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Biomedical subjects

M Fabbri

Publications and source records attributed to M Fabbri.

At least 55 records · Page 3Linked to original sources
PubMed1995

Endothelin-1 in idiopathic pulmonary fibrosis.

AIMS--To evaluate whether endothelin-1 is involved in the pathology of idiopathic pulmonary fibrosis (IPF). METHODS--Plasma endothelin-1 concentrations were evaluated in 37 patients with IPF and 27 normal controls by radioimmunoassay. In addition, expression of endothelin-1 in lung tissue was evaluated in biopsy specimens obtained from four patients with IPF. Three biopsy specimens of normal lung were used as controls. Endothelin-1 immunoreactivity was detected using immunohistochemistry. RESULTS--Elevated endothelin-1 plasma concentrations were found in patients with IPF compared with controls and a positive correlation was found with duration of disease. No significant difference was observed between treated and untreated patients with IPF. Increased endothelin-1 immunoreactivity was found in lungs of three of four patients with IPF. Endothelin-1 positive consisted mainly of small vessel endothelial cells. Some scattered macrophages were also positive. CONCLUSIONS--Elevated plasma concentrations and expression of endothelin-1 in lung tissue are suggestive of increased production of endothelin-1 in at least a proportion of patients with IPF. Consequently, endothelin-1 activity could play a role in the fibrogenic process of the disease.

Adult↗
PubMed1995

Alterations of striatal dopamine D2 receptors contribute to deteriorated response to L-dopa in Parkinson's disease: a [123I]-IBZM SPET study.

Single photon emission tomography with the ligand [123I]-IBZM was used to image central dopamine D2 receptors in Parkinson's disease patients. The aim was to assess striatal receptor densities in relation to response to L-Dopa therapy. In the parkinsonian patients group who were untreated until SPET study and in the group of patients with a sustained response to chronic L-Dopa, striatal [123I]-IBZM uptake did not differ significantly from mean values of the control group. On the contrary, significantly diminished uptake of [123I]-IBZM was found in the basal ganglia regions of the group of patients who developed a complicated/fluctuating response to chronic L-Dopa treatment. Our results indicate that striatal D2 receptor alterations in Parkinson's disease may contribute to the altered response to L-Dopa.

Adult↗
PubMed1994

Export of protein from the endoplasmic reticulum is regulated by a diacylglycerol/phorbol ester binding protein.

The export of vesicular stomatitis virus glycoprotein (VSV-G) from the endoplasmic reticulum (ER) involves sorting and concentration, and has been proposed to require the function of heterotrimeric G proteins. To begin to identify the basic elements of a potential signaling pathway involved in vesicle assembly, we have examined whether protein kinase C (PKC) is required for ER to Golgi transport. Calphostin C, a specific inhibitor of the highly conserved cysteine-rich C6H2 motif present in the regulatory domain of PKC was found to be a potent inhibitor of export of VSV-G and vesicle budding from the ER in vivo and in vitro (IC50 approximately 60 nM). In contrast, the diacylglycerol analog phorbol 12-myristate 13-acetate, which activates PKC, enhanced the migration of VSV-G from the ER to pre-Golgi intermediates. Neither reagent had detectable effects on the oligomerization of VSV-G prior to export nor perturbed transport of protein between compartments of the Golgi stack. In contrast to the striking effects of calphostin C, reagents that inhibit the function of the catalytic domain of PKC (including the general kinase inhibitor staurosporine, as well as the more specific inhibitors H-7, H-8, pseudosubstrate inhibitor, or chelerythrine) did not inhibit export from the ER. Export was also insensitive to down-regulation of various PKC isoforms. These results suggest that a novel protein containing the conserved C6H2 motif may serve as a potential link in a signaling pathway regulating vesicle budding from the ER.

3T3 Cells↗
PubMed1994

Granulates based on calcium phosphate with controlled morphology and porosity for medical applications: physico-chemical parameters and production technique.

