Polyethylene glycol, unique among laxatives, suppresses aberrant crypt foci, by elimination of cells.

OBJECTIVE: Polyethylene glycol (PEG), an osmotic laxative, is a potent inhibitor of colon cancer in rats. In a search for the underling mechanisms, the hypothesis that fecal bulking and moisture decrease colon carcinogenesis was tested. We also investigated the PEG effects on crypt cells in vivo. MATERIAL AND METHODS: Fischer 344 rats (n=272) were injected with the colon carcinogen, azoxymethane. They were then randomized to a standard AIN76 diet containing one of 19 laxative agents (5% w/w in most cases): PEG 8000 and other PEG-like compounds, carboxymethylcellulose, polyvinylpyrrolidone, sodium polyacrylate, calcium polycarbophil, karaya gum, psyllium, mannitol, sorbitol, lactulose, propylene glycol, magnesium hydroxide, sodium phosphate, bisacodyl, docusate, and paraffin oil. Aberrant crypt foci (ACF) and fecal values were measured blindly after a 30-day treatment regimen. Proliferation, apoptosis, and the removal of cells from crypts were studied in control and PEG-fed rats using various methods, including TUNEL and fluorescein dextran labeling. RESULTS: PEG 8000 reduced the number of ACF 9-fold in rats (p40-fold) a fecal marker of epitheliolysis in the gut (p<0.001). PEG normalized the percentage of fluorescein dextran labeled cells on the top of ACF (p<0.001). CONCLUSIONS: Among laxatives, only PEG afforded potent chemoprevention. PEG protection was not due to increased fecal bulking, but in all likelihood to the elimination of cells from precancerous lesions

Mécanisme de la suppression du cancer par le polyéthylène glycol : il élimine les cellules précancéreuses marquées au dextran fluorescent dans le colon du rat

Le polyéthylène glycol est un puissant agent de chimioprévention contre la cancérogenèse colorectale chez le rat. Mais le mécanisme est inconnu. Nous nous demandons si le PEG protège ou détruit les cellules des lésions prénéoplasiques dans la muqueuse colique. Pour tester ces hypothèses, cette étude a été réalisée sur des rats Fisher 344. La cancérogenèse a été initiée par injection d'un cancérogène colique, l'azoxyméthane (20mg/kg de poids vif). Les colonocytes ont été marqués en gavant les rats avec du dextran fluorescent (PM 4400) : il marque les cellules dont la menbrane est endommagée. 6 heures après ce gavage, les rats ont reçu un traitement à 5% de PEG8000 dans l'eau de boisson, pendant 18h, puis sacrifiés. Sur les colôns fixés, les cellules marquées ont été comptées dans les cryptes normales et les cryptes aberrantes, considérées comme pré-néoplasiques. Nous avons étudié 22 rats, examiné 2360 cryptes normales et 755 cryptes aberrantes. Les résultats sont extrêmement significatifs : -La proportion de cellules fluorescentes dans les cryptes aberrantes est plus du double de celle dans les cryptes normales. Nous pensons que les cryptes aberrantes sont constituées de cellules précancéreuses qui sont incomplètement différentiées. Leur menbrane serait plus fragiles et plus perméable au dextran de haut PM. - Le traitement par le PEG normalise la proportion de cellules fluorescentes dans les cryptes aberrantes. Il semble que le PEG élimine les cellules prénéoplasiques marquées. Les résultats suggèrent que la protection permise par le PEG contre la cancérogenèse colorectale vient de l'élimination des cellules précancéreuses de la surface de la muqueuse colique. Le PEG agit donc un peu comme une molécule de chimiothérapie. Sa faible toxicité en fait un candidat potentiel aux essais cliniques chez l'homme

Changes in surface hydrology, soil moisture and gross primary production in the Amazon during the 2015/2016 El Niño

The 2015/2016 El Niño event caused severe changes in precipitation across the tropics. This impacted surface hydrology, such as river run-off and soil moisture availability, thereby triggering reductions in gross primary production (GPP). Many biosphere models lack the detailed hydrological component required to accurately quantify anomalies in surface hydrology and GPP during droughts in tropical regions. Here, we take the novel approach of coupling the biosphere model SiBCASA with the advanced hydrological model PCR-GLOBWB to attempt such a quantification across the Amazon basin during the drought in 2015/2016. We calculate 30-40% reduced river discharge in the Amazon starting in October 2015, lagging behind the precipitation anomaly by approximately one month and in good agreement with river gauge observations. Soil moisture shows distinctly asymmetrical spatial anomalies with large reductions across the north-eastern part of the basin, which persisted into the following dry season. This added to drought stress in vegetation, already present owing to vapour pressure deficits at the leaf, resulting in a loss of GPP of 0.95 (0.69 to 1.20) PgC between October 2015 and March 2016 compared with the 2007-2014 average. Only 11% (10-12%) of the reduction in GPP was found in the (wetter) north-western part of the basin, whereas the north-eastern and southern regions were affected more strongly, with 56% (54-56%) and 33% (31-33%) of the total, respectively. Uncertainty on this anomaly mostly reflects the unknown rooting depths of vegetation.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.</p

The Role of the Noradrenergic System in the Exploration–Exploitation Trade-Off: A Psychopharmacological Study

