[Interest of several pharmaceutical activities to secure the care pathway of elderly patients?] / Sécurisation du parcours de soins du sujet âgé : intérêt d'une offre variée d'activités pharmaceutiques ?

OBJECTIVES: In order to prevent medication errors during patient's care pathway, all transition steps must be secured. The main objective of this study was to assess the interest of medication review at hospital discharge on the sustainability of therapeutic optimizations made during hospitalisation in a geriatric population. MATERIAL AND METHODS: This was a three months prospective, single-centre study performed in an acute geriatric unit of a university hospital. All patients hospitalized during the study were included. They were divided in two groups: the securing pathway (SP) group with admission reconciliation, step 3 prescription analysis (according to the French Society of clinical pharmacy) and medication review at hospital discharge were compared to the not concerned group (NSP) with only a step 2 (according to the French Society of clinical pharmacy) prescriptions analysis. The Medication Regimen Complexity Index was used to quantify the complexity of medication regimens. RESULTS: In total, 53 patients of the SP group and 44 patients of the NSP group got the benefit of whole clinical pharmaceutical activities put in places. The average medications on discharge's drug prescription is lower in SP group (SP 8.4±3.4 medications and NSP 9.6±3.2 medications, P=0.06). The discharge's drug prescription complexity index is lower in SP group compared to NSP group (SP 27.9±9.8 and NSP 32.7±11.5, P=0.02). The same trend is observed 30 days post discharge. CONCLUSION: A medication review at hospital discharge reduces the subsequent drug prescription's complexity score. This multidisciplinary dynamic makes easier the communication between health care professionals and contributes to strengthen the city-hospital link.

Clinical presentation of endometriosis identified at interval laparoscopic tubal sterilization: Prospective series of 465 cases.

OBJECTIVES: Women seeking sterilization are usually parous and have no major complains, such as pelvic pain. This could be a good model to indirectly assess the prevalence of endometriosis in the general population. Prevalence of endometriosis in women undergoing tubal sterilization by laparoscopy has been assessed in 17 published reports. Results indicate a surprising wide variation of prevalence of endometriosis, ranging from 1.4% to 43.3%. This clinical study describes the prevalence and clinical presentations of endometriosis identified at interval laparoscopic tubal sterilization, as a close representation of endometriosis in general population. MATERIAL AND METHODS: From July 1989 to February 2009, 465 women undergone interval laparoscopic tubal sterilization and were included in this series. Surgery was realised in a non universitary centre of gynecologic surgery. All patients were operated on by the same surgeon. A complete assessement of pelvic organs was achieved with a particular attention paid for endometriotic lesions. Endometriosis when present was staged according to r-AFS classification. Biopsies were sent for pathological examination to assess endometriosis. RESULTS: Mean age of women was 40.7 years (range 15-49 years). 20 women were nulliparous and 12 others had a past history of endometriosis. Endometriosis was visually identified in 55 patients (11.82%), and confirmed by histologic examination in most of cases (50/55: 90.9%). The mean age of women presenting endometriosis at the onset of tubal ligation was 41.27 years. Cases with endometriosis were classified according to the r-AFS. 39,7,8 and 1 cases corresponded to stages I, II, III and IV respectively. In the 20 nulliparous women, the prevalence of endometriosis was 20% (4/20). At the time of laparoscopic sterilization, 91 women presented a painfull condition (dysmenorrhea mainly or dyspareunia). Endometriosis was identified in 16 of them (17.58%). In the group of 360 asymptomatic parous women, the prevalence of endometriosis was 10% (36/360). Nulliparity, associated pelvic pain and retroverted uterus were associated with increased prevalence of endometriosis, without being significant. CONCLUSION: In our study, the prevalence of endometriosis identified at interval laparoscopic tubal sterilization was 11.82%. In parous asymptomatic women, the prevalence of endometriosis was 10%. The prevalence of endometriosis was slightly increased in nulliparous women, when pain was associated and in women with a retroverted uterus.

Metamorphosis in drosophila and other insects: the fate of neurons throughout the stages.