Since the pore size distribution of a material in contact with bone is decisive for its type of link with the tissue, many granules are commercially available as fillers and as bone reconstructing materials. We propose a new technological procedure. The optimum architectural design for obtaining the most suitable link in vivo is investigated. Particular attention is attached to the granulate texture: micropores, macropores, total volume of pores, pore size distribution, and the morphology and shape of the pores. These characteristics are studied in order to obtain the best porosity for hydroxyapatite granulates now applied in vivo, with interesting results in mechanical and hard tissue linkage terms.

Biocompatible Materials↗
PubMed1994

Trapidil (triazolopyrimidine), a platelet-derived growth factor antagonist, reduces restenosis after percutaneous transluminal coronary angioplasty. Results of the randomized, double-blind STARC study. Studio Trapidil versus Aspirin nella Restenosi Coronarica.

BACKGROUND: Trapidil is an antiplatelet drug with specific platelet-derived growth factor antagonism and antiproliferative effects in the rat and rabbit models after balloon angioplasty. METHODS AND RESULTS: The Studio Trapidil versus Aspirin nella Restenosi Coronarica (STARC) is a multicentric, randomized, double-blind trial to assess the effects of trapidil in angiographic restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Patients received either trapidil 100 mg TID or aspirin at the same dosage at least 3 days before angioplasty and for 6 months thereafter. Coronary angiograms before PTCA, after PTCA, and at 6-month follow-up were quantitatively analyzed with manual calipers. Of the initial 384 patients recruited, 254 were evaluable for restenosis analysis (128 trapidil, 126 aspirin). Restenosis, defined as a loss of initial percent gain after PTCA of at least 50% (primary end point), occurred in 24.2% of the trapidil group and 39.7% of the aspirin group (P < .01). A similar result was obtained when restenosis per vessel was considered (trapidil, 23.3%; aspirin, 36.9%; P = .018). Clinical events at follow-up were similar in the two groups except that recurrent angina was significantly more frequent in the aspirin group, 43.7% versus 25.8% in the trapidil group (P < .01). Trapidil was well tolerated: only 6 patients had to discontinue the drug because of side effects, which was not different from the aspirin group. CONCLUSIONS: Trapidil reduces restenosis after PTCA at the dosage of 100 mg TID and favorably influences the clinical outcome thereafter.

Aged↗
PubMed1994

Assessment of emphysema using high resolution CT, CT expiratory density mask, and plain chest films.

Pulmonary function tests (diffusing capacity for carbon monoxide of the lungs) and radiological imaging (plain chest film, high resolution computed tomography (CT) and CT expiratory density mask) were compared in the assessment of 29 patients with suspected airways obstruction. Conventional roentgenogram showed a good agreement with the diffusing capacity of the lungs and proved to be useful in predicting the presence of severe emphysema, but the extension of the disease was more precisely assessed by computed tomography. A good agreement was found between high resolution CT and density mask CT, although the "subjective" high resolution identified more patients with mild emphysema than the "automated" density mask. In conclusion, although the plain chest film is useful in the diagnosis of severe emphysema, CT (especially when high resolution is used) is helpful in identifying cases of mild disease and in diagnosing the type of emphysema.

Adult↗
PubMed1993

Antibodies to topoisomerase II in idiopathic pulmonary fibrosis.

Antibodies to DNA topoisomerase II (anti-topoisomerase II) were detected by ELISA in the sera of 18 out of 41 (44%) patients with idiopathic pulmonary fibrosis (IPF). Follow-up sera were also obtained from 19 of the patients. DNA topoisomerase II binding remained constantly high or low in the majority of follow-up sera, but 2 out of the 8 positive cases became negative while 3 out of the 11 negative cases became positive during follow-up. No association was found between occurrence of anti-topoisomerase II antibodies and any indices of disease severity. Furthermore, individual patient follow-up did not show any correlation between changes in topoisomerase II binding and deterioration or improvement of clinical status. In conclusion our study shows that although anti-topoisomerase II are detectable in a large fraction (approximately 50%) of IPF patients and are useful for diagnostic purposes, they do not provide a measure of clinical activity.

