[Translated article] Experience in major complications with total trapezometacarpal prostheses.

INTRODUCTION: The treatment of rhizarthrosis using trapeziometacarpal prostheses (TMP) is increasing. Complications may lead to loss of the implant and result in salvage surgery. Our aim was to assess major complications with the use of some TMP models and their rescue. MATERIAL AND METHOD: Retrospective study on TMP implanted between 2006 and 2021. Models studied: Arpe®, Elektra®, Ivory®, Maïa®, Isis® and Touch®. Demographic data were assessed, implant placement by radiographic study, technical data, complications, salvage surgeries and final survival. RESULTS: Review of 224 TMP, 45 Arpe® (95.5% survival, rate follow-up [R] 6-16 years), 5 Elektra® (80% survival, R 13-14), 14 Ivory® (92.8% survival, R 9-11), 7 Maïa® (100% survival, R 8-9), 115 Isis® (99.1% survival, R 1-8), 38 Touch® (100% survival, R 1-4). The medial angle of the dome with the proximal articular surface of the trapezium in the lateral plane, was: Arpe®: 8.85°, Elektra®: not assessable, Ivory®: 6.6°, Maïa®: 14.4°, Isis®: 3.8°, and Touch®: 5.95°. The Isis® was placed 100% with scopic guidance presenting a significantly lower angle respect to the medial angle of the dome with the proximal articular surface of the trapezium. As main complications, we observed 3.5% of dislocations and 4% of mobilisations, with the Elektra® being responsible for 47% of these. Nineteen salvage surgeries were performed, with 3% of the implants being lost. CONCLUSIONS: Dislocation and mobilisation are the most observed complications, the Elektra® responsible for almost half of them. Correct placement and implant design appear to be crucial to avoid them in the short and long term.

Experience in major complications with total trapezometacarpal prostheses. / Experiencia en complicaciones mayores con las prótesis totales trapeciometacarpianas.

INTRODUCTION: The treatment of rhizarthrosis using trapeziometacarpal prostheses (TMP) is increasing. Complications may lead to loss of the implant and result in salvage surgery. Our aim was to assess major complications with the use of some TMP models and their rescue. MATERIAL AND METHOD: Retrospective study on TMP implanted between 2006 and 2021. Models studied: Arpe®, Elektra®, Ivory®, Maïa®, Isis® and Touch®. Demographic data were assessed, implant placement by radiographic study, technical data, complications, salvage surgeries and final survival. RESULTS: Review of 224 TMP, 45 Arpe® (95.5% survival, rate follow-up [R] 6-16 years), 5 Elektra® (80% survival, R 13-14), 14 Ivory® (92.8% survival, R 9-11), 7 Maïa® (100% survival, R 8-9), 115 Isis® (99.1% survival, R 1-8), 38 Touch® (100% survival, R 1-4). The medial angle of the dome with the proximal articular surface of the trapezium in the lateral plane, was: Arpe®: 8.85°, Elektra®: not assessable, Ivory®: 6.6°, Maïa®: 14.4°, Isis®: 3.8°, and Touch®: 5.95°. The Isis® was placed 100% with scopic guidance presenting a significantly lower angle respect to the medial angle of the dome with the proximal articular surface of the trapezium. As main complications, we observed 3.5% of dislocations and 4% of mobilisations, with the Elektra® being responsible for 47% of these. Nineteen salvage surgeries were performed, with 3% of the implants being lost. CONCLUSIONS: Dislocation and mobilisation are the most observed complications, the Elektra® responsible for almost half of them. Correct placement and implant design appear to be crucial to avoid them in the short and long term.

Reproductive aspects of the yellowtail snapper Ocyurus chrysurus from the southern Gulf of Mexico.

