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Biomedical subjects

M Casas

Publications and source records attributed to M Casas.

At least 19 recordsLinked to original sources

Findings on Doppler echocardiography in asymptomatic intravenous heroin users.

To detect potential cardiac abnormalities induced by intravenous heroin use, 68 persons without a previous episode of infective endocarditis were studied by Doppler echocardiography. A control group of 41 normal subjects was studied for comparison. The following measurements were considered: (1) diameter of heart chambers, (2) systolic left ventricular function, (3) morphologic valvular abnormalities, (4) presence of valve regurgitations, (5) Doppler indexes of diastolic function, and (6) estimation of pulmonary arterial resistances. Results showed no significant differences regarding the size of the heart chambers or systolic left ventricular function. A significantly higher incidence of valvular abnormalities (focal thickening or valve prolapse) was found in drug addicts (p = 0.0009) at the mitral and tricuspid valves, as was valvular regurgitation detected by Doppler (p = 0.04). Also, a significantly prolonged deceleration time of mitral and tricuspid early diastolic Doppler flow was found in the study group (p = 0.0001 and 0.027, respectively) although a different hemodynamic condition in the study group (pharmacologically reduced preload) precluded these findings to be attributable to an actual diastolic dysfunction. No differences were observed in pulmonary arterial resistances. It is concluded that mitral and tricuspid valve abnormalities can be detected by echocardiography in asymptomatic intravenous heroin users, whereas no apparent effects are observed in morphologic or functional parameters of cardiac structures other than the valves.

Adolescent

Multi-centre double-blind trial on the efficacy and safety of sertaconazole 2% cream in comparison with miconazole 2% cream on patients suffering from cutaneous mycoses.

The efficacy and tolerance of 7-chloro-3-[1-(2,4-dichlorophenyl)-2- (1H-imidazol-1-yl)ethoxy-methyl]benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2) 2% dermatological cream in two daily applications compared with miconazole 2% cream in two daily applications were studied on 631 patients suffering from superficial cutaneous mycosis (sertaconazole n = 317, miconazole n = 314), in a double-blind, controlled multicentre trial with parallel groups. The therapeutic efficacy was evaluated by clinical assessment of the improvement of the lesion and symptoms, a microscopic test on the presence of hyphae or mycelia in the affected area and a culture test on the presence of active infection. Tolerance and safety were evaluated by a general blood analysis and interrogation of the patient on adverse effects. The rate of clinical cures for both treatments at the end of the follow-up was 95.6% for sertaconazole and 88.1% for miconazole, with the difference being statistically significant. In the comparative analysis of the actuarial curve, it was observed that the patients treated with sertaconazole were cured earlier and in a higher proportion than those treated with miconazole, with the difference being significant. The negative result of the microscope examination and culture test confirmed the superiority of sertaconazole over miconazole, already after 14 days of treatment. At the end of the follow-up, 98.6% of the patients in the sertaconazole group obtained a negative culture test result, as opposed to 91.7% in the miconazole group, with the difference being highly significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical

Postsynaptic dopamine/adenosine interaction: I. Adenosine analogues inhibit dopamine D2-mediated behaviour in short-term reserpinized mice.

Mice pretreated with reserpine 5 mg/kg (4 h prior to the start of motor activity recording) showed locomotor activation after the administration of the D-2 agonist bromocriptine (5 mg/kg). This bromocriptine-induced locomotor activity was dose dependently inhibited by the co-administration of a D-2 antagonist (sulpiride) and dose dependently potentiated by a D-1 agonist (CY 208-243). The potentiating effect of the D-1 agonist could be inhibited by either a D-1 or a D-2 antagonist (SCH 23390 1 mg/kg or sulpiride 100 mg/kg, respectively). The bromocriptine-induced locomotor activity was not altered by either blockade of D-1 dopaminergic receptors (SCH 23390 1 mg/kg) or by co-administration of a greater dose of reserpine (10 mg/kg) plus the dopamine synthesis inhibitor, alpha-methyl-p-tyrosine (200 mg/kg). The adenosine agonists, L-PIA (a preferentially A-1 adenosine agonist) and NECA (an A-1 and A-2 adenosine agonist with above 10-fold greater affinity for A-2 than L-PIA) inhibited in a dose-dependent manner the effect of bromocriptine, NECA being above ten times more potent than L-PIA. The findings show that bromocriptine stimulates postsynaptic D-2 receptors in dopamine-depleted mice and that this effect can be inhibited by adenosine stimulation. The existence of a postsynaptic D-2/A-2 interaction is suggested, the stimulation of A-2 receptors causing an inhibition of responses elicited by postsynaptic D-2 stimulation.

