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Biomedical subjects

M Minieri

Publications and source records attributed to M Minieri.

At least 19 recordsLinked to original sources
PubMed2002

Selective changes in DNA binding activity of transcription factors in UM-X7.1 cardiomyopathic hamsters.

UM-X7.1 hamsters (CH) are considered a representative model for human cardiomyopathy. CH display the loss of the cytoskeletal delta-sarcoglycan protein, associated with myocardium remodeling and fatal reduction of heart functional efficiency. Even though altered redox balance and calcium homeostasis have already been reported to affect cardiomyocyte function, the molecular mechanisms underlying this pathology are largely unknown. We found no significant differences in DNA binding activity of redox-related (NF-kappaB, Sp1, AP-1 and AP-2) transcription factors in heart ventricles of 90 day-old CH, compared to normal animals. On the other hand, DNA binding activity of calcium-dependent transcription factors NF-AT3 and CREB were increased and decreased respectively in CH vs. normal ventricles. Western blot experiments confirmed the down regulation of CREB levels and suggest a novel regulation mechanism for this transcription factor in the heart. Our results are consistent with recent studies on NF-AT3, GATA4 and CREB transgenic mice, and provide clues for the comprehension of pathogenetic mechanisms of hamster hereditary cardiomyopathy.

Animals↗
PubMed2001

Insulin deficiency and reduced expression of lipogenic enzymes in cardiomyopathic hamster.

Evidence is given that the heart of the cardiomyopathic UM-X7.1 hamster has a lipid composition different from that of the same tissue isolated from animals of the Syrian hamster parent strain. Also, noncardiac tissues from cardiomyopathic and healthy hamsters exhibit significant compositional differences. On the basis of these preliminary observations, a comparative study of the hepatic biosynthesis of lipids in cardiomyopathic and healthy Syrian hamsters was undertaken. The results obtained indicate that the cardiomyopathic hamster is characterized by a generalized disturbance of lipid metabolism. In particular, the fatty acid synthase and stearoyl-CoA desaturase activities were significantly lower in the liver of UM-X7.1 hamsters than in age-matched healthy controls fed the same diet. Northern blot analysis of the mRNAs encoding the two enzymatic proteins and the "lipogenic" S14 nuclear protein indicated that the transcription of the respective genes was impaired in UM-X7.1.Short-term dietary manipulations modulated the expression of the above-mentioned genes both in cardiomyopathic and healthy animals. However, dietary carbohydrates were less effective in inducing the expression of lipogenic enzymes in UM-X7.1 liver than healthy controls. The main determinant of the metabolic defect pointed out in the present work appears to be represented by the low insulin level detectable in the plasma of the cardiomyopathic hamster.-Vecchini, A., L. Binaglia, M. Bibeau, M. Minieri, F. Carotenuto, and P. Di Nardo. Insulin deficiency and reduced expression of lipogenic enzymes in cardiomyopathic hamster. J. Lipid Res. 2001. 42: 96;-105.

Age Factors↗
PubMed1999

The cardiomyopathic hamster as model of early myocardial aging.

Few experimental studies are available on aging, because of the lack of suitable experimental models to test specific pathophysiologic mechanisms. In the present study, the cardiomyopathic Syrian hamster is proposed as experimental model of the aging myocardium. In fact, the hamster myocardium develops an early alpha to beta myosin isoform shifting in ventricles that is independent of hemodynamic overload and repeats the phenomenon physiologically occurring in healthy hamsters during the entire lifespan. At the same time, in atria there is a progressive decline of ANF production that is independent of intracavitary pressure. Conversely, ANF production in ventricles is enhanced before the onset of hemodynamic overload, but parallel to the increase in the fibrotic proportion of the ventricular wall. These characteristics mimic the modifications occurring in otherwise healthy aged mammals and candidate the cardiomyopathic hamster as a model of early myocardial aging.

Animals↗
PubMed1997

Embryonic gene expression in nonoverloaded ventricles of hereditary hypertrophic cardiomyopathic hamsters.

