Hypertension, left ventricular hypertrophy, and heart rate variability.
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Animals↗
Biomedical subjects
C Fiorentini
Publications and source records attributed to C Fiorentini.
Evidence of Toscana virus infections without central nervous system involvement: a serological study.
In central Italy, acute lymphocytic meningitis and meningoencephalitis due to a Phlebotomus transmitted virus (Phlebovirus Toscana, TOSv) occurring throughout the summer are frequently observed. Several serum specimens of patients hospitalized with a clinical picture of viral meningitis/meningoencephalitis showed anti TOS-IgG reactivity suggestive of a previous infection occurring at an unknown time in the past. This observation led us to design a serological investigation of 83 household contacts of 46 summertime CNS infection patients (index cases) with the purpose of evaluating the percentage of both IgG and IgM in seropositive healthy individuals, living, like the index cases, in areas at high risk of phlebotomine sandfly bites. The serological study was carried out using an ELISA method: 22% of the sera showed a reactivity for anti-TOS IgG antibodies and 6% resulted IgG/IgM positive; none of them reported having had any symptoms of CNS involvement; the distribution of seropositive cases was similar in contacts of both TOS-confirmed and TOS-negative cases. Our results indicate: (1) that phlebovirus Toscana is frequently implicated in cases with CNS disease as well as in infections occurring without neurological involvement; (2) in our country the ecological requirements encompass the conditions in and around the human settlements for phlebotomine sandflies to become peridomestic thus amplifying the risk of TOSv infections, which are in fact widespread and frequent in Siena and its surroundings.
Adolescent↗
Prognostic value of residual ischaemia assessed by exercise electrocardiography and dobutamine stress echocardiography in low-risk patients following acute myocardial infarction.
BACKGROUND: Risk stratification after uncomplicated myocardial infarction is major clinical problem. In particular, the prognostic value of residual inducible ischaemia is still controversial. We compared the relative prognostic value of exercise ECG and dobutamine stress echocardiography performed in the early post-infarction period. METHODS: Four hundred and six patients (53 female) aged 57 +/- 9 years, undergoing maximal exercise ECG and dobutamine stress echocardiography within 10 days of an uncomplicated myocardial infarction off therapy, were prospectively followed-up for 8.8 months. Age, sex, diabetes, smoking habit, hypertension, dyslipidaemia, infarct location, thrombolysis and resting wall motion score index were taken into account among clinical variables. Prognostic correlations were made vs spontaneous events (cardiac death, non-fatal reinfarction and unstable angina requiring hospitalization) whilst patients undergoing revascularization (by means of percutaneous transluminal coronary angioplasty or coronary artery bypass surgery) at the time of the procedure were censored. RESULTS: One hundred and twenty-seven events occurred during the follow-up: 41 (10%) were spontaneous (five deaths, 12 reinfarctions and 24 unstable angina) and 86 procedural (27 angioplasty and 59 bypass surgery). Spontaneous events were not predicted by any clinical, exercise ECG or dobutamine stress echocardiography variable, but the negative predictive value of both tests was excellent (91% and 90% respectively). With a multivariate Cox analysis, male gender, positive low-workload (< 100 W) exercise ECG (P < 0.0001), positive low-dose dobutamine stress echocardiography (P < 0.0001) and rest-stress wall motion score index variation (P < 0.001) were found to predict cumulative cardiac events with an independent and additive value. Dobutamine stress echocardiography was significantly more sensitive (P < 0.05) and less specific (P < 0.01) in predicting the outcome of patients with anterior infarction, whilst exercise ECG was significantly more sensitive (P < 0.05) in patients with non-Q wave infarction. CONCLUSIONS: (1) Spontaneous events are poorly predicted by provocative tests in low-risk patients after uncomplicated myocardial infarction. (2) However, both exercise ECG and dobutamine stress echocardiography can predict a favourable outcome with a very high negative predictive value. (3) Dobutamine stress echocardiography should be considered a secondary option in cases where the exercise ECG is equivocal or when the location of ischaemia is a relevant issue. (4) The possibility that the two tests have a differential utility depending on the infarct location and type (Q wave vs non-Q wave) may be clinically relevant and deserves further evaluation.
Aged↗
Nerve growth factor suppresses the tumoral phenotype of human prolactinomas.
