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Biomedical subjects

R Testa

Publications and source records attributed to R Testa.

At least 127 records · Page 7Linked to original sources
PubMed1993

Effects of terflavoxate on stimulated contractions of urinary bladder in vitro.

The antispasmodic activity of terflavoxate (CAS 86433-39-8), a flavone derivative with spasmolytic properties on the urinary tract, has been studied in vitro, in comparison to the most common drugs utilized in the therapy of overactive detrusor, namely flavoxate, oxybutynin, and terodiline. Terflavoxate showed affinity for bladder (and brain) muscarinic receptors at micromolar level, however, its activity on carbachol-induced contractions of rat bladder was clearly non competitive, indicating that the compound is devoid of functional antimuscarinic property. Moreover, the observation that unlike antimuscarinic drugs, terflavoxate inhibited by more than 50% field stimulation-induced contractions of rabbit bladder strips, indicates that mechanisms other than the anticholinergic one should be responsible for its smooth muscle relaxant properties. Terflavoxate, flavoxate, oxybutynin, and terodiline were equally effective in inhibiting the two components of K(+)-induced contractions, while nifedipine and nicardipine were more potent than the other compounds, and more effective in inhibiting tonic than phasic contractions. In addition, while nifedipine and nicardipine antagonized in a competitive manner calcium-induced contractions of potassium-depolarized bladder strips, the other spasmolytics behaved as mixed antagonists. Differences in calcium antagonistic properties between nifedipine and nicardipine on one side, and terflavoxate on the other, are further demonstrated by the data on binding experiments. Nevertheless, present results suggest that Ca(++)-antagonistic effects are mainly responsible for terflavoxate smooth muscle relaxant properties.

Animals↗
PubMed1993

New basic esters of 2-phenyl-3-methyl-4-oxo-4H-1-benzopyran-8-carboxylic acid endowed with spasmolytic properties. Synthesis and pharmacological-pharmacokinetic evaluation.

In order to obtain new analogs of flavoxate endowed with higher stability and possibly higher potency, a new series of basic esters of 2-phenyl-3-methyl-4-oxo-4H-1-benzopyran-8-carboxylic acid (MFCA) has been prepared and investigated. Derivatives in which the structure of flavoxate was modified by branching and lengthening of the estereal alkyl chain were synthesized, together with the conformationally restricted N-piperidinyl derivatives. Esters containing in their structure various alicyclic tertiary amines which are present in natural or synthetic drugs endowed with spasmolytic properties, mainly of anticholinergic nature, were also prepared. The stability in aqueous solution, acute toxicity in mouse, and in vitro spasmolytic properties of the new compounds were investigated in comparison with flavoxate. Based on the results obtained from this screening procedure, 3 compounds were selected for further investigation. In this phase, further pharmacological and stability testing as well as preliminary animal pharmacokinetic investigations were carried out. The obtained results suggested the choice of 1,1-dimethyl-2-(1-piperidinyl)ethyl 2-phenyl-3-methyl-4-oxo-4H-1-benzopyran-8-carboxylate HCl (Rec 151 2053, terflavoxate, CAS 86433-39-8) as a candidate for preclinical development. The deeper pharmacological characterization of this compound, carried out mainly in comparison with flavoxate, terodiline, and oxybutynin confirmed its good spasmolytic activity.

Administration, Oral↗
PubMed1992

Molecular characterization of hemoglobin C in Sicily.

Analysis of polymorphisms of the beta-globin gene cluster was performed on 12 families and on one unrelated individual of Sicilian origin who carried hemoglobin C (Hb C). Two different haplotypes were found in association with beta c Sicilian alleles, corresponding to haplotypes I and II previously described in American blacks. In our population, the more frequent one (haplotype I) was linked to the lack of a polymorphic HpaI site 3' to the beta gene (13.0-kb fragment), similarly to haplotype I in blacks, while the less frequent one was linked to a 7.0-kb HpaI fragment attributable to a site that had never been previously described in linkage with beta c alleles. In Italy, these two haplotypes have been found in rare cases in association with beta A alleles. These findings provide new insights into the origin of Hb C present in Sicily, suggesting that (1) the beta c mutation detected in Sicily derived from African black chromosomes and does not represent a new mutation; and (2) Hb C may have originated either by multiple mutational events on separate chromosomes or by mutation in the HpaI site 3' to the beta gene in a pre-existing beta c chromosome.

