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Biomedical subjects

P Valentini

Publications and source records attributed to P Valentini.

At least 55 records · Page 3Linked to original sources

Binding of GC (VDBP) to membranes of human B lymphocytes following stripping of extant protein.

The presence of Gc (vitamin D binding protein) has been consistently demonstrated on the membrane of B lymphocytes. This protein appears to be spatially associated with surface immunoglobulins. The origin of this surface protein has not yet been determined and the purpose of the present paper was to investigate if Gc may bind to human lymphocytes after immunoglobulin (Ig) capping. For this purpose the presence of Gc on B lymphocytes was examined by three different approaches. First, when cells were examined by immunofluorescence and quantified by flow cytometry, membrane Ig capping was followed by a dramatic decrease in positivity for Gc when compared to native cells. In addition, incubation of capped cells with purified Gc was followed by a significant increase in fluorescence, indicating that this protein had been able to bind again. Second, analysis of solubilized lymphocytes by Western blotting showed that native lymphocytes and capped cells incubated with purified Gc contained a large quantity of a 56kDa protein which was immunoreactive with anti Gc antibodies. This protein band was much weaker on blots from capped cells not treated with Gc. Third, radiobinding assays indicated that, following capping, cells were able to bind Gc in saturable fashion. These results suggest that membrane Gc could play a role in the entry of vitamin D metabolites into lymphocytes.

B-Lymphocytes↗

Influence of plaque composition on luminal gain after balloon angioplasty, directional atherectomy, and coronary stenting.

This study was conducted to correlate the acute luminal enlargement achieved by three different nonsurgical revascularization procedures in 79 patients (32 treated by balloon angioplasty, 29 by directional atherectomy, and 18 by coronary stenting) with the morphologic characteristics of coronary plaques assessed by preprocedure intravascular ultrasound. The absolute luminal gain was 2.41 +/- 1.54 mm2 for balloon angioplasty, 3.17 +/- 1.8 mm2 for directional atherectomy, and 4.56 +/- 1.45 mm2 for coronary stenting (p = 0.00005). However, when luminal gain was corrected for the external vessel area (luminal gain index), such difference was no longer present (0.22 +/- 0.12 for balloon angioplasty, 0.24 +/- 0.15 for directional atherectomy, and 0.30 +/- 0.12 for coronary stenting, p = not significant). Concentric plaques treated by coronary stenting had a higher luminal gain index than eccentric plaques (p = 0.01). A comparison of the three devices showed that a similar luminal gain index was achieved in soft plaques, whereas coronary stenting was superior to directional atherectomy (0.41 +/- 0.10 vs 0.20 +/- 0.09, p = 0.002) and balloon angioplasty (0.41 +/- 0.10 vs 0.19 +/- 0.08, p = 0.0005) in concentric plaques. Coronary stenting also induced a greater luminal gain index than directional atherectomy in calcific plaques (0.30 +/- 0.11 vs 0.18 +/- 0.09, p = 0.04). In conclusion, these data show that plaque morphology assessed by preprocedure intracoronary ultrasound influences the acute luminal enlargement achieved by different coronary interventions. The knowledge of plaque composition may be useful in guiding the choice of the device to be used to obtain a larger acute luminal gain.

Adult↗

GST-pi and P-170 co-expression in multiple myeloma.

Bone marrow samples from 40 patients affected by multiple myeloma either treated or untreated were examined for expression of glutathione-S-transferase pi (GST-pi), P-glycoprotein and the protein product of ras oncogenes family, p-21, on plasma cells, by immunocytochemical detection. 72% of evaluated samples were positive for P-170 and 82% for GST-pi without any correlation with clinical or prognostic parameters. A significant relationship between GST-pi expression and P-170 positivity was found and co-expression was observed in 91% of evaluated samples. Expression of P-170 and GST-pi was found both in treated and untreated patients. However, patients evaluated before and after therapy showed an increase in the percentage of plasma cells positive for GST-pi or P-170 or both. Expression of p-21 was not associated with these mechanisms of drug resistance. These data suggest that different resistance mechanisms are present in multiple myeloma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Effect of the increasing use of coronary angioplasty on outcome at one year in patients with unstable angina.

