Étude retrospective observationnelle sur l'usage des biomarqueurs du liquide céphalo-rachidien de la maladie d'Alzheimer [Prospective and observational study of use of cerebrospinal fluid biomarkers of Alzheimer's disease]

Objectifs: Le dosage des biomarqueurs du liquide céphalorachidien (LCR) ne fait pas partie des recommandations de la démarche diagnostique de la maladie d'Alzheimer (MA) en France. Nous voulions analyser l'apport de leur dosage en pratique clinique quotidienne. Matériel et méthode: Étude rétrospective observationnelle, portant sur l'ensemble des dosages de biomarqueurs du LCR de la MA effectués entre le 1er novembre 2010 et le 30 septembre 2012 dans l'hôpital de jour (HDJ) et le service de médecine interne gériatrique (SMIG) du centre mémoire de ressources et de recherche (CMRR) des hôpitaux universitaires de Strasbourg (Alsace, France). Résultats: Quatre-vingt-dix-sept patients (femmes : 60,8 % ; âge moyen : 80 ± 6,5 ans) ont été considérés. En HDJ (n = 50), les biomarqueurs étaient utilisés pour le diagnostic positif de MA (64,0 %) ou le diagnostic différentiel entre les démences (36,0 %). Au SMIG (n = 47), leur dosage était effectué afin de confirmer une MA (19,1 %), de rechercher une pathologie cognitive sous-jacente à un syndrome confusionnel (17,0 %) ou pour diagnostiquer une démence chez des patients atteints de pathologies psychiatriques (29,8 %). Si 49,5 % des patients ont eu un diagnostic de MA confirmée, les biomarqueurs ont contribué à infirmer cette étiologie dans 9,2 % des cas. Le doute entre une MA et une autre étiologie persistait cependant encore chez 10 patients. Les analyses comparatives des taux des différents biomarqueurs ont montré que la protéine tau est observée avec un taux significativement plus élevé dans la MA que dans la démence vasculaire (p = 0,003) et à la limite de la significativité pour la maladie de Parkinson (p = 0,06). Le profil observé avec la Ptau est similaire mais avec une significativité atteinte vis-à-vis de la démence de la maladie de Parkinson (p = 0,01). En ce qui concerne l'Aβ1-42, si les taux moyens étaient les plus élevés dans les démences vasculaire et à corps de Lewy, (p < 0,0001 et p < 0,01), ils étaient plus faibles en cas de démence de la maladie de Parkinson mais sans atteindre le seuil de signification (p = 0,12). Conclusion: Cette étude a analysé l'utilisation des biomarqueurs de la MA en pratique courante. Si leur intérêt se positionne actuellement dans le diagnostic de la MA à un stade léger, ces biomarqueurs montrent leur utilité dans les situations où le diagnostic clinique est rendu difficile par un trouble psychiatrique et/ou une confusion, une clinique atypique où lorsque les tests cognitifs sont irréalisables.

Exercise performed immediately after fructose ingestion enhances fructose oxidation and suppresses fructose storage.

BACKGROUND: Exercise prevents the adverse effects of a high-fructose diet through mechanisms that remain unknown. OBJECTIVE: We assessed the hypothesis that exercise prevents fructose-induced increases in very-low-density lipoprotein (VLDL) triglycerides by decreasing the fructose conversion into glucose and VLDL-triglyceride and fructose carbon storage into hepatic glycogen and lipids. DESIGN: Eight healthy men were studied on 3 occasions after 4 d consuming a weight-maintenance, high-fructose diet. On the fifth day, the men ingested an oral (13)C-labeled fructose load (0.75 g/kg), and their total fructose oxidation ((13)CO2 production), fructose storage (fructose ingestion minus (13)C-fructose oxidation), fructose conversion into blood (13)C glucose (gluconeogenesis from fructose), blood VLDL-(13)C palmitate (a marker of hepatic de novo lipogenesis), and lactate concentrations were monitored over 7 postprandial h. On one occasion, participants remained lying down throughout the experiment [fructose treatment alone with no exercise condition (NoEx)], and on the other 2 occasions, they performed a 60-min exercise either 75 min before fructose ingestion [exercise, then fructose condition (ExFru)] or 90 min after fructose ingestion [fructose, then exercise condition (FruEx)]. RESULTS: Fructose oxidation was significantly (P < 0.001) higher in the FruEx (80% ± 3% of ingested fructose) than in the ExFru (46% ± 1%) and NoEx (49% ± 1%). Consequently, fructose storage was lower in the FruEx than in the other 2 conditions (P < 0.001). Fructose conversion into blood (13)C glucose, VLDL-(13)C palmitate, and postprandial plasma lactate concentrations was not significantly different between conditions. CONCLUSIONS: Compared with sedentary conditions, exercise performed immediately after fructose ingestion increases fructose oxidation and decreases fructose storage. In contrast, exercise performed before fructose ingestion does not significantly alter fructose oxidation and storage. In both conditions, exercise did not abolish fructose conversion into glucose or its incorporation into VLDL triglycerides. This trial was registered at clinicaltrials.gov as NCT01866215.

