[Subjective oral health, malocclusions and oral health related quality of life in patients with Duchenne muscular dystrophy]. / De subjectieve mondgezondheid, malocclusies en orale kwaliteit van leven van patiënten met Duchenne-spierdystrofie.

Duchenne muscular dystrophy is a hereditary progressive neuromuscular disorder. Deterioration and weakening of the muscles is also present in orofacial muscles. Both weakness of the muscles and the fact that patients become more dependent of care, can make oral care more difficult. At this moment, it is unknown how patients with Duchenne muscular dystrophy experience their oral health and which problems regarding oral health and oral care may impact their oral health related quality of life. In this cross-sectional study, we found that, despite a high percentage of gingivitis, a high percentage of patients who experience halitosis and a high percentage of malocclusions, patients score their oral health related quality of life as good.

A new multidrug-resistant enterotoxigenic Escherichia coli pulsed-field gel electrophoresis cluster associated with enrofloxacin non-susceptibility in diseased pigs.

AIMS: To describe the temporal trends in Escherichia coli pathotypes and antimicrobial resistance detected in isolates from diseased-pig cases submitted to the EcL from 2008 to 2016, in Quebec, Canada, and to investigate the presence of spatiotemporal and phylogenetic clusters. METHODS AND RESULTS: Detection of 12 genes coding for virulence factors in pathogenic E. coli in pigs by PCR and antimicrobial resistance standard disc diffusion assay were performed. Demographic and clinical data were entered in the Animal Pathogenic and Zoonotic E. coli (APZEC) database. ETEC:F4 was the most prevalent pathovirotype among the 3773 cases submitted. The LT:STb:F4 virotype was predominant until 2014, then was overtaken by the LT:STb:STa:F4 virotype. More than 90% of the ETEC:F4 isolates were multidrug resistant. A spatiotemporal cluster of LT:STb:STa:F4 isolates non-susceptible to enrofloxacin was detected between 4/2015 and 9/2016. Pulsed-field gel electrophoresis analysis of 137 ETEC:F4 isolates revealed the presence of a cluster composed mainly of LT:STb:STa:F4 isolates non-susceptible to enrofloxacin. CONCLUSIONS: The APZEC database was useful to highlight temporal trends in E. coli pathotypes. A high-risk ETEC:F4 clone might disseminate in the pig population in Quebec since 2015. SIGNIFICANCE AND IMPACT OF THE STUDY: Surveillance is crucial to identify new clones and develop control strategies.

Correction to: Adaptive capacity of 2- to 5-month-old infants to the flow, shape, and flexibility of different teats during bottle feeding: a cross-sectional study.

Following the publication of the article [1], the authors noticed that Fig. 3 used is not the updated version. The correct version is shown below.

Adaptive capacity of 2- to 5-month-old infants to the flow, shape, and flexibility of different teats during bottle feeding: a cross-sectional study.

BACKGROUND: Nutritive sucking is a complex activity, the biomechanical components of which may vary in relation to respiratory phase, swallow-rate per minute, suck-swallow ratio, and swallow non-inspiratory flow (SNIF). Quantitative measurement of these components during nutritive sucking in healthy infants could help us to understand the complex development of sucking, swallowing, and breathing. This is important because the coordination between these components is often disturbed in infants with feeding difficulties. The aims of this study were to describe the biomechanical components of sucking and swallowing in healthy 2- to 5-month-old infants during bottle feeding, to assess whether infants adapt to the characteristics of two different teats, and to determine which independent variables influence the occurrence of SNIF. METHODS: Submental muscle activity, nasal airflow, and cervical auscultation were evaluated during bottle-feeding with two different teats. RESULTS: Sixteen term-born infants (6 boys) aged 2-5 months were included. All infants showed variable inhalation and exhalation after swallowing. The swallow rate per minute was significantly higher when infants fed with a higher flow teat (Philips Avent Natural 2.0™). Infants had suck:swallow ratios ranging from 1:1 to 4:1. A suck:swallow ratio of 1:1 occurred significantly more often when infants fed with a higher flow teat, whereas a suck:swallow ratio of 2:1 occurred significantly more often when infants fed with a low-flow teat (Philips Avent Classic+™). A suck:swallow ratio of 1:1 was negatively correlated with SNIF, whereas a suck:swallow ratio of 2:1 was positively correlated with SNIF. CONCLUSION: Healthy infants aged 2-5 months can adapt to the flow, shape, and flexibility of different teats, showing a wide range of biomechanical and motor adaptations.