In this study, sex ratio, spawning season, fork length (L(F)) at maturity (L(F50)), batch fecundity and spawning frequency were characterized for the continental population of Ocyurus chrysurus from the Campeche Bank, in the southern Gulf of Mexico. A total of 1657 specimens were collected from February 2008 to January 2009. The overall sex ratio (male:female) and sex ratios by size-class showed no significant differences from an expected 1:1 ratio. The Campeche Bank population did not conform to the reproductive seasonality pattern characteristic of a continental population. A protracted spawning season that extended from January to September with peaks occurring mainly between April and May and additionally in September was observed. The population conformed, however, to the sexual maturity pattern observed for populations and species associated with a continental margin. Fish of both sexes reached the onset of sexual maturity at a similar and small L(F) of c. 14 cm, and L(F50) (L(F) at which 50% of females and males become mature) was 21·3 and 19·4 cm. Asynchronous-type ovarian development was observed for this species and batch fecundity estimates ranged from 14,102 to 164,756 oocytes (mean ±S.D. = 43,852 ± 32,684 oocytes). The overall spawning frequency estimate was once every 8·3 days or 26 times during the 9 month spawning season.

Total thumb carpometacarpal arthroplasty for failed trapeziometacarpal joint arthrodesis.

Trapeziometacarpal joint arthrodesis is a surgical option for osteoarthritis of the first carpometacarpal joint; however, it has well-known disadvantages such as non-union and reduced mobility. Revision procedures are often not discussed and lack consensus. We are reporting two cases of satisfactory thumb implant arthroplasty for failed trapeziometacarpal joint arthrodesis in order to discuss the surgical technique, its advantages compared with other surgical options and therefore its potential indications.

Initial survival of the Isis® total trapeziometacarpal prosthesis with conical trunk threaded cups. / Supervivencia inicial de la prótesis total trapeciometacarpiana de cúpula roscada Isis®.

INTRODUCTION: The treatment of trapeziometacarpal osteoarthritis through the implantation of total trapeziometacarpal prostheses is in continuous expansion. The Isis® prosthesis is a trunk-conical threaded anchorage prosthesis. Our objective was to assess the functional results and survival of this implant for at least one year of follow-up. MATERIAL AND METHOD: Prospective study on 53 Isis® prosthesis, implanted from april 2014 to january 2019. The Van Cappelle functional test, pain, strength, mobility, return to previous activity, radiological variables and placement of the trapezial component were evaluated. The surgical technique was performed with a guide wirefocused on the trapezius and control of the scopia. Observed complications were recorded and statistical analysis was performed. RESULTS: Fifty-one implants (49 patients) were reviewed. Mean follow-up was 2.1 years (1-5.7). Van Cappelle's test, pain, mobility, and grip and clamp strength improved significantly, as did the distance between the metacarpal head and the trapezius base; 96% of the patients returned in less than 6 months to their activities. Minor complications, 3 De Quervain's tendinopathy and 2 intra-operative metacarpal and 2 trapezium fractures were recorded, and one carpal tunnel syndrome. There was no dislocation, mobilization, or implant infection. CONCLUSIONS: The functional results of the Isis® prosthesis are excellent in the short term, far exceeding the first year of 100% of survival. The complications that arose were minor and few. The anchorage and placement of the trapezial component guided by scopia seem to be crucial for the good result.

Occupancy of platelet receptors for platelet-activating factor in patients with septicemia.

The possible involvement of platelet-activating factor (PAF) in the pathogenesis of endotoxemia, was investigated by using a binding assay to patients' platelets, complemented with the extraction and chemical characterization of PAF obtained from patients' platelets. Platelets from 12 human volunteers had 281 +/- 63 freely accessible high affinity binding sites (PAF-receptors) per platelet; whereas this number was of 49 +/- 37 PAF-receptors per platelet, n = 14 samples, P less than 0.01, in a group of 13 patients with positive blood culture. A group of patients with respiratory or cardiovascular disturbances and negative blood culture had 253 +/- 74, accessible receptors per platelet (n = 19 samples from 16 patients, P less than 0.01 as compared to septic patients, which was not significantly different when compared to control individuals). Patients with sepsis possessed significant amounts of PAF associated to their platelets, whereas this mediator could not be isolated from platelets of patients with respiratory or cardiovascular disturbances and negative blood culture, nor from platelets of control individuals. PAF was also assayed in whole blood samples and found at high concentrations in sepsis patients. These data indicate that occupancy of PAF receptors in combination with high amounts of platelet-associated PAF, is a common finding in patients with sepsis.

