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Biomedical subjects

F Mariano

Publications and source records attributed to F Mariano.

At least 37 records · Page 2Linked to original sources
PubMed1993

Role of platelet-activating factor in hypotension and platelet activation induced by infusion of thrombolytic agents in rabbits.

Infusion of the thrombolytic agents streptokinase (SK, 666 units/kg per minute for 60 minutes) and tissue-type plasminogen activator (t-PA, 10 micrograms/kg per minute for 15 minutes) in rabbits induced a significant hypotension and decrease in platelet count that were completely prevented by treatment with platelet-activating factor (PAF) receptor antagonists SDZ 63-675 and WEB 2170. PAF synthesis by vascular tissue was suggested by its extraction from blood-free heart and aorta of rabbits treated in vivo with SK or t-PA but not of control rabbits. In contrast, PAF was not detected in peripheral blood. Ex vivo studies on platelet aggregation response to ADP and PAF performed on platelet-rich plasma obtained before and after SK and t-PA infusion demonstrated an early hyperaggregable phase, abrogated by PAF receptor antagonists and followed by reduced sensitivity of platelets to PAF. The ED50 values for the aggregation of washed rabbit platelets induced by PAF but not thrombin were significantly increased at 60 and 120 minutes after SK and t-PA infusion, suggesting a specific desensitization of platelets to PAF. In contrast to PAF receptor antagonists, aspirin did not significantly modify the hypotension and the platelet hyperaggregability induced by SK or t-PA or the platelet hypoaggregability induced by t-PA. Thrombocytopenia induced by t-PA, but not by SK, was partially prevented by aspirin. The effect of SK, t-PA, and plasmin on the aggregation of washed platelets from untreated rabbits and from humans was also studied. Whereas SK and t-PA were inactive, plasmin induced dose-dependent platelet aggregation that was inhibited by platelet pretreatment with PAF receptor antagonists. In conclusion, the effect of PAF receptor antagonists observed in the present experimental model suggests that the hypotension and activation of platelets induced by SK and t-PA infusion are mediated by PAF.

Animals↗
PubMed1993

Role of platelet-activating factor in polymorphonuclear neutrophil recruitment in reperfused ischemic rabbit heart.

This study investigated the role of platelet-activating factor in the recruitment of polymorphonuclear neutrophils (PMN) in a rabbit model of cardiac ischemia and reperfusion. The accumulation of PMN was evaluated 2 and 24 hours after removal of 40 minutes of coronary occlusion by morphometric analysis and 111In-labeled PMN infiltration. The administration of two structurally unrelated platelet-activating factor-receptor antagonists (SDZ 63-675, 5 mg/kg body weight, and WEB 2170, 5 mg/kg body weight) before reperfusion significantly reduced the accumulation of PMN, as well as the hemodynamic alterations and the size of necrotic area. Two hours after reperfusion, the percentage of increase of 111In-labeled PMN in transmural central ischemic zone was significantly reduced in rabbits pretreated with SDZ 63-675 (51.4 +/- 7.9) or WEB 2170 (32.4 +/- 8.8) with respect to untreated rabbits (107.6 +/- 13.5). The morphometric analysis of myocardial sections confirmed the reduction of PMN infiltration at 2 hours and demonstrated that at 24 hours the phenomenon was even more significant. In addition, SDZ 63-675 and WEB 2170 prevented early transient bradycardia and hypotension and reduced the infarct size, judged by staining with tetrazolium at 2 and 24 hours after reperfusion, and by histological examination at 24 hours. These results suggest that platelet-activating factor is involved in the accumulation of PMN in the reperfused ischemic myocardium and contributes to the evolution of myocardial injury.

Animals↗
PubMed1993

Effect of cytokines on the cytoskeleton of resident glomerular cells.