Adult↗
PubMed1993

Elevated serum superoxide dismutase levels correlate with disease severity and neutrophil degranulation in idiopathic pulmonary fibrosis.

1. Tissue damage in idiopathic pulmonary fibrosis is due in part to oxidant-antioxidant imbalance. 2. We evaluated the serum levels of the antioxidant enzyme Cu/Zn superoxide dismutase (EC 1.15.1.1) in 25 patients with idiopathic pulmonary fibrosis, 34 patients with sarcoidosis and 40 healthy control subjects by an enzyme immunometric assay. 3. We found that patients with idiopathic pulmonary fibrosis have higher serum Cu/Zn superoxide dismutase levels than control subjects and patients with sarcoidosis. In addition, serum Cu/Zn superoxide dismutase levels correlate with disease severity indexes in patients with idiopathic pulmonary fibrosis. 4. The increase in serum Cu/Zn superoxide dismutase level in idiopathic pulmonary fibrosis could depend on degranulation of activated neutrophils or release from damaged cells. To elucidate the contribution of neutrophil degranulation we determined the polymorphonuclear cell elastase level in the same specimens. We found a strong correlation between serum Cu/Zn superoxide dismutase and polymorphonuclear cell elastase activities, and, in patients with idiopathic pulmonary fibrosis, we observed higher levels of polymorphonuclear cell elastase than in control subjects and patients with sarcoidosis, which correlated positively with disease severity indexes. 5. Cu/Zn superoxide dismutase can catalyse the dismutation of O2 into H2O2 and generate OH.. These oxygen radicals are probably the major factors responsible for tissue damage (in particular, alveolar and endothelial cells) and fibrosis in experimental lung injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effect of steroid eluting versus conventional electrodes on propafenone induced rise in chronic ventricular pacing threshold.

The aim of this study was to evaluate chronic ventricular pacing threshold increase after oral propafenone therapy. Eighty-three patients affected by advanced atrioventricular block and sick sinus syndrome were studied at least 3 months after pacemaker implantation, before and after oral propafenone therapy (450-900 mg/day based on body weight). The patients were subdivided into three groups according to the type of unipolar electrode that was implanted: group I (41 patients) Medtronic CapSure 4003, group II (30 patients) Medtronic Target Tip 4011, and group III (12 patients) Osypka Vy screw-in lead. In all cases a Medtronic unipolar pacemaker was implanted: 30 Minix, 23 Activitrax, 14 Elite, 12 Legend, and 4 Pasys. Propafenone blood level was measured in 75 patients 3-5 hours after propafenone administration. The pacing autothreshold was measured at 0.8 V, 1.6 V, and 2.5 V by reducing pulse width. At the three different outputs before and after propafenone, threshold increments were significantly lower in group I in comparison with group II and group III (propafenone ranging from < 0.001 to < 0.05). No significant difference was found in pacing impedance or in propafenone plasma concentration in the three groups. Strength-duration curves were drawn for each group at baseline and after propafenone administration. Before propafenone, in group I, the knee was markedly shifted to the left and downward as compared to the classic curve, so that the steep part was predominant; in group II and group III this shift was progressively less evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Dose and test for dipyridamole infusion and cardiac imaging early after uncomplicated acute myocardial infarction.