Current information regarding the molecular and biochemical mechanisms of myocardial hypertrophy, as obtained from isolated cardiomyocytes and/or healthy animals with aortic banding, does not permit dissection of the hierarchical relationship among different steps and triggers of the pathogenic process in vivo. The aim of the present study was to depict the temporal relationship among myocardial structural and functional characteristics, the embryonic gene program, and transforming growth factor (TGF) beta 1 expression in euthyroid hereditary hypertrophic cardiomyopathic hamsters (CMPH). This investigation was performed using Western and Northern blot and in situ hybridization techniques. The results show that in CMPH, the severity of the hemodynamic overload is not related to any modification in structural myocardial characteristics (cardiac mass, cardiomyocyte dimensions, total RNA, and protein content), whereas an early activation of the embryonic gene program occurs in not yet overloaded 90-day-old CMPH (left ventricular end diastolic pressure < 15 mm Hg). In these animals, a 30% to 90% decrease in the alpha myosin heavy chain (alpha MHC) relative content was found in ventricles, whereas beta MHC increased 5-fold. In addition, the alpha skeletal actin expression was enhanced 2-fold versus age-matched controls. No modifications were observed in myosin function evaluated by in vitro motility assay, whereas the administration of L-thyroxine (100 micrograms/kg intraperitoneally daily) to CMPH was able to reinduce the ventricular expression of the alpha MHC isoform (5-fold increase). Conversely, no changes were found in alpha cardiac actin and myosin light chain 2 (MLC2) expression. A close temporal relationship occurred in CMPH ventricles between the re-expression of the embryonic gene program and a 3-fold enhancement of the expression of TGF beta 1. These results indicate that the CMPH provides a useful model for investigating the expression of embryonic genes in hypertrophic ventricles in the absence of mechanical and hormonal stimuli, and that TGF beta 1 is involved in regulating in vivo the "embryonic step" of myocardial hypertrophy. Furthermore, the study offers new insights into the pathophysiologic mechanisms leading to heart failure.

Actins↗
PubMed1997

Proliferating cells in adult cardiomyopathic hamster ventricles.

Myocardium of hereditary hypertrophic cardiomyopathic hamsters UM.X7.1 between 60 and 90 days of life shows large clusters of densely packed, actively proliferating cells with a rhabdoid appearance. Immunohistochemical studies showed that most of proliferating cells express, although with variable patterns, muscular markers such as desmin, alpha-sarcomeric actin, myoglobin and alpha/gamma-smooth muscle actin. The simultaneous occurrence of a poorly differentiated appearance, intense proliferating activity and expression of muscular markers seems to indicate that cluster cells may be muscular in origin and that their proliferation can be a fundamental pathophysiological step in the onset of cardiomyopathy. The possibility that myocardial proliferating cells originated from de-differentiated adult cardiomyocytes, which undergo a short cellular proliferation program, or from not fully matured (fetal) cardiomyocytes scattered throughout the myocardium is discussed.

Animals↗
PubMed1996

Atrial natriuretic factor (ANF) and ANF receptor C gene expression and localization in the respiratory system: effects induced by hypoxia and hemodynamic overload.

Atrial natriuretic factor (ANF) and ANF receptor C (ANF.RC) expression have been investigated in healthy and cardiomyopathic hamsters (CMPH) with widespread necrosis of the diaphragm and myocardium leading to respiratory and heart failure. ANF- and ANF.RC-producing cells were localized in different structures of the respiratory system, and the regulation of their expression by the individual and/or combined action of hypoxia and hemodynamic overload was analyzed. The study was performed in 20-, 90-, and 150-day-old animals using immunohistochemistry, in situ hybridization, Northern blot, and RIA analyses. ANF was shown to be expressed in the tracheo-bronchial epithelium and muscle and, to a lesser extent, in the alveolar wall and muscular media of the pulmonary arteries and extraparenchymal pulmonary veins in both healthy hamsters and CMPH. In 150-day-old CMPH, hypoxia (PaO2 < 50 mm Hg) induced a 10-fold increase in ANF messenger RNA accumulation and a 6-fold increase in the immunoreactive ANF (IR-ANF) concentration in lungs, as quantitated by RIA. As plasma IR-ANF concentrations were elevated in all CMPH age groups, it was most likely produced by the myocardium. ANF.RC messenger RNA was homogeneously distributed throughout the entire respiratory system and was increased 2-fold in hypoxic 150-day-old CMPH only. These results suggest that ANF originating in the respiratory system exerts only paracrine effects on different structures of the respiratory system in addition to the action of circulating ANF. Hemodynamic overload (left ventricular end-diastolic pressure, 17.20 +/- 3.80 mm Hg) might contribute to enhanced ANF gene expression only in extraparenchymal pulmonary vein walls of 150-day-old CMPH. We also propose that ANF.RC overexpression might be a protective mechanism operated via either ANF clearance or inhibition of adenylate cyclase activity to counteract exaggerated smooth muscle relaxation.