Haploinsufficiency of the 22q11.2 microdeletion gene Mrpl40 disrupts short-term synaptic plasticity and working memory through dysregulation of mitochondrial calcium.

Hemizygous deletion of a 1.5- to 3-megabase region on chromosome 22 causes 22q11.2 deletion syndrome (22q11DS), which constitutes one of the strongest genetic risks for schizophrenia. Mouse models of 22q11DS have abnormal short-term synaptic plasticity that contributes to working-memory deficiencies similar to those in schizophrenia. We screened mutant mice carrying hemizygous deletions of 22q11DS genes and identified haploinsufficiency of Mrpl40 (mitochondrial large ribosomal subunit protein 40) as a contributor to abnormal short-term potentiation (STP), a major form of short-term synaptic plasticity. Two-photon imaging of the genetically encoded fluorescent calcium indicator GCaMP6, expressed in presynaptic cytosol or mitochondria, showed that Mrpl40 haploinsufficiency deregulates STP via impaired calcium extrusion from the mitochondrial matrix through the mitochondrial permeability transition pore. This led to abnormally high cytosolic calcium transients in presynaptic terminals and deficient working memory but did not affect long-term spatial memory. Thus, we propose that mitochondrial calcium deregulation is a novel pathogenic mechanism of cognitive deficiencies in schizophrenia.

A discrete choice experiment to assess people living with HIV's (PLWHIV's) preferences for GP or HIV clinic appointments.

OBJECTIVES: To understand which aspects of general practitioner (GP) and HIV clinic appointments people living with HIV (PLWHIV) most value when seeking advice for new health problems. METHODS: A discrete choice experiment using a convenience sample of people diagnosed with HIV. Participants were recruited from 14 general HIV clinics in the South East of England between December 2014 and April 2015. ORs were calculated using conditional logit (CLOGIT) and latent class models (LCMs). RESULTS: A total of 1106 questionnaires were returned. Most participants were male (85%), white (74%) and were men who have sex with men (69%). The CLOGIT analysis showed people particularly valued shorter appointment waiting times (ORs between 1.52 and 3.62, p<0.001 in all instances). The LCM analysis showed there were two distinct classes, with 59% and 41% of respondents likely to be in each. The first class generally preferred GP to HIV clinic appointments and particularly valued 'being seen quickly'. For example, they had strong preferences for shorter appointment waiting times and longer GP opening hours. People in the second class also valued shorter waiting times, but they had a strong general preference for HIV clinic rather than GP appointments. CONCLUSIONS: PLWHIV value many aspects of care for new health problems, particularly short appointment waiting times. However, they appear split in their general willingness to engage with GPs.

The 6-min mastication test: a unique test to assess endurance of continuous chewing, normal values, reliability, reproducibility and usability in patients with mitochondrial disease.

In patients with mitochondrial disease, fatigue and muscle problems are the most common complaints. They also experience these complaints during mastication. To measure endurance of continuous mastication in patients with mitochondrial diseases, the 6-min mastication test (6MMT) was developed. This study included the collection of normal data for the 6MMT in a healthy population (children and adults). During 6 min of continuous mastication on a chew tube chewing cycles per minute, total amount of chewing cycles and the difference between minute 1 (M1 ) and minute 6 (M2 ) were collected in 271 healthy participants (5-80 years old). These results were compared with those of nine paediatric and 25 adult patients with a mitochondrial disease. Visual analogue scale (VAS) scores were collected directly after the test and after 5 min. A qualitative rating was made on masticatory movements. The reproducibility of the 6MMT in the healthy population with an interval of approximately 2 weeks was good. The inter-rater reliability for the observations was excellent. The patient group demonstrated lower total amount of chewing cycles or had greater differences between M1 and M6 . The 6MMT is a reliable and objective test to assess endurance of continuous chewing. It demonstrates the ability of healthy children and adults to chew during 6 min with a highly stable frequency of mastication movements. The test may give an explanation for the masticatory problems in patient groups, who are complaining of pain and fatigue during mastication.

