Respiratory-chain and pyruvate metabolism defects: Italian collaborative survey on 72 patients.
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Cytochrome-c Oxidase Deficiency↗
Biomedical subjects
A Adami
Publications and source records attributed to A Adami.
Effect of single and repeated doses of a new nitroderivative of acetylsalicylic acid on platelet TXA2 production in rats.
The effects of a new ASA-nitroderivative compound, NCX 4016 (ASA-NO2), on platelet TXA2 synthesis after single and repeated doses in the rat were investigated. Compared to ASA, cumulative doses of ASA-NO2 showed similar inhibitory effects on platelet TXA2 synthesis and significant increases in nitrite/nitrate plasma concentrations 1 h after the last drug administration: 24 h later nitrite/nitrate plasma levels returned to the control values, while serum TXA2 concentrations did not change. A time-course study after a single dose of ASA-NO2 showed a significant inhibition of platelet TXA2 production also 24 h after drug administration and a significant increase in nitrite/nitrate plasma levels until 10 h.
Animals↗
High purity factor IX and prothrombin complex concentrate (PCC): pharmacokinetics and evidence that factor IXa is the thrombogenic trigger in PCC.
Recent studies using assays for surrogate markers of thrombogenicity in man have demonstrated that activation of the coagulation system occurs following infusion of clinical doses of prothrombin complex concentrates (PCC) but not after the same doses of high-purity factor IX concentrates (HP-FIX) in patients with haemophilia B. Here we have investigated the mechanism of such thrombogenesis by applying assays that detect early-through to late-events in coagulation system activation in a pharmacokinetic cross-over study of 50 IU/kg PCC and a new HP-FIX product in haemophilia B patients. Satisfactory recoveries and half-lives were observed for both concentrates. HP-FIX caused no increases in thrombin-antithrombin III complex (TAT), prothrombin activation peptide fragment F1+2 (F1+2), factor X activation peptide (FXAP) or factor VIIa (FVIIa). In contrast the same dose of factor IX in the form of PCC was followed by significant increases over pre-infusion levels of TAT, F1+2 and FXAP, but not FVIIa. Elevations of FIXAP occurred after both HP-FIX and PCC but did not reach normal levels and were attributed to normalisation of the FIX concentration in those patients whose levels of FIXAP were initially low. We conclude that the thrombogenic trigger associated with PCC infusion occurs at the level of factor X activation. In the absence of any increase in FVIIa, we would attribute this to the likely presence of FIXa in the PCC.
Adult↗
Antiaggregating and vasodilatory effects of a new nitroderivative of acetylsalicylic acid.
We studied in vitro the effects on platelet aggregation and vascular tone of a new nitrocompound (nitroxy-butyl-acetylsalicylate: NO-ASA). In order to elucidate any possible activity due to the release of nitric oxide or the inhibition of platelet cyclo-oxygenase we compared NO-ASA to acetylsalicylic acid. NO-ASA 1 mM inhibited arachidonic acid-induced platelet aggregation (basal 75.4 +/- 2.35%; NO-ASA 22 +/- 3.46%; M +/- SEM; P < 0.001; n = 6), but proved less active than acetylsalicylic acid (complete inhibition at 2 x 10(-5) M). NO-ASA also significantly reduced thrombin-induced (0.04-0.08 U/ml) platelet aggregation in acetylsalicylic acid-treated platelets (basal 70.5 +/- 1.7%; NO-ASA 35.4 +/- 2.2%; P < 0.001; n = 10; IC50 7 x 10(-5) M). Methylene blue reduced the effects of NO-ASA on thrombin-induced (NO-ASA 46.7 +/- 5.25%; NO-ASA+MB 59.1 +/- 4.3%; P < 0.01; n = 8), but not arachidonic acid-induced platelet aggregation. The inhibitory effects of NO-ASA on platelet aggregation were partially removed by oxyhaemoglobin. Platelet thromboxane A2 production (TXB2 concentration in the supernatant of the aggregate 35.38 +/- 7.81 ng/ml; n = 8), was totally abolished by acetylsalicylic acid (0.17 +/- 0.04 ng/ml; P < 0.001; n = 8) and reduced by NO-ASA (8.3 +/- 4.05 ng/ml; P < 0.01; n = 8). In vitro studies on isolated rat aortic rings showed NO-ASA 10(-3) M, but not ASA up to 10(-3) M, induce a dose dependent vasorelaxation (100% of epinephrine-induced contraction) both in intact and endothelium denuded arteries (IC50 5 x 10(-5) M). Addition of methylene blue reversed this relaxation. In conclusion these data demonstrate that NO-ASA acts through a double mechanism: a) by inhibiting cyclo-oxygenase and b) by releasing NO active on guanylyn cyclase both in platelets and in vascular smooth muscle cells.