Cytosolic phospholipase A2 and the distinct transcriptional programs of astrocytoma cells.

Astrocytes constitute the most abundant cell type in the nervous system. Under physiological conditions, they respond to the stimuli to which neurons are also responsive. The use of astrocytoma cell lines with well-defined morphological and functional markers has been helpful for addressing the mechanisms of signal transduction that operate in the nervous system. On the basis of the effects produced by agonists of different types of receptor (muscarinic ACh receptors, thrombin receptors, phospholipases A2 receptors and tumor necrosis factor alpha receptors), several different transcriptional programs that involve the MAP kinase-cytosolic phospholipase A2 system and the transcription factor NF-kappaB have been described.

Modulation of lyso-platelet-activating factor: acetyl-CoA acetyltransferase from rat splenic microsomes. The role of calcium ions.

The enzyme lyso-platelet-activating factor: acetyl-CoA acetyltransferase (EC 2.3.1.67) was assayed in microsomal fractions from rat spleens. The addition of micromolar Ca2+ rapidly enhanced acetyltransferase activity and this activation was reversed by the addition of EGTA in excess of Ca2+. The effect of Ca2+ was on the apparent Km of the enzyme for the substrate acetyl-CoA without showing any significant effect on the Vmax of the acetylation reaction. When microsomes were isolated in the presence of 5 mM EGTA, to remove endogenous calmodulin, the same enhancing effect of Ca2+ on the acetylation reaction was observed. The addition of exogenous calmodulin to this preparation had no effect on the enzyme activity. Preincubation of spleen microsomes with the calmodulin inhibitor trifluoperazine decreased acetyltransferase in both the presence and the absence of Ca2+, indicating an effect of this drug independently of calmodulin. The addition of Mg-ATP to the assay mixture also had no effect on the acetylation reaction. These data suggest that Ca2+ modulates acetyltransferase activity from rat spleen microsomes by a mechanism that seems to be independent of calmodulin or protein phosphorylation.

Modulation of lyso-platelet activating factor: acetyl-CoA acetyltransferase from rat splenic microsomes. The role of cyclic AMP-dependent protein kinase.

Incubation of rat splenic microsomes with the catalytic subunit of cyclic AMP-dependent protein kinase in the presence of Mg-ATP stimulated 2-3-fold lyso-platelet-activating factor: acetyltransferase activity. This activation was due to an increase in the Vmax of the acetylation reaction, whereas the Km for acetyl-CoA was not affected. The ATP derivative, AMPPNP, could not replace ATP and preincubation of the microsomes with the heat-stable inhibitor of protein kinase prevented the activation by Mg-ATP obtained in the presence of the protein kinase. Activation of the acetylation reaction by the protein kinase was reversible. Evidence is provided that the reversal of activation is due to dephosphorylation of the enzyme. These data provide evidence that in vitro lyso-platelet-activating factor: acetyltransferase from splenic microsomes is regulated by phosphorylation.

Distal radius fractures: Should we use supplemental bone grafts or substitutites in cases of severe osteoporotic or conminution?

