Search PubMed⌕ Search

Biomedical subjects

F Rossi

Publications and source records attributed to F Rossi.

At least 649 records · Page 36Linked to original sources

Activation of mouse macrophages causes no change in expression and function of phorbol diesters' receptors, but is accompanied by alterations in the activity and kinetic parameters of NADPH oxidase.

Mouse peritoneal macrophages activated in vivo by the injection of Corynebacterium parvum release larger amounts of superoxide anion (O2-) than macrophages from control mice when stimulated with phorbol myristate acetate (PMA). The biochemical bases for this enhanced response of activated macrophages have been investigated by studying the expression and function of receptors for the stimulant, and the activity of the enzyme NADPH oxidase which is responsible for the production of O2- in leucocytes. Studies of binding of phorbol dibutyrate, an agent closely related to PMA, showed that the affinity constants (Kds) and the number of binding sites were the same in resident and activated peritoneal macrophages. The activity of the NADPH oxidase was, however, different in the two macrophage populations which differ in their capacity to release O2-. NADPH oxidase activity was studied in macrophage monolayers after lysis with deoxycholate. The main features of this activity were as follows: stimulation of macrophages with PMA or zymosan caused an increase in NADPH-dependent O2- production; NADPH oxidase activity in the lysates followed the same dose-response curve for different concentrations of PMA as O2- release by intact macrophages; O2- release by intact macrophages could be fully accounted for by NADPH-dependent O2- production by macrophage lysates; activity was strictly substrate-specific, in that NADH could not substitute for NADPH; after stimulation with PMA or zymosan, NADPH oxidase activity was higher in lysates of C. parvum-activated macrophages than in lysates of resident macrophages; NADPH oxidase activities of activated and resident macrophages differed markedly in their kinetic parameters. The NADPH oxidase of macrophages activated by C. parvum or trehalose dimycolate of mycobacterial origin displayed a five to seven times lower Km compared to the enzyme in resident macrophages.

Animals↗

Organ tolerance of non-steroidal anti-inflammatory drugs: effect on liver cells.

Experimental studies in mice and in rats showed the good tolerance of a new non-steroidal anti-inflammatory drug, flunoxaprofen, by normal and CCl4 damaged liver. The activity of an enzyme-inducing drug, such as phenobarbital, showed a greater increase after pretreatment with indomethacin than with flunoxaprofen or benoxaprofen. High doses of benoxaprofen and indomethacin significantly decreased bromosulphonphthalein excretion in rats with normal or CCl4 damaged liver; the effect was not observed with flunoxaprofen administered at the same dose as benoxaprofen. Moreover, benoxaprofen and indomethacin but not flunoxaprofen induced a significant increase of some serum liver enzymes in CCl4 poisoned rats.

Animals↗

Effect of N-acetylcysteine in subjects with slow pulmonary mucociliary clearance.

There is significant evidence that in the general population there are subjects either with fast or slow pulmonary mucociliary clearance rates. At the moment we do not know the physiological importance of such finding. Slow clearers should be regarded as a subpopulation at risk for bronchopulmonary diseases. Therefore, it would be of considerable interest if their mucociliary function could be stimulated by drugs for preventive purposes. Twelve apparently healthy subjects with slow mucociliary clearance rate, selected in an epidemiologic survey in a non-smokers population were given 0.6 g oral N-acetylcysteine/day/60 days in a double-blind cross-over randomized study. After treatment their mucociliary clearance rates increased by about 35% as compared with baseline values, and returned to pre-treatment values after the washout period. Subjects were unresponsive to placebo treatment. It would seem that slow clearers are protected against lung aggressions by prevention and/or mucus-active drugs.

Acetylcysteine↗

[Cardiac insufficiency in infectious endocarditis].