To evaluate the relation of the dose of intravenous dipyridamole on results of thallium and echocardiographic testing, the results of standard- (0.56 mg/kg/4 minutes) versus high- (0.84 mg/kg/10 minutes) dose dipyridamole were obtained 9 +/- 3 days after uncomplicated acute myocardial infarction in 57 patients. New wall motion abnormalities were compared with redistribution of thallium imaging and results of discharge coronary angiography. The sensitivity of thallium in predicting the presence of multivessel coronary artery disease was significantly (p < 0.01) higher (85%) than echocardiography (53%) and was unaffected by the dose. However the sensitivity of echocardiography was better with the higher dose (53 vs 14%). Minor adverse effects occurred in 34 patients (59%) after receiving the high dose and only in 4 patients (7%) after the standard dose (p < 0.001). Thus, thallium-201 scintigraphy during standard-dose dipyridamole infusion is more effective than high-dose dipyridamole echocardiographic testing in safely identifying patients who could benefit from early invasive evaluation and therapy.

Angina Pectoris↗
PubMed1991

Topography of glycosyltransferases involved in the initial glycosylations of gangliosides.

We attempted to establish within which organelle UDP-Glc:ceramide beta 1----1'glucosyltransferase (GlcT) is located and moreover to obtain information about its orientation on intracellular membranes as well as that of UDP-Gal:glucosylceramide beta 1----4galactosyltransferase (GalT-2) and CMP-NeuAc:lactosylceramide alpha 2----3sialyltransferase (SAT-1). An extremely purified Golgi apparatus fraction was the only liver fraction where a ceramide-dependent formation of glucosylceramide could be demonstrated. This Golgi fraction, mainly constituted by stacks of intact cisternae which retained the same topographical orientation as in vivo, was then incubated with liposomal dispersions of glycosphingolipid-glycosyltransferase acceptors in reaction mixtures containing all the requirements for enzyme activity but no detergent. Under such conditions, SAT-1 and other late acting glycosyltransferases were over 90% latent, while both GlcT and GalT-2 were just as active as in the detergent-containing assay; they were still inhibited by EDTA. Sepharose-immobilized ceramide and Sepharose-immobilized glucosylceramide were found to be suitable acceptors for GlcT and GalT-2, respectively, still using intact Golgi cisternae as the enzyme source. Moreover, a part of GlcT and GalT-2 activity was released from intact Golgi cisternae upon cathepsin D treatment. These results provide strong evidence that GlcT and GalT-2 face the cytoplasmic side of the Golgi apparatus, whereas SAT-1 and the other late acting enzymes face the luminal side.

Animals↗
PubMed1991

[Thallium and echo- dipyridamole in the early selection of patients at risk after acute myocardial infarction. Which test? What dose?].

UNLABELLED: The optimal iv dose of Dipyridamole (Dip) in echocardiography (echo) or Thallium scintigraphy (Tl) remains undetermined. To select the high-risk patients (pts) subset, we performed echo and Tl with standard dose (SD) and high dose (HD) Dip infusion (0.56 mg/Kg/4'-0.84 mg/Kg/10' respectively) in 40 pts 9 +/- 3 days after admission for acute myocardial infarction (AMI). Of these, 38 pts had coronary artery disease at angiography and 2 had no significant lesions. Worsening in regional wall motion on echo and reversible perfusion defects on Tl were considered abnormal patterns. SD had no side effects; only in one pt was ischemic ventricular dysfunction detected on echo, whereas Tl redistribution was found in 24 pts (12 had multivessel disease and 12 had one coronary stenosis greater than or equal to 70%). HD caused adverse reaction in 24 pts, did not enhance SD-Tl sensitivity, but induced abnormal echo in 18/24 pts with transient defects on SD-Tl. Eleven of the 16 Tl negative pts had occlusive disease, 3 had one vessel disease and 2 showed no evidence of coronary artery disease. IN CONCLUSION: SD is safe but often provokes a submaximal coronary vasodilation. Failure to detect ischemia on echo may be explained by this. SD-Tl is, however, able to identify high-risk pts who may benefit from early myocardial revascularization. HD does not enhance SD-Tl sensitivity, but it is necessary to induce echo abnormalities which are all too often undetectable at SD.

Adult↗