A meal rich in palm oil or butter modifies the sphingolipid profile of postprandial triglyceride-rich lipoproteins from type 2 diabetic women.

Elevated concentrations of triglyceride-rich lipoproteins (TGRL) in the fasting and postprandial states are risk factors for cardiovascular events, especially in type 2 diabetes (T2D). T2D modifies the lipid composition of plasma and lipoproteins and some sphingolipids (SP) have been validated as potent predictive biomarkers of cardiovascular disease occurrence. The main objectives of the present study were to characterize the plasma SP profile in fasting T2D patients and to determine whether SP are modified in postprandial TGRL from these patients compared to fasting TGRL. In a randomized parallel-group study, 30 T2D women ingested a breakfast including 20g lipids from either hazelnut cocoa palm oil-rich spread (Palm Nut) or Butter. Plasma was collected and TGRL were isolated by ultracentrifugation at fasting and 4h after the meal. Fasting samples of 6 control subjects from another cohort were analyzed for comparison. SP were analyzed by tandem mass spectrometry. Plasma from fasting T2D patients had higher ceramide (Cer) and ganglioside GM3 concentrations, and lower concentrations of sphingosylphosphorylcholine vs healthy subjects. In postprandial TGRL from T2D patients compared to those in the fasting state, Cer concentrations and especially C16:0, C24:1 and C24:0 molecular species, increased after the Palm Nut or Butter breakfast. A positive correlation was observed in the Palm Nut group between changes (Δ4h-fasting) of summed C16:0+C22:0+C24:1+C24:0 Cer concentrations in TGRL, and changes in plasma TG, TGRL-TG and TGRL-C16:0 concentrations. Altogether in T2D, the altered profile of plasma SP and the increased Cer concentrations in postprandial TGRL could contribute to the increased atherogenicity of TGRL.

Postprandial Triglyceride-Rich Lipoproteins from Type 2 Diabetic Women Stimulate Platelet Activation Regardless of the Fat Source in the Meal.

SCOPE: The aim of this study is to examine whether postprandial (PP) triglyceride-rich lipoproteins (TGRL) secreted after a moderate fat intake would activate platelets differently according to their fatty acid (FA) composition. METHODS AND RESULTS: In a parallel single-blind randomized trial, 30 women with type 2 diabetes are assigned a breakfast containing 20 g lipids from butter versus hazelnut-cocoa spread (HCS) rich in palm oil. Blood samples are collected at fasting and 4 h PP. FA composition of fasting and PP TGRL and their effects on the activation of platelets from healthy blood donors are assessed. Both breakfasts similarly increase plasma ApoB-48, plasma, and TGRL triglycerides (p < 0.05). TGRL mean diameter increases after both breakfasts and is greater after the butter breakfast. Both breakfasts are rich in palmitic acid, and the HCS breakfast contains 45% oleic acid. TGRL FA composition reflects the dietary FA composition. Pre-incubation of platelets with fasting and PP TGRL increases collagen-stimulated aggregation (p < 0.01 vs control). Fasting and PP TGRL similarly increase agonist-induced thromboxane B2 concentrations, and this effect is concentration-dependent for PP TGRL. CONCLUSION: PP TGRL from type 2 diabetic women after a palm-oil spread versus butter-based mixed meal induce similar acute in vitro platelet activation.

Not an Aspirin: No Evidence for Acute Anti-Nociception to Laser-Evoked Pain After Motor Cortex rTMS in Healthy Humans.

BACKGROUND: High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has shown efficacy in relieving neuropathic pain. Whether its analgesic effect also applies to acute physiological nociception remains unclear due to previous contradictory findings. OBJECTIVE: To provide an in-depth investigation of the effects of motor cortex HF-rTMS on acute laser-evoked pain and excitability of nociceptive networks in healthy subjects. METHODS: Randomized, placebo-controlled, double-blind, cross-over study in 20 healthy participants. Laser heat stimuli at nociceptive threshold were delivered to the right hand, allowing assessment of: (a) subjective pain intensity and unpleasantness; (b) laser-evoked potentials (LEPs, 128 electrodes) and their source model; (c) sympathetic skin responses, and (d) spino-thalamic pathway excitability. Data were collected before and 20 minutes after a session of neuro-navigated 20 Hz rTMS to the contralateral motor cortex. RESULTS: Subjective pain reports to thermal laser pulses, amplitude of late cortical potentials and sympathetic skin responses were decreased after cortical stimulation, to a similar extent whether it was active or placebo. Early cortical potentials and nociceptive network excitability remained identical before and after rTMS, as did anatomical sources of LEPs. CONCLUSIONS: Our results do not provide evidence for a genuine anti-nociceptive effect of rTMS on acute physiological pain. We suggest that motor cortex rTMS may act upon high-order networks linked to the emotional and cognitive appraisal of chronic pain, and/or modulate pathologically sensitized networks, rather than change the physiological transmission within an intact nervous system. Such dichotomy is reminiscent of that observed with most drugs used for neuropathic pain.

Is Life better after motor cortex stimulation for pain control? Results at long-term and their prediction by preoperative rTMS.