Resident glomerular cells have complex cytoskeletal organizations relevant to maintaining functional and structural integrity. The ability of cells to change shape, develop coordinate directed movements, replicate and interact with contiguous cells or extracellular matrix depends on cytoskeletal functions. Several cytokines directly or indirectly change cytoskeletal organization. Cytokines may alter cytoskeletal organization in cultured glomerular epithelial and mesangial cells and vascular endothelial cells mainly by mechanisms involving production of secondary mediators, such as PAF and leukotrienes that stimulate cell contraction, or PGE2 and PGI2 that stimulate cell relaxation. Consequent assembly and disassembly of microfilaments leads to functional responses of cells that may account for the physiopathological changes induced by cytokines in vivo.

Animals↗
PubMed1992

Role of alpha 1-proteinase inhibitor in restraining peritoneal inflammation in CAPD patients.

The concentration and functional state of alpha 1-proteinase inhibitor (alpha 1-PI) may modulate the expression of peritoneal phlogosis by affecting the activity of proteases and synthesis of autacoids. alpha 1-PI is detectable in peritoneal effluents of peritonitis-free patients. alpha 1-PI purified from peritoneal fluid of these patients was biologically active both in terms of inhibition of elastase activity and of synthesis of platelet activating factor (PAF). The biological activity of alpha 1-PI could therefore explain the absence of detectable amounts of PAF in peritonitis free patients despite the presence of intraperitoneal concentrations of tumor necrosis factor-alpha (TNF alpha) that would be sufficient per se to induce the synthesis of PAF. In patients with acute infectious peritonitis, the concentration of immunoreactive alpha 1-PI was significantly increased in respect ot stable patients. However, alpha 1-PI purified from patients with acute peritonitis was functionally inactive both on proteolytic activity on elastase and on TNF alpha-induced PAF synthesis by purified human PMN. The loss of alpha 1-PI activity correlated with the number of peritoneal leukocytes and was probably dependent on oxidative inactivation. Indeed, treatment with reducing agent restored the inhibitory function of alpha 1-PI. The inactivation of alpha 1-PI in patients with peritonitis was associated with the presence of PAF in peritoneal dialysates. These results suggest that alpha 1-PI prevents the proteolytic action and cell activation leading to PAF synthesis in peritonitis free patients. However, inactivation of its function by oxidants generated during the inflammatory process may lead to proteolytic injury and unrestrained synthesis of inflammatory mediators during peritonitis.

Chromatography, High Pressure Liquid↗
PubMed1990

Role of platelet-activating factor in the reperfusion injury of rabbit ischemic heart.

This study shows that the administration of the PAF receptor antagonist SDZ 63.675 (5 mg/kg body weight) before reperfusion significantly reduced the hematologic and hemodynamic alterations, as well as the size of necrotic area in rabbits subjected to 40 minutes of coronary occlusion and reperfusion. Pretreatment with SDZ 63.675 prevented the reduction of platelet counts in the blood obtained from the right ventricle (86.6 +/- 2.8% of the control preischemia value) and the transient bradycardia (85.0 +/- 2.8%), the systemic hypotension (58.0 +/- 2.8%), and the increase in right ventricular pressure (125.0 +/- 3.6%) that were evident in the first minutes of reperfusion in untreated control rabbits. Two as well as 24 hours after reperfusion, the infarct size, judged by staining with tetrazolium, was significantly reduced in rabbits treated with SDZ 63.675 (infarct size in control animals, 66.0 +/- 2.9% and 63.46 +/- 2.09% of the risk region at 2 or 24 hours, respectively, compared with 38.9 +/- 5.2% and 37.11 +/- 2.44% of the risk region at 2 and 24 hours in rabbits treated with SDZ 63.675). This result was confirmed by histologic examination of cardiac tissue 24 hours after reperfusion. In addition, SDZ 63.675 markedly reduced the accumulation of 111In-oxine-labeled platelets that occurs 15 minutes after reperfusion in the central ischemic area of the heart and in the lungs. These results suggest that PAF plays a role in the evolution of myocardial injury observed during reperfusion.

Animals↗
PubMed1989

Platelet activating factor is produced during infectious peritonitis in CAPD patients.