OBJECTIVES: The purpose of this study was to assess the need of bone graft or bone substitutes in unstable distal radius fractures (DRF) treated with locking compression plates (LCP) PATIENTS AND METHODS: An observational and prospective study was conducted on 60 patients with DRF AO-type A3 and AO-type C3, treated surgically by LCP plates without bone grafts or substitutes. Ranges of motion in flexion (F), extension (E), pronation (P), and supination (S) were measured in the injured wrist and compared with the healthy contralateral wrist. X-ray parameters: palmar tilt (PT), radial inclination (RI), ulnar variance (UV), and radial height (RH) were calculated in the injured wrist one year after surgery and then compared, with those parameters in the healthy contralateral wrist and in the follow-up postoperative x-ray of the injured wrist. PRWE and DASH scores were used to evaluate patient satisfaction. RESULTS: The range of motion loss was F 12° ± 16.1°, E 9° ± 13.1°, P 2.5° ± 7.5°, and S 5°±10°, but they remained within functional parameters. Good results were also obtained in the PRWE and DASH scores (DASH 12.6 ± 14.16 and PRWE 9.5 ± 9.5). All the fractures were healed without significant collapse (IP 0.55 ± 1.7°, IR 0.31 ± 1.5°, VC 0.25±0.8mm, and AR 0.1 ± 0.9 mm). CONCLUSIONS: All fractures healed without problems or with significant loss of reduction. Bone graft and bone substitutes are not mandatory for treatment of unstable DRF with LCP plates. Their use increases the cost and is not exempt of morbidities. This study also reinforces the role of LCP plates in surgical treatment of unstable DRF.

Comparative study of the effect of PTH (1-84) and strontium ranelate in an experimental model of atrophic nonunion.

UNLABELLED: This study aimed to set up an experimental model of long bone atrophic nonunion and to explore the potential role of PTH-1-84 (PTH 1-84) and strontium ranelate (SrR). A model of atrophic nonunion was created in Sprague-Dawley rats at the femoral midshaft level. The animals were randomised into four groups. Group A1: control rodents, fracture without bone gap; Group A2: rodents with subtraction osteotomy (non-union model control) treated with saline; Group B: rodents with subtraction osteotomy treated with human-PTH (PTH 1-84); and Group C: rodents with subtraction osteotomy treated with strontium ranelate (SrR). The groups were followed for 12 weeks. X-rays were be obtained at weeks 1, 6 and 12. After sacrificing the animals, we proceeded to the biomechanical study and four point bending tests to evaluate the resistance of the callus and histological study. In second phase, the expression of genes related to osteoblast function was analysed by reverse transcription-quantitative PCR in rats subjected to substraction osteotomy and treated for 2 weeks. The animals were randomised into three groups: Group A2: rodents treated with saline; Group B: rodents treated with PTH 1-84 and Group C: rodents treated with SrR. RESULTS: No significant histological differences were found between animals subjected to subtraction osteotomy and treated with either saline or PTH (p=0.628), but significant difference existed between animals receiving saline or SrR (p=0.005). There were no significant differences in X-ray score between the saline and PTH groups at either 6 or 12 weeks (p=0.33 and 0.36, respectively). On the other hand, better X-ray scores were found in the SrR group (p=0.047 and 0.006 in comparison with saline, at 6 and 12 weeks, respectively). In line with this, biomechanical tests revealed improved results in the SrR group. Gene expression analysis revealed a slightly decreased levels of DKK1, a Wnt pathway inhibitor, in rats treated with SrR. CONCLUSIONS: SrR increases has a beneficial effect in this atrophic non-union model in rats. This suggests that it might have a role may have important implications for the potential clinical role in the treatment of fracture nonunion.

Evidence of sensitized basophils in renal transplanted patients.

The participation of basophil polymorphonuclear leukocytes in the response to kidney allografts in man has hardly been studied. In 23 patients, followed from the immediate post-transplant period for several years, the number of circulating basophils, expressed either as absolute number or as percentage of leukocytes, was significantly low in relation to that of controls. IgE on the basophil surface was determined by radioimmunoassay in 14 patients. All patients but one had elevated numbers of IgE molecules per basophil, values being higher in patients with cadaver grafts and in patients with a graft functioning at 6 months or less. When the count of circulating basophils was roughly normal, six of the eight patients showed a positive basophil degranulation test against the donor lymphocytes. These results suggest the existence of specific IgE antibodies for HLA antigens in renal transplanted patients.