Adult↗
Plasma concentrations and pharmacokinetic parameters of nitrofenac using a simple and sensitive HPLC method.
An accurate and sensitive HPLC method has been developed for the determination of nitrofenac, a new, original diclofenac derivate showing a good tolerability and a wide anti-inflammatory profile, diclofenac, and its metabolites in plasma. This method has been applied to evaluate the pharmacokinetic parameters of the drugs, using a noncompartmental model, after the oral administration of 5 mg/kg nitrofenac to rats. Nitrofenac and the internal standard flufenamic acid were dissolved in acetonitrile, and diclofenac was dissolved in methanol. The drugs were eluted from a 5 microns LC-8 column with a mobile phase consisting of acetonitrile/water (50/50 v/v) adjusted to pH 3.3 with glacial acetic acid, at a flow rate of 2 mL/min with UV detection at 280 nm for diclofenac and 275 nm for nitrofenac. The detection limit for the drugs in plasma was 25 ng/mL. The peak concentration of nitrofenac was reached 7 h after drug administration, while with diclofenac we observed three peaks at 2, 5, and 10 h; the mean residence time and the elimination rate constant for nitrofenac were 6.18 +/- 0.09 h and 0.37 +/- 0.03 h-1 respectively, while those for diclofenac were 12.24 +/- 0.11 h and 0.11 +/- 0.04 h-1. Under our conditions, the metabolism of nitrofenac produced 23% diclofenac and other metabolites: the plasma concentrations and kinetic characteristics of diclofenac are enough to induce an anti-inflammatory activity, while the clinical importance of the other metabolites remains to be elucidated.
Animals↗
Effect of acute exercise on some haematological parameters and neutrophil functions in active and inactive subjects.
In this work we studied the possible effects of acute exercise on some haematological parameters and on some functions of neutrophils in seven active and six inactive subjects. Physical exercise (10 min on a cycle ergometer at a heart rate of 150 beats.min-1) induced a significant increase in total leucocyte, lymphocyte and neutrophil concentrations in active subjects; serum iron and ferritin concentrations were lower in active compared to inactive subjects. Cellular adhesion, bactericidal activity and superoxide anion production did not change after exercise, while we also observed some differences between active and inactive subjects before exercise. In particular, the neutrophils from active subjects showed a significantly higher percentage of adhesion, higher bactericidal activity and lower superoxide anion production. In conclusion, the training induced changes in some neutrophil functions, while acute exercise influenced, overall, leucocyte concentrations.
Adult↗
Anti-inflammatory potency and gastrointestinal toxicity of a new compound, nitronaproxen.
Naproxen and its derivative nitronaproxen at the doses of 5 and 10 mg kg-1 were compared for their acute anti-inflammatory efficacy in a carrageenan oedema model and gastrointestinal toxicity in rats. Moreover, the effects of the two drugs were evaluated in the adjuvant arthritis, after chronic doses of 4 and 8 mg kg-1 administered orally for 18 days. The oedema reduction was maintained much longer (until 5 h) with nitronaproxen; the inhibition of arthritis was 50% or more with both doses of the examined drugs. From the histological examination of the stomachs, an extensive mucosal vasocongestion and haemorrhagic lesions have been observed in some rats treated with naproxen. The percentages of animals with ulcers were 50, 100 and 10 with naproxen 6 and 18 mg kg-1 and nitronaproxen 54 mg kg-1 respectively. A better gastrointestinal tolerability has been observed in arthritic and oedemic rats treated with nitronaproxen compared to naproxen: this could be due to the presence of nitric oxide that acts in maintaining the tissue perfusion and integrity.