Toward a comprehensive care of HIV patients: finding a strategy to detect depression in a Spanish HIV cohort.

Depression is a common but frequently undiagnosed feature in individuals with HIV infection. To find a strategy to detect depression in a non-specialized clinical setting, the overall performance of the Hospital Anxiety and Depression Scale (HADS) and the depression identification questions proposed by the European AIDS Clinical Society (EACS) guidelines were assessed in a descriptive cross-sectional study of 113 patients with HIV infection. The clinician asked the two screening questions that were proposed under the EACS guidelines and requested patients to complete the HADS. A psychiatrist or psychologist administered semi-structured clinical interviews to yield psychiatric diagnoses of depression (gold standard). A receiver operating characteristic (ROC) analysis for the HADS-Depression (HADS-D) subscale indicated that the best sensitivity and specificity were obtained between the cut-off points of 5 and 8, and the ROC curve for the HADS-Total (HADS-T) indicated that the best cut-off points were between 12 and 14. There were no statistically significant differences in the correlations of the EACS (considering positive responses to one [A] or both questions [B]), the HADS-D ≥ 8 or the HADS-T ≥ 12 with the gold standard. The study concludes that both approaches (the two EACS questions and the HADS-D subscale) are appropriate depression-screening methods in HIV population. We believe that using the EACS-B and the HADS-D subscale in a two-step approach allows for rapid, assumable and accurate clinical diagnosis in non-psychiatric hospital settings.

Which aspects of health care are most valued by people living with HIV in high-income countries? A systematic review.

BACKGROUND: Increasing numbers of people with HIV are living into older age and experiencing comorbidities. The development of new models of care to meet the needs of this population is now a priority. It is important that the views and preferences of patients inform the development of services in order to maintain high levels of patient satisfaction and engagement. The aim of this systematic review was to determine which aspects of healthcare are particularly valued by people living with HIV. METHODS: We searched electronic databases and reference lists of relevant articles. The search strategy was developed to identify articles reporting on HIV positive patients' perceptions, evaluations or experiences of healthcare services and factors associated with satisfaction with care. Peer-reviewed papers and conference abstracts were included if the study reported on aspects of health care that were valued by people living with HIV, data were collected during the era of combination therapy (from 1996 onwards), and the paper was published in English. A thematic approach to data synthesis was used. RESULTS: Twenty-three studies met the inclusion criteria. Studies used both qualitative and quantitative methods. Six studies specifically reported on relative importance to patients of different aspects of care. The valued aspects of care identified were grouped into seven themes. These highlighted the importance to patients of: a good health care professional-patient relationship, HIV specialist knowledge, continuity of care, ease of access to services, access to high quality information and support, effective co-ordination between HIV specialists and other healthcare professionals, and involvement in decisions about treatment and care. We were unable to determine the relative importance to patients of different aspects of care because of methodological differences between the studies. CONCLUSIONS: This review identified several attributes of healthcare that are valued by people living with HIV, many of which would be relevant to any future reconfiguration of services to meet the needs of an ageing population. Further research is required to determine the relative importance to patients of different aspects of care.

Predictive factors for early mortality among patients with methicillin-resistant Staphylococcus aureus bacteraemia.

