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Biomedical subjects

M Romano

Publications and source records attributed to M Romano.

At least 415 records · Page 23Linked to original sources

Effects of long-term molsidomine treatment versus isosorbide dinitrate and placebo on exercise tolerance in stable angina.

A single-blind study (n = 59) was performed to assess the effect of long-term (4 week) orally administered molsidomine (2 mg 4 X daily), isosorbide dinitrate (10 mg 4 X daily), and placebo on exercise tolerance performed on the bicycle ergometer by patients with stable angina on effort and with significant coronary artery disease. Isosorbide dinitrate had similar effects to placebo, both failed to modify the pressure-rate product, the sustained work load, and the ST segment depression, but slightly decreased, although not significantly, the incidence of angina. Although not affecting the pressure-rate product and the mean blood pressure, molsidomine decreased significantly the ST segment depression (p less than .05). In conclusion, by markedly reducing preload and because of its long-lasting effect (up to 6 h), the new vasodilator drug molsidomine plays a useful role in the long-term management of stable angina on effort.

Angina Pectoris↗

[Triple valve replacement. Evaluation of 90 surgically treated patients].

Ninety patients, aged 17 to 59 years (average 39.8 yrs) underwent triple valve replacement from January 1967 to December 1979. The aetiology was rheumatic carditis in 84% of cases. There had been previous surgery in 29 cases (19 mitral commissurotomies). All patients were severely symptomatic: 68 (76%) had atrial fibrillation and the cardiothoracic ratio was 0.70 +/- 0.085. In 24 cases, triple valve stenosis (aortic, mitral and tricuspid) was observed; 13 patients had triple regurgitation and 53 patients had mixed lesions (stenosis and regurgitation). Triple mechanical valve prostheses were implanted in 35 cases (Björk or Starr), triple bioprostheses were implanted in 12 cases, and 43 patients received a combination of mechanical and bioprostheses (tricuspid bioprostheses in all 43 cases). The patients were divided into two groups according to the type of valve replacement; Group I: 57 patients, subdivided into Group IA (35 cases, 39%) with triple mechanical prosthesis, and Group IB (22 cases, 25%) with mechanical aortic and mitral valve prostheses and tricuspid bioprostheses; Group II, 33 patients, subdivided into Group IIA (12 patients, 13%) with triple bioprostheses, and Group IIB (21 patients, 23%) with mitral and tricuspid bioprostheses and a mechanical aortic valve prosthesis. Techniques of myocardial protection have have improved since the beginning of this series and at present comprise cardioplegia associated with general hypothermia to 25 degrees C and pericardial irrigation with ice cold saline. The overall operative mortality was 37% (34/90) but in 1979 alone it was only 10%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Prostaglandin endoperoxide synthetase and the activation of benzo(a)pyrene to reactive metabolites in vivo in guinea pigs.

The role of prostaglandin endoperoxide synthetase in the in vivo activation of benzo(a)pyrene to reactive metabolites capable of interacting irreversibly with cellular macromolecules was studied in guinea pig liver, lung, kidney, spleen, small intestine, colon, and brain. DNA and protein covalent binding experiments were made after systemic administration of acetylsalicylic acid (200 mg/kg) followed by radiolabeled benzo(a)pyrene (4 microgram/kg). Results are compared with a control situation in which the prostaglandin endoperoxide synthetase inhibitor (acetylsalicylic acid) was not administered. No decrease in the level of DNA or protein benzo(a)pyrene-derived covalent binding was observed in any of the tissues studied.

Animals↗

Chemotherapy-increased antineoplastic effects of antibody-toxin conjugates.

A model, employing murine L1210 leukemia to which the artificial determinant TNP was bound in vitro and an anti-DNP antibody-ricin A-chain conjugate, was used to explore the in vivo therapeutic potential of combined immunotoxin-chemotherapy treatment. Under conditions in which immunotoxin and chemotherapy as single therapies had only marginal therapeutic activity, their combined use was markedly effective.