OBJECTIVE: To determine whether the increasing use of percutaneous transluminal angioplasty in patients with unstable angina has reduced the need for bypass surgery and whether this change in the choice of treatment affected the outcome at one year in patients with unstable angina who were admitted to hospital in two different periods of time. DESIGN: Retrospective analysis of consecutive patients with unstable angina (angina at rest with ST-T changes during pain) who underwent coronary arteriography in two different periods of time. PATIENTS: 158 patients were admitted to hospital between January 1988 and June 1989 (group 1) and 140 patients admitted between January 1992 and June 1993 (group 2). RESULTS: Coronary angioplasty procedures nearly doubled from 29% in group 1 to 56% in group 2 whereas bypass surgery decreased from 36% in group 1 to 23% in group 2 (P < 0.01). Coronary angioplasty increased and bypass surgery decreased in patients with one vessel disease (P < 0.01), two vessel disease (P < 0.05), and three vessel disease (P < 0.01). Coronary angioplasty also increased and bypass surgery decreased in refractory angina and in patients with ejection fraction < 0.50 (both P < 0.05). At 1-year follow up, 14 patients in group 1 (9%) and 10 in group 2 (7%) either died or had myocardial infarction (P = NS). Revascularisation procedures were needed in 16 group 1 patients (10%) and 27 group 2 patients (19%, P < 0.05). CONCLUSIONS: Coronary angioplasty became more widely used in patients with unstable angina. This reduced the need for bypass surgery in patients with multivessel disease, refractory angina, and depressed left ventricular function. This change in treatment did not affect 1-year mortality or the myocardial infarction rate. More patients in the more recent group in which angioplasty was the preferred treatment required a further revascularisation procedure than in the earlier group in which bypass grafting was more often used as the initial treatment.

Adult↗

[The evolution of the therapeutic choice in patients with the outcomes of non-Q myocardial infarct: 2 periods compared].

BACKGROUND: Over the last years there has been a tremendous increase in coronary angioplasty procedures (PTCA), due to the availability of better materials and to the refinement of operators skill. It is not known however if this "PTCA boom" has modified our approach to the patients with particular clinical situations, such as those with non-Q wave myocardial infarction. The purpose of this study was to verify, in patients undergoing coronary angiography for clinical reasons after a non-Q wave myocardial infarction, the clinical decision concerning the therapeutical choice in two different periods (101 patients in 1988 vs. 102 patients in 1992). METHODS AND RESULTS: Patients in the two groups had similar clinical manifestations whereas patients observed in 1992 had more frequently 2-vessel disease than single vessel disease as compared to patients studied in 1988 (p < 0.05). The distribution of patients with normal coronary arteries or with 3-vessel disease was similar in the two periods. In 1988 medical therapy was the most recommended treatment at discharge (47%), followed by aorto-coronary bypass (29%) and coronary angioplasty (24%). On the contrary, in 1992 PTCA was performed in 48% of patients, medical therapy was recommended in 28% while the incidence of coronary surgery was reduced to 24% (p < 0.01). From a clinical point of view a significant increase in PTCA procedures was seen in patients presenting with unstable angina after the non-Q wave myocardial infarction (54% of these patients undergoing PTCA in 1992 vs. 30% in 1988, p = 0.03) and in patients with effort angina and a positive exercise test at low workload (53% of these patients undergoing PTCA in 1992 vs. 22% in 1988, p < 0.05). Moreover, in 1992 PTCA procedures increased in patients with single vessel disease (64% in 1992 vs. 49% in 1988) and in patients with 2-vessel disease (64% in 1992 vs. 9% in 1988). Therefore, in these patients the need of aorto-coronary by pass was reduced from 39% in 1988 to 19% in 1992 (p < 0.05). The success rate of PTCA procedures was 98% in 1992 and 83% in 1988. No major complications were observed in the two study periods and no patients underwent urgent coronary surgery. CONCLUSIONS: These data show an increase in PTCA procedures over the last years in patients undergoing coronary angiography for clinical reasons after a non-Q wave myocardial infarction. The greater experience of operators allowed for improved results, thus reducing the need of coronary surgery in these patients.

