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M Gardinali

Publications and source records attributed to M Gardinali.

At least 19 recordsLinked to original sources
PubMed1998

Complement system is not activated in primary biliary cirrhosis.

There is controversial evidence suggesting that the classical pathway of complement system is chronically activated in primary biliary cirrhosis (PBC) and that complement activation may be important in development of bile duct injury. We have reevaluated this issue by measuring by-products of complement activation such as C4a, C3a, Bb, and terminal complement complexes (SC5b-9) in plasma of 44 PBC patients with sensitive methods not previously used to detect complement activation in this disease. Age-matched healthy women and patients with chronic hepatitis of different etiology were studied as controls. We found that PBC patients have normal C4a concentrations. This finding argues strongly against chronic classical pathway activation. Although a minor increase of C3a levels was observed in a minority of PBC patients, the C3a/C3 ratio, an index used to evaluate the extent of native protein conversion, was remarkably similar in all groups. Potentially lytic terminal complement complexes were not increased. PBC patients had normal Bb plasma levels, indicating that the alternative pathway is also not activated. C3 concentration was higher in PBC patients than in healthy subjects and in chronic hepatitis patients, particularly in the early stages of the disease. C3 and C4 concentrations became lower in PBC and chronic hepatitis with the progression of the disease. The increase of C3 concentration in PBC does not reflect liver inflammation, since serum levels of C-reactive protein are normal. We found high serum C3 levels in patients with rare chronic cholestatic syndromes without superimposed infections and observed that serum C3 levels paralleled those of bilirubin in a patient with benign recurrent intrahepatic cholestasis. In conclusion, our data indicate that complement is not activated in PBC and that the increase of serum C3 levels is related to cholestasis.

Adult↗
PubMed1994

Abrupt complement activation and transient neutropenia in patients with acute myocardial infarction treated with streptokinase.

BACKGROUND: Whether and to what extent complement is activated in acute myocardial infarction (AMI) and how it contributes to inflammation of the ischemic area are not yet clear. Fibrinolytic agents used for thrombolysis are known to activate complement in vitro and may contribute to its activation in vivo. The aim of this study was to measure the extent of complement activation in AMI patients, some treated and some not treated with streptokinase. In addition, because abrupt complement activation in vivo is usually associated with leukocyte margination, plugging of cells in the microcirculation, and hypotension, we correlated complement activation with leukocyte numbers and mean arterial pressure. METHODS AND RESULTS: Forty AMI patients were studied: 20 were treated with streptokinase (1.5 million IU IV over 60 minutes), and 20 were not given any fibrinolytic agent. The extent and severity of AMI were not significantly different in both groups. Blood samples were drawn on arrival at the hospital, during streptokinase infusion, and then daily for 1 week. Time-matched samples were also drawn from patients not treated with streptokinase. We measured plasma levels of anaphylatoxin C4a, C3a, and C5a by radioimmunoassay and membrane attack complexes SC5b-9 by enzyme immunoassay. Leukocytes and arterial pressure also were measured when samples were obtained. C4a, C3a, and SC5b-9 levels increased about 10-fold (P < .0001) during infusion of streptokinase. There were no significant increases in complement catabolic products in AMI patients not treated with streptokinase. There was a significant transient leukopenia (mean +/- SEM, -29.5 +/- 7.0%; P = .001) and decreases in systolic and diastolic pressures (systolic, -29.3 +/- 3.2%, P < .0001; diastolic, -27.5 +/- 3.4%, P < .0001) after 15 minutes of streptokinase infusion in coincidence with the peak of anaphylatoxins in plasma. CONCLUSIONS: Streptokinase treatment of AMI causes abrupt activation of the complement system, whereas no significant complement activation can be detected in plasma of AMI patients not treated with fibrinolytic agents. Complement activation causes a transient leukopenia, as reported for such other clinical conditions as dialysis and cardiopulmonary bypass, and possibly contributes to the hypotension observed during streptokinase treatment.

Aged↗
PubMed1994

Activation of complement and kinin systems after thrombolytic therapy in patients with acute myocardial infarction. A comparison between streptokinase and recombinant tissue-type plasminogen activator.

