 week following drug withdrawal. SCH 33844 was given once daily at 2 dose levels (1 and 5 mg/kg orally) and its effects were compared with those of captopril (60 mg/kg orally). Systolic blood pressure was recorded twice weekly just before administration and at varying time intervals up to 6 hr after dosing; recordings were continued for 1 week after drug withdrawal. SCH 33844 was found to produce dose-related antihypertensive effects. Given at 1 mg/kg, the compound elicited small but significant blood pressure changes during the treatment. After drug withdrawal, systolic blood pressure returned to pre-drug levels within 1 week. SCH 33844 at 5 mg/kg, and captopril at 60 mg/kg, both reduced blood pressure markedly and to a similar extent. After each administration the effect was rapid in onset, lasted for over 6 hr and was not subject to tolerance. Drug withdrawal resulted in a gradual return of systolic blood pressure toward pre-treatment levels within 1 week, with no evidence of rebound phenomena. These results indicate that SCH 33844, like captopril, produces an effective antihypertensive action throughout a repeated dosing.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

Comparative oto-vestibular effects in the pigmented guinea pig after dibekacin and netilmicin treatment.

We treated groups of pigmented guinea pigs with either intramuscular netilmicin or dibekacin at 100 and 150 mg/kg per day for 3 weeks. Saline was used as the control solution. All animals were tested weekly for both vestibular and auditory functions. The vestibular function was evaluated by the duration of post-rotatory nystagmus (PRN) elicited by interrupting the rotation of the animal around the vertical axis; auditory function was evaluated by the threshold response for the Preyer's pinna reflex (PPR). All animals were then sacrificed and either their labyrinths or Corti organs were processed for further investigations using the scanning electron microscope (SEM). The duration of PRN decreased over the treatment period in all of the groups as a result of adaptation. However, 150 mg/kg dibekacin produced a significant decrease of the PRN responses as compared to the control and other groups. This effect also continued during the recovery period. Likewise, the PPR threshold of the animals receiving 150 mg/kg dibekacin showed a significant increase at the end of the treatments and during the recovery period, while the other dibekacin group had no significant auditory impairment. Netilmicin at both doses did not significantly affect responses following either vestibular or auditory stimulations. SEM observations demonstrated that the sensory epithelia of the labyrinths and Corti organs affected by 150 mg/kg dibekacin had great losses of stereocilia, while comparable doses of netilmicin (150 mg/kg) had only very moderate losses of stereocilia in the labyrinths but not in the Corti organs.

Animals↗
PubMed1986

Comparative actions of four aminoglycoside antibiotics on the vestibular function in guinea-pigs.

This study was designed to assess the actions of 4 representative aminoglycoside antibiotics on the vestibular functions in guinea-pigs as evidenced by the measurements of the vestibulo-ocular reflex (VOR) either in the horizontal (HVOR) or in the vertical plane (VVOR). VOR responses were evaluated over a wide range of stimulation frequencies prior to and after 10 and 18 days of a multiple dose regimen with dibekacin (150 mg/kg), gentamicin (100 mg/kg), netilmicin (150 mg/kg), tobramycin (100 mg/kg) or saline. All drugs or saline were given intramuscularly twice a day. The labirinthine function was found to be differently impaired by drug administration. Gentamicin induced severe vestibular impairment, which had early onset. Dibekacin greatly reduced all VOR responses, but changes occurred after a longer period of time. Tobramycin and netilmicin induced slight vestibular impairment only after 18 days of treatment. Tobramycin affected both HVOR and VVOR responses at the high frequencies, while netilmicin impaired only the HVOR. Histological examination of vestibular epithelia was conducted by using the Scanning Electron Microscope (SEM). Gentamicin and dibekacin greatly damaged both the cristae of semicircular canals and utriculi, structures which are involved in the generation of VOR responses. Conversely, tobramycin provoked damages only in the cristae of semicircular canals and netilmicin did not affect the vestibular sensory epithelia. These findings indicate that each aminoglycoside produces characteristic actions on the vestibular function which depend on the damage distribution in the labirinthine structures. Among the aminoglycoside examined, netilmicin appears to possess the lowest potential for producing impairment of the vestibular function.

Aminoglycosides↗
PubMed1985

A beta-carboline antagonizes benzodiazepine actions but does not precipitate the abstinence syndrome in cats.

