Insulin sensitivity : modulation by the gut-brain axis

Er zijn steeds meer aanwijzingen dat neuropeptiden in de hypothalamus en maagdarmhormonen die hun werking hebben op de hypothalamus en betrokken zijn bij de regulatie van voedselinname, ook betrokken zouden kunnen zijn bij de regulatie van insuline gevoeligheid. Daarom hebben we eerst de effecten van voedselstatus zelf op insuline gevoeligheid gekarakteriseerd en vervolgens gekeken naar de effecten van een aantal signalen voor voedselstatus binnen de maagdarm-brein as op insuline gevoeligheid. Insuline gevoeligheid in lever, spier en vetweefsel hebben we in alle studies in wildtype muizen gemeten met een hyperinsulinemische euglycemische clamp in combinatie met radioisotopen. De studies die uitgevoerd zijn binnen dit proefschrift laten zien dat samenwerking tussen het maagdarmstelsel en het brein niet alleen een belangrijke rol speelt bij de regulatie van voedselinname reguleert, maar ook bij de regulatie van de insuline gevoeligheid van het glucose metabolisme in de lever en perifere weefsels, zoals spier en vetweefsel, afhankelijk en onafhankelijk van voedingsstatus. Op deze manier kan op ieder moment de weefsel-specifieke insuline gevoeligheid nauwkeurig worden gereguleerd, afhankelijk en onafhankelijk van voedingsstatus. Deze eigenschappen maken dat maagdarmhormonen mogelijk ideale nieuwe farmaceutische aangrijpingspunten zijn voor de behandeling van obesitas en type II diabetes mellitus.LEI Universiteit LeidenLilly, Hope farms/abdiets, Woerden, MSD, Novo Nordisk, TNO-kwaliteit van leven, Dutch Diabetes Research FoundationDe pathogenese, kliniek en behandeling van arterieel en veneus vaatlijde

Bone Resorption Is Increased in Pheochromocytoma Patients and Normalizes following Adrenalectomy

Context: The sympathetic nervous system (SNS) controls bone turnover in rodents, but it is uncertain whether a similar role for the SNS exists in humans. Pheochromocytomas are catecholamine-producing neuroendocrine tumors. Because catecholamines are the neurotransmitters of the SNS, we hypothesized that pheochromocytoma patients have increased bone turnover. Objective: Our objective was to compare bone turnover in pheochromocytoma patients and controls. Design and Setting: This retrospective case-control study was performed at the Endocrine Department of the Academic Medical Center of the University of Amsterdam in The Netherlands from 2007 until 2011. Patients: All patients were screened for pheochromocytoma. Cases (n = 21) were identified by 24-h urinary excretion of fractionated metanephrines above the institutional reference value and confirmed by histology after adrenalectomy. All patients screened and diagnosed as not having pheochromocytoma served as controls (n = 126). Main Outcome Measure: The difference in bone turnover markers C-terminal cross-linking telopeptides of collagen type I (CTx) and procollagen type 1 N propeptide (P1NP) between cases and controls was the main outcome measure. Results: CTx concentrations were higher in cases [343 ng/liter; interquartile range (IQR), 295 ng/liter] than in controls (232 ng/liter; IQR, 168 ng/liter; P <0.001) and decreased after adrenalectomy [before, 365 ng/liter (IQR, 450 ng/liter); after, 290 ng/liter (IQR, 241 ng/liter); P = 0.044]. The effect remained after adjustment for possible confounders. P1NP concentrations did not differ. Conclusions: This study shows that pheochromocytoma patients have increased bone resorption, which normalizes after adrenalectomy. This finding supports the concept of regulation of bone remodeling by the SNS in humans. (J Clin Endocrinol Metab 97: E2093-E2097, 2012

Polynomial algorithm for finding the largest independent sets in graphs without forks

