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R Testa

Publications and source records attributed to R Testa.

At least 163 records · Page 9Linked to original sources

Anticonvulsant effect of denzimol in DBA/2 mice.

The anticonvulsant activity of N-[beta-[4-beta-phenylethyl)phenyl]-beta-hydroxyethyl]-imidazole hydrochloride, denzimol, was studied following intraperitoneal administration in DBA/2 mice (seizures induced by sound). Protection against sound-induced seizures was observed after intraperitoneal administration of denzimol (3-15 mg/kg). The ED50 values for the suppression of tonic, clonic and wild running phases of sound-induced seizures were 1.24, 2.61 and 6.03 mg/kg, respectively. This protective action was significantly reduced by pretreatment with aminophylline (25 mg/kg i.p.), CGS 8216 (1 or 5 mg/kg i.p.) and Ro 15-1788 (2.5 mg/kg i.p). The present experiments suggest an involvement of purinergic and benzodiazepine mechanisms in the anticonvulsant action of denzimol.

Acoustic Stimulation↗

Relationship between the brain levels and the anticonvulsant activity of denzimol after its acute and repeated administration to mice.

The relationship between the brain concentration of denzimol and its anticonvulsant activity was studied in mice after acute and repeated administration (14 days) of this drug to mice. Anticonvulsant activity was assessed against maximal electroshock seizures (MES). When denzimol was administered at 30 mg/kg p.o. to repeatedly treated mice, its brain concentration and anticonvulsant activity were reduced in comparison to non-treated mice and t1/2 beta was significantly changed from 2.10 to 1.53 hr. Tonic hindlimb extension was completely abolished at a brain denzimol concentration higher than 15 mcg/g, whereas the minimum effective brain concentration was between 2-3 mcg/g both in acute and repeatedly treated animals. The brain concentration of denzimol is closely correlated with its anticonvulsant effect both in acute and repeatedly treated animals. Furthermore these findings seem to suggest that the decreased anticonvulsant activity of denzimol, following repeated administrations, might be due to a development of pharmacokinetic tolerance.

Animals↗

Reduction of cerebral blood flow in subclinical hepatic encephalopathy and its correlation with plasma-free tryptophan.

Cerebral blood flow (CBF), measured by the noninvasive xenon-133 inhalation method, EEG, and plasma levels of ammonia (NH3) and free tryptophan were determined in 18 hospitalized cirrhotic patients affected with subclinical hepatic encephalopathy, as diagnosed by the Kurtz test. CBF results were significantly lower (p less than 0.001) in the patients' group as compared with a sex- and age-matched normal control population, although seven patients had values in the normal range. NH3 was increased only in six, while free tryptophan was increased in all but two patients. A significant negative correlation (p = 0.02) between CBF and free tryptophan was found, even though it appears to be difficult to interpret. We suggest that CBF impairment in some cirrhotic patients with subclinical hepatic encephalopathy may be related to the systemic metabolic derangement caused by the liver disease; free tryptophan could have some implication in producing CBF reduction.

Adult↗

[Ambulatory electrocardiography in patients with angina pectoris].

In the diagnosis of ischemic heart disease, long-term ECG recording has several distinct advantages. It allows one to relate patient symptoms to cardiac disturbances and to detect asymptomatic events, reveals the possible ischemic genesis of arrhythmias, and it is the most suitable method to assess the acute and chronic effectiveness of treatment and the evolution of the disease. In spite of these advantages, Holter monitoring has several limitations: the analysis of a single lead, is responsible in most systems for the low sensitivity in detecting ischemia occurring in unexplored regions; the period of 24-48 hours may not be sufficient for screening patients due to the unpredictable spontaneous variability of the disease; a common standard of analysis is still lacking even if the European Communities concerted action in Ambulatory Monitoring could represent the solution to this problem. Nevertheless the role of Holter monitoring appears essential in the ambulatory screening of patients with suspected ischemia for a better characterization of patients with ascertained myocardial ischemia, and for the evaluation of treatment and of the evolution of the disease.

Angina Pectoris↗

The diagnosis and prognosis of the 2nd clinical stage of the endometrial carcinoma.

The clinical and histopathological findings of 35 patients with endometrial carcinoma, 2nd Clinical Stage, allow us to conclude: the exclusive cervical involvement does not signify an important impoverishment of the prognosis. As in the 1st Clinical Stage, the outer myometrial infiltration and histologic differentiation are reliable prognostic parameters. The cervical participation in the endometrial carcinoma as is observed in the diagnostic D & C was only corroborated in 61% of the operated cases.