The beta-carbolines, which are potent ligands for benzodiazepine receptors, antagonize the pharmacological actions of benzodiazepines. In the cat, the stable beta-carboline derivative methylamide-beta-carboline-3-carboxylate, FG 7142, and the specific benzodiazepine antagonist Ro 15-1788 reversed behavioral and electroencephalographic (EEG) changes produced by a single dose of diazepam. Surprisingly, the beta-carboline did not elicit signs of withdrawal when given after 22 days of a daily dose regimen of diazepam, while Ro 15-1788 precipitated an acute abstinence syndrome largely characterized by tremors, increased muscle tone, back arching, myoclonic jerks and pupil dilatation. Unlike Ro 15-1788, the beta-carboline produced effects of its own such as behavioral states of arousal and fearfulness. These findings indicate that the beta-carboline functionally interacts with benzodiazepine receptors in a manner unlike that seen with typical agonists and antagonists.

Animals↗
PubMed1984

Effects of the R, R-isomer of labetalol, SCH 19927, in isolated tissues and in spontaneously hypertensive rats during a repeated treatment.

The alpha 1- and beta 1-adrenoceptor blocking activity of the R, R-isomer of labetalol, SCH 19927, was assessed in isolated tissues and compared with that of labetalol. The antihypertensive actions of both compounds were then evaluated during a 10-day dose regimen in spontaneously hypertensive rats (SHR). SCH 19927 produced a competitive alpha 1- and beta 1-blockade in vitro as indicated by the parallel shift to the right of the dose-response curves for norepinephrine and isoprenaline, respectively. SCH 19927 was found 4 times more potent as beta 1-blocker and 6.5 times less potent as alpha 1-blocker than labetalol. In conscious SHR, both SCH 19927 and labetalol produced long-lasting antihypertensive effects during the 10-day period of repeated administration with 10 mg/kg p.o. No tolerance to the antihypertensive activity occurred during the treatment. These findings suggest that SCH 19927 is more potent as a beta-blocker than as an alpha-blocker in isolated tissues and produces an effective antihypertensive activity during a repeated dose regimen.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Selective adenosine A2A receptor antagonists.

In the early 1990s it became clear that the A2A adenosine receptor had characteristics that made it distinct from the other A1, A2B and A3 adenosine receptors. Great progress has been made with the discovery of selective A2A receptor antagonists. A variety of synthetic substitutions on the xanthine moiety led the chemists of Kyowa-Hakko to discover that introduction of the styryl group in the 8 position of xanthines was critical in achieving compounds endowed with selective A2A receptor antagonistic properties. One compound, KW 6002, (E)1,3-diethyl-8-(3,4-dimethoxystyryl)-7-methylxanthine, is currently being developed for treatment of Parkinson's disease. A number of non-xanthine heterocycles have also been synthesized starting from the non-selective adenosine antagonist CGS 15943, a triazoloquinazoline. Thus, replacement of the phenyl ring of CGS 15943 with a heterocyclic ring such as pyrazole or imidazole, led to a series of interesting compounds whose prototype, SCH 58261, 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, has become a reference A2A receptor antagonist. Modification of N7 substituents has progressed to optimize A2A receptor selectivity and pharmacokinetic characteristics. A related class of compounds having a bicyclic instead of the tricyclic ring structure is also of interest. The prototype of these triazintriazolo derivatives, ZM 241385, is a potent A2A receptor antagonist; however, it also shows interactions with A2B receptors. The relevance of the A2A receptors in specific disease states, especially in the central nervous system, makes this class of adenosine receptor blockers of interest for treatment of neurodegenerative disorders such as Parkinson's disease.

Animals↗
PubMedDate not supplied

Effect of long-term administration of two beta-blocking agents on myocardial structure in spontaneously hypertensive rats.

Two vasodilating beta-blockers, dilevalol and pindolol, were studied for their effects on the development of hypertension and left ventricular hypertrophy in spontaneously hypertensive rats. Dilevalol has agonist activity at beta 2-, whereas pindolol interacts with both beta 1- and beta 2-receptor subtypes. Groups of 7-week old spontaneously hypertensive rats were given dilevalol (30 mg/kg) or pindolol (3 mg/kg) in the drinking water for 3 months. A control group of spontaneously hypertensive rats and age-matched normotensive Wistar Kyoto rats were also used. Systolic blood pressure and heart rate were recorded weekly. Cardiac structural changes were determined by morphometric analysis. Control spontaneously hypertensive rats developed hypertension and left ventricular hypertrophy as compared with normotensive rats. Dilevalol and pindolol prevented the rise in blood pressure, but only dilevalol lowered heart rate. However, neither of the compounds prevented the development of left ventricular hypertrophy, but they differently influenced myocardial structure as measured by the volume fraction of fibrotic tissue in the left ventricle. Dilevalol markedly prevented the amount of fibrosis to a level comparable to that found in normotensive rats, whereas pindolol had a weaker effect. The data suggest that individual pharmacologic characteristics, such as partial agonist activity of each beta-blocker examined, may account for differential effects on the myocardial structure.

Analysis of Variance↗