Adult↗

Induction of multidrug resistance (MDR) by transfection of MCF-10A cell line with c-Ha-ras and c-erbB-2 oncogenes.

To investigate the relationship between oncogene activation and appearance of multidrug resistance (MDR) we transfected the human breast epithelial cell line MCF-10A, negative for the expression of the P-glycoprotein, with c-Ha-ras and/or c-erbB-2 oncogenes. The appearance of the MDR phenotype was then studied by evaluating mdr-1 mRNA expression, the presence of P-glycoprotein on the cell membrane and the onset of doxorubicin resistance, together with the effect of the reversing agent verapamil. We found that only MCF-10A transfected with both c-Ha-ras and c-erbB-2 oncogenes acquired the MDR phenotype.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Effects of glycosaminoglycans on U-937 leukemia cell proliferation and differentiation: structure-function relationship.

Glycosaminoglycans (heparins, dermatan sulfate, chondroitin sulfate) with different structures and physicochemical properties were evaluated for their capacity to influence proliferation and differentiation of U-937 cell line. The contrasting and specific effects of glycosaminoglycans (depending on their structures and properties) on a leukemia cell line could help explain the regulation of proliferative and/or differentiative processes of hematopoietic cells in order to clarify the control of development and differentiation of hematopoietic progenitor cells by bone marrow extracellular matrix. Heparin from beef intestinal mucosa, heparan sulfate from beef spleen, dermatan sulfate from beef intestinal mucosa, and chondroitin sulfate from bovine trachea were extracted and purified, and their purity, structures, and physicochemical properties were evaluated. Fast-moving heparin was obtained by its selective precipitation as barium salt, and partially desulfated and re-N-sulfated heparin was produced by chemical modifications. Different glycosaminoglycans were tested to evaluate their effects on proliferation and differentiation processes of a monoblastic leukemia cell line (U-937). Heparin and derivatives (from 0.1 to 100 micrograms/ml) inhibit cell proliferation; heparan sulfate does not produce modifications, while chondroitin sulfate and dermatan sulfate (from 0.01 to 100 micrograms/ml) significantly stimulate cell growth. Cell differentiation was evaluated by cytoenzymatic determination of alpha-naphthyl butyrate esterase and by fluorescein-labeled anti-HLA-DR, anti-CD11b, and anti-CD14 antibodies. Nitro blue tetrazolium reduction and phagocytosis were also evaluated. Heparin and derivatives significantly increase U-937 differentiation. Heparin sulfate has no effect, while chondroitin sulfate and, to a lesser extent, dermatan sulfate, induce a strong decrease of differentiative markers. The regulation of U-937 cell properties appears to be related to charge density and to the amount of N-sulfate and N-acetyl groups. In particular, glycosaminoglycans with lower sulfate-to-carboxyl ratios and N-sulfate group percentages (chondroitin sulfate and dermatan sulfate) stimulate proliferation and produce a decrease of differentiative markers; on the contrary, polysaccharides with high charge density and N-sulfate group amounts (heparin and derivatives) inhibit U-937 proliferation and induce terminal differentiation. A previous paper (N. Volpi, L. Bolognani, A. Conte, and M. Petrini, (1993) Leukemia Res. 17, 789-798) demonstrates dissimilar effects on U-937 cells by chondroitin sulfates with different structures and physicochemical properties. In this study we confirm the importance of glycosaminoglycan structures and physicochemical properties in regulating cell functions. Possible mechanisms of action are discussed.