Female↗

Detection of spontaneous episodes in post-infarction angina. Comparison between CCU and Holter monitoring.

The objects of this study are: to evaluate the incidence of early post-infarction angina in patients who developed transmural infarction (Q-AMI) or sub-endocardial infarction (no Q-AMI) during hospitalization; to compare data obtained from patients monitored in Coronary Care Unit (CCU) with those obtained from Holter monitoring. The 107 patients under study (55 with Q-AMI and 52 with no Q-AMI) presented the acute event on average 7.4 and 5.1 days after admittance in the CCU, respectively. A history of angina was present in all except 1 patient with Q-AMI and in all with no Q-AMI. After AMI the angina disappeared in 22 of the patients with Q-AMI and in 31 with no Q-AMI, while it continued in 33 and 21 of these patients, respectively. Twenty-one patients underwent ECG recording according to the Holter technique while in CCU, for an average of 4.4 days before and 5.2 days after the onset of AMI. The comparative analysis of the results obtained from the CCU and from Holter monitoring shows that the CCU greatly underestimates the number of ischaemic episodes, even when pain is present (4.5 episodes per patient per day before AMI and 2 after, versus 13.7 and 6.8 with Holter monitoring). The number of ventricular arrhythmias also seemed lower when analysing data from CCU monitoring. These data demonstrate the importance of Holter monitoring, even in patients admitted to a CCU, for a precise evaluation of the ischaemic and arrhythmic phenomena.

Adult↗

[Derivatives of 1,2-condensed pyrimidines. II. Synthesis and pharmacological study of N,N-disubstituted 5-amino-7H-thiazol [3,2-a]pyrimdine-7-ones].

Reaction of 2-aminothiazole with the N,N-dialkyl or (N-alkyl, N-phenyl) ethoxycarbonylacetamide/POCl3 reactant (I), in refluxing 1,2-dichloroethane, yielded the corresponding N,N-disubstituted 5-amino-7H-thiazolo[3,2-a]pyrimidin-7-ones (VII) along with lower quantities of isomeric N,N-disubstituted 7-amino-5H-thiazolo[3,2-a]pyrimidin-5-ones (VIII). Structures attributed to isomeric compounds (VII) and (VIII) were supported both by spectroscopic and chemical evidences. Some compounds (VII) were submitted to pharmacological investigation and results are described: only (N-alkyl, N-phenyl)derivatives (VII f,g) showed a significant, even if mild, activity as peripheral analgesics.

Animals↗

Relationship between plasma and brain concentrations of Denzimol and its anticonvulsant and neurotoxic effects in the rat.

The relationship between plasma, brain and cerebellum concentrations of Denzimol a new anticonvulsant agent, and its anticonvulsant and neurotoxic effects were studied in the rat. Sixty minutes after oral administration, a high brain/plasma concentration ratio of 10:1 was found. Mean plasma, brain and cerebellum half-lives of the drug were 8.4, 7.1 and 9.2 hr, respectively. The anticonvulsant activity of the drug was examined by maximal electroshok seizures (MES). Neurotoxicity was determined both by the rotarod performance test and by behavioural observation. Denzimol was effective against MES, in the ranges of 0.8-5 micrograms/ml and 10-50 micrograms/ml for plasma and brain concentrations, respectively, without causing clear signs of neurological toxicity. It is concluded that the anticonvulsant and neurotoxic effects of denzimol are correlated to its plasma and brain concentrations.

Animals↗

In-hospital myocardial infarction. Pre-infarction features and their correlation with short-term prognosis.