Alleles↗
PubMed1992

Clinical, hematological, and molecular features in Sicilians with Hb S-beta-thalassemia.

The clinical, hematological, and molecular features of 81 patients with Hb S-beta-thalassemia and relatives from 76 unrelated families are reported. We analyzed the beta-thalassemia mutations and the beta S haplotypes in all patients and detected 6 different beta-thalassemia alleles: codon 39 (C-->T) (39 cases), IVS-I-1 (G-->A) (12 cases), IVS-II-1 (G-->A) (4 cases), IVS-I-6 (T-->C) (6 cases), IVS-I-110 (G-->A) (14 cases), and IVS-II-745 (G-->C) (6 cases). Eighty patients had haplotype #19 or the Benin type and one had haplotype #17 or the Cameroon type. The type of beta-thalassemia allele had the greatest influence on the phenotypic expression; this was observed for patients with Hb S-beta-thalassemia and for simple beta-thalassemia heterozygotes. The mild IVS-I-6 (T-->C) mutation produced borderline abnormal erythrocytic indices and Hb A2 levels in heterozygotes. Overall, there was a milder expression in beta(S) beta(+) patients (only 7.7% presented severe disease) than in those with the beta(S)beta(0) condition (22.6% had the severe form of the disease).

Alleles↗
PubMed1992

In vivo effects of different antispasmodic drugs on the rat bladder contractions induced by topically applied KCl.

The model originally proposed by Postius and Szelenyi for in vivo screening of spasmolytic compounds on the rat urinary bladder, has been modified and tested to verify its predictivity. The topically applied KCl induced reproducible contractions of the bladder that were dose dependently inhibited by i.v. administration of calcium antagonists like nifedipine, nicardipine, and verapamil. The other spasmolytics tested (oxybutynin, terodiline, flavoxate, and papaverine), showed a non-dose-related inhibition of the contractions. The in vivo potency of the calcium antagonists was related to their in vitro activity on the agonist-induced contractions of rat bladder strips, whereas the activity of the other spasmolytics appeared higher than that predicted on the basis of their in vitro efficacy. Nicardipine showed a dose-dependent inhibition of KCl-induced contractions also after oral administration, whereas oxybutynin and papaverine behaved as after i.v. administration. The described model represents, therefore, a good, quantitative, and reproducible tool of screening at the bladder level only for antispasmodic drugs endowed with strong calcium antagonistic activity.

Administration, Topical↗
PubMed1992

Splanchnic haemodynamic effects of ketanserin in anaesthetized cirrhotic rats.

The effects of ketanserin, atenolol and their association on portal vein pressure (PVP), portal and caval bile acid concentrations (PBA and CBA), and extraction ratio of bile acids (ER) after oral loading with chenodeoxycholic acid were investigated in anaesthetized cirrhotic rats. PVP was significantly reduced by ketanserin and by the association ketanserin plus atenolol; PBA was significantly decreased in all the treated groups, whereas the reduction of CBA was significant only in the rats treated with ketanserin and atenolol alone. ER was increased by atenolol and ketanserin, but it was not modified by their association. Moreover, a significant correlation was observed between PBA and CBA and between PVP and ER. These results suggest that, in anaesthetized cirrhotic rats, ketanserin reduces PVP probably through more complex mechanisms than the simple indirect reduction of portal flow, and that the association of ketanserin plus atenolol has no additive effect in reducing PVP.

Animals↗
PubMed1992

Clinical, hematological, and molecular features in Sicilians with sickle cell disease.

We report the clinical, hematological, and molecular findings observed in 32 Sicilian patients with sickle cell disease. None of our patients received regular blood transfusions and careful infectious disease prophylaxis was carried out for all. Haplotyping of beta S chromosomes was performed in all patients; all were homozygous for haplotype #19 (Benin). Gene mapping excluded the presence of an alpha-thalassemia in 13 of our patients; none of the relatives showed any evidence of the presence of alpha-thalassemia. Hb F levels were 11.8 +/- 5.9% with G gamma representing 39.6 +/- 3.6% of total gamma chain. Hb F levels were higher in females than in males (12.5 +/- 5.9% versus 9.7 +/- 6.5%) but the difference was not statistically significant. All patients, regardless of age and sex, were anemic with normal mean corpuscular hemoglobin concentration, high mean corpuscular volume and mean corpuscular hemoglobin, and mild reticulocytosis. Analysis of clinical manifestations suggests that our patients have a disease of moderate severity.