We summarize here our data showing that various phenotypical characteristics distinguish prolactinoma cell lines obtained from responder and nonresponder patients, as defined by their responses to bromocriptine administration. Nonresponder cell lines have a higher degree of malignancy than responder cells and do not express D2 receptors for dopamine. Both cell lines express NGF receptors. Exposure of the most malignant nonresponder cell lines to NGF, both in vitro and when transplanted in vivo in nude mice, results in their differentiation into the responder phenotype reexpressing D2 receptors. Sequential administration of NGF and bromocriptine thus may be a promising therapy for patients refractory to bromocriptine.
Animals↗
Clostridium difficile: an update on virulence mechanisms.
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Journal Article↗
Okadaic acid induces changes in the organization of F-actin in intestinal cells.
Okadaic acid, a polyether fatty acid associated with diarrhetic seafood poisoning, is capable of inhibiting protein phosphatases 1 and 2A which are considered among the major protein phosphatases in the cytosol of mammalian cells. One of the substrates for these phosphatases has been reported to be the cytoskeleton. In this paper, we focused on the effects of okadaic acid in intestinal cells, the more physiological target for this toxin. By fluorescence and scanning electron microscopy, we evidenced a dose- and time-dependent effect on F-actin which preceded any detectable change of tubulin and vimentin network. By a flow cytometric approach, we observed that plasma membrane permeability and transmembrane potential, two indicators of early cell damage or activation, respectively, remained unaffected in intoxicated cells. The present data strongly support the theory that actin is one of the main cytosolic targets for the phosphatases inhibited by okadaic acid in intestinal cells.
Actins↗
Influence of oral antidiabetic treatment on electrocardiac alterations induced by myocardial infarction.
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Action Potentials↗
Type II atrial flutter interruption with transesophageal pacing: use of propafenone and possible change of the substrate.
Type II atrial flutter (AFII) is an arrhythmia which usually cannot be interrupted by atrial pacing: the underlying mechanism is considered to be a leading circle without an excitable gap. We investigated whether the administration of propafenone, an antiarrhythmic drug, which primarily decreases conduction velocity, has a beneficial effect on AFII interruption using transesophageal pacing. Twelve patients with an AFII were randomized into 2 groups in which pacing was performed without treatment (group A) or two hours after the administration of 600 mg of oral propafenone (group B). Sinus rhythm was attained in 0 of 6 patients in group A and in 4 of 6 patients in group B (P < 0.05). The baseline mean cycle length was the same in both groups (175 +/- 7 (A) vs 168 +/- 8 ms (B); it lengthened significantly after the administration of propafenone (219 +/- 33 vs 168 +/- 8 ms; P < 0.05). Propafenone did not significantly lengthen the cycle in the two patients in whom interruption of the arrhythmia was impossible. Our data show that propafenone has a facilitating effect on atrial pacing only when it significantly prolongs the cycle length of the arrhythmia, possible expression of a conversion of AFII into type I, with an anatomical substrate and an excitable gap allowing arrhythmia capture and interruption. In the two patients in whom sinus rhythm was not restored, the absence of a direct dependence of the cycle length on the change in conduction velocity induced by propafenone may be explained by the persistence of a functionally determined circuit, resistant to atrial pacing.
Administration, Oral↗
Bacteroides fragilis enterotoxin induces cytoskeletal changes and surface blebbing in HT-29 cells.
Certain strains of the anaerobic bacterium Bacteroides fragilis are known to produce an enterotoxin of about 20 kDa which is able to induce a fluid response in ligated intestinal loops and a cytotoxic response in HT-29 cells. It presents protease activity, belonging to a family of metalloproteases termed metzincins. In order to investigate the mode of action of the enterotoxin in cultured cells, we performed a study with HT-29 cells, using both fluoresence and electron microscopy. Treated cells underwent morphological changes, mainly consisting of the retraction of the cell body and the formation of numerous blebs on the cell surface. The microfilament system was reorganized, the F-actin being condensed as a ring at the cell periphery, whereas other cell organelles appeared to be unaffected. All these changes, clearly visible after 3 h of exposure to the toxin, were reversed within 24 h of treatment. By inhibiting the protease activity of the toxin with specific metal chelators, the cytoskeletal effects were also prevented. Thus, B. fragilis enterotoxin appears to act on cells by reversibly modifying the actin cytoskeleton, an effect probably dependent on its proteolytic activity.
Bacterial Toxins↗
Nuclear cardiology and echocardiography for the assessment of myocardial viability.