Peritonitis, a frequent complication of continuous ambulatory peritoneal dialysis (CAPD), is a model of inflammation which provides the opportunity to recover the exudate fluid. To date, various endogenous mediators (histamine, bradykinin, activated complement factors, prostanoids) have been implicated in the mediation of peritoneal inflammation and increased peritoneal permeability. In the present study, a lipid compound with physicochemical and biological characteristics similar to platelet activating factor (PAF) (1-0-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) was extracted in significant amounts from the dialysate of eight out of nine peritonitis episodes in seven CAPD patients (Group A; 6771.4 +/- 3025.9 pM, mean +/- SEM at the first exchange during peritonitis). The amounts of PAF recovered in the first exchange dialysate from patients of Group A were linearly correlated with the loss of albumin (y = -3157.64 + 91.4x; r = 0.7394; N = 9; P less than 0.03) and number of leukocytes (y = 902.45 + 1.52x; r = 0.7576 N = 9; P less than 0.02). PAF was not detectable in the dialysate fluid from patients of Group A after recovery. Twelve patients on CAPD who had no past or present history of peritonitis (Group B) were used as controls; no PAF (9 patients) or only minimal amounts (3 patients: 7.0 pM; 23.0 pM; 70.0 pM) of this mediator were detected. This is the first direct demonstration of the local generation of PAF in a septic inflammatory reaction involving the peritoneal serosa in man. PAF produced by various cell types (neutrophils, peritoneal macrophages, endothelial cells) during peritoneal inflammation may contribute to the increased permeability of the peritoneal vascular bed.

Adult↗
PubMed1989

CAPD versus hemodialysis (HD): 7 years of experience.

The purpose of this work is to compare survival and drop-out in 2 groups of patients undergoing either CAPD (42 pts) or standard HD (48 pts) as first treatment, from November 1981 to December 1988. Mean age and number of risk factors were not significantly different. At the end of the study 50.0% of pts on CAPD and 37.5% on HD were still on first treatment; clinical problems were the most frequent cause of drop-out. The total period of observation was significantly higher in the CAPD group (1391.0 months vs 850.4), but the life table analysis showed no significant differences in the incidence of death and of drop-out in the two groups. The follow-up of the CAPD group was subdivided into two periods, due to the fact that a scheme for clinical and social survey of patients undergoing dialysis and a policy of more frequent home visits were introduced at the end of 1985. A significant decrease of peritonitis episodes was observed in the second period.

Female↗
PubMed1989

Need of a partner on home peritoneal dialysis (HPD): incidence and an alternative choice.

Among 63 patients (pts) on HPD 26 (41.7%) had need of a partner (PN) in conducting dialysis. In most cases the role of a partner is performed by the consort (26.9%) or by a son or daughter (19.3%). Forty-four percent of all partners worked in the home. The PN is significantly higher (P = 0.0001) in pts aged 65 or more. The most frequent cause of PN (38.6%) was a memory and learning deficiency (MLD) of the exact sequence of dialysis maneuvers, in particular in elderly pts. The Talking Cricket (TC), a tape recorder device with a series of automated and safety features, conceived and settled in our center to guide the patient through the dialysis procedures at home, represents a valid alternative choice to the partner in pts with MLD. Seven pts with MLD, aged between 69 and 80 years, used the TC at home with a Y-set with Amuchina. During a follow-up of 84.4 months we observed 3 peritonitis episodes, 4 accidental infusions of disinfectant in to the peritoneal cavity; and 3 pts discontinued the use of the TC. The TC has been used in the hospital to train 5 pts undergoing CAPD: standardization and uniformity of teaching facilitates both learning by the patients and teaching by the nurses.

Adolescent↗
PubMed1987

The pattern of cardiovascular alterations induced by infusion of platelet-activating factor in rabbit is modified by pretreatment with H1-H2 receptor antagonists but not by cyclooxygenase inhibition.