Adolescent↗
PubMed1991

Effects of beta-adrenoreceptor antagonists on cerebral blood flow of cirrhotic patients with portal hypertension.

The current study evaluated the effect of two beta adrenergic-blocking agents, propranolol (PRP) and atenolol (ATN), versus placebo on cerebral blood flow (CBF) of three homogeneous groups of cirrhotic patients with portal hypertension. CBF was measured by the noninvasive 133-Xenon inhalation method at rest and 1 hour after a single oral dose of PRP (40 mg), or ATN (100 mg), or placebo. Blood pressure and heart rate (HR) were measured at the beginning of each examination, and end-tidal pCO2(PeCO2) was monitored. The HR decreased significantly in both the PRP and ATN groups (P less than .01), whereas no changes were recorded for both PeCO2 and mean arterial blood pressure (MABP). The comparisons of the CBF differences among groups (ANOVA with the significance levels adjusted by the Bonferroni's correction) showed a significant increase in CBF after ATN as compared with both placebo (P less than .02) and PRP (P less than .01), whereas no significant differences were seen after PRP as compared with placebo. Our results confirm that PRP does not significantly affect CBF, whereas ATN induces an increase in CBF, although the underlying mechanism is difficult to explain.

Adrenergic beta-Antagonists↗
PubMed1991

Effects of different drugs on the cystometrogram in conscious rats.

The effects on urodynamic parameters of i.v. administration of different drugs utilized in the therapy of detrusor instability, have been studied in conscious catheterized rats. Emepronium bromide, oxybutynin and nifedipine affected in a dose-dependent way the micturition pressure (MP), with sporadic changes in bladder volume capacity (BVC). Terodiline induced significant increases in BVC values in a wide range of doses. These changes, however, were always not dose-dependent. The drug significantly reduced MP only at the higher administered dose (10 mg/kg). Flavoxate induced increases of bladder capacity (BVC) not dependent on the administered doses, with no changes in micturition pressure (MP). Indomethacin significantly increased BVC and weakly reduced MP, but the effects were not dose-related. The effects of drugs on BVC were unrelated with the basal value of this parameter, whereas the decrease of MP seems to be related to high basal values before treatment. From a quantitative point of view, cystometrographic recordings in conscious normal rats can provide comparative data among drugs acting on bladder contractility (MP) such as anticholinergics and strong calcium antagonists.

Animals↗
PubMed1991

Effects of oxybutynin, terodiline, and nifedipine on the cystometrogram in conscious rats with infravesical outflow obstruction.

The effects of i.v. administration of different drugs utilized in the therapy of detrusor instability have been studied in conscious catheterized female rats with infravesical outflow obstruction induced by partial urethral ligature, in comparison to normal animals. The effects of oxybutynin (1 mg/kg), terodiline (10 mg/kg), and nifedipine (1 mg/kg), were evaluated with regard to bladder capacity (BVC) and micturition pressure (MP) both in normal and obstructed rats. The effects on micturition and residual volume, as well as on spontaneous contractile activity representative of bladder instability, were also observed in obstructed rats. In normal animals, terodiline and oxybutynin induced a significant decrease in micturition pressure without changes in BVC. In obstructed rats, these drugs administered at the same doses did not induce any significant change in all the observed parameters. Nifedipine that in normal rats also reduced the MP, in obstructed animals induced an inhibition of bladder instability (about 50%) with no effects on the other cystometrographic parameters.

Animals↗
PubMed1990

Comparative approach to the evaluation of hemoglobin A2 by two different methods: high-performance liquid chromatography and DE-52 microchromatography.

Hb A2 was determined in 477 subjects: 77 were affected by iron deficiency anemia, 172 were carriers of beta-thalassemia trait and 228 were normal controls. Hb A2 was determined by both DE-52 microchromatography and high-performance liquid chromatography (HPLC). The analysis of the data by linear regression demonstrated that the methods furnish overlapping results. Our findings show that HPLC is a rapid and easily reproduced method which allows a quantitative and qualitative discrimination of the various Hb fractions, making it a valid tool in screening programs for hemoglobinopathies.

Adult↗
PubMed1990

Analysis of circadian fluctuations of bile salt concentration and pH in the stomach of normal subjects and patients suspected of having duodenogastric reflux.

