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Biomedical subjects

R Testa

Publications and source records attributed to R Testa.

At least 145 records · Page 8Linked to original sources
PubMed1989

Tryglycylvasopressin-reduced portal and systemic concentrations of serum bile acids after exogenous chenodeoxycholic acid load in rats as a reflection of reduced splanchnic blood flow.

The effect of triglycylvasopressin (TGVP) on the absorption of chenodeoxycholic acid (CDCA) was investigated in three groups of six rats (controls, CDCA, CDCA + TGVP) through the evaluation of portal and caval serum bile acids (SBA) concentrations after an oral load with CDCA to investigate whether changes in this parameter reflect variations in splanchnic blood flow induced by a vasoconstrictor. The results indicate that CDCA was absorbed and led to a significant increase in SBA. This increase was reduced by TGVP administration: portal blood 380.0 +/- 61.2 vs 279.7 +/- 45.3; caval blood 151.8 +/- 45.7 vs 41.7 +/- 12.5 (mumol/l; mean +/- s.d.). This suggests that variations in SBA concentrations could reflect changes in splanchnic circulation.

Animals↗
PubMed1989

Increase of walking capacity after acute aminophylline administration in intermittent claudication.

In the presence of peripheral atherosclerotic disease, inappropriate adenosine release during exercise might promote excessive arteriolar dilation leading to steal phenomena and ischemia. In order to test this hypothesis, IV aminophylline (6 mg/kg over fifteen minutes), a dosage known to effectively block adenosine receptors, was acutely administered--in a double-blind, placebo-controlled study design--in 13 patients with intermittent claudication and documented atherosclerotic disease. All patients performed two treadmill exercise tests at the same hour on two consecutive days, five minutes after aminophylline or placebo administration randomly allocated. Pain-free time was 109 +/- 133 (mean +/- SD) seconds after placebo and 173 +/- 165 seconds after aminophylline (p less than .01); maximum time to claudication was 273 +/- 191 seconds after placebo and 397 +/- 318 seconds after aminophylline (p less than .05). The authors conclude that intravenous aminophylline markedly increases the walking capacity in patients with intermittent claudication, possibly by preventing flow maldistribution phenomena through adenosine receptors blockade.

Aminophylline↗
PubMed1989

Evidence for the single origin of HB G-San Jose in Sicily.

Hb G-San Jose [alpha 2 beta 2 7(A4)Glu----Gly] was detected in four families and three unrelated individuals from Eastern Sicily. Polymorphic restriction sites within the beta-globin gene cluster bearing the mutation were characterized. A complete association of beta-G-San Jose alleles with Mediterranean haplotype IV was found in the families examined and the same haplotype was also present in the unrelated individuals. These findings support the hypothesis of an unicentric origin of the beta-G-San Jose mutation which may have arisen in Eastern Sicily.

Cluster Analysis↗
PubMed1989

Synthesis and anticonvulsant evaluation of 1,2-diphenylethane derivatives, potential metabolites of denzimol.

A number of new 1,2-diphenylethane derivatives were synthesized and tested for anticonvulsant activity. Their structure was designed on the basis of the potential metabolic degradation of the imidazole ring present in denzimol ( ( +/- )-N-[2-[4-(beta-phenylethyl)phenyl]-2-hydroxethyl]imidazole), a potent anticonvulsant. The compounds which inhibited the electroshock-induced seizures (MES) in mice, namely N-[4-(beta-phenylethyl)phenacyl]formamide (VII) and N-[2-[4-(beta-phenylethyl)phenyl]-2-hydroxyethyl]formamide (IX), proved active also as inhibitors of the pentylenetetrazole-induced tonic seizures. The results of the pharmacological screening were evaluated in relation to the lipophilicity of the compounds.

Animals↗
PubMed1988

Receptor binding studies of the flavone, REC 15/2053, and other bladder spasmolytics.

The new flavone derivative REC 15/2053, a compound with spasmolytic activity on the lower urinary tract, was examined for its in vitro interaction with alpha- and beta-noradrenergic receptors, dopaminergic, muscarinic, serotoninergic, and opiate receptors, and calcium-channel binding sites labeled with 1,4-dihydropyridines from normal rat brain. All the investigated receptors are directly or indirectly involved in the nervous control of the lower urinary tract functions. The activity of REC 15/2053 on these receptors was studied in comparison to the most common drugs used in the management of urinary bladder disorders such as flavoxate, emepronium bromide, oxybutynin, terodiline, and imipramine. REC 15/2053 showed only weak binding to [3H]nitrendipine sites (IC50 = 14 microM) and muscarinic receptors (IC50 = 18 microM), whereas flavoxate was slightly active only at muscarinic receptors (IC50 = 12.2 microM). Emepronium bromide, oxybutynin, and terodiline were active only at muscarinic receptors, with IC50 values of 236, 5.4, and 588 nM, respectively. Oxybutynin showed a weak affinity to [3H]nitrendipine binding sites (IC50 = 44.4 microM). Imipramine was active at alpha 1-adrenergic and muscarinic receptors (IC50 = 248 and 653 nM, respectively). The activity of REC 15/2053 at muscarinic receptors and 1,4-dihydropyridine binding sites seems too low to account for its mechanism of action.