The aim of this study of 101 cases of infective endocarditis was to determine the factors predisposing to cardiac failure, the prognostic factors of this complication and the therapeutic implications. A significant (p less than 0.05) Chi square test was the statistical reference. Fifty-two per cent of patients developed cardiac failure which was biventricular in 48 p. 100 of cases and the presenting symptom in 64 p. 100. The mean age of the patients with cardiac failure was 56.6 years with a clear male predominance. In 48 p. 100 of cases, cardiac failure complicated a pre-existing cardiac lesion which was usually acquired (84 p. 100). The commonest condition was valvular insufficiency of the aortic and mitral valves (70 p. 100 of cases with cardiac failure). Severe cardiac failure was observed more frequently and earlier in aortic than in mitral regurgitation. The commonest infecting organism was the streptococcus (53 p. 100 of cases with cardiac failure) and the most frequent presumed portal of entry was dental (25 p. 100). Arrhythmias were observed in 51 p. 100 of patients in cardiac failure, the commonest being atrial fibrillation (34 p. 100) complicating mitral valve disease in 56 p. 100 of cases; 17 p. 100 of arrhythmias were ventricular. Conduction defects were observed in 26 p. 100 of cases with cardiac failure, 55 p. 100 of which had aortic valve disease. Valvular vegetations were demonstrated by echocardiography in 43 p. 100 of cases with cardiac failure. Valve replacement had to be performed for resistant cardiac failure in 13 p. 100 of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Current aspects of infectious endocarditis. Review of 101 cases].

One hundred and one cases of infectious endocarditis were reviewed, from 1966 to 1982. The mean age of the patients was 56.3 +/- 15 years. There was a marked predominance of men (70.2 p. 100); the commonest portal of entry was dental (45.9 p. 100); the number of iatrogenic portals of entry and cases of endocarditis on prosthetic valves has been increasing in recent years. Blood cultures were positive in 83 p. 100 of cases; the commonest responsible organism was the non-D streptococcus (31 p. 100 of cases) followed by the D streptococcus (18.8 p. 100), the staphylococcus aureus (17.8 p. 100), and the staphylococcus epidermidis (2.9 p. 100). Gram-negative bacilli were isolated in 9.9 p. 100 of cases. Rare and slow growing organisms have been isolated since 1977. Echocardiography was then introduced and helped the diagnostic in 70 p. 100 of cases. Circulating immune complexes were measured in 25 patients and were found to be raised in 14 cases (56 p. 100). The commonest complication was cardiac failure (43 p. 100) which led to valve replacement in the acute phase in 14 p. 100 of cases. The occurrence of cardiac arrhythmias was a poor prognostic factor. The other complications were neurological (15 p. 100), renal (10 p. 100), embolic (19 p. 100), and pulmonary (9 p. 100). The mortality rate in the acute phase was 30 p. 100 and the probability of a five year survival was 54 p. 100.

Adult↗

Synthesis and pharmacological activity of derivatives of exo-trimethylenenorbornane. V.

The synthesis of two series of amides and glycinamides starting from N-phenyl exo-5,6-trimethylenenorbornan-2-endo-amine, prepared from exo-5,6-trimethylenenorbornan-2-one via sodium borohydride reduction of its N-phenyl imine, is described. All amides showed a moderate hypotensive activity in rats, whereas some glycinamides and amides showed weak infiltration anesthesia and antiarrhythmic activity in mice. Effects on heart rate in rats are also reported.

Amides↗

[Cardiac manifestations of chronic atrophic polychondritis].

The authors present a case of chronic atrophic polychondritis with cardiovascular complications, consisting of aortic incompetence due to dilatation of the aortic ring associated with an aneurysm of the ascending aorta and a first degree atrio-ventricular block occurring six months after the onset of the disease. The progression towards heart failure resulted in the replacement of the ascending aorta and of the aortic valve. The authors discuss the cardiovascular complications of this disease.

Aorta↗

[Cardiac complications of infectious endocarditis].