Platelet-activating factor antagonists do not protect against the development of experimental autoimmune encephalomyelitis.

There is evidence suggesting the involvement of the platelet-activating factor (PAF) in central nervous system (CNS) functions. The possibility exists that PAF may be relevant in eliciting cell-mediated autoimmune phenomena in CNS. To assess the role of PAF in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), male Lewis rats were primed with whole spinal cord from guinea pig, emulsified in Freund's adjuvant supplemented with 10 mg/ml of Mycobacterium tuberculosis, H37Ra strain. Treatment with two different PAF antagonists (PCA 4248, WEB 2170) was applied starting from day 1 or day 5 postinoculation on a twice-daily basis. Neither PCA 4248 nor WEB 2170 suppressed the clinical signs of EAE. PAF concentration was measured in CNS tissue from the 9th day after inoculation to the 15th day, and no differences were found between control and EAE animals. These results suggest that PAF is not involved in the mediation of EAE.

4-trifluoromethyl derivatives of salicylate, triflusal and its main metabolite 2-hydroxy-4-trifluoromethylbenzoic acid, are potent inhibitors of nuclear factor kappaB activation.

1. The effect of two derivatives of salicylate, 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) and 2-acetoxy-4-trifluoromethylbenzoic acid (triflusal), on the activation of NF-kappaB elicited by tumour necrosis factor-alpha (TNF-alpha) on human umbilical vein endothelial cells (HUVEC) was tested. 2. The expression of the mRNA of vascular cell adhesion molecule-1 (VCAM-1) was studied as an example of a gene the expression of which is regulated by NF-kappaB. To extend these findings to other systems, the induction of nitric oxide synthase in rat adherent peritoneal macrophages was studied. 3. Both HTB and triflusal were more potent than aspirin or salicylate as inhibitors of the nuclear translocation of NF-kappaB. The calculation of the IC50 values showed approximately 2 mM for HTB, 4 mM for aspirin and >4 mM for salicylate. 4. Comparison of the potency of these compounds on VCAM-1 mRNA expression showed complete inhibition by both triflusal and HTB at a concentration of 4 mM whereas aspirin and salicylate produced only 36-43% inhibition at the same concentration. 5. Inhibition of NF-kappaB activation was also observed in rat peritoneal macrophages stimulated via their receptors for the Fc portion of the antibody molecule with IgG/ovalbumin immune complexes. This was accompanied by a dose-dependent inhibition of nitrite production by the L-arginine pathway via iNOS. IC50 values for this effect were 1.13+/-0.12 mM (triflusal), 1.84+/-0.34 (HTB), 6.08+/-1.53 mM (aspirin) and 9.16+/-1.9 mM (salicylate). 6. These data indicate that the incorporation of a 4-trifluoromethyl group to the salicylate molecule strongly enhances its inhibitory effect on NF-kappaB activation, VCAM-1 mRNA expression and iNOS induction, irrespective of the presence of the acetyl moiety involved in the inhibition of cyclo-oxygenase.

Study of the effector mechanism involved in the production of haemorrhagic necrosis of the small intestine in rat passive anaphylaxis.