Animals↗
PubMed1988

The contribution of ventricular tachyarrhythmias to the genesis of cardiac pain during transient myocardial ischaemia in patients with variant angina.

The 24-h ambulatory electrocardiograms of 15 patients with both variant angina and ischaemia-related arrhythmias were analyzed to correlate cardiac pain with the following variables: site, type, duration and magnitude of ECG changes, presence and type of arrhythmias and time of occurrence of ischaemic attacks during the 24-h. Apart from sublingual nitrate therapy, Holter monitoring was performed in the Coronary Care Unit (CCU), in the drug-free state in all patients. During a total of 79 days of monitoring, patients had 1385 ischaemic episodes, of which only 30% were painful. The site of ischaemia did not predict the occurrence of pain. Pain was more frequently associated with ST-segment elevation, longer ischaemic duration, increased time to peak ECG change, and greater ST-segment shift and arrhythmias. When the 259 attacks in association with ventricular arrhythmias were compared to the arrhythmia-free episodes, they were more frequently painful for the same duration and magnitude of ECG ischaemic changes. Furthermore, the complexity of arrhythmias increased the probability of cardiac pain. Most ischaemic episodes occurred at night and a decrease in the frequency of painful episodes (apart from those associated with arrhythmias) was apparent. Thus, in addition to electrocardiographic severity and duration of ischaemia, the presence of ventricular arrhythmias and the time of occurrence seem to influence pain perception during ischaemia.

Adult↗
PubMed1988

Propranolol reduces the response of serum bile acids to oral chenodeoxycholic acid, possibly as a reflex reaction to reduced portal blood flow in healthy and cirrhotic subjects.

To evaluate if a drug that affects splanchnic and portal flow reduces intestinal bile acid absorption, we studied the effect of propranolol (40 mg oral dose) both on the response of total bile acids (SBA) to oral chenodeoxycholic acid (CDCA 250 mg) and on the estimated hepatic flow by indocyanine green kinetics in 10 healthy and 14 cirrhotic subjects. In 18 subjects who showed a reduction in resting heart rate of almost -5%, propranolol significantly reduced the SBA area under the curve after CDCA in both healthy (mumol/l/h m +/- SD from 181.7 x 144.9 to 56.5 +/- 36.4 p less than 0.02) and cirrhotic (from 1412.1 +/- 1044.8 to 1129.2 +/- 978.8 p less than 0.01) subjects. Variable but not significant modifications were observed in estimated hepatic flow. These results suggest that the propranolol-induced changes in SBA response to CDCA could be a reflex reaction to changes in splanchnic/portal flow.

Bile Acids and Salts↗
PubMed1988

Interaction of the anticonvulsants, denzimol and nafimidone, with liver cytochrome P450 in the rat.

The presence of an imidazole moiety in the chemical structure of denzimol and nafimidone suggested that these new anticonvulsants might interfere with cytochrome P450-mediated mixed function monooxygenase activities. We therefore investigated their ability to bind reversibly to rat liver cytochrome P450. Both drugs displayed a type II spectra. The Ks values of binding were 6.66 and 7.00 mM, respectively, for denzimol and nafimidone. In other in-vitro studies the IC50 of the inhibition caused by denzimol and nafimidone was determined on carbamazepine (CBZ) epoxidation and diazepam C3-hydroxylation and N1-dealkylation. The IC50 values for CBZ epoxidation were 4.46 x 10(-7) and 2.95 x 10(-7) M, respectively, in the presence of denzimol and nafimidone. The IC50 values for diazepam C3-hydroxylation were 1.44 x 10(-6) and 1.00 x 10(-6) M, respectively, and those for N1-dealkylation 6.66 x 10(-7) and 5.95 x 10(-7) M. The inhibition of CBZ metabolism was also investigated ex-vivo and in-vivo after single oral doses (15 and/or 60 mg kg-1) of denzimol or nafimidone. Inhibition of CBZ-10,11-epoxidation by the two drugs was time- and dose-dependent. Further studies in-vivo showed that denzimol and nafimidone prolong pentobarbitone sleeping times indicating that both drugs bind to rat liver microsomes and are potent inhibitors in the rat of mixed function monooxygense activities both in-vitro and in-vivo.