Animals↗

Effects of coronary angioplasty on left ventricular function.

It is well known that myocardial revascularization after successful coronary bypass surgery results in improved left ventricular function. Coronary angioplasty also results in successful revascularization, favorably affecting both stunned and hibernating myocardium. We studied 22 patients with chronic stable angina who underwent successful angioplasty for an isolated narrowing of the proximal or midportion of the left anterior descending artery. These patients also performed isometric exercises before and after angioplasty, which can be used to characterize left ventricular function. Revascularization after angioplasty induced an immediate improvement in left ventricular function in those patients with dysfunction secondary to hibernating myocardium. Further studies are needed to assess the possibility of the myocardial stunning phenomenon occurring after angioplasty in those patients without left ventricular improvement.

Angioplasty, Balloon, Coronary↗

Idarubicin is active on MDR cells: evaluation of DNA synthesis inhibition on P388 cell lines.

Multidrug resistance is frequently found in patients affected by hematological malignancies and has been related to a poor prognosis of acute leukemia. In the present paper we report results concerning the activity of idarubicin, an anthracycline derivative, on the leukemic P388 and P388 doxorubicin-resistant cell lines. The results clearly show that idarubicin inhibits DNA synthesis in the resistant cell line more actively than doxorubicin.

Animals↗

Is binding of vitamin D binding protein related to cell differentiation?

Vitamin D binding protein (Gc) is present on the surface of several blood cells and may interfere with the activity of 1,25(OH)2D3. It has previously been reported that Gc may bind to the U-937 line which is known to differentiate upon exposition to 1,25(OH)2D3. In the present paper, we evaluate the expression of Gc on the surface of U-937 and HL-60 lines. Both cell lines did not express Gc on their surface but U-937 cells were able to bind human purified Gc added to the medium whereas HL-60 were not. After culturing with 1,25(OH)2D3, HL-60 became able to bind Gc. This property seems to be related to the monocytic differentiation induced by 1,25(OH)2D3. Conversely, when present together, 1,25(OH)2D3 reduces binding on U-937.

Calcitriol↗

Membrane exposure during bone regeneration before implant placement: management and results. A report of two cases.

Two patients with apical lesions on maxillary central incisors showed large osseous defects of the residual ridge. E-PTFE membranes were used for ridge reconstruction, which allowed for the placement of implants of appropriate diameters. In the two cases described, the membranes were exposed and replaced. This technique facilitated atrophic ridge reconstruction in spite of premature membrane exposure.

Adult↗

[Coronary angioplasty in unstable angina].

Percutaneous transluminal coronary angioplasty is now largely applied either to stable or unstable patients suffering from angina pectoris. The procedural success rate and the incidence of acute complications are now comparable in the 2 population of patients. Very recent data have also shown that there is no difference in restenosis between patients with stable or unstable angina. Therefore, by now, in such unstable coronary syndromes the choice of surgical therapy is mainly determined by the presence of multivessel disease or by depressed left ventricular function. However, the possibility to obtain a complete revascularization by angioplasty or to stabilize the patients treating only the "culprit" vessel, may increase the number of unstable patients shifting from surgery to angioplasty.

Angina, Unstable↗

[Mexiletine in patients with progressive infarction and reduced ventricular function: anti-arrhythmic efficacy and hemodynamic effects].