AbstractA fork is a graph that is obtained from K1,3 by subdividing one edge. It is known [6–8] that for K1,3-free graphs the problem of finding the largest independent set can be solved in a polynomial time. In this paper, we prove that this is also true for the wider class of fork-free graphs

Гігієнічні аспекти відновлення відкритих техногенних бедлендів із застосуванням осадів міських стічних вод

Зростання індивідуального водоспоживання у великих містах породжує проблему утворення і розміщення на території населених пунктів значної кількості осадів стічних вод. Часто вони представляють епідемічну небезпеку для людини і с джерелом потрапляння у довкілля техногенних хімічних речовин. На основі санітарно-гігієнічної оцінки осадів комунальних стічних вод м. Кривого Рогу розглядається можливість і даються рекомендації для її безпечного використання при створенні вторинних природних ландшафтів у місцях «місячних поверхонь» після відкритого видобутку залізної руди.Рост индивидуального водопотребления в крупных городах порождает проблему образования и размещения на территории населенных пунктов значительного количества осадков сточных вод. Часто они представляют эпидемическую опасность для человека и являются источником поступления в окружающую среду техногенных химических веществ. На основе санитарно-гигиенической оценки осадков коммунальных сточных вод г. Кривого Рога рассматривается возможность и даются рекомендации для их безопасного использования при создании вторичных природных ландшафтов в местах «лунных поверхностей» после открытой добычи железной руды.Growth of individual water consumption in large cities generates a problem of formation and placing of a considerable quantity of deposits of sewage. Often they represent epidemic danger to the person and are a receipt source in environment of technogenic chemical substances. On the basis of a sanitary-and-hygienic estimation of deposits of sewage in a city* of Krivoi Rig consider possibility and definition of the recommendation for safe use of deposits at creation of secondary natural landscapes in places of open-pit mining of iron ore

Report from the HarmoSter study: inter-laboratory comparison of LC-MS/MS measurements of corticosterone, 11-deoxycortisol and cortisone.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) panels that include glucocorticoid-related steroids are increasingly used to characterize and diagnose adrenal cortical diseases. Limited information is currently available about reproducibility of these measurements among laboratories. The aim of the study was to compare LC-MS/MS measurements of corticosterone, 11-deoxycortisol and cortisone at eight European centers and assess the performance after unification of calibration. Seventy-eight patient samples and commercial calibrators were measured twice by laboratory-specific procedures. Results were obtained according to in-house and external calibration. We evaluated intra-laboratory and inter-laboratory imprecision, regression and agreement against performance specifications derived from 11-deoxycortisol biological variation. Intra-laboratory CVs ranged between 3.3 and 7.7%, 3.3 and 11.8% and 2.7 and 12.8% for corticosterone, 11-deoxycortisol and cortisone, with 1, 4 and 3 laboratories often exceeding the maximum allowable imprecision (MAI), respectively. Median inter-laboratory CVs were 10.0, 10.7 and 6.2%, with 38.5, 50.7 and 2.6% cases exceeding the MAI for corticosterone, 11-deoxycortisol and cortisone, respectively. Median laboratory bias vs. all laboratory-medians ranged from -5.6 to 12.3% for corticosterone, -14.6 to 12.4% for 11-deoxycortisol and -4.0 to 6.5% for cortisone, with few cases exceeding the total allowable error. Modest deviations were found in regression equations among most laboratories. External calibration did not improve 11-deoxycortisol and worsened corticosterone and cortisone inter-laboratory comparability. Method imprecision was variable. Inter-laboratory performance was reasonably good. However, cases with imprecision and total error above the acceptable limits were apparent for corticosterone and 11-deoxycortisol. Variability did not depend on calibration but apparently on imprecision, accuracy and specificity of individual methods. Tools for improving selectivity and accuracy are required to improve harmonization

Uptake of prenatal diagnostic testing for retinoblastoma compared to other hereditary cancer syndromes in the Netherlands