Effect of meal ingestion on liver stiffness in patients with cirrhosis and portal hypertension.

BACKGROUND AND AIMS: Liver stiffness is increasingly used in the non-invasive evaluation of chronic liver diseases. Liver stiffness correlates with hepatic venous pressure gradient (HVPG) in patients with cirrhosis and holds prognostic value in this population. Hence, accuracy in its measurement is needed. Several factors independent of fibrosis influence liver stiffness, but there is insufficient information on whether meal ingestion modifies liver stiffness in cirrhosis. We investigated the changes in liver stiffness occurring after the ingestion of a liquid standard test meal in this population. METHODS: In 19 patients with cirrhosis and esophageal varices (9 alcoholic, 9 HCV-related, 1 NASH; Child score 6.9±1.8), liver stiffness (transient elastography), portal blood flow (PBF) and hepatic artery blood flow (HABF) (Doppler-Ultrasound) were measured before and 30 minutes after receiving a standard mixed liquid meal. In 10 the HVPG changes were also measured. RESULTS: Post-prandial hyperemia was accompanied by a marked increase in liver stiffness (+27±33%; p<0.0001). Changes in liver stiffness did not correlate with PBF changes, but directly correlated with HABF changes (r = 0.658; p = 0.002). After the meal, those patients showing a decrease in HABF (n = 13) had a less marked increase of liver stiffness as compared to patients in whom HABF increased (n = 6; +12±21% vs. +62±29%,p<0.0001). As expected, post-prandial hyperemia was associated with an increase in HVPG (n = 10; +26±13%, p = 0.003), but changes in liver stiffness did not correlate with HVPG changes. CONCLUSIONS: Liver stiffness increases markedly after a liquid test meal in patients with cirrhosis, suggesting that its measurement should be performed in standardized fasting conditions. The hepatic artery buffer response appears an important factor modulating postprandial changes of liver stiffness. The post-prandial increase in HVPG cannot be predicted by changes in liver stiffness.

Europeana metadata ingestion

Francesca Morsellin esitys Europeana työpajassa 20.11.2012 Helsingissä.

Diagnose of the ingestion of Asclepias mellodora St. Hil. by sheep through microhistological analysis of their digestive contents

Asclepias mellodora St. Hil. is a native acute toxic species frequent in the grasslands of the Buenos Aires province, Argentina, whose toxicity had not been assessed until now. This study evaluates the minimal lethal dose of this species for sheep, and the possibility of microscopically recognizing its fragments in gastrointestinal contents as a complementary diagnostic tool in necropsies. Three Frisona sheep (average LW=55±4.5 kg) were dosed via an esophageal tube with each one of the following doses of asclepias: 8.0, 5.0, 2.0 and 0.8 g DM.kg LW-1. Sheep poisoned with the three higher doses died between 10 and 85 h after intoxication, but those receiving the lower dose did not. During necropsies we: 1) determined the dry weight of the contents of rumen+reticulum, omasum+abomasum, and large intestine, 2) estimated the percentages of asclepias fragments by microanalysis correcting for digestion effects on fragment recognition, and 3) calculated the total mass of asclepias in the digestive tract of each animal. For the three higher doses, the mass of asclepias identified in the total ingesta was 12.3±3.4% of the amount supplied, possibly because of the strong diarrhea its ingestion produced. The percentages of asclepias in rumen+reticulum did not differ from the average quantified for the entire tract. The results of this study indicate that the minimal lethal doses of asclepias for sheep is between 2.0 and 0.8g DM·kg LW-1, and that the microhistological analysis of the rumen+reticulum, the easiest region to sample, can be used to confirm the ingestion of this toxic species, although the estimated percentage will be not a good estimator of the ingested percentage.

Multi-source ingestion of publisher articles - The SCOAP3 repository experience

Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

Does the Ingestion of Isoxaflutole Herbicide Affect the Midgut and Salivary Glands of Pentatomidae Predators?