OBJECTIVES: A high proportion of patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia die within a few days of the onset of infection. However, predictive factors for early mortality (EM) have barely been examined. The aim of this study was to determine the predictive factors for EM in patients with MRSA bacteraemia. METHODS: All episodes of MRSA bacteraemia were prospectively followed in 21 Spanish hospitals from June 2008 to December 2009. Epidemiology, clinical data, therapy and outcome were recorded. All MRSA strains were analysed in a central laboratory. Mortality was defined as death from any cause occurring in the 30 days after the onset of MRSA bacteraemia. EM was defined as patients who died within the first 2 days, and late mortality (LM) for patients who died after this period. Multivariate analyses were performed by using logistic regression models. RESULTS: A total of 579 episodes were recorded. Mortality was observed in 179 patients (31%): it was early in 49 (8.5%) patients and late in 130 (22.5%). Independent risk factors for EM were [OR (95% CI)] initial Pitt score >3 [3.99 (1.72-3.24)], previous rapid fatal disease [3.67 (1.32-10.24)], source of infection lower respiratory tract or unknown [3.76 (1.31-10.83) and 2.83 (1.11-7.21)], non-nosocomial acquisition [2.59 (1.16-5.77)] and inappropriate initial antibiotic therapy [3.59 (1.63-7.89)]. When predictive factors for EM and LM were compared, inappropriate initial antibiotic therapy was the only distinctive predictor of EM, while endocarditis and lower respiratory tract sources both predicted LM. CONCLUSIONS: In our large cohort of patients several factors were related to EM, but the only distinctive predictor of EM was inappropriate initial antibiotic therapy.

LDL from obese patients with the metabolic syndrome show increased lipid peroxidation and activate platelets.

AIMS/HYPOTHESIS: This study assessed oxidative stress in LDL from obese patients with the metabolic syndrome and compared it with that in LDL from type 2 diabetic patients or control volunteers. It also determined the effect on platelets of LDL from the three groups. METHODS: The profiles of lipids, fatty acids and fatty acid oxidation products were determined in LDL isolated from plasma of patients with the metabolic syndrome, patients with type 2 diabetes and volunteers (n = 10 per group). The effects of LDL from the participant groups on the platelet arachidonic acid signalling cascade and aggregation were investigated. RESULTS: Compared with LDL from control volunteers, LDL from obese metabolic syndrome and type 2 diabetic patients had lower cholesteryl ester, higher triacylglycerol and lower ethanolamine plasmalogen levels. Proportions of linoleic acid were decreased in phosphatidylcholine and cholesteryl esters in LDL from both patient groups. Among the markers of lipid peroxidation, oxidation products of linoleic acid (hydroxy-octadecadienoic acids) and malondialdehyde were increased by 59% and twofold, respectively in LDL from metabolic syndrome and type 2 diabetic patients. LDL from metabolic syndrome and type 2 diabetic patients were equally potent in activating the platelet arachidonic acid signalling cascade through increased phosphorylation of p38 mitogen-activated protein kinase and cytosolic phospholipase A(2), and through increased thromboxane B(2) formation. LDL from patients with the metabolic syndrome and type 2 diabetes potentiated platelet aggregation by threefold and 3.5-fold respectively, whereas control LDL had no activating effects on platelets. CONCLUSIONS/INTERPRETATION: The metabolic syndrome in obese patients, without or with diabetes, is associated with increased oxidative stress in LDL, which triggers platelet activation.

Tongue movements and teat compression during bottle feeding: A pilot study of a quantitative ultrasound approach.

Nutritive sucking is a complex process, essential to proper growth and development. The complexity of this oral sensorimotor activity includes movements of the tongue and jaw. Tongue movements during nutritive sucking can only be visualized with instrumented methods such as ultrasound. Until now, studies using ultrasound during nutritive sucking performed measurements on each individual ultrasound image frame, which was quite time-consuming. The aim of this pilot study was to automatically process ultrasound video recordings in healthy infants during bottle feeding to measure teat compression and tongue movements. Tongue movements and teat compression during bottle feeding were visualized and recorded using 2D dynamic ultrasound imaging. A custom-made semi-automated analysis-routine was developed. Teat compression was expressed as the median difference in teat diameter during the recording. Tongue movements were expressed as the displacement of the tongue along four evenly distributed image lines and the corresponding time-shifts between those lines. The recordings of 12 out of 14 participants were adequate for the analysis of tongue movements. Teat compression could be analysed in the recordings of 6 participants. The reliability of our analysis-routine was considered to be good, and the analysis-routine was more time-efficient than manual frame-by-frame analysis. This quantitative analysis-routine is a promising tool, that can be used efficiently and accurately in the future to collect normative data that can serve as reference values to distinguish normal from abnormal tongue movements in infants with feeding difficulties.