Animals↗
Changes in several neutrophil functions in basketball players before, during and after the sports season.
Neutrophils play an important role in the immune system, forming the "first line of defence" against invading microorganisms and there are few data available concerning neutrophil functions in relation to exercise. We investigated in 7 basketball professional players possible changes before, during and after the sports season, in some haematological parameters and in several aspects of the phagocytic process of neutrophils, such as adhesion, superoxide anion release and bactericidal activity. Training and competitions produced a significant rise in the number of total leukocytes and differential counts, but the values returned to the pre-start levels 3 weeks after the end of the championship. The bactericidal activity and the superoxide anion released were significantly greater during the sports season, while the percentage of cellular adhesion significantly decreased during the championship; after the sports season the values returned to the control levels. As in the literature data concerning neutrophil functions in relation to exercise are non-convergent, it is important in our opinion, to understand whether the alterations induced by exercise can persist after repeated stimuli.
Adult↗
An ELISA for factor X activation peptide: application to the investigation of thrombogenesis in cardiopulmonary bypass.
An ELISA for measurement of factor X activation peptide (FXAP) in plasma has been developed. The capture antibody was generated by immunization with a carrier-coupled synthetic peptide based on the amino acid sequence of the C terminal region of native human FXAP: the tag antibody was a commercial polyclonal antibody to factor X. Because of limited specificity of the capture antibody to FXAP compared with factor X, a plasma processing step precipitated plasma factor X and also permitted a concentration step, enabling detection of FXAP below the lower limit of the normal range in plasma. The overall intra- and inter-assay coefficients of variation were approximately 5% and approximately 11%, respectively. 18 normal laboratory control subjects had FXAP levels of 2.12 +/- 0.82 ng/ml (mean +/- SEM). Eight patients undergoing surgery and cardiopulmonary bypass progressively generated FXAP throughout the surgery with mean FXAP rising to 11.73 +/- 4.66 ng/ml, and this resulted in increased generation of thrombin detected by measurement of plasma levels of F1 + 2. Levels of FXAP rose significantly ahead of those of factor IX activation peptide (FIXAP), supporting a suggestion that contact system activation can not be the primary stimulus to coagulation in bypass. The ELISA to FXAP will be useful in the study of mechanisms of thrombogenesis in clinical situations where the coagulation system is activated.
Adult↗
Inhibition by sodium nitroprusside of the expression of inducible nitric oxide synthase in rat neutrophils.
A well-known nitric oxide (NO)-releasing compound, sodium nitroprusside (SNP), decreases in a dose-dependent manner NO synthase (NOS) activity induced in rat neutrophils by treatment with lipopolysaccharide (LPS). This inhibitory action of SNP seems not to be due to its direct effect on the enzyme activity. The strong nitrosonium ion (NO+) character of SNP could be responsible for its inhibition of NOS induction in neutrophils.
Amino Acid Oxidoreductases↗
Effect of a new non-steroidal anti-inflammatory drug, nitroflurbiprofen, on the expression of inducible nitric oxide synthase in rat neutrophils.
The effects of a non-steroidal anti-inflammatory drug, flurbiprofen, and its nitro-derivative, nitroflurbiprofen, on inducible nitric oxide synthase in rat neutrophils were examined. Nitroflurbiprofen was shown to inhibit nitric oxide synthase induction caused by lipopolysaccharide administration, while flurbiprofen had no effect on nitric oxide synthase induction. This inhibitory action may be ascribed to nitric oxide released from nitroflurbiprofen.
Administration, Oral↗
Protective effect of NO on gastric lesions and inhibition of expression of gastric inducible NOS by flurbiprofen and its nitro-derivative, nitroflurbiprofen.
Nitroflurbiprofen (NFP) causes significantly less gastric lesions than flurbiprofen (FP), probably because of its capacity to release nitric oxide (NO) in the stomach. Lipopolysaccharide (LPS), which induces the expression of an inducible type of NO synthase (iNOS) in rat stomach, also reduces gastric mucosal damage elicited by FP. Furthermore, both FP and NFP decrease significantly the amount of mRNA encoding iNOS induced by LPS in the stomach. The inhibitory effect of NFP seems to be due at least in part to its ability to release NO.