Adenosine

Postsynaptic dopamine/adenosine interaction: II. Postsynaptic dopamine agonism and adenosine antagonism of methylxanthines in short-term reserpinized mice.

Caffeine and its first-stage metabolites (paraxanthine, theophylline and theobromine) caused a significant potentiation of the locomotor activity induced by bromocriptine, 5 mg/kg, in mice pretreated with reserpine, 5 mg/kg (4h prior to the start of motor activity recordings). None of these substances significantly enhanced locomotor activity in reserpinized mice when administered alone. The rank order of potency was caffeine greater than paraxanthine greater than theophylline greater than theobromine. A high dose of a D-2 antagonist (sulpiride 100 mg/kg) caused a marked inhibition of the locomotor activity induced by bromocriptine, 5 mg/kg, plus 25 mg/kg of caffeine, paraxanthine or theophylline. However, a high dose of a D-1 antagonist (SCH-23390 1 mg/kg) caused a significant decrease of the locomotor activity induced by bromocriptine 5 mg/kg, plus 25 mg/kg of caffeine or paraxanthine, but did not change the locomotor activity caused by bromocriptine, 5 mg/kg, plus theophylline 25 mg/kg. The inhibitory effect of 5'-(N-ethyl)carboxamido-adenosine (NECA), 0.025 mg/kg, on bromocriptine-induced locomotor activation in reserpinized mice was reversed by the simultaneous administration of 10, 25 and 50 mg/kg of caffeine, paraxanthine or theophylline. The rank order of potency for reversal was theophylline greater than paraxanthine = caffeine. We suggest that methylxanthines act postsynaptically by potentiating the effects of D-2 stimulation and that this potentiation can be produced by D-1 agonism (paraxanthine or caffeine) and by adenosine antagonism (theophylline, paraxanthine or caffeine), most probably involving A-2 receptors.

Adenosine

Paraxanthine displaces the binding of [3H]SCH 23390 from rat striatal membranes.

We present evidence showing that paraxanthine (1,7-dimethylxanthine), the main metabolite of caffeine in man, displaces the binding of [3H]SCH 23390, a radioligand which selectively labels dopamine D-1 receptors when used at low concentrations, from striatal membranes of the rat. The displacement was competitive and indicated the existence of two affinity states (Hill coefficient = 0.49; K(high) = 0.15 microM; K(low) = 95.9 microM, %R(high) = 32.4). When the stable GTP analog Gpp(NH)p was included, the displacement curve indicated the presence of only the low-affinity state (Hill coefficient = 1.16; Ki = 72.1 microM). However, paraxanthine did not displace the specific binding of [3H]spiperone. After injection of 30 mg/kg s.c. of caffeine, a maximum of 10 microM of paraxanthine was found in striatal homogenates, which could be sufficient to occupy dopamine D-1 receptors. Our results suggest that a dopaminergic action of paraxanthine could be involved in the behavioural stimulation produced by caffeine.

Animals

T-maze performance in rats following chronic neuroleptic treatment.

The effects of chronic haloperidol treatment (0.5 mg/kg/day for 21 days) on maze learning in the rat were studied. There were no differences between haloperidol- and saline-treated groups in percentage of correct responses, but the latency to respond was longer and extinction was faster in the haloperidol-treated group. We speculated that differences between both groups were due to a decrease of appetitive motivation in haloperidol-treated animals, probably caused by a decrease of dopaminergic neurotransmission.

