The role of platelet-activating factor in the biocompatibility of hemodialysis membranes.
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Animals↗
Biomedical subjects
F Mariano
Publications and source records attributed to F Mariano.
[Systemic mucormycosis in dialysis: computed tomography picture and histologic lesions].
Mucormycosis (zygomycosis) is an uncommon mycosis which can be contracted from the environment and which is responsible for rhino-orbital, pulmonary, gastrointestinal, cerebral or disseminated infections. Severe immunodepression, such as that caused by leukemia, lymphomata and organ graft, or treatment by desferrioxamine, may predispose to pulmonary and systemic forms. In the present work the authors describe a case of systemic mucormycosis, with unfavourable outcome, which arose in a pediatric peritoneal dialysis patient, then transferred to hemodialysis, without evident predisposing factors. In particular they refer to the CAT reports and to lymphonodal and peritoneal histological lesions which allowed them to attain the diagnosis.
Adult↗
Lipopolysaccharide binding protein and CD14 modulate the synthesis of platelet-activating factor by human monocytes and mesangial and endothelial cells stimulated with lipopolysaccharide.
The biosynthesis of platelet-activating factor (PAF) during Gram-negative involves the interaction of LPS with the cells of the host. We have investigated the molecular mechanism that controls cell recognition and PAF biosynthetic response to LPS in human monocytes (MO), glomerular mesangial cells (MC), and HUVEC in culture. The synthesis of PAF by MO and MC involves two proteins, plasma LPS binding protein (LBP) and cell membrane CD14 (mCD14). As MO, MC were shown to express the mCD14 molecule by several mAbs. MO and mCD14-positive MC were stimulated to synthesize PAF either by the 63D3 and IOM-2 mAbs or by the natural ligand LBP-LPS complex. Moreover, LeuM3, 28C5, and 18E12 mAbs that were themselves unable to stimulate the synthesis of PAF blocked PAF synthesis initiated by LBP-LPS complex. LBP was required for synthesis of PAF by MO. In MC, which synthesize PAF also after stimulation by LPS alone, the LBP was shown to speed and significantly enhance the synthesis of PAF. The soluble form of CD14 (sCD14), when added to MO stimulated with LBP-LPS complexes, inhibited the synthesis of PAF possibly by competing with mCD14. In contrast, sCD14 was shown to be required for LPS-induced synthesis of PAF by HUVEC, which did not express mCD14. Therefore, membrane receptors (mCD14) and plasma soluble proteins (LBP and sCD14) may enable different human cell types to synthesize PAF after LPS stimulation.
Acute-Phase Proteins↗
Removal of platelet-activating factor in experimental continuous arteriovenous hemofiltration.
OBJECTIVE: There is a positive correlation between the amount of ultrafiltration and the improved survival rate of patients with ischemia or sepsis-induced acute renal failure. Continuous arteriovenous hemofiltration (CAVH) removes vasoactive substances with a molecular weight of < 1000 daltons. This study evaluated the removal of platelet-activating factor, a lipid mediator of endotoxic shock, by CAVH with respect to kinetics, adsorption, and ultrafiltration. DESIGN: Prospective laboratory study. SUBJECTS: Normal human subjects. INTERVENTIONS: Radioactive [3H] or biologically active platelet-activating factor was added to whole blood or washed blood resuspended in Tris-buffered (pH 7.2) physiologic saline with 4% human serum albumin or plasma. Whole or washed blood cells or plasma were recirculated at 100 mL/min through polysulfone hemofilters for 120 mins with ultrafiltration (condition A), without ultrafiltration (condition B), or in a static condition (condition C). Concentrations of albumin, total protein, and radioactive or biologically active platelet-activating factor in samples obtained from the blood and ultrafiltrate compartment were determined. MEASUREMENTS: Biologically active platelet-activating factor was quantified on washed rabbit platelets and results were expressed in ng/mL over a calibration curve obtained with synthetic platelet-activating factor. MAIN RESULTS: [3H]-platelet-activating factor added to recirculated whole blood was ultrafiltered (percent of ultrafiltered platelet-activating factor/min: 0.48 +/- 0.02 [SD]; total platelet-activating factor removed in 120 mins: 15.52%; condition A) at significantly (p < .001) higher amounts than when added to washed blood cells (percent of ultrafiltered platelet-activating factor removed/min: 0.195 +/- 0.06; total platelet-activating factor removed in 120 mins: 7.46%). The highest amounts of [3H]-platelet-activating factor were bound to polysulfone membranes after recirculation with whole blood (44.5 +/- 12.2%) than with washed blood (1.1 +/- 0.3%) or plasma (11.9 +/- 0.7%). Biologically active platelet-activating factor concentrations significantly decreased in both conditions A and B (maximal decrease at 120 mins: 63% and 59%, respectively). No significant reduction could be observed in condition C. CONCLUSIONS: These studies provide experimental evidence for the prompt, efficient removal of platelet-activating factor in CAVH and provide a possible rationale for the beneficial effect of this therapy in the development of multiple organ failure in sepsis.
Adsorption↗
[Changes in dialysis methods. 10 years' experience].
A retrospective survey has been done on 175 chronic patients who underwent dialysis in one center, between January 1982 and June 1992. The purpose of the work was to evaluate the use of the first treatment and the cause which determined a change of treatment. Diffusive haemodialysis and CAPD were the most frequent first choice techniques, respectively in extracorporeal and peritoneal dialysis, whereas changes were conditioned by the need for a more personalized treatment, especially in the filed of extracorporeal dialysis.
Adult↗
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↗
Immunomodulation and biomaterials.
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Adjuvants, Immunologic↗
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↗
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↗
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↗
Leukocyte-derived mediators and biocompatibility.
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Biocompatible Materials↗
Can we obtain a further reduction of peritonitis episodes in CAPD patients already using a Y-set with disinfectant?
A protocol of patient selection and more frequent home visits have significantly reduced peritonitis episodes in CAPD patients using Y-set with Amuchina. However, no change in dropout rates were observed.
Anti-Infective Agents, Local↗
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↗
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↗
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↗
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↗
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↗
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↗