Factors predisposing to cardiac complications and influencing hospital survival, were analysed in a retrospective study of 101 cases of infective endocarditis. Heart failure occurred in 52 p. 100 of our patients. A significantly greater incidence of heart failure was observed in endocarditis with no preexisting heart disease (p less than 0.01), aortic and mitral valve involvement (p less than 0.01), staphylococcus aureus infections (p less than 0.05), arrhythmias (p less than 0.001), and conduction disturbances (p less than 0.01). Significantly more patients with congestive cardiac failure died in hospital (51 p. 100) than those without congestive cardiac failure (17 p. 100) (p less than 0.001). Severe heart failure before treatment (p less than 0.05), streptococcus D endocarditis (p = 0.05), supraventricular arrhythmias (p less than 0.05), and intracardiac conduction disturbances (p less than 0.05), significantly increased the hospital mortality in patients with congestive heart failure. Electrocardiographic findings revealed arrhythmias in 34 p. 100 of cases, more commonly with mitral valve involvement (71 p. 100) and 52 p. 100 died in hospital. The development of intracardiac conduction disturbance during the course of 18 cases of endocarditis (aortic valve in 11 cases) was associated with a hospital mortality rate of 60 p. 100. The incidence of pericarditis and pulmonary embolism was 4 and 7 p. 100 respectively, and all patients died in hospital. Acute inferior myocardial infarction compatible with coronary embolism was suspected in one patient. Early cardiac valve replacement improved the hospital survival in patients with cardiac complications of infective endocarditis.

Adult↗

Composition of partially purified NADPH oxidase from pig neutrophils.

The superoxide (O2.-)-forming enzyme NADPH oxidase from pig neutrophils was solubilized and partially purified by gel-filtration chromatography. The purification procedure allowed the separation of NADPH oxidase activity from NADH-dependent cytochrome c reductase and 2,6-dichlorophenol-indophenol reductase activities. O2.-forming activity was co-purified with cytochrome b-245 and was associated with phospholipids. However, active fractions endowed with cytochrome b were devoid of ubiquinone and contained only little FAD. The cytochrome b/FAD ratio was 1.13:1 in the crude solubilized extract and increased to 18.95:1 in the partially purified preparations. Most of FAD was associated with fractions containing NADH-dependent oxidoreductases. These results are consistent with the postulated role of cytochrome b in O2.-formation by neutrophil NADPH oxidase, but raise doubts about the participation of flavoproteins in this enzyme activity.

Animals↗

Isolation from neutrophil membranes of a complex containing active NADPH oxidase and cytochrome b-245.

NADPH-dependent O2- forming activity was extracted with deoxycholate from subcellular particles of guinea-pig neutrophils following stimulation with phorbol myristate acetate. The solubilized enzyme was purified by chromatography on Ultrogel AcA22, by isopycnic glycerol density gradient centrifugation and by treatment with 0.4 M NaCl. This procedure yielded a high-molecular-weight complex containing phospholipids, cytochrome b-245 and NADPH oxidase activity. Cytochrome b was found to be purified to the same extent as NADPH oxidase activity. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of the various purification fractions showed a progressive enrichment of a band whose molecular weight is 3.2 X 10(4). The enrichment of this protein band paralleled those of NADPH oxidase activity and of cytochrome b, indicating that it is a component of the oxidase system. The possibility that this band corresponds to either cytochrome b or a flavoprotein/cytochrome b complex is considered.

Animals↗

NADPH oxidase of neutrophils forms superoxide anion but does not reduce cytochrome c and dichlorophenolindophenol.

Superoxide (O-2) production by partially purified NADPH oxidase from guinea pig neutrophils was markedly increased when the cells were activated by exposure to phorbol-myristate acetate. On the contrary, NADPH-dependent cytochrome c and 2,6-dichlorophenolindophenol (DCIP) reductase activities in preparations from resting and activated neutrophils were similar. The apparent Km values for NADH and NADPH of the reductase activities were different from those of the O-2 producing enzyme. The electron acceptors did not inhibit the oxygen consumption by NADPH oxidase in the presence of superoxide dismutase. Even in anaerobiosis the oxidase failed to reduce cytochrome c and DCIP. These results suggest that NAD(P)H-dependent dye reductase activities are not involved in the electron transport system responsible for the O-2 production by neutrophils.