The review aims to make a comparative analysis of the nuclear cardiology and echocardiographic approaches for the assessment of myocardial viability on the basis of the most recent literature. Preliminarily the most extensively used methods are described: 1) metabolic tracers, especially as regards FDG-F18 (quantitative uptake; mismatch FDG uptake/perfusion); 2) sarcolemmal integrity tracers (201Tl- with stress-redistribution-reinjection or with rest-redistribution protocols; rest MIBI 99mTc); 3) low dose dobutamine stress echocardiography (LDDSE) for the detection of residual contractility reserve. Global sensitivity values of thallium studies are reported to be similar to those of LDDSE, but in selected patients populations with akinetic or severely hypokinetic segments the LDDSE sensitivity seems to be significantly lower, when metabolic viability assessed by FDG studies is assumed as gold standard. According to the Authors' opinion thallium study with a protocol including a rest injestion can be considered at the moment the first choice for myocardial viability assessment because of its convenience, reproducibility, possibility of technical and interpretative standardization, amount of clinical and experimental validations. Anyway further clinical trials with adequate follow-up are necessary in order to define the scintigraphic and echocardiographic patterns that provide the best accuracy in the prediction of the post-revascularization clinical outcome.
Coronary Disease↗
Atrial flutter termination by overdrive transesophageal pacing and the facilitating effect of oral propafenone.
Transesophageal overdrive atrial pacing is effective and safe for atrial flutter termination. The influence of antiarrhythmic drug therapy on this procedure is controversial. In this study, we investigated whether oral propafenone may facilitate this procedure. Thirty patients with type I atrial flutter were randomized into 2 groups in which transesophageal pacing was attempted: group A, without treatment; and group B, after oral administration of propafenone 600 mg. Transesophageal pacing was effective in interrupting atrial flutter in 53% of patients (8 of 15) in group A and in 87% of patients (13 of 15) in group B. A significant lengthening of the flutter cycle was observed with respect to the baseline in patients given propafenone (261 +/- 23 vs 217 +/- 25, p < 0.01). Sinus rhythm resumed at a shorter paced cycle in group A patients (166 +/- 13 vs 187 +/- 14 ms, p < 0.01). The transesophageal threshold for stable atrial capture was significantly lower in group A (20.5 +/- 0.2 vs 23.3 +/- 1.2, p < 0.01). In no patient was the threshold for atrial capture higher than the pain threshold. We did not observe abrupt enhancement of atrioventricular conduction. We conclude that propafenone is effective and safe when used with transesophageal pacing in the termination of atrial flutter. The slowing effect of the drug on intraatrial conduction and the possible stabilizing effect on the reentry circuit appear to be outweighed by the positive effect of propafenone on the excitable gap of the circuit, facilitating its capture and accounting for the beneficial effect of the drug on arrhythmia termination.
Administration, Oral↗
Dobutamine stress echocardiography for the identification of multivessel coronary artery disease after uncomplicated myocardial infarction: the importance of test end-point.
Our aim was to verify whether the sensitivity of pharmachological stress echocardiography for multivessel disease after acute myocardial infarction may be improved by a more aggressive protocol, i.e. not considering the appearance of the first wall motion abnormality as the absolute end-point if it occurs in the infarcted area without clinical or instrumental markers of extensive ischemia or left ventricular dysfunction. One-hundred twenty-one consecutive patients (age 32-71 years) prospectively underwent dobutamine-atropine stress echo (dobutamine infusion up to 40 micrograms/kg/min with additional atropine 1 mg) 11.8 +/- 4.8 days after uncomplicated myocardial infarction and coronary angiography within 6 weeks. Criteria for stopping the test were: significant ST depression or elevation, typical chest pain, major arrhythmias and left ventricular dysfunction. The test was considered as positive if a deterioration of basal wall motion pattern was observed: it was defined homozonally positive (the deterioration occurred in the myocardial area fed by the culprit vessel) or heterozonally positive (the deterioration occurred in a different vascular area). A coronary stenosis > 70% of vessel lumen was defined as critical. Thirty-four patients showed a negative test result. Among the 87 patients with positive test, 65 had no further wall motion deterioration from the first-induced wall motion abnormality (WMA) to peak test (Group A), whereas nine patients showed further homozonal (Group B) and 13 further heterozonal (Group C) asynergies. Sensitivity, specificity and accuracy of dobutamine stress echocardiography for multivessel disease were, respectively, 63%, 96% and 82% using the first-induced wall motion abnormality as test end-point, whilst they were 84% (P < 0.01), 93% and 89% according to the aggressive approach previously described. Dobutamine stress time of patients with multivessel disease was higher in Groups B and C (13.1 +/- 3.6 min) than in Group A (9.8 +/- 3.7 min, P < 0.01) and, finally, the mean obstruction of non-culprit vessel was higher in Group A (62.2%) than in Group C (47.4%, P < 0.05). No major complications were found. We conclude that the sensitivity of dobutamine stress echocardiography for multivessel disease following recent myocardial infarction is critically dependent on the test end-point. It may be improved by a more aggressive approach capable to identify less severe heterozonal coronary lesions.