The nervous system of insects is profoundly reorganised during metamorphosis, affecting the fate of different types of neuron in different ways. Almost all adult motor neurons derive from larval motor neurons that are respecified for adult functions. A subset of larval motor neurons, those which mediate larval- or ecdysis-specific behaviours, die before and immediately after eclosion, respectively. Many adult interneurons develop from larval interneurons, whereas those related to complex adult sense organs originate during larval life from persisting embryonic neuroblasts. Sensory neurons of larvae and adults derive from essentially two distinct sources. Larval sensory neurons are formed in the embryonic integument and - with few exceptions - die during metamorphosis. Their adult counterparts, on the other hand, arise from imaginal discs. Special emphasis is given in this review to the metamorphic remodelling of persisting neurons, both at the input and output levels, and to the associated behavioural changes. Other sections deal with the programmed death of motor neurons and its causes, as well as with the metamorphic interactions between motor neurons and their target muscles. Remodelling and apoptosis of these two elements appear to be under independent ecdysteroid control. This review focusses on the two most thoroughly studied holometabolous species, the fruitfly Drosophila melanogaster and the tobacco hornworm moth Manduca sexta. While Manduca has a long tradition in neurodevelopmental studies due to the identification of many of its neurons, Drosophila has been increasingly used to investigate neural reorganisation thanks to neurogenetic tools and molecular approaches. The wealth of information available emphasises the strength of the insect model system used in developmental studies, rendering it clearly the most important system for studies at the cellular level.

Dual signaling of human Mel1a melatonin receptors via G(i2), G(i3), and G(q/11) proteins.

Mel 1a melatonin receptors belong to the super-family of guanine nucleotide-binding regulatory protein (G protein)-coupled receptors. So far, interest in Mel 1a receptor signaling has focused mainly on the modulation of the adenylyl cyclase pathway via pertussis toxin (PTX)-sensitive G proteins. To further investigate signaling of the human Mel 1a receptor, we have developed an antibody directed against the C terminus of this receptor. This antibody detected the Mel 1a receptor as a protein with an apparent molecular mass of approximately 60 kDa in immunoblots after separation by SDS-PAGE. It also specifically precipitated the 2-[125I]iodomelatonin (125I-Mel)-labeled receptor from Mel 1a-transfected HEK 293 cells. Coprecipitation experiments showed that G(i2), G(i3), and G(q/11) proteins couple to the Mel 1a receptor in an agonist-dependent and guanine nucleotide-sensitive manner. Coupling was selective since other G proteins present in HEK 293 cells, (G(i1), G(o), G(s), G(z), and G12) were not detected in receptor complexes. Coupling of the Mel 1a receptor to G(i) and G(q) was confirmed by inhibition of high-affinity 125I-Mel binding to receptors with subtype-selective G protein alpha-subunit antibodies. G(i2) and/or G(i3) mediated adenylyl cyclase inhibition while G(q/11) induced a transient elevation in cytosolic calcium concentrations in HEK 293 cells stably expressing Mel 1a receptors. Melatonin-induced cytosolic calcium mobilization via PTX-insensitive G proteins was confirmed in primary cultures of ovine pars tuberalis cells endogenously expressing Mel 1a receptors. In conclusion, we report the development of the first antibody recognizing the cloned human Mel 1a melatonin receptor protein. We show that Mel 1a receptors functionally couple to both PTX-sensitive and PTX-insensitive G proteins. The previously unknown signaling of Mel 1a receptors through G(q/11) widens the spectrum of potential targets for melatonin.

The modification of the oxidative metabolism of cells derived both locally and at distance from the site of an acute inflammatory reaction.

During an acute nonspecific inflammatory reaction initiated in the pleural cavity by a nondiffusible stimulus (calcium pyrophosphate crystals), the oxidative metabolism, as measured by chemiluminescence and superoxide release, of cells harvested from both the inflammatory site and at points distant from it was studied. The oxidative metabolism of peritoneal macrophages, obtained from rats undergoing an inflammatory reaction (pleurisy), demonstrated a transient decrease in activity compared with the resident population when using both zymosan and phorbol myristate acetate as stimulants. This metabolic unresponsiveness induced by inflammation may be related to the concomitant changes in the levels of prostacyclin in the peritoneal cavity. It should be emphasized that the peritoneal cellular composition or number did not change during these events. On the other hand alveolar macrophages from inflamed animals showed no significant changes in their superoxide production or chemiluminescence compared to controls. The precise reason for these inflammation-induced changes is unknown; however the acute nonspecific inflammatory reaction was able to modulate the oxidative metabolism of cells not only at the site of inflammation, but at points distant from it.