BACKGROUND: We have previously shown that treatment with streptokinase induces abrupt complement activation and transient neutropenia in patients with acute myocardial infarction (AMI). The purpose of this study was to compare the effects of two different thrombolytic agents--streptokinase (SK) and recombinant tissue-type plasminogen activator (rTPA)--on activation of the complement and kinin systems in plasma of patients with AMI. METHODS AND RESULTS: Forty-one patients with AMI who were eligible for thrombolytic therapy were studied. Twenty-three patients were treated with streptokinase (1.5 million IU IV over 60 minutes) and 18 were treated with rTPA (8 with bolus of 10 mg IV, followed by 50 mg infused over 60 minutes and then 40 mg infused over 120 minutes; 10 patients were administered rTPA and heparin according to the accelerated infusion protocol indicated by the GUSTO study). C4a and C3a were measured by radioimmunoassay, soluble terminal complement components (SC5b-9) and anti-SK IgG antibodies were measured by ELISA. Cleaved high molecular weight kininogen (HK) was quantitated in plasma by SDS-PAGE and immunoblotting analysis. C4a levels were significantly and similarly increased in both groups, whereas the levels of C3a and SC5b-9 after rTPA infusion were only slightly elevated and were significantly lower than after SK. No differences were observed between patients treated with slow or accelerated rTPA regimens. The titer of antibodies to SK was highly correlated with the levels of C3a and SC5b-9, whereas a lesser correlation was observed with C4a. Treatment with rTPA did not induce the transient neutropenia observed after SK infusion. The cleavage products of HK were significantly greater after SK than after rTPA infusion. CONCLUSIONS: Our results show that both thrombolytic agents activate the classic complement pathway and that plasmin could be the common trigger for this phenomenon. A significant activation of the complement common pathway (from C3 to terminal components) was observed only with SK infusion and is attributable to the rapid formation of immunocomplexes between SK and anti-SK antibodies present in plasma as a consequence of previous streptococcal infections. The minimal activation of C5 component of the common pathway explains the absence of leukopenia in patients treated with rTPA. Cleavage of HK, larger after SK than after rTPA infusion, represents a condition enhancing the generation of bradykinin by kallikrein. The recent experimental data that indicate a damaging effect of complement activation on the infarcted zone and the contrasting favorable effect consequent to bradykinin formation raise some questions about the clinical importance of the different biological consequences of SK versus rTPA.

Adult↗
PubMed1994

Complement activation in dialysis: effects on cytokines, lymphocyte activation and beta 2 microglobulin.

Anaphylatoxins generated by complement activation by filter membranes are present in plasma during hemodialysis (HD). In the presence of endotoxins which may contaminate the dialysate, they can trigger monocytes to produce interleukin-1 (IL-1) and tumor necrosis factor (TNF), with detrimental effects for the patients. We have investigated whether or not the use of complement activating (cuprophan) and non- (or less-) activating membranes (polysulfone, polymethylmethacrylate or polyacrylonitrile) per se influences cytokine levels in HD patients. Our results indicate that if a sterile bicarbonate solution is used as dialysate, there are no significant increases in IL-1, TNF, interleukin-2 (IL-2) and soluble IL-2 receptors (sIL-2r) throughout HD, even with cuprophan membranes. Moreover even a prolonged use of this membrane (three months) did not change pre-dialysis levels of cytokines and receptors. Use of complement activating membranes also does not influence beta 2 microglobulin levels.

Acrylic Resins↗
PubMed1992

Complement activation and polymorphonuclear neutrophil leukocyte elastase in sepsis. Correlation with severity of disease.