Adult↗
Incidence and correlates of complex ventricular arrhythmias during dobutamine stress echocardiography after acute myocardial infarction.
Although previous studies have confirmed the safety of dobutamine stress echocardiography, complex ventricular arrhythmias have been reported. Our aim was (1) to identify the markers of increased arrhythmic risk during dobutamine stress echocardiography and (2) to assess whether the occurrence of major ventricular arrhythmias during the test may represent a clinically useful marker of electrical instability. Three hundred and seventy-seven consecutive survivors from acute myocardial infarction, off cardioactive therapy, underwent dobutamine stress echocardiography 11.4 days after the acute event. Holter monitoring with assessment of heart rate variability and echocardiographic determination of left ventricular ejection fraction. In addition, exercise stress testing, signal averaged ECG and coronary angiography were carried out, respectively, in 357, 150 and 273 patients. Ten subjects showed complex ventricular arrhythmias (eight non-sustained and one sustained ventricular tachycardia and one ventricular fibrillation) during dobutamine stress echocardiography (group A), whilst 366 did not (group B). Complex ventricular arrhythmias were detected by Holter monitoring in 8/10 patients in group A and 45/367 patients in group B (odds ratio 28.6, 95% CI 5.4-92.2) and by exercise testing in 4/10 patients in group A and 33/347 patients in group B (odds ratio 6.3, 95% CI 1.4-27.2). Ejection fraction < 40% was present in 3/10 patients in group A and 50/367 in group B (odds ratio 2.7, 95% CI 0.3-12.2), whilst multivessel disease was present, respectively, in 8/10 and 176/263 patients (odds ratio 1.9, 95% CI 0.3-25.5). Reduced heart rate variability and the presence of late potentials on signal averaged ECG were found in, respectively, 40/367 and 13/140 patients in group B, but none were found in group A. A total of 61 events (35 CABG, 15 PTCA, four cardiac deaths and seven non-fatal reinfarctions) occurred during the follow-up (11.4 months, range 6 to 20): four in group A and 57 in group B. No documented major arrhythmic event was reported. We conclude that (1) complex arrhythmias during dobutamine stress may occur in patients early after acute myocardial infarction; (2) the preexisting evidence of frequent, as well as repetitive, arrhythmias represents a potential marker of increased risk in this connection and, finally, (3) dobutamine-induced arrhythmias seem to represent an uncommon, even though potentially dangerous, event but not a useful new "window' on electrical instability of post-MI patients.
Adult↗
Escherichia coli cytotoxic necrotizing factor 1: evidence for induction of actin assembly by constitutive activation of the p21 Rho GTPase.
Cytotoxic necrotizing factor type 1 (CNF1) induces in HEp-2 cells an increase in F-actin structures, which was detectable by fluorescence-activated cell sorter analysis 24 h after addition of this factor to the culture medium. Increase in F-actin was correlated with the augmentation of both the cell volume and the total cell actin content. Actin assembly-disassembly is controlled by small GTP-binding proteins of the Rho family, which have been reported recently to be modified by CNF1 treatment. Clostridium difficile toxin B and Clostridium botulinum exoenzyme C3, both known to act on the Rho GTPase, were used as biological tools to study the effect of CNF1 on this protein. CNF1 incubated before, during, or after exposure to the chimeric toxin C3B (which is the product of a genetic fusion between the DNA coding for C3 and the one coding for the B fragment of diphtheria toxin) protected HEp-2 cells from the disruption of F-actin structures caused by inactivation of the Rho GTPase through its ADP-ribosylation. On the other hand, C. difficile toxin B cytopathic effect was not observed upon preincubation of cells with CNF1. Toxins acting through a Rho-independent mechanism, such as cytochalasin D and Clostridium spiroforme iota-like toxin, could not be modified in their cellular activities by CNF1 treatment. All of our results suggest that CNF1 modifies the Rho molecule, thus probably protecting this GTPase from further bacterial toxin modification.
ADP Ribose Transferases↗
Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization, in vitro.