Animals↗
PubMed1988

Improvement of walking distance in patients with intermittent claudication by chronic local therapy with isosorbide dinitrate ointment.

Isosorbide dinitrate ointment (100 mg tid) was directly applied to 30 male patients with stable, documented intermittent claudication on the areas where ischemic pain was experienced. The symptom-free distance walked (DWA) and the maximum distance reached (MDR) basally, after one, three, six, and twelve months were evaluated by means of treadmill stress tests (TSTs) (angle 0 degree-velocity constant/patient). After the basal TST, patients were randomly divided into two groups: placebo group and therapy group (double blind), and a further TST was administered one month later. DWA results were 74 +/- 8 m vs 297 +/- 83 m and MDR results were 163 +/- 22 m vs 506 +/- 86 m in the therapy group (basal vs one month TST: p less than .01) and 94 +/- 24 m vs 96 +/- 15 m and 232 +/- 53 m vs 183 +/- 26 m in the placebo group, respectively (basal vs one month TST: NS). Being confident that a significant placebo effect was absent, the authors opened the trial and treated all patients, repeating further TSTs at three, six, and twelve months. The following results were obtained: DWA was 84 +/- 13 m, 316 +/- 63 m, 374 +/- 55 m, and 452 +/- 61 m; and MDR was 197 +/- 29 m, 431 +/- 59 m, 514 +/- 57 m, and 547 +/- 59 m, respectively, in basal conditions and after three, six, and twelve months of treatment (p less than .01 for all the values for both DWA and MDR vs basal values).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1988

Distribution of enzyme polymorphisms in six Sicilian communes.

The relations between seven genetic systems in six Sicilian communes (a commune is the smallest unit in the Italian administrative system) were explored in a sample of 719 young adults. It was found that there is some correspondence between geographic location and genetic differentiation, through kinship analysis and correspondence analysis. A probable bottleneck or mutation effect was observed in the commune of Vizzini, in Southeastern Sicily, which is characterized by a polymorphic frequency of the allele H of 6PGD.

Adult↗
PubMed1988

Reverse cascade filtration of ascitic fluid--preliminary results.

Refractory ascites is an infrequent complication of cirrhosis. Paracentesis and ultrafiltration of the ascitic fluid with intravenous or intraperitoneal reinfusion of the concentrated ascites has been used as therapy for this condition since 1971. The technique is cumbersome and has high morbidity and mortality rates, even if effective. In this paper we describe a new technique that couples secondary filtration for the removal of macromolecules, with ultrafiltration of ascitic fluid. In its very first application 6 patients underwent 8 treatments. No adverse effect was observed and clinical efficacy was good. Up to 60 g of albumin can be saved in a single session lasting less than 2 hours.

Aged↗
PubMed1987

Findings from long-term electrocardiographic monitoring of patients with variant angina in a coronary care unit.

Eleven patients with frequent episodes of variant angina underwent 24-hour electrocardiographic monitoring in a coronary care unit for a total of 70 days to assess circadian variation in ischemic episodes and its correlation with circadian heart rate (HR) rhythm. In each patient a series of 4 to 13 consecutive days, in the absence of therapy, with 8 or more ischemic episodes per day were analyzed. Harmonic regression models were fitted to the hourly number of ischemic episodes and the hourly values of HR. Out of 54 days, with 8 or more episodes per day for a total of 1,357 episodes, a circadian rhythm was observed for 34 days (64%), in at least 1 day in all patients and during the entire period of observation in only 3. Its presence was independent of the number of episodes; the peak of periodic functions occurred at 2.9 +/- 2.7 AM. A cadian rhythm for HR was observed in 61 of the 70 days (87%), consistently in 7 patients; the nadir occurred at 2.4 +/- 1.5 AM; simultaneous cycling in HR and transient ischemia was found on 32 days. The intrapatient difference between the peak and the nadir of the ischemic and the HR function was, on average, 2.6 +/- 3.3 hours. Thus, a circadian rhythm of ischemic episodes was present in all patients although it was not consistently present; simultaneous occurrence of circadian variation in ischemic episodes and HR was observed only in 60% of the days with a sufficiently high number of attacks and when this occurred, a significant phase shift was observed; occasional loss of HR cycling was observed in some patients, without an apparent cause.

Adult↗