Animals↗
Apparent heterozygous type II protein C deficiency caused by the factor V 506 Arg to Gln mutation.
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Arginine↗
[Glomus tumor of the stomach with extraserous development].
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Adult↗
Role of factor XII in thrombin generation and fibrinolysis during cardiopulmonary bypass.
During cardiopulmonary bypass, thrombin is generated, which is thought to be initiated by activation of factor XII on the surface of the bypass equipment. We present a patient with severe factor XII deficiency who underwent cardiac surgery. As much thrombin was formed during cardiopulmonary bypass (measured by the prothrombin activation fragment F1 + 2 and thrombin-antithrombin complexes) as in normal patients, showing that factor XII was not necessary for thrombin generation. Factor X, but not factor IX, was activated (as measured by their activation peptides), and this activation correlated with F1 + 2 and thrombin-antithrombin complexes, suggesting that the tissue-factor/factor-VIIa pathway is the trigger for thrombin formation.
Antithrombin III↗
Hepatitis C virus in dialysis units: a multicenter study.
Three hundred and eighty-seven chronic hemodialysis patients were evaluated, in a multicenter study, to investigate the epidemiology of hepatitis C virus. In anti-HCV seropositive patients, serum ALT values and blood transfusions were retrospectively compared; blood donors were studied for serum transaminases. In seropositive patients without previous blood transfusions, analysis of dialysis schedule was done. Eventually, the intrafamilial transmission of hepatitis C virus was studied in 104 family members. The prevalence of HCV infection in hemodialysis patients was 15.7%. The incidence of acute hepatitis was frequent, while chronic hepatitis incidence was less than expected (17.5%). Intrafamilial diffusion was low (1.9%). Blood-transfusion-related infections seem to be negligible, while cross-contamination in dialysis units seems to be very important.
Alanine Transaminase↗
Comparison between first- and second-generation test for anti-hepatitis C virus antibodies in hemodialysis patients.
The serum of 387 hemodialysis patients from 9 dialysis units was checked for anti-hepatitis C virus antibodies with a 1st-generation ELISA (Ortho) test: 61 patients were repeatedly positive. In order to avoid false-positive results, these sera were tested with a 1st-generation confirmatory RIBA test, 2nd-generation screening ELISA test and 2nd-generation confirmatory RIBA test. The 2nd-generation ELISA test confirmed data obtained with 1st-generation ELISA, however, the 1st-generation confirmatory RIBA test underestimated the number of anti-HCV-positive patients.
Diagnostic Errors↗
[Heart valve involvement in systemic lupus erythematosus: an echocardiographic study].
The purpose of this study was to evaluate the spectrum of morphologic and functional cardiac involvement in a selected population of patients with systemic lupus erythematosus (SLE) by means of echocardiography. Thirteen patients (2 male and 11 female) affected by SLE, mean age 41.9 years (range, 21-64), underwent M-Mode, two-dimensional and Doppler echocardiography. Eleven patients had renal disease and 3 of them were undergoing dialysis. One patient had findings of active disease. Six patients had systemic hypertension. None had a history suggestive of rheumatic fever or infective endocarditis. At echocardiographic study nine patients demonstrated findings of valvular involvement. These alterations were defined, according to the echocardiographic features, in two types: vegetation (verrucous Libman-Sacks endocarditis) and thickening. Vegetations were present in 6 patients, involving the mitral valve in all six and the aortic valve in three. The mitral valve vegetations were more frequent on the subannular portion of the posterior leaflet. Seven patients had valvular thickening: involvement of both mitral and aortic valve was present in five, and isolated mitral or aortic valve lesions in the remaining two patients. Combined valvular vegetation and thickening were observed in 4 patients. Eight patients had mild valvular dysfunction on Doppler examination: five isolated mitral regurgitation, two combined mitral and aortic regurgitation and one combined mitral stenosis and regurgitation. In agreement with previous reports, our study shows that valvular involvement in SLE is relatively frequent. Echocardiography can identify additional patterns of valvular lesions different from the known "verrucous Libman-Sacks endocarditis". The degree of valvular dysfunction is not important.
Adult↗