1. The effector mechanism of intestinal necrosis in rat anaphylaxis was studied following several complementary approaches: (i) the use of monoclonal antibodies (mAb) belonging to different classes (IgG1, IgG2b and IgE anti-DNP), (ii) the assay of mediators, and (iii) the use of pharmacological tools. 2. Lethality and haemorrhagic necrosis of the small intestine were observed in IgE-sensitized rats, whereas IgG mAb produced milder physiological disturbances. 3. Inhibition of leukotriene biosynthesis reduced the drop of systemic blood pressure (BP) and the extent of protein-rich plasma exudation but it did not influence the haemorrhagic component of intestinal necrosis. 4. The antihistamine, pyrilamine, partially diminished the haemorrhagic component of the intestinal necrosis. 5. The involvement of mediators related to platelet-activating factor (PAF) was studied by examining the pharmacological effects of these autacoids and of PAF-receptor antagonists (PCA4248, UR12460 and BB823). PAF induced intestinal lesions similar to those observed in IgE-sensitized rats and PAF-receptor antagonists markedly decreased haemorrhage in IgE-sensitized rats. 6. PAF levels were transiently increased after dinitrophenol (DNP)- bovine serum albumin (BSA) challenge in the small intestine of IgE-sensitized rats. 7. These data stress differences in the outcome of anaphylaxis related to the type of receptors for the Fc portion of immunoglobulins that are involved. IgE is the antibody class that elicits the most severe response due to the activation of mast cells via Fc epsilon RI (surface receptors that bind IgE antibodies with high affinity), and the only one able to produce intestinal haemorrhagic necrosis. 8. The mast-cell-derived mediators PAF/acyl-PAF and histamine, most probably associated with tumour necrosis factor alpha/cachectin (TNF-alpha), seem to play a central role in the production of the vascular changes required for the extravasation of erythrocytes in the small intestine mucosa.

The role of platelet-activating factor and peptidoleukotrienes in the vascular changes of rat passive anaphylaxis.

1. The role of platelet-activating factor (PAF) and peptidoleukotrienes as putative mediators of some of the vascular changes triggered by antigen was investigated in rats passively sensitized with monoclonal anti-DNP (2,4-dinitrophenyl) IgE. 2. Lethal anaphylaxis with respiratory distress, systemic hypotension, detachment of the intestinal mucosa, leukopenia and extravasation of protein-rich plasma was observed after antigen challenge of rats sensitized with partially purified monoclonal IgE at concentrations of 15 mg protein kg-1. 3. Analysis of the peritoneal fluid obtained after i.v. challenge with DNP-BSA (bovine serum albumin) showed the presence of significant amounts of PAF (101 +/- 8 pg/rat), whereas this mediator was undetectable in control animals. Leukotriene D4 was the predominant peptidoleukotriene that could be recovered after antigen challenge, and showed an extremely high concentration (92 +2- 15 ng/rat) as compared to PAF levels. 4. Extravasation of protein-rich plasma was observed shortly after challenge and reached a maximum at 30 min. Treatment of animals with i.v. PCA 4248 (1-2 mg kg-1) and WEB 2086 (1 mg kg-1), two chemically unrelated compounds which are antagonists of the PAF-receptor, produced a significant reduction of the extravasation of protein-rich plasma. 5. The same degree of protection could be afforded by MK-886, an inhibitor of leukotriene biosynthesis. Combined treatment with WEB 2086 and MK-886 provided greater inhibition of protein-rich plasma extravasation than either compound alone. PCA 4248 was also found to inhibit in a dose-dependent manner the systemic hypotension observed upon DNP-BSA challenge.6. These data indicate that the lipid mediators PAF and peptidoleukotrienes are major effectors of the vascular disturbances observed in rat passive IgE-mediated anaphylaxis.

Lack of platelet-activating factor release on acute myocardial ischemia in the isolated interventricular septum of rabbit heart.

The effects of platelet-activating factor (PAF) on myocardial injury after 1 h global ischemia-30 min reperfusion were investigated in isolated arterially perfused interventricular septum of rabbit heart. PAF did not significantly affect developed tension, +/- dT/dtmax, resting tension and the times of active state in non-ischemic septa. The recovery of developed tension was significantly reduced by PAF (100 nM), after an ischemia-reperfusion challenge, from the control value of 20.9 +/- 3.5% to 10.5 +/- 1.8%, without a change in the resting tension (15.7 +/- 2.8 vs. 15.6 +/- 1.3 g). BN 52021 (20 microM), alone did not modify either parameter of ischemic damage, but antagonized the aggravating effect of PAF. Evidence of PAF activity was not found in any of the samples of the effluent perfusate obtained from ischemic control experiments. On the basis of the present results, we suggest a direct role for PAF in aggravating the myocardial damage induced by ischemia, and discard heart cells as the source of PAF in this state.