Reduced left ventricular function and ventricular arrhythmias are the main risk factors associated with sudden death in patients with previous acute myocardial infarction. Antiarrhythmic therapy may have side-effects on myocardial contractility and sometimes makes the arrhythmia itself worse, especially when the pump function is seriously compromised. The aim of this study was to evaluate the efficacy of oral mexiletine as well as any modifications in left ventricular function by means of ambulatory ECG monitoring and angiocardiography with Tc 99m, at rest and after the handgrip test, in 20 patients with previous myocardial infarction and ventricular arrhythmias who were grouped into NYHA class II and class III. The mexiletine therapy lasted three weeks. Both classes showed a significant decrease in the number of ventricular extrasystoles/hour and in the number of couples (p less than 0.01). The decrease in the number of the ventricular runs proved to be higher in the general analysis (p less than 0.01) than in each NYHA class (p less than 0.05). At the end of the study, significant modifications were not observed either in the end-diastolic and end-systolic volumes, or in the ventricular ejection fraction.

Aged↗

[Pharmacologic treatment of duodenal ulcer. Short and long-term results with pirenzepine in ambulatory patients].

Pirenzepine is an antimuscarinic drug highly selective for M1 receptors, which proved to be effective in the treatment of peptic ulcer. Aim fo the present study was to assess the frequency of relapses over a 12-month period subsequent to the anatomic healing of duodenal ulcer, obtained with pirenzepine (PRZ). Sixty patients (44 M, 16 F, mean age 42,9 years range 19-73) entered the study. They were allocated at random to a double-blind treatment with placebo or PRZ given at two different dosages, 50 or 100 mg/day respectively, over a consecutive period of 12 months. Clinical evaluations were foreseen every 3 months, while endoscopy and hematology, gastrin plasma levels and intra-ocular pressure assessment at the end of the 6th and 12th month. The intake of antacids or equivalent drugs, in addition to the baseline treatment, was not allowed. Statistical evaluation of the results was performed by chi-square test with Yates' corrections. Difference in percentage of patients without relapses at 6th month and at 12th month was clearly in favour of PRZ compared with placebo. Non changes in the indices of gastrin plasma levels, liver or renal functions and intraocular pressure were reported. No patients complained of side-effects pirenzepine-related. The treatment with full dosage (100 mg/day) did not increase the rate of positive responsiveness compared to that of standard dosage (50 mg/day). It might confirm the importance of the role played by nocturnal acid secretion. For this reason, a decrease in relapses could be expected with the dosage of 100 mg if it was given in a single evening dose. However, therapy with PRZ turned out effective and did not produce side-effects. Its selectivity avoided clinical effects related to a cholinergic system block.

Adult↗

[Alcoholic gastropathy. Notes on its epidemiology and the therapeutic experience using pirenzepine].

Chronic alcoholic gastritis is a very important social problem in the Health District of Arezzo, which covers an area where wine is an integral part of the diet. The etiology of this disease is related to the alcohol induced rupture of the gastric mucosal barrier. For this reason we wanted to verify the therapeutic effect of a "barrier acting drug" such as pirenzepine. A selected group of 50 randomized patients (46 males and 4 females, mean age 52.6 years) received in a double blind fashion 50 mg b.i.d. of pirenzepine or placebo for consecutive 4 weeks. Endoscopy and histological examinations performed before and after treatment together with the clinical evaluation of the dyspeptic symptoms, showed that pirenzepine was more active than placebo. In addition our results suggest that pirenzepine stimulates defence mechanisms of the gastric mucosa.

Adult↗

[Use of pirenzepine in prevention of stress ulcers in high-risk surgical patients].

In an endoscopic controlled trial the effectiveness of pirenzepine in preventing stress ulcer in high risk patients for surgical operation was studied. 40 patients of both sexes aged between 19-72 were at random distributed to pirenzepine treatment (10 mg e.v./8 hours, starting the day before surgery to 10th day after it), or to "void" period (without specific therapy). Endoscopic findings was performed before and after treatment and every patient was daily monitored for: dyspepsia, defecation, residual intragastric volume, intestinal peristalsis, beginning oral food intake, haemodynamic and metabolic parameters. The results obtained showed the gastric and duodenal cyto-protective effect and the better post-operative clinical course, when pirenzepine was administered by parenteral infusion.

Adult↗