Animals↗
PubMed1993

Myocardial expression of atrial natriuretic factor gene in early stages of hamster cardiomyopathy.

Ventricular cardiomyocytes represent the most important source of atrial natriuretic factor (ANF) in pathological conditions such as congestive heart failure (CHF). It has been suggested that in cardiomyopathic Syrian hamster ventricles the ANF gene can be reactivated during the hypertrophic stage occurring before heart failure. The present study was undertaken to investigate ANF gene expression during early stages of myocardial damage and its distribution throughout atrial and ventricular myocardium in UM-X7.1 cardiomyopathic Syrian hamsters (CMPH) before hypertrophy and cardiac failure occur. Atria, right and left ventricles, and interventricular septum of hearts of 20-23 days old (young) and 90-95 days old (adult) CMPH were studied. The absence of hypertrophy and cardiac failure was preliminarly ascertained by microscopic and hemodynamic evaluation. ANF-mRNA as well as tissue and plasma immunoreactive ANF were assayed. Moreover, ANF secretion pattern was evaluated by immunocytochemical techniques. Young and adult CMPH hearts were in the necrotic stage of myocardial disease, as demonstrated by histopathological evaluation and by decreased wet weights (mg/g body weight) of different heart regions. Hemodynamic assessment showed no significant changes of left ventricular end-diastolic pressure (LVEDP) and a decrease of the left ventricular peak systolic pressure (LVSP) and +dP/dt. Plasma immunoreactive ANF (IR-ANF) levels were higher in young (3-fold) and adult (6-fold) CMPH than in age-matched normal hamsters. A reduced IR-ANF concentration (per milligram protein) was observed in both young and adult cardiomyopathic atria in respect to healthy controls, whereas a higher IR-ANF concentration was present in ventricles. A 3-fold, 6-fold and 20-fold increase of IR-ANF concentration was found in right ventricular free-wall (RV), left ventricular free-wall (LV) and interventricular septum (IVS), respectively. Northern-blot analysis confirmed that IVS was the major site of ventricular ANF-mRNA transcription in both young and adult CMPH. ANF-mRNA was increased also in atria where a faster peptide secretion can be hypothesized to lower tissue IR-ANF concentration. ANF secretion in ventricular myocardium was achieved via constitutive pathway as demonstrated by immunocytochemistry. Different patterns of ANF gene reactivation occur in CMPH myocardium before intraventricular pressure increases and structural hypertrophic modifications are detectable. The extent of ANF gene reactivation in CMPH ventricles parallels the severity of necrotic damage. Moreover, ANF gene expression is heterogeneously distributed throughout the myocardium, suggesting that interventricular septum, the ontogenically youngest heart region, might preserve foetal characters which can be rapidly reactivated in pathological conditions.

Animals↗
PubMed1993

Effects of alpha-human atrial natriuretic peptide in guinea-pig isolated heart.

The aim of the present investigation has been to ascertain whether or not atrial natriuretic peptides (ANP) can exert a direct effect on myocardial contractility. Alpha-human ANP (alpha-hANP) concentrations ranging from 1 pM to 50 nM have been used to perfuse guinea-pig isolated hearts in a non-recirculating Langendorff apparatus. A dual concentration-related effect has been induced by alpha-hANP on myocardial function. A maximal increase of +LV dP/dtmax (+56%; P < 0.001) has been observed when guinea-pig hearts were perfused with 100 pM alpha-hANP, whereas a 25% decrease (P < 0.01) occurred with 50 nM alpha-hANP. Similar effects have also been induced by alpha-hANP on the coronary flow rate (CFR). A significant CFR increase (maximal at 10 pM alpha-hANP) was induced by picomolar concentrations of alpha-hANP, whereas a progressive decrease, which was maximal (-28%; P < 0.01) at 50 nM alpha-hANP, was observed with nanomolar concentrations of the peptide. No effects have been observed on heart rate. These results suggest that ANP has direct effects on both vascular and myocardial muscle cells. Coronary vasoconstriction induced by nanomolar concentrations of ANP can contribute to the cardiodepression, whereas ANP in picomolar concentrations can induce a coronary vasodilation which is not coupled with the enhanced myocardial contractility. The latter is the likely expression of a direct effect of the peptide on myocardial function.