2,6-Dichloroindophenol↗

[Chronic atrophic polychondritis. Critical analysis of the therapeutic efficacy of dapsone. 2 cases].

Dapsone has been used since 1976 in the treatment of relapsing polychondritis. A critical analysis of its therapeutic effectiveness based on 2 personal cases and 14 cases reported in the literature, all treated with dapsone alone, showed that treatment had to be discontinued in 4 on account of side effects (haemolytic anaemia, erythema multiforme, somnolence, headache, nausea); 1 patient showed no improvement and 5 relapsed; 6 responded favourably and without relapse during a 3 months' to 4 years' follow-up. Considering the unpredictable course of relapsing polychondritis and the fact that some of its clinical manifestations, notably auricular chondritis, may spontaneously resolve, the response of the disease to dapsone is difficult to establish and requires to be confirmed by a controlled clinical trial.

Aged↗

Possible adverse effects on the cardiovascular system of an antiarrhythmic drug mexiletine.

Mexiletine (MXT) is a drug endowed with a marked antiarrhythmic activity which may be included in 1B class of drugs employed in the therapy of arrhythmias. In experimental cardiovascular research, MXT at very high doses induces a decrease in the arterial blood pressure and cardiac performance of dogs. MXT reduces the carotid baroreceptor responses, the fall in blood pressure following pharadic stimulation of the peripheral trunk of the vagus nerve and it also inhibits catecholamine uptake. All these effects may be related to the local anaesthetic activity which MXT possesses and which need careful consideration in the clinical use of the drug.

Animals↗

Chronic granulomatous disease in two sisters.

Two sisters with chronic granulomatous disease (CGD) have been studied. The diagnosis was suggested by the histopathological findings from the spleen and lymph nodes of the proband and confirmed by the low values obtained in the following tests performed on polymorphonuclear leukocytes (PMN): chemiluminescence, nitroblue tetrazolium (NBT) reduction, killing of Staphylococcus aureus, and O2- production. NADPH oxidase activity was not detected in the homogenates of the patients' PMN but cytochrome b was normally present. In addition, PMN depolarization induced by phorbol-myristate acetate was absent, thus suggesting a defect of the activation mechanism of the respiratory enzyme. The normal depolarization induced by ouabain indicated that the membrane polarity regulated by the Na/K pump in the patients' cells was not affected. The low, but not completely absent, respiratory activity of the patients' PMN could suggest an X-linked mode of inheritance with incomplete Lyonization. From a clinical point of view, one sister had mild symptoms whereas the other was almost symptomless, thus confirming once more the heterogeneity of CGD syndrome.

Adolescent↗

[Infectious endocarditis in the elderly].

Thirty three cases of infectious endocarditis in patients over 65 years of age (mean age: 72,5 years) observed between 1966 and 1982, were analysed; there were 22 male and 11 female patients, a male predominance of 67%. The data was compared with 68 cases of patients aged less than 65 years of age (mean age: 48,4 years; 49 male and 19 female patients, a male predominance of 72%) treated during the same period. In the patients over 65 years old, compared to those under the age of 65, we observed that: the previous condition of the cardiac valves was more commonly unknown (39% compared to 21%), rheumatic valvular disease was rare (12% of cases), the diagnosis was not delayed, the reason for hospital admission was usually a complication (30% compared to 7%), the two cardinal signs (pyrexia and a cardiac murmur) were always present, as in the younger age group, the urinary tract was the only commoner site of primary infection, the blood cultures were as frequently positive in both groups (79% compared to 85%), in cases with negative blood cultures, antibiotics had not always been given beforehand, but this was commoner than in the younger age group, the causal organisms and usual biological changes were unremarkable, echocardiography, often more difficult because of the high incidence of valvular thickening, remained a valuable tool for diagnosis and management, cardiac failure was more common (55% compared to 37%) as were neurological complications (24% compared to 10%) and renal failure, mortality was greater (39% compared to 25%) and higher in both groups in patients with aortic valve disease and infection with staph-aureus.

Aged↗