This study was undertaken to evaluate whether intrigastric pH measurements and bile salt concentrations show synchronous fluctuations, in both postprandial and fasting states. It was performed on 5 normal volunteers and 17 non-operated patients suspected of having duodenogastric reflux. In controls the two variables showed different behaviour, especially after eating, while in suspected refluxers they presented more synchronous elevations both in postprandial states and in the nocturnal period. The first derivatives of both pH and bile salt interpolations using Fourier's truncated Series give evidence that these two variables behave differently in the time domain of the two groups. In fact, their first derivatives show equal signs for 521 min (36.2%) out of the 1440 of the study in controls (p less than 0.05) and for 1024/1440 min. (71.1%) in suspected refluxers (p less than 0.005). The difference between the time elapsed in min with equal sign derivatives in the two groups is significant (p less than 0.005). Despite this more coherent behaviour of pH and bile salt fluctuations in patients with suspected reflux, the two variables do not present coincident numerical values even in this population and therefore a close quantitative relationship between them can be excluded in both groups. As a consequence of these results, the use of bile salt concentrations seems inadequate to validate the fact that alkalinizations observed in pH-metry studies are related to episodes of duodenograstric reflux.

Adult↗
PubMed1990

[Hemoglobin Shepherds Bush in a Sicilian family].

A case of Hb Shepherds Bush observed in a Sicilian family is reported. The iron status has been evaluated since chronic haemolysis may cause hemosiderosis. The paper also refers to the diagnostic workout for all chronic hemolytic anemias.

Adult↗
PubMed1989

Cerebral blood flow and plasma free tryptophan in cirrhotics with and without hepatic encephalopathy.

Cerebral blood flow (CBF), measured by the non-invasive 133-Xenon inhalation method, plasma levels of ammonia (NH3) and free tryptophan (fTRP) were determined in 30 cirrhotic patients without overt encephalopathy. Psychometric evaluation detected subclinical hepatic encephalopathy (SHE) in 20 of them, and was normal in the other 10. A significant CBF difference (p less than 0.05) was found between the SHE and the non-SHE patients. fTRP levels were significantly (p less than 0.05) higher in patients with SHE than in those without SHE, and a significant negative correlation (p = 0.003) was found between CBF values and fTRP in the whole group of patients. NH3 did not differ in the two subgroups and did not correlate with CBF values. It is concluded that CBF could have some implications in SHE, although its relevance is still unclear. The negative correlation between CBF and fTRP prompts further investigation concerning the relationships between plasma fTRP, brain serotonin, cerebral metabolism and blood flow in the development of brain derangement during cirrhosis.

Adult↗
PubMed1989

Antimycobacterial chemotherapy in inflammatory bowel disease.

We report on a case, ulcerative colitis and another of Crohn's disease. During a relapse which was unresponsive to conventional therapy, acid-fast bacilli were found in colonic biopsies. Conventional therapy was substituted with antimycobacterial chemotherapy (rifampicin, isoniazid and ethambutol) which was responsible for a marked improvement. However, a relapse occurred during chemotherapy and no acid-fast bacilli were found. The patients became responsive to sulphasalazine and corticosteroid therapy once again. It appears that Mycobacteria play a collateral role in inflammatory bowel disease and that once they have been eliminated the original disease re-emerges.

Adult↗
PubMed1989

Profile of in vitro binding affinities of neuroleptics at different rat brain receptors: cluster analysis comparison with pharmacological and clinical profiles.

A series of 21 neuroleptics with different chemical structures (phenothiazines, thioxanthenes, dibenzodiazepines, butyrophenones, benzamides, etc.) was examined for their in vitro interactions with 12 neurotransmitter binding sites in the rat brain (alpha- and beta-noradrenergic, dopaminergic, muscarinic, serotoninergic, histaminic, and opioid receptors, calcium channels, and serotonin uptake binding sites). The biochemical profile obtained from the binding data was compared with reported pharmacological and clinical profiles for this class of compounds by cluster analysis. Cluster analysis on binding data classified the compounds in three main subgroups: benzamides, compounds with an affinity mainly for DA2 and 5-HT2 receptors and inactive at muscarinic receptors, and compounds with a high affinity for alpha 1-adrenergic receptors and muscarinic receptors. The main subgroups resulting from cluster analysis of previously published pharmacological and clinical data for neuroleptics contain compounds common to the present study, with some correlations. The results extend previous observations that a complete binding profile corresponds to the pharmacological and clinical profile of this class of compounds.

Animals↗