Animals↗
PubMed1992

Kinetic changes of ethanolamine base exchange activity and increase of viscosity in sarcolemmal membranes of hamster heart during development of cardiomyopathy.

The activity of the phospholipid base exchange enzyme specific for ethanolamine has been measured in cardiac sarcolemmal membrane preparations from Syrian golden and UM-X7.1 cardiomyopathic hamsters. In Syrian golden hamsters, the Km of the enzyme for ethanolamine does not change with age, whereas it almost doubles in membranes from cardiomyopathic animals, from the 30th to the 150th day of age. During the same period, the membrane cholesterol content increases by 68% in cardiomyopathic hamsters, whereas it does not change significantly in the Syrian golden hamster strain. As a consequence, in the adult animal, the cholesterol to phospholipid ratio and the viscosity of sarcolemmal membranes are higher in UM-X7.1 strain than in Syrian golden hamsters. A cause-consequence relationship between the enzymatic changes and the compositional modifications in the sarcolemma occurring in UM-X7.1 hamsters during the development of cardiomyopathy is proposed.

Animals↗
PubMed1992

Phospholipid base exchange enzyme activity in sarcolemmal membranes from the heart of cardiomyopathic hamsters.

The activity of phospholipid base exchange enzymes has been evaluated in cardiac sarcolemmal membranes from Syrian Golden hamsters and from a hamster strain (UM-X7.1) characterized by a genetic form of hypertrophic cardiomyopathy. No choline base exchange activity and only a little serine base exchange activity were detected, whereas the ethanolamine base exchange enzyme was found highly active in membranes from both strains. For this reason, the present study is focussed on the ethanolamine base exchange enzyme. The apparent Km for ethanolamine of ethanolamine base exchange enzyme from Syrian Golden membranes and from UM-X7.1 strain membranes are 18 and 32 microM, respectively. The specific activity of the sarcolemmal ethanolamine base exchange enzyme is lower in the UM-X7.1 strain than in Syrian Golden hamsters. The calcium-dependence of the enzyme appears different when the membranes from the two strains are compared. Indeed, after removal of the membrane-bound divalent cations, comparable activities are found in both membrane preparations, whereas, upon addition of Ca2+ to the incubation mixtures, the activity of the enzyme is enhanced in the membranes from Syrian Golden strain more than in those from UM-X7.1 strain. The cholesterol content of sarcolemmal membranes is higher in the cardiomyopathic strain than in the Syrian Golden hamsters. A possible relation between changes of the membrane lipid composition and of the ethanolamine base exchange activity is discussed.

Animals↗
PubMed1992

[The physiopathological aspects and new therapeutic approaches in cardiac-circulatory failure].

Pathophysiological mechanisms are reviewed concerning the onset and the perpetuation of the clinical features of congestive heart failure. This syndrome is a severe condition of poor prognosis and bad life quality which in the last decades has reached, in the western industrial countries, the highest levels of general mortality, mainly due to the high prevalence of hypertensive and ischaemic myocardiopathies in the last years. To the clinical features of heart failure mainly contributes a deregulation of the physiological compensatory mechanisms contemporarily and concurrently activated following the primary deficiency of the heart pump function. In physiological conditions, following the myogenic adapting mechanisms reflex mechanisms intervene, activated by intracardiac and aortic and carotid-sinus mechanoreceptors following the variations in intracardiac and intravascular pressure and generally evoking negative feed-back effects. In patients with heart failure arterial high pressure mechanoreceptors respond to the reduction in effective arterial pressure thus provoking a deactivation of the tonic inhibition on the sympathetic cardiovascular drive. This leads to an activation of peripheral and renal vasoconstrictor tone, to a raised medullary catecholamine incretion, to heart rate and inotropism stimulation, and to an increase in pituitary gland ADH production as well as to an activation of renin-angiotensin-aldosterone system (RAAS). Analogous vasoconstrictive, and sodium and water retentive effects can be elicited by endothelin produced by endothelial cells and found in high plasma levels in CHF. These excitatory effects, leading to a rise in systemic vascular resistance and to hydro-electrolytic retention with volume expansion, are not efficiently counteracted by the opposite effects triggered by cardiopulmonary vagally mediated mechanoreceptors activated by the raised cardiac filling pressure and leading to sympathetic nervous inhibition, peripheral and renal vasodilation, ADH and RAAS inhibition. Analogous effects should be provoked by the raised production, due to enhanced heart wall distension, of atrial natriuretic factor leading to vasodilation, natriuresis and diuresis. Reduced sensitivity of cardiopulmonary baroreceptors and lowered production of ANF due to structural cardiac changes could represent, according to most opinions, the main factors responsible for the prevailing sympathetic activation and hydro-saline retention in CHF. The activation of cardiopulmonary sympathetic positive-feed back afferents, could be also involved in the characteristic alteration of the vago-sympathetic balance in heart failure. The persistent reduction in heart pump function could lead to the instauration of vicious circles among the various regulatory systems and create an overcompensation condition.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗
PubMed1991