Since the 1980s the genetic cause of many hereditary tumor syndromes has been elucidated. As a consequence, carriers of a deleterious mutation in these genes may opt for prenatal diagnoses (PND). We studied the uptake of prenatal diagnosis for five hereditary cancer syndromes in the Netherlands. Uptake for retinoblastoma (Rb) was compared with uptake for Von Hippel–Lindau disease (VHL), Li–Fraumeni syndrome (LFS), familial adenomatous polyposis (FAP), and hereditary breast ovarian cancer (HBOC). A questionnaire was completed by all nine DNA-diagnostic laboratories assessing the number of independent mutation-positive families identified from the start of diagnostic testing until May 2013, and the number of PNDs performed for these syndromes within these families. Of 187 families with a known Rb-gene mutation, 22 had performed PND (11.8%), this was significantly higher than uptake for FAP (1.6%) and HBOC (<0.2%). For VHL (6.5%) and LFS (4.9%) the difference was not statistically significant. PND for Rb started 3 years after introduction of diagnostic DNA testing and remained stable over the years. For the other cancer syndromes PND started 10–15 years after the introduction and uptake for PND showed an increase after 2009. We conclude that uptake of PND for Rb was significantly higher than for FAP and HBOC, but not different from VHL and LFS. Early onset, high penetrance, lack of preventive surgery and perceived burden of disease may explain these differences

Acoustic and optical variations during rapid downward motion episodes in the deep north-western Mediterranean Sea

An Acoustic Doppler Current Profiler (ADCP) was moored at the deep-sea site of the ANTARES neutrino telescope near Toulon, France, thus providing a unique opportunity to compare high-resolution acoustic and optical observations between 70 and 170 m above the sea bed at 2475 m. The ADCP measured downward vertical currents of magnitudes up to 0.03 m s-1 in late winter and early spring 2006. In the same period, observations were made of enhanced levels of acoustic reflection, interpreted as suspended particles including zooplankton, by a factor of about 10 and of horizontal currents reaching 0.35 m s-1. These observations coincided with high light levels detected by the telescope, interpreted as increased bioluminescence. During winter 2006 deep dense-water formation occurred in the Ligurian subbasin, thus providing a possible explanation for these observations. However, the 10-20 days quasi-periodic episodes of high levels of acoustic reflection, light and large vertical currents continuing into the summer are not direct evidence of this process. It is hypothesized that the main process allowing for suspended material to be moved vertically later in the year is local advection, linked with topographic boundary current instabilities along the rim of the 'Northern Current'.Comment: 30 pages, 7 figure

Search for a diffuse flux of high-energy νμ\nu_\mu with the ANTARES neutrino telescope

A search for a diffuse flux of astrophysical muon neutrinos, using data collected by the ANTARES neutrino telescope is presented. A $(0.83\times 2\pi)$ sr sky was monitored for a total of 334 days of equivalent live time. The searched signal corresponds to an excess of events, produced by astrophysical sources, over the expected atmospheric neutrino background. The observed number of events is found compatible with the background expectation. Assuming an $E^{-2}$ flux spectrum, a 90% c.l. upper limit on the diffuse $\nu_\mu$ flux of E^2\Phi_{90%} = 5.3 \times 10^{-8} \ \mathrm{GeV\ cm^{-2}\ s^{-1}\ sr^{-1}} in the energy range 20 TeV - 2.5 PeV is obtained. Other signal models with different energy spectra are also tested and some rejected.Comment: 14 pages, 6 figure

Time calibration of the ANTARES neutrino telescope

The ANTARES deep-sea neutrino telescope comprises a three-dimensional array of photomultipliers to detect the Cherenkov light induced by upgoing relativistic charged particles originating from neutrino interactions in the vicinity of the detector. The large scattering length of light in the deep sea facilitates an angular resolution of a few tenths of a degree for neutrino energies exceeding 10 TeV. In order to achieve this optimal performance, the time calibration procedures should ensure a relative time calibration between the photomultipliers at the level of similar to 1 ns. The methods developed to attain this level of precision are described