Polyphosphoinositide metabolism in polymorphonuclear cells from healthy and thermally injured rats: effect of the immunomodulator RU 41740.

Burn trauma is associated with alterations of various components of host defenses, including impaired neutrophil functions. In an animal model of experimental thermal injury, we studied if the modifications of cellular reactivity result from alterations in signalling systems by comparing polyphosphoinositide breakdown, particularly the production of inositol phosphates (IP, IP2 IP3), in healthy and burned rat polymorphonuclear neutrophil leukocytes (PMNs). Neutrophil activators such as N-formyl-methionyl-leucyl-phenylalanine (fMLP) and serum-opsonized zymosan increased in vitro production of inositol phosphates in PMNs from healthy rats. The immunomodulator RU 41740 had no effect by itself, but decreased the stimulating effect of fMLP and zymosan. In PMNs from burned rats, the stimulating effects of fMLP and zymosan were decreased, while RU 41740 stimulated inositol phosphate generation. In vivo treatment with RU 41740 inhibited the activation of phosphoinositide metabolism by fMLP or zymosan in healthy rat PMNs. Similar treatment of burned rats after injury restored the stimulating effect of fMLP and zymosan on inositol phosphate accumulation in PMNs. Thus, RU 41740 can modulate fMLP and zymosan receptor-mediated signal transduction, inducing an attenuation of the phosphatidylinositol hydrolysis response. After burn injury, when the activating effects of fMLP and zymosan are inhibited, RU 41740 can, on the contrary, stimulate phospholipase C-mediated polyphosphoinositide turnover and the formation of intracellular messengers such as IP3. These data show that RU 41740 has different effects on polyphosphoinositide metabolism in rat PMNs, according to the physiological and pathological state of the animals. Interestingly, it has a beneficial action on the post-burn decrease in PMN reactivity.

Mapping of the X-breakpoint involved in a balanced X;12 translocation in a female with mild mental retardation.

Balanced chromosomal abnormalities such as translocations and inversions have been identified in many genetic diseases. Cloning of the breakpoints involved in these abnormalities has led to the identification of the disease-related genes. Recent reports suggest the presence of a mental retardation locus at Xq11-12. We have identified a female patient with a balanced translocation t (X;12) (q11;q15) associated with mild mental retardation. We identified a yeast artificial chromosome spanning the X-chromosome breakpoint by using fluorescent in situ hybridization techniques. A cosmid library of this YAC has been constructed and the search for candidate genes is in progress.

Effect of piracetam on polyphosphoinositide metabolism, cytosolic calcium release, and oxidative burst in human polymorphonuclear cells: interaction with fMLP-induced stimulation.

We investigated the action of piracetam on human polymorphonuclear leukocyte (PMN) responsiveness in vitro. We first studied phosphoinositide metabolism and calcium release with and without fMLP (formyl-methionyl-leucyl-phenylalanine) stimulation. Piracetam at concentrations from 10(-4) to 10(-2) M induced a slight increase in inositol 1,4,5-trisphosphate (IP3) release and phosphatidylinositol 4,5-bisphosphate (PIP2) breakdown. At concentrations above 10(-3) M, piracetam sensitized PMNs to subsequent stimulation by fMLP used at subliminal concentrations (10(-9) and 10(-8) M), inducing a significant increase in IP3 release and PIP2 breakdown similar to that obtained with cells stimulated by the highest effective concentrations of fMLP (10(-7) and 10(-6) M). In the same way, piracetam greatly enhanced calcium release induced by weak concentrations of fMLP. However, piracetam had no effect on oxidative metabolism. We then studied the binding of (3H)fMLP to the PMN membrane in the presence of various concentrations of piracetam. We were not able to demonstrate an obvious action of piracetam either on receptor recruitment or on receptor affinity to fMLP. The difference between the actions of piracetam on phosphoinositide metabolism and calcium release on the one hand and oxidative burst on the other could be explained by an uncoupling of the triggering and activating effects of piracetam on PMNs. The enhancement by piracetam of intracellular cyclic AMP levels rapidly induced termination of the PMN response and accounted for the lack of effect on superoxide production. Thus, piracetam was able to modulate human PMN reactivity and in particular to exert a "priming effect" (rather due to structural modifications of the membrane), which might be of importance in infectious episodes given the absence of deleterious actions such as oxygen free radical production leading to tissue injury.