[Esaprazole vs sulglicotide in the treatment of dyspeptic patients with chronic superficial gastritis of the antrum].

Fifty dyspeptic patients with histologically proven chronic superficial antral gastritis were treated for 6 weeks, in a randomized single-blind study, with esaprazole (450 mg bid) or sulglicotide (200 mg tid). Both drugs significantly improved the symptomatic score after 3 and 6 weeks (p less than 0.01), and the percentual rate of improvement was similar in the two groups studied. Similarly, both treatments significantly reduced the inflammation of gastric mucosa. Drugs were ineffective in clearing Helicobacter pylori from the antral mucosa (as assessed by the urease test, performed at entry and after 6 weeks). No side effects occurred after esaprazole or sulglicotide administration. The results of the present study suggest that esaprazole, a new gastroprotective drug, may have a role in the therapy of dyspeptic patients with chronic superficial gastritis.

Adolescent↗
PubMed1991

Clinical efficacy and safety of cisapride and clebopride in the management of chronic functional dyspepsia: a double-blind, randomized study.

The clinical efficacy and the safety of chronic oral administration of cisapride, a new gastrointestinal prokinetic agent, (10 mg tid) and clebopride (0.5 mg tid) was assayed in 48 outpatients affected with functional dyspepsia, in a randomized double-blind study. Each of the drugs induced a significant reduction in dyspeptic symptoms after 2 and 4 weeks (p less than 0.001). Two patients, given clebopride, dropped out of the study because of severe side effects during the first week of treatment. Mild adverse reactions were reported in 6 out of 23 cisapride-treated patients and in 10 out of 20 clebopride-treated patients who completed the study. The most common side effect of cisapride was diarrhoea and that of clebopride was drowsiness. Cisapride appears to be as effective as clebopride in reducing dyspeptic symptoms and seems to induce less severe side effects.

Administration, Oral↗
PubMed1990

The influence of severe bulb deformity on duodenal ulcer relapse.

In order to evaluate the prognostic role of duodenal bulb deformation in the recurrence of peptic ulcer, duodenal bulb morphology and the complete healing of duodenal ulcer were endoscopically evaluated in sixty patients, who were subsequently allocated at random to either maintenance therapy with ranitidine or no treatment. Endoscopic checkups were done at regular intervals, up to the first ulcer recurrence. As expected, long-term ranitidine treatment significantly reduced the relapse rate (12 month cumulative relapse rate was 32% versus 86% in the untreated). A set of prognostic factors which might interfere with this result (sex, age, alcohol consumption, history of ulcerous relatives, duration of the disease, previous H2-blocking treatment, previous complications, smoking and morphology of the duodenal bulb) were evaluated by multivariate analysis using the Cox regression model. Only duodenal bulb morphology appeared to have any independent prognostic value. In the untreated group ulcer recurrence seemed to occur earlier (median relapse time = 2 months) in the patients with severe non-stenosing bulb deformity, and later in those with normal or mildly deformed bulb (median relapse time = 8 months); ranitidine treatment delayed relapse in deformed bulb patients (median relapse time = 14 months) and almost eliminated it in those with normal duodenal bulb morphology. No association was found between the presence of duodenal bulb deformity and the above-mentioned covariates. Our study confirms the primary importance of anti-H2 treatment and suggests that anatomical characteristics of the duodenal bulb also influence the occurrence of ulcer relapse.

Adult↗