Animals↗

Quantitative profiling of prostaglandins and thromboxane by high-resolution gas chromatography-selected--ion monitoring.

The development and biological application of a rapid method for quantitative profiling of prostaglandins and thromboxane using high-resolution gas chromatography (HRGC) coupled with mass spectrometry in the selected-ion monitoring technique (SIM) are described. The method is based on the single-step extraction of prostaglandins from biological samples on C18 reversed-phase cartridges after addition of deuterated analogues as internal standards, followed by derivatization of functional groups and final analysis by HRGC-SIM with wall-coated open tubular persilanized capillary columns. Biological applications include the determination of endogenous arachidonic acid cascade profiles in rat tissue homogenates and thromboxane synthetase inhibition studies in human serum.

6-Ketoprostaglandin F1 alpha↗

Perinatal development of styrene monooxygenase and epoxide hydrolase in rat liver microsomes and nuclei.

Nuclear enzymes were found to develop earlier than the corresponding microsomal activities. In fact styrene monooxygenase enzymatic activity at 18 days gestational age reached about half the values of adult animals, whereas fetal microsomal activity was only about 1/20 the adult level at the same age. In microsomes and nuclei the ontogenic development of epoxide hydrolase is slightly slower than styrene monooxygenase. This suggests that fetuses and newborn animals are exposed to higher risk of accumulation of styrene-7,8-oxide, a toxic and possibly teratogenic product of styrene monooxygenase.

Age Factors↗

Partial structure of the active moiety of a lipoprotein complexing proteoglycan from human aorta.

Proteoglycans and glycosaminoglycans of the intima-media extracellular matrix have been stated to play a role in lipoprotein deposition associated with atherogenesis. It is therefore important to characterize the active lipoprotein-complexing moiety of these macromolecular aggregates. We have isolated a soluble proteoglycan aggregate of approximately 5 X 10(6) molecular weight after homogenization of human aortic intima-media in an isosmotic sucrose solution, sequential differential centrifugation, dialysis, exclusion chromatography and preparative electrophoresis. This proteoglycan aggregate, labelled lipoprotein-complexing proteoglycan (LCP), has been previously shown to form specific complexes with low density lipoproteins, either isolated or in sera. Density gradient centrifugation in dissociative conditions of the LCP, cellulose acetate acetate electrophoresis of the subfractions, chondroitinases treatment and high performance liquid chromatography of the unsaturated disaccharides indicated that the glycosaminoglycan moiety was composed of 56% chondroitin-6-SO4, 26% hyaluronate and/or undersulfated chondroitin and 17% chondroitin-4-SO4. In pore-gradient polyacrylamide gel electrophoresis, the hyaluronate monomer appeared to have a molecular weight of 250000 while that of the chondroitin sulfates ranged between 50000 and 70000 after extensive treatment with protease. The fractions enriched in the chondroitin sulfate monomers were the most reactive towards LDL and their reactivity was abolished by chondroitinase AC indicating that the lipoprotein-complexing capacity of the LCP aggregate is associated to these molecules.

Aorta↗

Mutagenic relevance of rat hepatocyte nuclei in the activation and inactivation of xenobiotica. Cyclophosphamide and epichlorohydrin activity on the yeasts S. pombe and S. cerevisiae.

The influence on the mutagenicity of cyclophosphamide (Cy) and epichlorohydrin (ECH), of liver nuclei and hepatic post-mitochondrial (S9) preparations from phenobarbital-treated rats, was examined. The study was conducted in vitro, with 2 yeasts, Schizosaccharomyces pombe (P1 strain) which allows the detection of forward mutations, and Saccharomyces cerevisiae (D5 strain), in which the induction of different genetic effects, such as mitotic recombination, can be evaluated. The results indicated that the nuclear fraction has a qualitative capacity for biotransformation of compounds, overlapping that of S9. From a quantitative point of view, the Cy-activating capacity of the nuclear fraction was twice as high as that of S9 whereas the two fractions showed a similar ECH-inactivating ability. The present study strengthens the hypothesis of the relevance of nuclei as a site of metabolic activation and inactivation of exogenous compounds.

