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Biomedical subjects

M Mantovani

Publications and source records attributed to M Mantovani.

At least 55 records · Page 3Linked to original sources

Defibrotide decreases cholesterol amount in hypercholesterolemic rabbit aorta, with no modification of plasma or lipoprotein cholesterol.

Defibrotide, (D) an antithrombotic agent, when administered i.v. to cholesterol-fed rabbits decreased cholesterol in the aorta without changing total plasma cholesterol, triglyceride or phospholipid, nor the cholesterol, triglyceride, phospholipid and protein of plasma lipoproteins. Platelet aggregation was decreased in rabbits treated with D. There were fewer vascular lesions in the hearts and kidneys of animals treated with D than in animals fed cholesterol and treated with placebo. These data suggest that the antithrombotic activity of D and its ability to reduce platelet sensitivity could help to reduce the amount of cholesterol in the cardiovascular system in atherosclerosis-prone situations.

Adenosine Diphosphate↗

Circadian rhythm of natural killer cell activity in vitiligo.

Ten patients with vitiligo, either in the active (six cases) or static (four cases) phase, and twelve healthy control subjects were studied with a standard cytotoxicity assay to evaluate the circadian rhythm of natural killer cell activity from peripheral blood mononuclear cells. The natural killer cell activity was measured at the zero, sixth, twelfth, and eighteenth hours of the day. The results demonstrated that patients with vitiligo had significantly higher natural killer cell activity compared with normal controls. When patients with static and active vitiligo were compared, those with the static form had increased natural killer cell activity at all times except noon, whereas those with active form had increased natural killer cell activity only at 0600 and 1800. These changes shifted the acrophase of the circadian rhythm of each group. Indeed, by cosinor analysis, both patients with vitiligo and normal controls had similar circadian rhythms, but the acrophase was shifted from 0602 in control subjects to 0435 in the ten patients with vitiligo. The acrophase in the six patients with active vitiligo was found to be closest to that of normal controls (0508). These findings indicate that natural killer cell activity abnormalities are more marked in the static rather than in the active form of vitiligo.

Adult↗

Thrombolytic activity of defibrotide against old venous thrombi.

The age of the thrombus is probably a very important determinant of the outcome of thrombolysis. The clinical potential for rapidly dissolving thrombi by thrombolytic therapy is considerable because restoration of the blood flow can rescue the jeopardized district served by the occluded vessel such as for myocardial infarction, deep vein thrombosis, arterial thrombosis, pulmonary embolism, and occlusion of retinal vessels. Defibrotide was effective against 3-, 7-, or 10-day-old thrombi; its ED50s were 32, 65, or 118 mg/kg-1 hour-1, respectively, suggesting that the age of the thrombus could play a role in the outcome of thrombolysis. A similar pattern was also shown for urokinase.

Animals↗

[A case of pericarditis in acute brucellosis].

A case of brucellosis pericarditis in a patient affected with acute brucellosis hospitalized in the Infectious Disease Department of Asti Hospital is described. During the hospitalization, the patient revealed (in addition to the classical symptoms and signs), a modest shooting pain in the chest and typical electrocardiographic alterations confirmed by an echocardiography that revealed slight pericardial effusion at both front and rear, subsequently and by steroid and specific antibiotic therapies. The real possibility of finding this complication, considered so rare in the literature, in cardiovascular brucellosis is pointed out as is the capacity of modern echocardiographic research to confirm and reinforce diagnosis and consequently also the description of modest pericardial effusions with unclear symptoms and electrocardiographic signs that were once practically ignored when the pericardial involvement often escaped a clinical identification, being concealed by the most important signs of the primary infection.

Acute Disease↗

Macrolidic antibiotics: effects on primary in vitro antibody responses.

The effect of two macrolidic antibiotics, josamycin and erythromycin, on the primary immune response in cultures of human peripheral blood mononuclear cells (PBMC), were studied using a soft agar hemolytic plaque assay. Both compounds induced an appreciable reduction in the primary antibody response in total PBMC cultures. The removal of plastic-adherent cells, however, profoundly modified the effect of macrolides on the immune response. Both josamycin and, to a lesser extent, erythromycin enhanced, rather than suppressed, the antibody response. Furthermore, the macrolide-induced immunodepression in cultures of total PBMC was completely reversed by the addition of catalase (8000 U/ml). Taken together, these findings suggest that the macrolide-induced depression of the antibody response depends upon the presence of adherent monocytic cells and is mediated by the production of hydrogen peroxide.

Antibody Formation↗

Calcitonin levels in normal women of various ages evaluated with a new sensitive radioimmunoassay.

In order to establish the normal range of serum Calcitonin (CT), evaluated with a new, sensitive radioimmunoassay in normal women of various ages, 67 female subjects were examined. CT levels were detectable in all the subjects, with a reference interval (bounded by the 2.5 and 97.5 percentiles) of 3.6-16.9 pg/ml; a very slight decrease with age was observed (correlation coefficient = -0.24; P = 0.05; regression equation: CT = 9.55--0.042 x age). This assay seems sensitive enough to permit the measurement of CT in physiological conditions.