Complement activation is necessary for an adequate immune and inflammatory response to infections. Activation releases anaphylatoxins that cause vasodilation, increase vascular permeability, and trigger release of polymorphonuclear neutrophil leukocyte (PMN) lysosomal enzyme and oxygen radicals. Under normal circumstances, an orderly progression of such events has a beneficial antimicrobial effect. The same mechanism, however, when uncontrolled, may damage host tissues. To provide information about the clinical importance of such events in sepsis, different complement parameters (C3, C4, and the desarginated forms of C3a [C3a(des)-Arg] and C5a [C5a(des)-Arg]), PMN elastase, and malondialdehyde (a by-product of membrane peroxidation by oxygen radicals) were measured daily in 26 septic patients and correlated with two objectively assessed and previously validated severity scores (acute physiology and chronic health evaluation [APACHE II] and Sepsis Severity Score [SSS]). Nonsurvivors (n = 12) had significantly greater and longer lasting complement activation than that in survivors, as reflected by higher levels of catabolic peptides (C3a(des)-Arg) and lower levels of native proteins (C3 and C4). C3a(des)-Arg, C3, C4, and the C3a(des)-Arg-C3 ratio were correlated with Sepsis Severity Scores. Polymorphonuclear neutrophil leukocyte elastase levels were higher in nonsurvivors and were correlated with C3a(des)-Arg and the C3a(des)-Arg-C3 ratio. Malondialdehyde levels were significantly higher in all patients than in controls, without, however, any relationship to severity of disease or clinical outcome. Since the higher and more persistent the complement activation and polymorphonuclear neutrophil leukocyte stimulation, the worse the patient's prognosis, we conclude that these mechanisms may be important in the clinical development of sepsis.

Adult↗
PubMed1992

Leukotriene B4 and peptido-leukotriene levels during radiographic contrast media infusion.

The pathogenic mechanisms of radiographic contrast media (CM) reactions are still not well understood. Recently it has been proposed that leukotrienes (LT) may be involved in CM reactions. We measured plasma LTB4 and peptido-LT levels in 20 subjects undergoing urography with 2 low osmolality CM (ioxaglate and iopamidol) in order to elucidate if CM infusion determines LT release in plasma. LTB4 and peptido-LT did not change significantly during infusion of the 2 CM. Blood pressure, heart rate, and the number of circulating granulocytes were not affected by CM infusions, further evidence that LT release did not occur. We conclude therefore that LT are not released during infusion with the CM studied.

Adult↗
PubMed1991

Complement activation in diabetes mellitus.

To see whether or not there is complement activation in patients with diabetes mellitus, we investigated the plasma concentrations of C4, C3, C4a, C3a and SC5b-9 in either juvenile or adult onset insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients at least 2 years after diagnosis. C4, C3, SC5b-9 plasma levels were not significantly different in IDDM and NIDDM patients than in age-matched controls. Anaphylatoxin peptide conversion product C4a, but not C3a, was found significantly higher in adult-onset IDDM patients than in patients with juvenile onset IDDM, NIDDM patients and age-matched controls. Complement activation did not appear to be correlated with the metabolic control, nor the duration of disease nor the presence of circulating antibodies (including islet cells (ICA), insulin (IA), thyroid microsomal (TMA), and thyroglobulin (TGA)). Although there are many factors that may trigger complement activation, we found the highest levels of C4a in elderly subjects (both diabetics and control subjects) and particularly in those who had clinically detectable vascular complications.

Adolescent↗
PubMed1990

Blood--artificial surface interactions during cardiopulmonary bypass. A comparative study of four oxygenators.

Evaluation of the biocompatibility of four different types of oxygenator (bubble, membrane, hollow fibre and 'hybrid') was performed on 26 patients undergoing cardiopulmonary bypass during elective coronary surgery. More platelet derangement and an increased degree of hemolysis, revealed by higher plasmatic concentration of beta-thromboglobulin, platelet factor 4 and plasmatic free hemoglobin (p less than 0.05), was seen when using the bubble oxygenator. Damage to blood cells was minimal with the membrane oxygenator while the 'hybrid' and the hollow fibre oxygenators proved to rank at an intermediate level. Complement activation at the beginning of the cardiopulmonary bypass occurred via the alternative pathway as demonstrated by C3ades arg increase (up to nine times) without a concomitant elevation of C4ades arg. Cardiopulmonary bypass complement activation was quantitatively similar with all the oxygenators. A further activation via the classical pathway occurred in all the patients after protamine injection. Consistent differences as far as clinical and biological effects exist among the various commercially available cardiopulmonary bypass apparatus; our study provides guidelines for the evaluation and selection of devices which might reduce postoperative sequelae.

Anaphylatoxins↗
PubMed1989

Complement activation during hemodialysis.

Hemodialysis, as other extracorporeal circulation treatments, determines activation of the complement system. In this paper molecular mechanism of complement activation by different hemodialysis membranes are reviewed as well as the biological consequences and clinical relevance of the activation.

Anaphylatoxins↗