The intravenous infusion of platelet activating factor (PAF) (0.8 micrograms/kg b.w.) induced ECG and hemodynamic alterations characterized by the following sequential three phases. Phase I (15 sec) consisted of a transient bradycardia with reduction in left ventricular pressure (LVPs), mean arterial pressure (MAP) and cardiac output (CO). Phase II developed within 30 sec and consisted of a rise in cardiac frequency, increase in LVPs, MAP and total peripheral resistances (TPR), which were associated with a decrease in CO. Finally, phase III, that occurred about 90 sec after PAF infusion, was characterized by marked ECG changes (ST segment depression and conduction arrhythmias), a decrease in LVPs and MAP, as well as a rise in TPR and in right atrial pressure (RAP). All these alterations were reversible within 30-60 min. Pretreatment with promethazine and cimetidine, as H1 and H2 histamine receptor antagonists, markedly prevented the development of phase II, namely the rise in cardiac frequency, LVPs, MAP and TPR, but did not significantly modify phase I and III. In contrast, pretreatment with indomethacin, an inhibitor of cyclooxygenase, moderatively attenuated, but did not abolish, the three phases of cardiovascular changes induced by PAF infusion.

Animals↗
PubMed1987

Protective effect of verapamil on the cardiac and circulatory alterations induced by platelet-activating factor.

The role of calcium channels in the mediation of the cardiovascular effects of synthetic (1-O-octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) platelet-activating factor (PAF) was studied in vivo in the rabbit and in vitro in the coronary-perfused isolated heart and papillary muscle of the guinea pig following pretreatment with verapamil, a calcium antagonist. In the rabbit, verapamil (0.3 mg/kg) abrogated the ECG changes, and reduced all the hemodynamic alterations caused by PAF (0.8 microgram/kg). Verapamil (20 nmol) reduced both the electrical and mechanical alterations observed in the isolated heart and papillary muscle after the infusion of PAF (0.2 nmol). These results suggest that the transmembranal calcium channels play a crucial role in the mechanism by which PAF acts on the cardiovascular tissues.

Animals↗
PubMed1986

Effect of platelet-activating factor (PAF) on human cardiac muscle.

The effect of platelet activating factor (PAF) on three mechanical [maximal mechanical tension (Pmax); time to peak tension; maximal rate of rise of tension (+dP/dt)] and four electrical [action potential duration (APD); resting membrane potential; overshoot; maximum rate of depolarization] parameters of cardiac function was studied on fragments of isolated human cardiac papillary muscle. 20 specimens of small tissue fragments excised from the left ventricle by open heart surgery were challenged with various doses of synthetic PAF (10(-10)-10(-6) M). PAF, but not its biologically inactive 2-lyso-derivative (lyso-PAF), induced a biphasic dose-dependent effect, characterized by a transient positive effect on inotropism (increased Pmax, +dP/dt) and of APD, followed by a marked, prolonged negative effect on both inotropism (decreased Pmax, time to peak tension, +dP/dt) and APD. No changes in resting membrane potential, overshoot and maximum rate of depolarization were detected after PAF challenge. Propranolol (2 X 10(-7) M) completely prevented the positive inotropic effect suggesting a stimulation of beta-receptors, possibly exerted by endogenous catecholamines. Indomethacin (1 X 10(-4) M) did not modify the initial positive effect, but markedly reduced the subsequent negative effect induced by PAF on inotropism. These findings are consistent with the interpretation that the effect of PAF on the inotropism is related to liberation of cyclooxygenase-derived metabolites.

Action Potentials↗
PubMed1986

Cardiovascular alterations in the rabbit infused with platelet activating factor (PAF): effect of kadsurenone, a PAF-receptor antagonist.