Policy interventions that attract nurses to rural areas: a multicountry discrete choice experiment.

OBJECTIVE: To evaluate the relative effectiveness of different policies in attracting nurses to rural areas in Kenya, South Africa and Thailand using data from a discrete choice experiment (DCE). METHODS: A labelled DCE was designed to model the relative effectiveness of both financial and non-financial strategies designed to attract nurses to rural areas. Data were collected from over 300 graduating nursing students in each country. Mixed logit models were used for analysis and to predict the uptake of rural posts under different incentive combinations. FINDINGS: Nurses' preferences for different human resource policy interventions varied significantly between the three countries. In Kenya and South Africa, better educational opportunities or rural allowances would be most effective in increasing the uptake of rural posts, while in Thailand better health insurance coverage would have the greatest impact. CONCLUSION: DCEs can be designed to help policy-makers choose more effective interventions to address staff shortages in rural areas. Intervention packages tailored to local conditions are more likely to be effective than standardized global approaches.

Double lipoxygenation of polyunsaturated fatty acids of nutritional interest.

Double lipoxygenation of polyunsaturated fatty acids having at least three methylene-interrupted double bonds can be made by two lipoxygenases, e.g. 5- and 12-LOX, or 15-LOX only, followed by reduction of the hydroperoxide products through the glutathione peroxidase action. Several biological activities have been reported for such a double 15-LOX product of docosahexaenoic acid, called protectin DX to differentiate it from protectin D1, a stereo and geometric isomer described for its potent anti-inflammatory potential. The geometric characteristic of the double lipoxygenase products is the conjugated triene E,Z,E (trans,cis,trans), which appears crucial in their biological activities. A focus is also done on single lipoxygenation of mono-hydroxylated products first made by aspirin-treated cyclooxygenase-2. The resulting (R,S)-diOH, E,Z,E conjugated trienes, instead of the (S,S)-diOH isomer in case of double lipoxygenation, seem to be even more active for some biological effects, making biologically relevant the single lipoxygenation in aspirin-treated situations.

The lipid peroxidation end-product 4-HNE induces COX-2 expression through p38MAPK activation in 3T3-L1 adipose cell.

Oxidative stress and low grade chronic inflammation are increased in accumulating fat. Our objective was to test whether 4-hydroxynonenal (4-HNE), an end-product of lipid peroxidation, affects cyclooxygenases in 3T3-L1 adipose cells. 4-HNE increased COX-2 mRNA and protein expression and p38MAP-kinase phosphorylation in a dose-dependent manner. Pretreatment of 3T3-L1 cells by a selective inhibitor of p38MAPK (PD 169316) abolished 4-HNE and glucose oxidase induced COX-2 expression. Our results show that oxidative stress induces COX-2 expression through the production of 4-HNE which activates p38MAPKinase, suggesting that 4-HNE links oxidative stress and chronic inflammation through the activation of cyclooxygenase.

Involvement of type 4 cAMP-phosphodiesterase in the myogenic differentiation of L6 cells.