Animals

Is experimental catalepsy properly measured?

Following logarithmic transformation (ln) of total duration of haloperidol-induced catalepsy in the rat, measured by means of the bar test, a normalization of the results is achieved. With the help of this transformation we have been able to study what are probably the most important variables involved in the measuring of experimental catalepsy and to establish some criteria for a better use of such measures: 1) repeated measures of catalepsy have to be taken in order to avoid the stress-induced inhibition of catalepsy caused by the new experimental situation, 2) the dose of neuroleptic used has to be sufficiently low to permit the measurement of total or real duration of catalepsy between two determinations, and 3) the dose of neuroleptic has to be sufficiently high to prevent the development of a learned "pseudocatalepsy."

Adrenal Glands

Relationship between rotational behaviour induced by apomorphine and caffeine in rats with unilateral lesion of the nigrostriatal pathway.

The contralateral rotational behaviour produced by apomorphine and caffeine has been studied in 100 rats with unilateral lesion of the nigrostriatal pathway induced with 6-OHDA. Rats with a two-peak rotational pattern induced by apomorphine, showed a greater number of contralateral turns, induced by apomorphine and caffeine, than rats which did not show this rotational pattern. A correlation was observed between the number of rotations induced by apomorphine and those induced by caffeine. A relationship between the two-peak rotational pattern induced by apomorphine and the initial-peak pattern induced by caffeine was also observed.

Animals

Rotational behaviour induced by theophylline in 6-OHDA nigrostriatal denervated rats is dependent on the supersensitivity of striatal dopaminergic receptors.

We studied apomorphine- and theophylline-induced rotational behaviour in rats with a unilateral 6-hydroxydopamine lesion of the dopaminergic nigrostriatal pathway. It was seen that there was a direct correlation between the number of apomorphine- and theophylline-induced contralateral turns. These data suggest the existence of a relationship between theophylline-induced rotational behaviour and the degree of supersensitivity of the striatal dopaminergic receptors. Because the rotational behaviour induced by theophylline is in the same direction as dopaminergic agonists, contralateral to the nigrostriatal pathway lesion, these results suggest the possibility of a direct dopaminergic agonism of methylxanthines.

Animals

Caffeine produces contralateral rotation in rats with unilateral dopamine denervation: comparisons with apomorphine-induced responses.

Like the dopamine agonist apomorphine, the methylxanthines caffeine, theophylline and theobromine produced dose-dependent contralateral rotation in rats with unilateral 6-hydroxydopamine denervation, a response considered to be dependent upon dopamine receptors rendered supersensitive. This response was also observed after the injection of the substances into the denervated striatum. Indeed, intrastriatal administration of caffeine into the dopamine denervated striatum produced, dose-dependently (1.0-50.0 micrograms/ul), contralateral rotation. However, while apomorphine produced ipsilateral rotation in rats with unilateral striatal kainic acid lesions, a response considered to be dependent upon normosensitive dopamine receptors, neither caffeine nor theophylline produced rotational responses. As for apomorphine, the rotational behaviour elicited by caffeine (15.0 mg/kg SC) and theophylline (25.0 mg/kg SC) was inhibited by the dopamine antagonists cis-(Z)flupentixol, haloperidol and sulpiride. Nevertheless, despite the fact that cis-(Z)flupentixol was the most potent inhibitor of the caffeine response, no more than 50% inhibition was produced with doses as high as 1.0-10.0 mg/kg SC of cis-(Z)flupentixol. Pretreatment with alpha methyl-p-tyrosine inhibited the rotational response produced by caffeine in 6-OHDA-lesioned animals, but did not significantly modify the apomorphine response. Furthermore, the benzodiazepine diazepam produced a dose-dependent inhibition of the caffeine rotation, but again, the apomorphine response, although qualitatively modified, was not significantly inhibited.

Animals

Theophylline reverses haloperidol-induced catalepsy in the rat. Possible relevance to the pharmacological treatment of psychosis.