The ECG and haemodynamic alterations caused by the i.v. infusion of platelet-activating factor (PAF) in the rabbit were studied after pretreatment with Kadsurenone, a specific PAF-receptor antagonist. Infusion of PAF at 0.8 microgram/kg in the rabbit caused important ECG changes, such as ST-segment depression and conduction arrhythmias, concomitantly with a marked reduction in left ventricular systolic pressure, mean arterial pressure and cardiac output, with a rise in total peripheral resistances and mean right atrial pressure. These physiological parameters became maximal at 75-120 seconds after PAF challenge, and returned to near prechallenge values within 25-60 minutes. Pretreatment with Kadsurenone, administered either intravenously (0.014 M, 1 ml/kg) or intraperitoneally (0.14 M, 1 ml/kg), exerted a quite complete protective effect in regard to the ECG changes and caused a significant reduction in the magnitude of all the haemodynamic alterations observed after intravenous infusion of PAF (0.8 microgram/kg). These results suggest that Kadsurenone is an effective inhibitor of PAF-induced cardiovascular changes in the rabbit, probably due to its competitive antagonism against PAF binding to specific receptors.

Animals↗
PubMed1985

The role of platelet-activating factor in experimental immune complex pathology.

Tissue localization of immune complexes (IC) after infusion of synthetic platelet-activating factor (PAF) in rabbits was studied. Bovine serum albumin (BSA) was injected intravenously either before or after the infusion of synthetic PAF, later followed by the administration of anti-BSA antibodies over a 30-min period. Control rabbits received both BSA and anti-BSA antibodies, followed by lyso-PAF or saline-BSA instead of PAF. The infusion of PAF induced structural alterations in the heart, lung and kidney which were consistent with an increased vascular permeability. Deposits of BSA, IgG, and C3 were found in the heart, lung, and kidney of rabbits infused with PAF but not in control rabbits. In the liver of PAF-infused rabbits, immune deposits were only infrequently observed, whereas they were constantly present in the cardiac valves, thoracic aorta and at the bifurcation of the renal artery as they were in the control rabbits. These results suggest that PAF favors the localization of IC in the heart, lung and kidney vessels but does not influence the formation of immune deposits at the sites of turbulence of the blood flow.

Animals↗
PubMedDate not supplied

Alterations of the cytokine network in hemodialysis.

This study focuses on the mechanisms responsible for monocyte activation and enhanced cytokine production in hemodialysis. Particular emphasis is given to recent recognition of a link between cytokine production and chronic inflammation following long-term complications in today's hemodialysis population, namely cardiovascular disease and malnutrition.

Chronic Disease↗
PubMedDate not supplied

[Dialytic therapy in severely burnt patients with acute renal failure].

BACKGROUND: Appearance of acute renal failure (ARF) in severely burnt patients (GU) is a serious complication. It has a negative prognostic value and almost always develops in the context of multiple organ dysfunction syndrome (MODS) induced by sepsis. Over the last 20 years, according to data available, the mortality rate has been reported to reach about 75%. We have analyzed the initial results obtained in GU patients who were admitted to the Intensive Care Unit of the Burns Center in Turin. METHODS: Out of 105 GU patients admitted between July 1999 and September 2000 (burned surface area (BSA) 23.8%, range 2-95%, mortality rate 13.7%), 7 patients (6.4%) had complications of ARF requiring extracorporeal dialytic therapy (38 HF sessions lasting 4-6 hours, 2 HF + 12 HDF + 1 UF sessions lasting 8-11 hours). RESULTS: Total BSA of 7 GU patients with ARF was 62.5+/-11.3% (mean +/-SEM). Mortality rate was 71.4% which was due to septic shock and MODS. ARF onset was at 28.4+/-8.4 days from admission. Dialytic treatment started at Crs 2.3+/-0.42 mg/dl, and patients were treated for 7.6+/-3.5 days with a weight loss of 1859+/-161 gr/die. Circuit anticoagulation was obtained by minimal amount of heparin (132.2+/-26.5 U/hour) and no hemorrhagic complications were observed. CONCLUSIONS: In GU patients with ARF the dialytic treatment with daily long-lasting convective- diffusive techniques permitted us to achieve a survival and dialytic adequacy similar to those reported with continuous renal replacement therapies; however, mortality rate is high and related to septic shock and MODS.

Acute Kidney Injury↗