Myogenic cell differentiation is induced by Arg(8)-vasopressin, whereas high cAMP levels and protein kinase A (PKA) activity inhibit myogenesis. We investigated the role of type 4 phosphodiesterase (PDE4) during L6-C5 myoblast differentiation. Selective PDE4 inhibition resulted in suppression of differentiation induced by vasopressin. PDE4 inhibition prevented vasopressin-induced nuclear translocation of the muscle-specific transcription factor myogenin without affecting its overall expression level. The effects of PDE4 inhibition could be attributed to an increase of cAMP levels and PKA activity. RNase protection, reverse transcriptase PCR, immunoprecipitation, Western blot, and enzyme activity assays demonstrated that the PDE4D3 isoform is the major PDE4 expressed in L6-C5 myoblasts and myotubes, accounting for 75% of total cAMP-hydrolyzing activity. Vasopressin cell stimulation caused a biphasic increase of PDE4 activity, which peaked at 2 and 15 min and remained elevated for 48 h. In the continuous presence of vasopressin, cAMP levels and PKA activity were lowered. PDE4D3 overexpression increased spontaneous and vasopressin-dependent differentiation of L6-C5 cells. These results show that PDE4D3 plays a key role in the control of cAMP levels and differentiation of L6-C5 cells. Through the modulation of PDE4 activity, vasopressin inhibits the cAMP signal transduction pathway, which regulates myogenesis possibly by controlling the subcellular localization of myogenin.

Mitochondrial H2O2 production is reduced with acute and chronic eccentric exercise in rat skeletal muscle.

Oxidative stress with acute/chronic exercise has been so far examined using exercise involving a combination of concentric and eccentric contractions, but skeletal muscles are likely to be injured to a greater extent by pliometric contractions. In the present study, the effects of acute and chronic bouts of downhill running exercise on mitochondrial hydrogen peroxide (H2O2) generation (fluorimetric detection of a dimer with homovanillic acid in presence of horseradish peroxidase) and oxygen consumption in conjunction with antioxidant enzymes activity were examined. The results show that acute eccentric exercise was accompanied by a significantly reduced mitochondrial H2O2 production that is likely due to a decrease in complex I of the electron transport chain (ETC). On the other hand, eccentric training leads to positive adaptations, reflected by a higher citrate synthase activity and decreased mitochondrial H2O2 production. The decrease in mitochondrial H2O2 cannot be attributed to alterations in antioxidant capacities but rather to changes in mitochondrial membrane composition characterized by an increased polyunsaturated to saturated fatty acids ratio, and decreased contents in arachidonic acid and plasmalogens. These results suggest that changes in mitochondrial membrane properties with eccentric training can affect H2O2 production by muscle mitochondria. It is hypothesized that these changes resulted in a mild uncoupling sufficient to reduce electron back flow through complex I of the ETC, the major generator of reactive oxygen species by skeletal muscle mitochondria.

Hydroxy-alkenals from the peroxidation of n-3 and n-6 fatty acids and urinary metabolites.

4-Hydroxy-2E-hexenal (4-HHE) and 4-hydroxy-2E-nonenal (4-HNE) have been characterized as prominent by-products of n-3 and n-6 hydroperoxy derivatives of n-3 and n-6 fatty acids, respectively. We also have characterized the homolog 4-hydroxy-2E,6Z-dodecadienal (4-HDDE) as a specific by-product of the 12-lipoxygenase product of arachidonic acid 12-hydroperoxy-eicosatetraenoate (12-HpETE). The three hydroxy-alkenals have been found in human plasma with 4-HHE being the most prominent followed by 4-HNE. They were found increased in tissues submitted to oxidative stress, according to the fatty acid characteristic of those tissues, e.g., 4-HNE and 4-HDDE in blood platelets and 4-HHE in the retina. We have shown they covalently bind to the primary amine moiety of ethanolamine phospholipids (PE), especially the plasmalogen subclass, with the highest hydrophobic alkenal (4-HDDE) being the most reactive. Their carboxylic acid metabolites, 4-hydroxy-2E-hexenoic acid (4-HHA), 4-hydroxy-2E-nonenoic acid (4-HNA) and 4-hydroxy-2E,6Z-dodecadienoic acid (4-HDDA), respectively, were found in human urine and measured in higher amounts in situations in which oxidative stress has been reported such as aging and diabetes. As reported above with their hydroxy-alkenals precursors, 4-HHA proved to be the most prominent followed by 4-HNA. Altogether, the three hydroxy-alkenals, either in their free form or bound to membrane PE, may be considered as specific markers of lipid peroxidation able to discriminate between n-3 and n-6 fatty acids. This is corroborated by the measurement of their urinary carboxylic acid metabolites.