The intracellular signaling involved in the mechanism of action of zonula occludens toxin (ZOT) was studied using several in vitro and ex vivo models. ZOT showed a selective effect among various cell lines tested, suggesting that it may interact with a specific receptor, whose surface expression on various cells differs. When tested in IEC6 cell monolayers, ZOT-containing supernatants induced a redistribution of the F-actin cytoskeleton. Similar results were obtained with rabbit ileal mucosa, where the reorganization of F-actin paralleled the increase in tissue permeability. In endothelial cells, the cytoskeletal rearrangement involved a decrease of the soluble G-actin pool (-27%) and a reciprocal increase in the filamentous F-actin pool (+22%). This actin polymerization was time- and dose-dependent, and was reversible. Pretreatment with a specific protein kinase C inhibitor, CGP41251, completely abolished the ZOT effects on both tissue permeability and actin polymerization. In IEC6 cells ZOT induced a peak increment of the PKC-alpha isoform after 3 min incubation. Taken together, these results suggest that ZOT activates a complex intracellular cascade of events that regulate tight junction permeability, probably mimicking the effect of physiologic modulator(s) of epithelial barrier function.
Actins↗
Cytotoxic necrotizing factor type 2 produced by virulent Escherichia coli modifies the small GTP-binding proteins Rho involved in assembly of actin stress fibers.
Cytotoxic necrotizing factor type 2 (CNF2) produced by Escherichia coli strains isolated from intestinal and extraintestinal infections is a dermonecrotic toxin of 110 kDa. We cloned the CNF2 gene from a large plasmid carried by an Escherichia coli strain isolated from a lamb with septicemia. Hydropathy analysis of the deduced amino acid sequence revealed a largely hydrophilic protein with two potential hydrophobic transmembrane domains. The N-terminal half of CNF2 showed striking homology (27% identity and 80% conserved residues) to the N-terminal portion of Pasteurella multocida toxin. Methylamine protection experiments and immunofluorescence studies suggested that CNF2 enters the cytosol of the target cell through an acidic compartment and induces the reorganization of actin into stress fibers. Since the formation of stress fibers in eukaryotic cells involves Rho proteins, we radiolabeled these small GTP-binding proteins from CNF2-treated and control cells with a Rho-specific ADP-ribosyltransferase. The [32P]ADP-ribosylated Rho proteins from CNF2-treated cells migrated slightly more slowly in SDS/PAGE than did the labeled proteins from the control cells. This shift in mobility of Rho proteins in SDS/PAGE was also observed when CNF2 and the RhoA protein were coexpressed in E. coli. We propose that Rho proteins are the targets of CNF2 in mammalian cells.
Actin Cytoskeleton↗
Effects of glibenclamide on ventricular fibrillation in non-insulin-dependent diabetics with acute myocardial infarction.
BACKGROUND: Glibenclamide, a hypoglycemic sulfonylurea, has shown antiarrhythmic effects in acutely ischemic myocardium. The aim of the present study was to evaluate the effectiveness of the drug in preventing ventricular fibrillation in diabetic patients with acute myocardial infarction. METHODS: We studied 232 patients with non-insulin-dependent diabetes mellitus (106 on glibenclamide, group A1; 126 treated with another hypoglycemic drug or with diet only, group A2) and 830 non-diabetic people. All the patients were admitted to our coronary care unit with their first myocardial infarction. RESULTS: Ventricular fibrillation occurred in 1.9% of group A1, 7.9% of group A2, and 9.9% of the non-diabetic (A1 versus A2, P < 0.05; A2 versus the non-diabetic group, NS; A1 versus the non-diabetic group, P < 0.01). Sustained ventricular tachycardia was not significantly different among the groups. CONCLUSIONS: The antiarrhythmic effectiveness of glibenclamide might be related to its blocking action on the ATP-dependent potassium channel, with consequent attenuation of the efflux of potassium induced by ischemia. We also observed a higher mortality rate resulting from heart failure in group A2 than in group A1 or the non-diabetic group. Since glibenclamide has never shown significant effects on myocardial contractility, this finding remains to be elucidated. Glibenclamide therefore appears to have an antifibrillatory effect in acute myocardial infarction; with respect to acute coronary events, the drug might be able to prevent ventricular fibrillation, which is most often fatal when it occurs before hospitalization.
Adult↗
Bacterial protein toxins acting on the cell cytoskeleton.
A number of bacterial protein toxins are known to exert their cytotoxic activity via a modification of cytoskeletal components. Some toxins induce the ADP-ribosylation of actin whereas others interact with the cytoskeleton by an unknown mechanism. Understanding the mode of action of such toxins at cellular level could provide useful information on their role in vivo as virulence factors.
Actin Cytoskeleton↗