The effect of theophylline (5, 15, or 30 mg/kg sc) on the catalepsy induced by haloperidol in the rat was studied. Theophylline was shown to induce a dose-dependent inhibition of this catalepsy. These data support the hypothesis that the methylxanthines are dopamine agonists and suggest that coffee, tea, and cola drinks should be avoided by patients undergoing neuroleptic treatment.

Animals

Comparison between apomorphine and amphetamine-induced rotational behaviour in rats with a unilateral nigrostriatal pathway lesion.

Apomorphine and amphetamine-induced rotational behaviour in 310 rats with a unilateral 6-OHDA nigrostriatal pathway lesion has been studied. Animals presenting an apomorphine-induced contralateral rotation with a "two-peak" pattern, showed a greater number of contralateral turns induced by apomorphine and fewer ipsilateral turns induced by amphetamine than rats without this pattern. In addition, we have not found any correlation between apomorphine and amphetamine-induced turning behaviour.

Amphetamine

Conditioning of rotational behavior after the administration of a single dose of apomorphine in rats with unilateral denervation of the dopaminergic nigrostriatal pathway: relevance to drug addiction.

Our aim is to study the relationship of drug activation of the dopamine neurotransmission system and the conditioning of environmental stimuli present at the time of drug administration. We injected a single dose of apomorphine (0.05 mg/kg SC) in rats with the nigrostriatal dopamine pathways unilaterally denervated with 6-hydroxydopamine, which generates rotational behavior contralateral to the lesioned hemisphere. We observed rotational behavior without apomorphine administration when animals were reexposed at different time intervals to the same environment in which they performed turning behavior. The present findings show that this rotational behavior can be conditioned to environmental stimuli in a strong and long-lasting way. In light of the relationship between opioids and the dopaminergic system, similar conditioning could take place in the learning processes implicated in drug addiction.

Animals

Effect of chronic ethanol administration on iron metabolism in the rat.

This study shows that the ingestion of ethanol provokes alterations in iron metabolism which may lead to iron overload. Impaired release of reticuloendothelial iron was shown by a decrease of the maximum red blood cell utilization when radioactive iron was supplied as colloidal iron. An impairment in the erythropoietic activity of ethanol-treated animals was also observed, as can be seen from the reduced plasma iron turnover and red blood cell utilization within 24 h of iron administration. A rise in marrow transit time was also observed. In ethanol-treated rats there was an increase in the amount of iron retained both in the liver and the spleen. This was observed in both sexes and also in the offspring from ethanol-treated mothers.

Animals

Striatal adenosine levels measured 'in vivo' by microdialysis in rats with unilateral dopamine denervation.

Adenosine, inosine, hypoxanthine and guanosine were measured in perfusates collected from the right and left striatum of halothane-anaesthetized naive and 6-hydroxydopamine-denervated rats by using microdialysis. Samples were taken under basal and KCl-stimulated conditions. Dopamine, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were simultaneously measured. Purines and monoamines were assayed by HPLC-UV and HPLC-EC respectively. In naive rats, basal adenosine (1 microM), inosine (2 microM), hypoxanthine (4 microM), guanosine (0.5 microM) and dopamine (DA, 0.02 microM) levels (corrected by using the in vitro % recovery of each probe) were increased by the inclusion of 100 mM of KCl into the perfusion medium (2.5-, 3-, 3.5-, 1.5- and 30-fold, respectively, while DOPAC (6 microM), HVA (5 microM) and 5-HIAA (3 microM) levels were (72%, 68% and 45% respectively). DA was strongly diminished in the denervated striatum, but when detectable, could be increased (1- to 12-fold) by KCl stimulation. Adenosine, inosine, hypoxanthine and guanosine were, however, largely unaffected by the DA denervation and could be enhanced by KCl stimulation (2-, 3-, 4- and 1.5-fold respectively). The present results indicate that: (1) as in the case for DA, there is a pool of striatal adenosine which is releasable by high concentrations of extracellular K+; however, (2) this pool of adenosine seems not to be significantly modified by mesencephalic dopamine deafferentation.

3,4-Dihydroxyphenylacetic Acid