Animals↗

Evaluation of epichlorohydrin (ECH) genotoxicity. Microsomal epoxide hydrolase-dependent deactivation of ECH mutagenicity in Schizosaccharomyces pombe in vitro.

The mutagenic effect of epichlorohydrin (ECH) on the yeast Schizosaccharomyces pombe was studied in vitro in the presence of mouse-liver S9 mix and microsomal and cytosolic fractions. The incubations were always performed in the absence of NADPH-generating systems. S9 mix and microsomes from phenobarbital-pretreated mice significantly reduced ECH mutagenicity, whereas the cytosol did not result in any deactivating effect. The various protein contents of the subcellular fractions were not involved in any scavenger effect as regards ECH mutagenic activity. Moreover, the addition of reduced glutathione to the incubation mixtures indicated that it did not play an important role, either per se or through the enzyme(s) glutathione-S-epoxide transferase(s), in preventing ECH genotoxicity. Our results suggest that microsomal epoxide hydrolase(s) represents the major step in the detoxifying pathway of ECH. These observations were supported by measurements of the specific epoxide hydrolase activity in the various fractions on the same substrate.

Ascomycota↗

The intragastric host-mediated assay for the assessment of the formation of direct mutagens in vivo.

The intragastric host-mediated assay (h.m.a.) was devised and carried out with a view to assessing the formation of direct mutagens in the gastrointestinal tract of mammals. The h.m.a. consists in the injection of nitrosable compounds, NaNO2 and cells of the yeast S. pombe, by gavage into the animals' stomachs and in the recovery of the target cells from the faeces for mutation-induction analysis. Methylurea was chosen as a model nitrosable compound, and the effects of nitrosation modulators such as ascorbic acid and thiocyanate were studied. Cimetidine, a drug nitrosable in vitro, was tested with the system. Positive results were obtained only at very large doses and in artificially produced low pH. The new host-mediated assay seems to be efficient in revealing the formation, in vivo, of direct, short-living mutagens.

Animals↗

Exercise induced ventricular arrhythmias. Angiographic correlation with the severity of coronary artery disease.

We correlated the incidence and degree of exercise induced ventricular arrhythmias (EIVA) with the angiographic severity of coronary artery disease (CAD) in 162 patients with a history of stable effort angina, all showing a positive exercise stress test for myocardial ischemia and a greater than or equal to 70% stenosis of a major coronary artery. Patients were grouped according to the following criteria: presence of electrocardiographic evidence of old transmural myocardial infarction (MI), number of significant coronary stenoses and number of left ventricular (LV) areas showing abnormal segmental wall motion (ASWM). The incidence of EIVA in patients with multivessel CAD was higher than in patients with single vessel CAD, but this difference was not statistically significant. The number of LV areas with ASWM was better correlated with the frequency of EIVA, which was 20.0% in patients with normal LV wall motion, 31.2% in patients with 1 area of ASWM, 54.0% in patients with 2 areas of ASWM (p less than 0.005 vs normal LV wall motion), 74.1% in patients with 3 or more areas of ASWM (p less than 0.001 vs normal LV wall motion and 1 area of ASWM), and 81.8% in patients with LV aneurysm (p less than 0.001 vs normal LV wall motion and 1 area of ASWM, p less than 0.005 vs 2 areas of ASWM). Patients with old MI showed a significantly higher incidence of EIVA than those without MI (p less than 0.001), but this difference was due to the more severe LV asynergy in the MI group. In conclusion, our results show that, in a selected population of patients with CAD, the incidence of EIVA correlates better with the extent of LV segmental wall motion abnormalities than with the number of diseased coronary arteries or the presence of an old transmural MI.

Adult↗