Role of platelet-activating factor in adriamycin-induced nephropathy in rats.

The effect of steroids, heparin and specific PAF-acether antagonists (BN 52021 and triazolobenzodiazepines) on proteinuria and renal histological changes induced in rats by adriamycin was studied. Adriamycin evoked a marked proteinuria that was unaffected by methylprednisolone and slightly reduced by heparin. In contrast, adriamycin-injected rats treated with PAF-acether antagonists had a low proteinuria, if any, and no ultrastructural glomerular alterations. These data suggest that PAF-acether could play a major role in the occurrence of proteinuria and that PAF-acether antagonists might provide a new therapeutic approach in certain human nephropathies.

Effects of the platelet-activating factor antagonist BN 52021 on the hemodynamics of rats with experimental cirrhosis of the liver.

Previous studies from this laboratory have shown that rats with experimental cirrhosis of the liver induced by the combined administration of oral phenobarbital and inhaled carbon tetrachloride show an hyperdynamic status with enhanced cardiac output (CO), and decreased mean arterial pressure (MAP) and peripheral vascular resistance (PVR). Cirrhotic rats also showed an increased vascular permeability. All these phenomena are similar to some of the known effects of the systemic infusion of low doses of synthetic platelet-activating factor into the systemic circulation of normal rats. The measurement of the levels of platelet-activating factor in samples of blood demonstrated significantly higher levels in cirrhotic (2.65 +/- 0.39; n = 10) than in control rats (1.50 +/- 0.57 ng/ml; n = 10; p less than 0.05). The hemodynamic changes induced by the intravenous injection of the platelet-activating factor receptor antagonist BN 52021 (5 mg/kg body weight) have been measured in 10 control and 10 cirrhotic male Wistar rats, using a radioactive microsphere technique. BN 52021 induced no significant hemodynamic changes in control animals. However, in cirrhotic animals it induced a significant decrease in CO with increase in PVR. MAP increased slightly but not significantly. From these data it can be deduced that platelet-activating factor plays a role in the hemodynamic derangement shown by cirrhotic rats and that these derangement can be reversed by BN 52021, a highly selective antagonist of the platelet-activating factor receptor.

Synthesis of platelet-activating factor from human polymorphonuclear leukocytes: regulation and pharmacological approaches.

Human polymorphonuclears release a platelet-activating factor (PAF-acether) when challenged with various stimuli. PAF-acether is a mediator that is synthesized during cell activation in a process in which a phospholipase A2 and an acetyltransferase take part. These enzymes are finely regulated and accordingly PAF-acether release may be modulated. The authors have studied some of the transductory mechanisms which are triggered during cell stimulation and the effect of their pharmacological modulation on PAF-acether release. Theophylline, methylisobutylxanthine and dipyridamole, which block phosphodiesterase of cyclic nucleotides, induce a dose-dependent inhibition of PAF-acether release without affecting phagocytic uptake. Polyamines (dansylcadaverine, rimantadine and amantadine) reduced PAF-acether release and the phagocytic process in an order of potency similar to their ability to inhibit phospholipid methylation and the cholinephosphotransferase pathway. The calmodulin antagonist trifluoperazine induced a dose-dependent inhibition of PAF-acether release and acetyltransferase at concentrations from 10(-4) to 10(-5) M. Hence it appears that modulation of PAF-acether release can be obtained by different pharmacological blockades: phosphodiesterase of cyclic nucleotides, phospholipid metabolism and calcium-calmodulin.