A retrospective study of 107 patients who sustained an acute myocardial infarction (AMI) during hospitalization was undertaken to assess the early prognosis of Q wave AMI (55 patients, group 1) and no-Q wave AMI (52 patients, group 2). Forty-one patients in group 1 and 31 in group 2 had documented ischaemia at rest in the period preceding AMI. The incidence of pre-infarction ischaemic attacks was similar in Q wave AMI compared with non-Q wave AMI (average daily incidence per patient 3.1 +/- 4.3 vs 3.0 +/- 4.3). A 'crescendo' pattern of pre-infarction angina was rarely observed in both groups. The incidence of post-infarction ischaemia (documented in 28 patients of group 1 and in 28 of group 2) was greater, but not significantly, in group 2 (average daily incidence per patient 1.0 +/- 2.6 vs 1.4 +/- 3.2). All patients with pre-infarction ischaemia sustained infarction in the same territory. AMI in group 1 was always symptomatic while 12 AMIs in group 2 were totally asymptomatic. Fifty patients from group 1 and 27 from group 2 were on therapy while AMI developed. Twenty-one patients from group 1 showed life threatening arrhythmias (ventricular tachycardia, ventricular fibrillation, third degree AV block or asystole) during AMI; of these, 14 did not survive the arrhythmias; they all had signs of left ventricular failure. Only one patient from group 2 had runs of ventricular tachycardia, unrelated to AMI but during pre- and post-infarction ischaemia. The overall mortality rate of Q wave AMI was 29% while no deaths occurred in the non-Q wave AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Electrocardiographic monitoring: temporal versus spatial information and data processing.

In the diagnosis of ischemic heart disease, long-term electrocardiographic recording has several distinct advantages. It allows one to relate patient symptoms to cardiac disturbances and to detect asymptomatic events, furnishes the whole spectrum of electrocardiographic alterations accompanying ischemic attacks, reveals the possible ischemic genesis of dysrhythmias, and is the most suitable method to assess the acute and chronic effectiveness of treatment and the evolution of the disease. In addition to its valuable application in the screening and follow-up of ambulatory patients, its use in the Coronary Care Unit is of great interest, being in this context much more sensitive than visual electrocardiographic monitoring. In spite of these advantages, Holter monitoring has several limitations: the recording and replay systems are below recommended standards; the analysis of a single lead is responsible in most systems for the low sensitivity in detecting ischemia occurring in unexplored regions; the period of 24-48 hours, usually adopted for Holter monitoring, may not be sufficient for screening patients with suspected myocardial ischemia due to the unpredictable spontaneous variability of the disease; a common standard of analysis is still lacking and a reliable computerized analysis is needed to manage data overflow. In conclusion, although further research and technical developments are desired to improve reliability and data processing, the role of Holter monitoring appears essential in the ambulatory screening of patients with suspected ischemia for a better characterization of patients with ascertained myocardial ischemia, and for the evaluation of treatment and of the evolution of the disease.

Angina Pectoris, Variant↗

Differential antagonism of denzimol to various components of metrazol-induced seizures in rats and mice.

The antagonism of various components of maximal metrazol-seizures and the induction of ataxia have been studied in mice and rats by comparing Denzimol to 10 standard antiepileptic drugs. The data were analyzed by Cluster and Principal Components Analysis. Denzimol, phenytoin, carbamazepine and AD-810 showed an antagonistic effect on tonic but not on clonic seizures regardless of the animal species. Barbiturates, benzodiazepines and valproic acid, on the other hand, antagonized the whole pattern of metrazol-seizures. The selective activity of Denzimol and phenytoin against tonic seizures was also confirmed from literature data, which reported the activity of these compounds against bicuculline, thiosemicarbazide or picrotoxin induced convulsions.

Administration, Oral↗

Enhancement of diazepam activities induced by denzimol in mice.

Denzimol, a new anticonvulsant drug, enhances the depressant and antimetrazol activities of diazepam in mice, in a dose and time-dependent fashion. The depressant and anticonvulsant activities of phenobarbital were not affected by Denzimol. It is suggested that Denzimol induces an increase in the number of the benzodiazepine receptors, and that such increase might be responsible for the enhancement of the diazepam's activities.

Animals↗

Increase of F cells during acute hemolysis in glucose-6-phosphate dehydrogenase-deficient males.

Five male Sicilian children with glucose-6-phosphate dehydrogenase deficiency were studied shortly after hemolytic crisis in order to evaluate the immediate effects of massive hemolysis on fetal Hb (HbF) levels and the number of circulating F cells. Hematological values seen 4 months after the children recovered from the crisis were considered representative of the patients' steady state. All patients had an increase in HbF levels (2.26 +/- 0.24%) and F cell number (29 +/- 4.79%) in the acute phase and their HbF values and F cells returned to normal range at control. Globin synthesis was balanced in the peripheral blood and bone marrow and there was a small peak of gamma chains. Globin chain electrophoresis showed that both G gamma and A gamma genes were active in all patients. These results confirm that hemolytic stress produces increased F cell release in peripheral blood. Such release is rapid enough (less than 72 h) to be consistent with the hypothesis of an induction of HbF synthesis in late erythroid precursors.

Acute Disease↗