Studies on polyenoic acid incorporation into human platelet lipid stores: interactions with linoleic and arachidonic acids.

Several polyunsaturated fatty acids (C18-C22 acids) have been compared in their uptake by human platelets and their acylation into glycerophospholipid subclasses. This was also studied in the presence of linoleic and/or arachidonic acids, the main fatty acids of plasma free fatty acid pool. Amongst C20 fatty acids, dihomogamma linolenic acid (20:3(n-6)), 5,8,11-icosatrienoic acid (20:3(n-9)) and arachidonic acid (20:4(n-6)) were better incorporated. The uptake of 5,8,11,14,17-icosapentaenoic acid (20:5(n-3)) was significantly lower and comparable to that of C22 fatty acids (7,10,13,16-docosatetraenoic acid (22:4(n-6)) and 4,7,10,13,16,19-docosahexaenoic acid (22:6(n-3)) and linoleic acid (18:2(n-6)). In this respect, linolenic acid (18:3(n-3)) appeared the poorest substrate. The bulk of each acid was acylated into glycerophospholipids although the presence of linoleic and/or arachidonic acids diverted a part towards neutral lipids. This was prominent for 18:3(n-3) and C22 fatty acids. The glycerophospholipid distribution of each acid differed substantially and was not affected by the presence of linoleic and or arachidonic acids, except for 18:3(n-3) and 22:6(n-3) that were strongly diverted towards phosphatidylethanolamine (PE) at the expense of phosphatidylcholine (PC). The main features were an efficient acylation of 20:3(n-9) into phosphatidylinositol (PI) followed by 20:3(n-6) and 20:4(n-6), then by 20:5(n-3) and 22:4(n-6), and finally 22:6(n-3) and C18 fatty acids. This was reciprocal to the acylation into PE and to a lesser extent into PC which remained the main storage species in all cases. We conclude that human platelets may exhibit a certain specificity for taking up polyunsaturated fatty acids both in terms of total uptake and glycerophospholipid subclass distribution. Also the presence of polyunsaturated fatty acids of normal plasma, like linoleic and arachidonic acids, may interact specifically with such an uptake and distribution.

Interactions between prostaglandin precursors during their oxygenation by human platelets.

The oxygenation through the prostaglandin synthase complex and the lipoxygenase pathways of the three prostaglandin precursors was investigated in human platelets. These precursors (dihomogammalinolenic (8,11,14-eicosatrienoic; 20:3 (8,11,14)), arachidonic (5,8,11,14-eicosatetraenoic; 20:4 (5,8,11,14)) and 5,8,11,14,17-eicosapentaenoic (20:5 (5,8,11,14,17)) acids) were used alone or simultaneously. We have found that 20:4 (5,8,11,14) increases the oxygenation of 20:3 (8,11,14) by the prostaglandin synthase complex while 20:5 (5,8,11,14,17) decreases the oxygenation of 20:4 (5,8,11,14) by the same enzyme complex. On the other hand, the utilization of 20:5 (5,8,11,14,17) by the prostaglandin synthase complex and the lipoxygenase was markedly enhanced in the presence of 20:3 (8,11,14), 20:4 (5,8,11,14) or both. Besides, the increased concentrations of 20:5 (5,8,11,14,17) failed to enhance its oxygenation to such an extent while the addition of 20:3 (8,11,14) or 20:4 (5,8,11,14) allows the marked potentiation of the 20:5 (5,8,11,14,17) oxygenation at any concentration. This indicates that, to be efficient, the utilization of 20:5 (5,8,11,14,17) by platelet oxygenases needs the presence of 20:3 (8,11,14), 20:4 (5,8,11,14) or their derivatives. In addition, using small concentrations of each prostaglandin precursor close to concentrations presumably released from platelet phospholipids during aggregation, all show the same tendencies. We conclude that the interactions we have observed between prostaglandin precursors during their oxygenation by human platelets could be of primary importance to explain the modifications of platelet reactivity reported after dietary manipulations.