BACKGROUND: A positive effect of motor cortex stimulation (MCS) (defined as subjective estimations of pain relief ≥ 30%) has been reported in 55 - 64% of patients. Repetitive magnetic cortical stimulation (rTMS) is considered a predictor of MCS effect. These figures are, however, mostly based on subjective reports of pain intensity, and have not been confirmed in the long-term. OBJECTIVES: This study assessed long-term pain relief (2 - 9 years) after epidural motor cortex stimulation and its pre-operative prediction by rTMS, using both intensity and Quality of Life (QoL) scales. STUDY DESIGN: Analysis of the long-term evolution of pain patients treated by epidural motor cortex stimulation, and predictive value of preoperative response to rTMS. SETTING: University Neurological Hospital Pain Center. PATIENTS: Twenty patients suffering chronic pharmaco-resistant neuropathic pain. INTERVENTION: All patients received first randomized sham vs. active 20 Hz-rTMS, before being submitted to MCS surgery. MEASUREMENT: Postoperative pain relief was evaluated at 6 months and then up to 9 years post-MCS (average 6.1 ± 2.6 y) using (i) pain numerical rating scores (NRS); (ii) a combined assessment (CPA) including NRS, drug intake, and subjective quality of life; and (iii) a short questionnaire (HowRu) exploring discomfort, distress, disability, and dependence. RESULTS: Pain scores were significantly reduced by active (but not sham) rTMS and by subsequent MCS. Ten out of 20 patients kept a long-term benefit from MCS, both on raw pain scores and on CPA. The CPA results were strictly comparable when obtained by the surgeon or by a third-party on telephonic survey (r = 0.9). CPA scores following rTMS and long-term MCS were significantly associated (Fisher P = 0.02), with 90% positive predictive value and 67% negative predictive value of preoperative rTMS over long-term MCS results. On the HowRu questionnaire, long-term MCS-related improvement concerned "discomfort" (physical pain) and "dependence" (autonomy for daily activities), whereas "disability" (work, home, and leisure activities) and "distress" (anxiety, stress, depression) did not significantly improve. LIMITATIONS: Limited cohort of patients with inhomogeneous pain etiology. Subjectivity of the reported items by the patient after a variable and long delay after surgery. Predictive evaluation based on a single rTMS session compared to chronic MCS. CONCLUSIONS: Half of the patients still retain a significant benefit after 2 - 9 years of continuous MCS, and this can be reasonably predicted by preoperative rTMS. Adding drug intake and QoL estimates to raw pain scores allows a more realistic assessment of long-term benefits and enhance the rTMS predictive value. The aims of this study and its design were approved by the local ethics committee (University Hospitals St Etienne and Lyon, France).

Exploration of beneficial and deleterious effects of inflammation in stroke: dynamics of inflammation cells.

The inflammatory process during stroke consists of activation of resident brain microglia and recruitment of leucocytes, namely neutrophils and monocytes/macrophages. During inflammation, microglial cells, neutrophils and macrophages secrete inflammatory cytokines and chemokines, and phagocytize dead cells. The recruitment of blood cells (neutrophils and macrophages) is mediated by the leucocyte-endothelium interactions and more specifically by cell adhesion molecules. A mathematical model is proposed to represent the dynamics of various brain cells and of immune cells (neutrophils and macrophages). This model is based on a set of six ordinary differential equations and explores the beneficial and deleterious effects of inflammation, respectively phagocytosis by immune cells and the release of pro-inflammatory mediators and nitric oxide (NO). The results of our simulations are qualitatively consistent with those observed in experiments in vivo and would suggest that the increase of phagocytosis could contribute to the increase of the percentage of living cells. The inhibition of the production of cytokines and NO and the blocking of neutrophil and macrophage infiltration into the brain parenchyma led also to the improvement of brain cell survival. This approach may help to explore the respective contributions of the beneficial and deleterious roles of the inflammatory process in stroke, and to study various therapeutic strategies in order to reduce stroke damage.

Neurological basis of language and sequential cognition: evidence from simulation, aphasia, and ERP studies.

The current research addresses the hypothesis that certain aspects of sequential cognition have made substantial contributions to the human language processing capability, from a functional neurophysiology perspective. We first describe a cognitive sequence processing model that was developed based on the functional neuroanatomy of primate cortex and basal ganglia. We demonstrate how this model is capable of simulating the behavior of human infants in extracting serial, temporal and abstract structure from language-like sound sequences as revealed in recent psycholinguistic experiments. We then demonstrate how, through training, this model can perform adult level syntactic comprehension, based on dissociated processing streams for open vs. closed class words. The model subsequently predicts: (1) that impaired syntactic processing (as in agrammatic aphasia) will be associated with impairments in corresponding non-linguistic cognitive sequencing tasks, and (2) that neurophysiological processes (as revealed by ERPs) involved in syntactic processing should also be involved in the corresponding non-linguistic cognitive sequencing tasks. Data confirming these predictions are reviewed. We conclude that the study of sequential cognition will provide a new paradigm for the investigation of the neurophysiological bases of language.

Human brain potentials reveal similar processing of non-linguistic abstract structure and linguistic syntactic structure.

This research tested the hypothesis that shared or related neurophysiological processes are required for treating (a) non-linguistic abstract structure and (b) some aspects of linguistic syntactic structure. In language, one syntactic structure can be used to create an open class of sentences. We have previously proposed a relation between this generative aspect of syntactic structure and the abstract structure of non-linguistic sequences. For instance, the sequences 'ABCBAC' and 'DEFEDF' have different serial order or serial structure, but share the same abstract structure '123213'. Our recent studies of neuropsychology, simulation and ERPs argued that similar neurophysiological processes are involved in treating non-linguistic abstract structure and certain aspects of linguistic syntactic structure. The current research tests this hypothesis by examining the ERP profile evoked during the processing of non-linguistic sequences vs. sentences. Ten healthy subjects were trained to discriminate between syntactically correct and incorrect sequences and sentences presented visually on a video screen. During the subsequent ERP recording, subjects discriminated between correct and incorrect sequences and sentences presented visually on the screen. This discrimination task yielded, for anomalies in both the abstract and syntactic conditions, a late positivity around 550 ms with partially overlapping topography. These results support our hypothesis that shared or related neurophysiological processes are required for treating non-linguistic abstract structure and aspects of linguistic syntactic structure. However, they also suggest that the overlap between these two types of processing is not complete.