Adult↗

NK cell activity and monocyte dysfunctions in a patient with common variable hypogammaglobulinemia.

A 57-year-old man with a history of recurrent infections from the age of 50 was hospitalized with a diagnosis of common variable hypogammaglobulinemia (CVH). Immunological studies revealed a severe reduction of circulating immunoglobulins of all classes. Immunophenotyping of peripheral blood mononuclear cells (PBMC) with monoclonal antibodies, revealed normal values of total B and T cells with CD4/CD8 ratio sharply reduced (0.35) as compared to normal (1.6) because of an increase of CD8 and a decrease of CD4 cells. The surface expression of IL-2 receptor was normal. Natural cytotoxic and phagocytic system presented several abnormalities: a deep impairment of NK activity was found in spite of a normal number of NK cells, as ascertained by Leu 19 and B73.1 monoclonal antibodies. The defective NK activity was not restored by interferon alfa, but was normalized by recombinant IL-2. Phagocytic function, as defined by zymosan-stimulated O2- production was almost absent. The involvement of natural cytotoxic and phagocytic systems in CVH has been rarely reported; the possible causative role of a chronic viral infection (Epstein-Barr virus?) is discussed, on the base of anamnesis.

Antibodies, Monoclonal↗

Modulation of natural killing by cyclo- and lipo-oxygenase inhibitors.

The effect on NK activity of two oxygenase inhibitors, indomethacin which is cyclo-oxygenase-specific at 10(-6) M and BW755C which blocks both cyclo- and lipo-oxygenase, has been analysed. The NK activity of human peripheral blood mononuclear cells (PBMC) has been studied in a 18-hr 51Cr-release assay. PBMC were incubated with the drugs for different periods of time before and during NK assay in order to analyse the correlations between the time of incubation and the modulation of NK activity. The results show that the inhibition of the cyclo-oxygenase alone, by indomethacin, enhances the NK activity if the drug is added both during and prior to the assay. In the latter case the enhancement is time dependent, reaching a maximum level after 18 hr of incubation. The simultaneous inhibition of lipo- and cyclo-oxygenase by BW755C has a rather more complex effect. The NK activity is similar to that of untreated cells after 6 hr incubation with BW755C, but is inhibited or greatly enhanced after 4 and 18 hr of incubation, respectively. These effects seem largely independent of the presence of monocytes because they can be observed with non-adherent PBMC (NA-PBMC).

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

The anticoagulant, hepatic lipase-releasing and lipoprotein lipase-releasing activities of several natural and chemically modified heparins differ.

Several 'natural' heparins have been found to have different potencies for releasing hepatic lipase and lipoprotein lipase. These differences can also be obtained by treating heparins with physical and chemical methods, which also affect the anticoagulant activity. These differences in potency in hepatic lipase-releasing activity are discussed in terms of the role of this lipase in lipoprotein and cholesterol metabolism.

Animals↗

Therapy for advanced thyroid cancer: treatment of a high risk case.

The treatment of a high risk case of an advanced thyroid cancer is reported. The patient had a thyroid cancer with metastatic lesions of the frontal bone, left temporal bone, left sacroiliac joint, lytic destruction of C6 and lytic lesion of C7. A pre-operative immobilization of the cervical spine was performed by a halo cast set on a corset of gypsum. After this, the patient underwent a thyroidectomy and, at the same time, a metallic plate was applied to immobilize C5-C7. A month after he underwent reoperative surgery to stabilize definitively the cervical spine. Subsequently he was treated by TCT and 131I subdivided in several cycles. The latest total body scan demonstrated a complete regression of secondary lesions.

Adenocarcinoma↗

Protective activity of defibrotide against lethal acute myocardial ischemia in the cat.

Defibrotide (D) is a natural polydeoxyribonucleotide from mammalian lungs with profibrinolytic and antithrombotic activities. D also has PGI2-stimulating and tissue plasminogen activator (TPA)-releasing activities, but has no anticoagulant properties. The protective effects of D were demonstrated very recently in a model for non-lethal ischemia in the cat. In the experiments reported here Defibrotide was tested in a model for acute myocardial ischemia leading to ventricular fibrillation (VF) and death of the cat. Occlusion of the coronary artery (LAD) at its origin induced VF and death in 17 of 20 control cats. When cats were treated with D (32 mg Kg-1, bolus i.v., + 32 mg Kg-1 h-1, i.v., after LAD occlusion) 19 of 20 animals survived until the end of experiments. D also prevented changes in plasma and myocardial CPK, hemodynamics and ECG. D was compared with a variety of pharmacological agents which are used clinically for specific cardiovascular diseases. The ability of D to promote considerable generation of PGI2 from vascular walls plus its ability to prevent the decreases in CPK-activity and ATP in the myocardial tissue may have roles in its beneficial effects against ischemic heart in the cat. However, the mechanism/s of the substantial protective effect of D against cardiac death has still to be clarified.

Animals↗