Effects of tripeptides derived from milk proteins on polymorphonuclear oxidative and phosphoinositide metabolisms.

The tripeptide GLF (glycyl-leucyl-phenylalanine) was isolated from human milk proteins. This peptide increased phagocytosis by human and murine macrophages and protected mice against Klebsiella pneumoniae infection. Specific binding sites on human polymorphonuclear leukocytes (PMNs) have been demonstrated recently. The aim of the present research was to study the action of this peptide on rat and human PMN oxidative burst and to investigate the consequences of cell stimulation on polyphosphoinositide hydrolysis. A biphasic stimulating concentration-dependent effect of GLF on PMN chemiluminescence and superoxide anion generation was demonstrated. One of the peaks of the oxidative response occurred around 10(-9) M, which correlates with the Kd of high affinity receptors of GLF. The other maximum, around 10(-4) M, might be due to the hydrophobic nature of the tripeptide. O2- generation mimicked the phorbol myristate acetate response: after a lag period of 2-5 min, O2- release gradually increased for 10-15 min until a plateau was reached. Furthermore, GLF enhanced phosphoinositide breakdown with maximal IP3 production at 10(-7) M. Various analogs of GLF were synthesized in order to define the relative importance of the different amino acids and their position in the tripeptide molecule: glycyl-phenylalanine-leucine was devoid of biological properties but enhanced the activity of GLF on the metabolic burst at high concentrations; peptides leucyl-leucyl-phenylalanine and leucyl-leucyl-tyrosine, which displaced GLF from its specific membrane receptors, exerted stimulating effects on PMN oxidative and phosphoinositide metabolisms. It is quite conceivable that these short peptides, which may be generated in the newborn during digestion and which are able to stimulate phagocytic cells, are implicated in the defense of the neonate immature organism against infection.

Immunomodulatory effects of ornithine alpha-ketoglutarate in rats with burn injuries.

OBJECTIVE: To investigate the influence of enterally administered ornithine alpha-ketoglutarate (OKG) on muscular amino acid content, eicosanoid release, and polymorphonuclear leukocyte responsiveness after induction of burn injury in rats. DESIGN: Experimental trial. MATERIALS AND METHODS: Four groups of rats were considered: (1) healthy rats that received a standard diet supplemented with 5 g/kg per day of OKG; (2) rats with burn injuries that received the same nutrition as group 1; (3) healthy rats that received standard diet supplemented with glycine in an isonitrogenous amount relative to OKG; and (4) rats with burn injuries that received the same nutrition as group 3. The thymus and 1 skeletal muscle were weighed. The oxidative metabolism of pleural polymorphonuclear leukocytes was measured by means of superoxide generation (O2-) and the chemiluminescent response to opsonized zymosan. Prostaglandin E2 and 6-keto-prostaglandin F1 alpha were measured in the supernatants of pleural and peritoneal cells. RESULTS: The weights of the thymus and the muscle from healthy rats were similar. Those of rats from group 4 were significantly lower (P < .05), whereas those of rats from group 2 were not. Metabolism of OKG led to enhanced amounts of arginine and glutamine in skeletal muscle. The metabolic bursts of polymorphonuclear leukocytes from healthy rats were similar. Those of glycine-treated rats with burn injuries were significantly depressed (P < .05), whereas those of the OKG-treated group were not. Pleural and peritoneal cells from the rats with burn injuries that received OKG generated significantly more prostaglandins (P < .01) than did cells from the other groups of rats. CONCLUSION: Ornithine alpha-ketoglutarate administered to rats with burn injuries displays immunomodulatory properties that can enhance host-defense mechanisms in animals that are affected by a severe injury.

Eicosanoid release and early changes in two acute non specific inflammatory reactions. Major role of prostacyclin and leukotrienes.

We have compared the early development (0-4h) of two acute non-specific inflammatory reactions induced by the intrapleural injection of isologous serum or a suspension of CaPP crystals. The intensity of the reactions was assessed in terms of the exudate volume, the number and ratio of pleural cells and different cell functions and secretions. The number of exudative cells elicited by isologous serum was higher than with CaPP but the PMN/Monocytes ratio was the same. The amount of protein in the serum-induced exudate was constant from 1 h to 4 h and was similar in the CaPP-induced pleural exudate at the latter time. The amount of complement increased similarly in the two models. The chemotactic potency of the exudates and cell supernatants following incubation showed similar values in the two models. Eicosanoid levels were higher in CaPP--than in isologous serum-induced exudates. Prostacyclin and peptidoleukotrienes were released in specially large amounts at the very outset of the inflammatory reactions.