Podisus nigrispinus is a generalist predator naturally occurring in agricultural and forestry systems that effectively contributes to the population balance of phytophagous insects, especially defoliating caterpillars. Histological changes were evaluated in the salivary glands and midgut of P. nigrispinus caused by ingestion of systemic herbicide isoxaflutole. These predator females were fed with leaves of eucalyptus plants, Tenebrio molitor pupae or water, contaminated or not by herbicide. Salivary glands and midguts were dissected, processed and analyzed under a light microscope. Activity level and cell morphology of the salivary glands and midgut showed differences among insects fed on plants, contaminated water or pupae. The epithelia of the salivary gland and midgut of individuals which had no contact with the herbicide showed homogeneous cytoplasm, nucleus with predominance of decondensed chromatin and evident nucleoli, intense cell activity features. As for the insects in contact with contaminated food, they presented undeveloped nucleus and condensed chromatin. The luminal contents of the salivary glands in the contaminated insects had become more acidophilus than in insects without poisoning, as well as having heterogeneous and granular secretion, being more evident in the bioassay in which the insects fed on contaminated water. There was a marked morphological change in the midgut cells in contaminated insects. High degree of apoptosis, disorganization and secretory vacuoles in the epithelial cytoplasm were observed. The apical portion of the midgut cells proved undeveloped, irregular and partially destroyed. It is concluded that isoxaflutole causes morphological changes in the digestive system of the predator P. nigrispinus.

Sucrose ingestion causes opioid analgesia

The intake of saccharin solutions for relatively long periods of time causes analgesia in rats, as measured in the hot-plate test, an experimental procedure involving supraspinal components. In order to investigate the effects of sweet substance intake on pain modulation using a different model, male albino Wistar rats weighing 180-200 g received either tap water or sucrose solutions (250 g/l) for 1 day or 14 days as their only source of liquid. Each rat consumed an average of 15.6 g sucrose/day. Their tail withdrawal latencies in the tail-flick test (probably a spinal reflex) were measured immediately before and after this treatment. An analgesia index was calculated from the withdrawal latencies before and after treatment. The indexes (mean ± SEM, N = 12) for the groups receiving tap water for 1 day or 14 days, and sucrose solution for 1 day or 14 days were 0.09 ± 0.04, 0.10 ± 0.05, 0.15 ± 0.08 and 0.49 ± 0.07, respectively. One-way ANOVA indicated a significant difference (F(3,47) = 9.521, P<0.001) and the Tukey multiple comparison test (P<0.05) showed that the analgesia index of the 14-day sucrose-treated animals differed from all other groups. Naloxone-treated rats (N = 7) receiving sucrose exhibited an analgesia index of 0.20 ± 0.10 while rats receiving only sucrose (N = 7) had an index of 0.68 ± 0.11 (t = 0.254, 10 degrees of freedom, P<0.03). This result indicates that the analgesic effect of sucrose depends on the time during which the solution is consumed and extends the analgesic effects of sweet substance intake, such as saccharin, to a model other than the hot-plate test, with similar results. Endogenous opioids may be involved in the central regulation of the sweet substance-produced analgesia.

Interaction between repeated restraint stress and concomitant midazolam administration on sweet food ingestion in rats

Emotional changes can influence feeding behavior. Previous studies have shown that chronically stressed animals present increased ingestion of sweet food, an effect reversed by a single dose of diazepam administered before testing the animals. The aim of the present study was to evaluate the response of animals chronically treated with midazolam and/or submitted to repeated restraint stress upon the ingestion of sweet food. Male adult Wistar rats were divided into two groups: controls and exposed to restraint 1 h/day, 5 days/week for 40 days. Both groups were subdivided into two other groups treated or not with midazolam (0.06 mg/ml in their drinking water during the 40-day treatment). The animals were placed in a lighted area in the presence of 10 pellets of sweet food (Froot loops®). The number of ingested pellets was measured during a period of 3 min, in the presence or absence of fasting. The group chronically treated with midazolam alone presented increased ingestion when compared to control animals (control group: 2.0 ± 0.44 pellets and midazolam group: 3.60 ± 0.57 pellets). The group submitted to restraint stress presented an increased ingestion compared to controls (control group: 2.0 ± 0.44 pellets and stressed group: 4.18 ± 0.58 pellets). Chronically administered midazolam reduced the ingestion in stressed animals (stressed/water group: 4.18 ± 0.58 pellets; stressed/midazolam group: 3.2 ± 0.49 pellets). Thus, repeated stress increases appetite for sweet food independently of hunger and chronic administration of midazolam can decrease this behavioral effect.