Animal research and computational modeling have indicated an important role for the neuromodulatory locus coeruleus–norepinephrine (LC–NE) system in the control of behavior. According to the adaptive gain theory, the LC–NE system is critical for optimizing behavioral performance by regulating the balance between exploitative and exploratory control states. However, crucial direct empirical tests of this theory in human subjects have been lacking. We used a pharmacological manipulation of the LC–NE system to test predictions of this theory in humans. In a double-blind parallel-groups design (N = 52), participants received 4 mg reboxetine (a selective norepinephrine reuptake inhibitor), 30 mg citalopram (a selective serotonin reuptake inhibitor), or placebo. The adaptive gain theory predicted that the increased tonic NE levels induced by reboxetine would promote task disengagement and exploratory behavior. We assessed the effects of reboxetine on performance in two cognitive tasks designed to examine task (dis)engagement and exploitative versus exploratory behavior: a diminishing-utility task and a gambling task with a non-stationary pay-off structure. In contrast to predictions of the adaptive gain theory, we did not find differences in task (dis)engagement or exploratory behavior between the three experimental groups, despite demonstrable effects of the two drugs on non-specific central and autonomic nervous system parameters. Our findings suggest that the LC–NE system may not be involved in the regulation of the exploration–exploitation trade-off in humans, at least not within the context of a single task. It remains to be examined whether the LC–NE system is involved in random exploration exceeding the current task context

Changes in surface hydrology, soil moisture and gross primary production in the Amazon during the 2015/2016 El Niño

The 2015/2016 El Niño event caused severe changes in precipitation across the tropics. This impacted surface hydrology, such as river run-off and soil moisture availability, thereby triggering reductions in gross primary production (GPP). Many biosphere models lack the detailed hydrological component required to accurately quantify anomalies in surface hydrology and GPP during droughts in tropical regions. Here, we take the novel approach of coupling the biosphere model SiBCASA with the advanced hydrological model PCR-GLOBWB to attempt such a quantification across the Amazon basin during the drought in 2015/2016. We calculate 30-40% reduced river discharge in the Amazon starting in October 2015, lagging behind the precipitation anomaly by approximately one month and in good agreement with river gauge observations. Soil moisture shows distinctly asymmetrical spatial anomalies with large reductions across the north-eastern part of the basin, which persisted into the following dry season. This added to drought stress in vegetation, already present owing to vapour pressure deficits at the leaf, resulting in a loss of GPP of 0.95 (0.69 to 1.20) PgC between October 2015 and March 2016 compared with the 2007-2014 average. Only 11% (10-12%) of the reduction in GPP was found in the (wetter) north-western part of the basin, whereas the north-eastern and southern regions were affected more strongly, with 56% (54-56%) and 33% (31-33%) of the total, respectively. Uncertainty on this anomaly mostly reflects the unknown rooting depths of vegetation.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.</p

Serum Lipoprotein(a) and Bioprosthetic Aortic Valve Degeneration

AIMS: Bioprosthetic aortic valve degeneration demonstrates pathological similarities to aortic stenosis. Lipoprotein(a) [Lp(a)] is a well-recognized risk factor for incident aortic stenosis and disease progression. The aim of this study is to investigate whether serum Lp(a) concentrations are associated with bioprosthetic aortic valve degeneration. METHODS AND RESULTS: In a post hoc analysis of a prospective multimodality imaging study (NCT02304276), serum Lp(a) concentrations, echocardiography, contrast-enhanced computed tomography (CT) angiography, and 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) were assessed in patients with bioprosthetic aortic valves. Patients were also followed up for 2 years with serial echocardiography. Serum Lp(a) concentrations [median 19.9 (8.4-76.4) mg/dL] were available in 97 participants (mean age 75 ± 7 years, 54% men). There were no baseline differences across the tertiles of serum Lp(a) concentrations for disease severity assessed by echocardiography [median peak aortic valve velocity: highest tertile 2.5 (2.3-2.9) m/s vs. lower tertiles 2.7 (2.4-3.0) m/s, P = 0.204], or valve degeneration on CT angiography (highest tertile n = 8 vs. lower tertiles n = 12, P = 0.552) and 18F-NaF PET (median tissue-to-background ratio: highest tertile 1.13 (1.05-1.41) vs. lower tertiles 1.17 (1.06-1.53), P = 0.889]. After 2 years of follow-up, there were no differences in annualized change in bioprosthetic hemodynamic progression [change in peak aortic valve velocity: highest tertile [0.0 (-0.1-0.2) m/s/year vs. lower tertiles 0.1 (0.0-0.2) m/s/year, P = 0.528] or the development of structural valve degeneration. CONCLUSION: Serum lipoprotein(a) concentrations do not appear to be a major determinant or mediator of bioprosthetic aortic valve degeneration

Nifedipine versus atosiban in the treatment of threatened preterm labour (Assessment of Perinatal Outcome after Specific Tocolysis in Early Labour: APOSTEL III-Trial)

Background: Preterm birth is the most common cause of neonatal morbidity and mortality. Postponing delivery for 48 hours with tocolytics to allow for maternal steroid administration and antenatal transportation to a centre wit

Взаємодія системи "політика-релігія"

Досліджено феномен суспільних явищ політики і релігії у перерізі їх взаємодії, вивчено історичний досвід такого взаємного впливу. Окреме місце відведено аналізу практичного застосування закону України “Про свободу совісті та релігійні організації”.The article explores the phenomenon of social phenomena politics and religion in the context of their interaction, exploring the historical experience of such mutual influence. A separate analysis is given to the practical application of the Law of Ukraine “On Freedom of Conscience and Religious Organizations”

D6.2 - Prototype description and field trial results

Deliverable D6.2 del projecte FARAMIRPostprint (published version