Expression of m1 and m4 muscarinic receptor mRNA in the striatum following a selective lesion of striatonigral neurons.

Cholinergic stimulation has opposing effects on striatopallidal and striatonigral neurons. Most striatal projection neurons express m1 muscarinic receptor mRNA with m4 mRNA found in 40-50%. Expression of m4 mRNA is found in most preprotachykinin neurons but only a subset of preproenkephalin neurons, suggesting preferential localization of m4 receptors to striatonigral neurons. A volkensin lesion of striatonigral neurons reduced striatal m4 mRNA by 63% and m1 mRNA by only 18%, suggesting that preferential expression of m4 receptors by striatonigral neurons may contribute to their differential response.

Effect of encapsulation on the anti-inflammatory properties of superoxide dismutase after oral administration.

Anti-inflammatory properties of free superoxide dismutase and superoxide dismutase encapsulated into liposomes, with or without ceramides, have been investigated. Two models were investigated: carrageenan paw oedema and pleurisy. Animals were fed by repeated doses, twice daily from day 1 until day 4. Evaluation consisted of measurement of paw oedema volume with determination of prostaglandin E2, thromboxane B2 and 6-keto-prostaglandin F1 alpha levels. Polymorphonuclear oxidative metabolism was evaluated by measurement of superoxide anion production. Levels of superoxide dismutase were determined in cells and pleural exudates. Higher anti-inflammatory effects were obtained after eight administrations of encapsulated forms (0.5 mg/kg) whereas free superoxide dismutase have shown no effects. Ceramides enhanced the results obtained.

Substance-P-like levels in inflammatory exudates.

Levels of SP-like immunoreactivity were assessed by enzyme immunoassay in exudates induced in the rat by intrapleural injection of either calcium pyrophosphate (CaPP) or carrageenan. SP-like levels increased during the first hour, up to approximately 2 ng/ml, and remained significantly higher than control values from 1 to 6 h after the induction of pleurisy by CaPP. With carrageenan as the irritant, SP-like levels rose during the first 4 h, up to 3 ng/ml, and remained significantly higher than control values from 4 to 24 h. In terms of the total volume of exudate induced by carrageenan, total amounts increased up to 8 ng/rat at 16 h after the beginning of the reaction. Our data demonstrate a detectable release of SP-like material in these pleural exudates and suggest its involvement in the inflammatory response, either directly, or through other mediators, or simply by acting on nociceptive fibers and inducing vascular changes.

Bradykinin levels in inflammatory exudates.

An enzyme immunoassay was used to measure the levels of bradykinin (BK)-like immunoreactivity in inflammatory exudates provoked by calcium pyrophosphate (CaPP) or carrageenin. BK-like immunoreactivity increased from 4 to 18 ng/ml in exudates provoked by CaPP and collected from 30 min to 3 h after induction of pleurisy. BK levels decreased progressively (from 16 to 3 ng/ml) in the samples collected at 4 and 6 h. BK levels did not increase in exudates provoked by carrageenin. Control samples of exudates provoked by CaPP but not treated with peptidase inhibitors [orthophenanthroline (OPH) or a mixture of EDTA-captopril-thioglycolic acid (ECT)] as well as samples containing one or the other peptidase inhibitors dissolved in saline, were also negative. The present results indicate that an increased production of kinins is detectable only in exudates induced by CaPP and not in those provoked by carrageenin. Our data also suggest that the kinins are rapidly metabolized, both in vitro (in the exudate sample) and in vivo (in the rat pleural cavity).

Effects of niflumic acid on polyphosphoinositide and oxidative metabolism in polymorphonuclear leukocytes from healthy and thermally injured rats.

Thermal injury in rats leads to an impairment of polymorphonuclear leukocyte (PMN) functions, particularly oxidative metabolism and phosphoinositide turnover. As prostaglandin E2, which has immunosuppressive properties, is released in high levels after burn trauma, we investigated the in vitro and in vivo effects of a nonsteroidal antiinflammatory drug, niflumic acid, on oxidative and phosphoinositide metabolism in PMNs from healthy and burned rats. Given the role of fluoride ions on PMN, the influence of niflumic acid was compared with that of sodium fluoride (NaF) at equivalent doses of F-. In vitro, niflumic acid and sodium fluoride had no effect on oxidative metabolism in stimulated by formyl methionyl-leucyl-phenylalanine (FMLP) or opsonized zymosan (OZ) or nonstimulated PMNs from healthy and burned rats. Niflumic acid slightly increased the production of inositol phosphate by nonstimulated PMNs from healthy and burned rats. Niflumic acid and NaF partly restored the stimulating effect of FMLP on inositol phosphate production by PMNs from burned rats. In vivo treatment with niflumic acid and NaF increased the oxidative metabolism of PMNs from burned rats but not healthy rats. Niflumic acid, more than NaF, restored the activity of both stimulants on phosphoinositide metabolism in PMNs from burned rats. In conclusion, at non-antiinflammatory doses, while inhibiting cyclooxygenase activity, niflumic acid exerts a complex effect on the burn-induced depression of PMN functions. The fluoride anion induces similar but generally weaker effects and seems to be involved in the restoring effects of niflumic acid on PMN functions in burned rats.

Qualitative and quantitative differences in cuticular hydrocarbons between laboratory and field colonies of Pogonomyrmex barbatus.

Ants held in the laboratory and field ants of the species Pogonomyrmex barbatus have quantitative differences in their cuticular hydrocarbons and a qualitative difference in their methyl-branched hydrocarbons. Laboratory-held workers showed twice the hydrocarbon content as field ants. This difference was mainly due to higher amounts of straight-chain alkanes and methyl-branched alkanes in laboratory ants, whereas the proportion of the alkenes remained the same for both groups. In addition to the absence of some hydrocarbons in the field colonies, one of the methyl-branched hydrocarbons differed in amount and branching pattern between the two groups of ants. Whereas, notable peaks of 2-methylalkanes were identified in ants kept in the laboratory, these compounds could not be identified in ants living in their natural habitat. However, a trace amount of 4-methyltriacontane was found in lieu of the 2-methyltriacontane counterpart in field ants. Possible explanations for both qualitative and quantitative differences are discussed.

Novel wax esters and hydrocarbons in the cuticular surface lipids of the red harvester ant, Pogonomyrmex barbatus.

The cuticular surface lipids of the red harvester ant, Pogonomyrmex barbatus, were found to contain minor amounts of novel wax esters, in addition to the major components, hydrocarbons. The wax esters ranged in carbon number from C19 to C31 and consisted of esters of both odd- and even-numbered alcohols and acids. Each wax ester with a given carbon number eluted at several different retention times indicating possible methyl branching in either the fatty acid or alcohol moiety, or in both moieties. Each eluting peak of wax esters consisted of a mixture of wax esters of the same carbon number in which the fatty acid moiety ranged from C8 to C18, and the alcohol moiety ranged from C8 to C17. Some wax esters were largely found on the head indicating they may be of a glandular origin. The hydrocarbons consisted of: n-alkanes, C23 to C33; odd-numbered n-alkenes, C27 to C35; and the major components, methyl-branched alkanes, C26 to over C49. Notable components of the methyl-branched alkanes were 2-methyltriacontane, and the novel trimethylalkanes with a single methylene between the first and second branch points, 13,15,19-trimethylhentriacontane and 13,15,21-trimethyltritriacontane.

Effects of plasma lipoproteins on the production of superoxide anion by human polymorphonuclear leukocytes in vitro.

Polymorphonuclear leukocytes (PMN) generate highly reactive oxygen derived free radicals that may cause lipoprotein lipid oxidation and so contribute to the pathogenesis of atherosclerosis. On the other hand it has been shown that lipoproteins can alter cell functions in vitro. We therefore studied the effects of atherogenic lipoproteins, VLDL and LDL, on the production of superoxide anion by human PMN in the presence or absence of formyl-methionyl-leucyl-phenylalanine (fMLP). VLDL and LDL stimulate PMN superoxide production and potentialize PMN stimulation by fMLP. The lipid moiety of the lipoproteins might be mainly involved in these effects. The binding of radio-labelled fMLP to its specific membrane receptor was significantly enhanced in the presence of VLDL and only slightly in the presence of LDL. The study of the signal transduction suggests that modulation of phospholipase D and A2 activities could be involved in the modification by LDL of PMN response to fMLP.