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101.
Vanhees K Godschalk RW Sanders A van Waalwijk van Doorn-Khosrovani SB van Schooten FJ 《Toxicology》2011,290(2-3):350-358
The flavonoid quercetin is a powerful iron chelator, capable of oxidizing heme iron in hemoglobin from Fe(2+) to Fe(3+). Moreover, quercetin crosses the placenta and accumulates in the fetus. Since adaptations made by the fetus to cope with inappropriate nutrition may lead to permanent changes, a relative high intake of quercetin may have detrimental affects later in life. Therefore, we investigated the effects of maternal exposure to quercetin (302 mg/kg feed), starting from 3 days before conception until the end of gestation, on erythropoiesis and iron homeostasis at embryonic day 14.5 and in 12-week old mice. During fetal development, quercetin exposure had no effect on the erythroid lineage switch and concomitant globin switch. However, adult mice prenatally exposed to quercetin had significant increase iron storage in the liver, by upregulating iron-associated cytokine expression (hepcidin, IL-1β, IL-6 and IL-10). These long term changes in gene expression could be mediated through epigenetic modifications, as prenatal quercetin exposure resulted in a modest hypermethylation of repetitive elements. Despite the increased iron levels, oxidative stress was significantly decreased in the liver of these animals as assessed by 8-oxo-dG levels. These data suggest that prenatal quercetin exposure results in increased iron storage, while decreasing oxidative stress induced DNA damage together with a shift towards increased expression of inflammation associated cytokines in the liver at adult age. 相似文献
102.
Blackburn AC Coggan M Shield AJ Cappello J Theodoratos A Murray TP Rooke M Larter CZ Koina ME Dahlstrom JE Matthaei KI Board PG 《Laboratory investigation; a journal of technical methods and pathology》2011,91(11):1572-1583
Glutathione transferase kappa (GSTK1-1) is a highly conserved, mitochondrial enzyme potentially involved in redox reactions. GSTK1-1-deficient mice were generated to further study the enzyme's biological role. Reduced and total glutathione levels in liver and kidney were unchanged by GSTK1-1 deficiency and NADPH quinone oxidoreductase 1 expression was not elevated indicating that there is no general underlying oxidative stress in Gstk1(-/-) mice. Electron microscopy of liver and kidney showed no changes in mitochondrial morphology with GSTK1-1 deficiency. The death of a number of Gstk1(-/-) males with urinary tract problems prompted close examination of the kidneys. Electron microscopy revealed glomerular basement membrane changes at 3 months, accompanied by detectable microalbuminuria in male mice (albumin:creatinine ratio of 2.66±0.83 vs 1.13±0.20?mg/mmol for Gstk1(-/-) and wild-type (WT), respectively, P=0.001). This was followed by significant foot process effacement (40-55% vs 10% for Gstk1(-/-) and WT, respectively) at 6 months of age in all Gstk1(-/-) mice examined. Kidney tubules were ultrastructurally normal. Compared with human disease, the Gstk1(-/-) kidneys show changes seen in glomerulopathies causing nephrotic syndrome. Gstk1(-/-) mice may offer insights into the early development of glomerular nephropathies. 相似文献
103.
Nellist M van den Heuvel D Schluep D Exalto C Goedbloed M Maat-Kievit A van Essen T van Spaendonck-Zwarts K Jansen F Helderman P Bartalini G Vierimaa O Penttinen M van den Ende J van den Ouweland A Halley D 《European journal of human genetics : EJHG》2009,17(3):319-328
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterised by the development of hamartomas in a variety of organs and tissues. The disease is caused by mutations in either the TSC1 gene on chromosome 9q34 or the TSC2 gene on chromosome 16p13.3. The TSC1 and TSC2 gene products, TSC1 and TSC2, interact to form a protein complex that inhibits signal transduction to the downstream effectors of the mammalian target of rapamycin (mTOR). Here we investigate the effects of putative TSC1 missense mutations identified in individuals with signs and/or symptoms of TSC on TSC1-TSC2 complex formation and mTOR signalling. We show that specific amino-acid substitutions close to the N-terminal of TSC1 reduce steady-state levels of TSC1, resulting in the activation of mTOR signalling and leading to the symptoms of TSC. 相似文献
104.
Minke G. Barendse-Hofmann MD MSc Pascal Steenvoorde Louk van Doorn Anneke Zeillemaker 《European journal of trauma and emergency surgery》2009,35(1):74-78
Abstract
A compartment syndrome is an increased tissue pressure within a closed osteofascial compartment. This compromises blood flow
to the muscles and nerves within that compartment, which –if not treated adequately in an early stage-results in permanent
tissue and nerve damage. It most frequently occurs in the lower leg, but can also occur elsewhere when muscles are enclosed
in tight fascial compartments, such as the forearm and hand. In this report a patient is described who developed an acute
compartment syndrome of the arm after a cable-wakeboard accident in which his arm was strangulated. Cable-wakeboarding is
an extreme sport that has become very popular over the last years. Early recognition and treatment of an acute compartment
syndrome is of extreme importance since in short term necrotic muscles can lead to severe irreversible complications. Accidents
with cable-wakeboarding often occur during the start. This is caused by the strong forces that are on the cable during the
start. Strangulation injuries of the arm can cause a compartment syndrome of the arm. Possibly a wet-suit or dry-suit offers
some protection. However, the duration of strangulation determines much of the damage. Although diagnosis of a compartment
syndrome can be difficult, a high index of suspicion combined with fast and adequate treatment with a fasciotomy improve outcome
and prognosis. 相似文献
105.
106.
107.
Gerard J.B. Sonder MD PhD Gini G.C. van Rijckevorsel MD MPH Anneke van den Hoek MD PhD 《Journal of travel medicine》2009,16(1):18-22
Objectives. Behavioral studies in travelers suggest that 33% to 76% of all travelers to hepatitis B virus (HBV)–endemic countries are at risk for HBV infection. We study the incidence and risk factors for HBV infection in travelers.
Methods. Retrospective analysis of the characteristics and risk factors of all reported acute HBV patients in Amsterdam, the Netherlands, from January 1, 1992, until December 31, 2003.
Results. The estimated incidence in travelers from Amsterdam to HBV-endemic countries is 4.5/100,000 travelers. Two thirds of these patients were immigrants who lived in Amsterdam and who had visited their friends and relatives in their country of origin. In 12 years, only three Dutch short-term tourists contracted HBV while traveling, all by heterosexual contacts.
Conclusions. Dutch tourists who travel to HBV-endemic countries run a very low risk of contracting HBV. Vaccination of short-term Dutch tourists is not necessary. Immigrants run a higher risk irrespective of travel or duration of travel. This group should be advised vaccination. 相似文献
Methods. Retrospective analysis of the characteristics and risk factors of all reported acute HBV patients in Amsterdam, the Netherlands, from January 1, 1992, until December 31, 2003.
Results. The estimated incidence in travelers from Amsterdam to HBV-endemic countries is 4.5/100,000 travelers. Two thirds of these patients were immigrants who lived in Amsterdam and who had visited their friends and relatives in their country of origin. In 12 years, only three Dutch short-term tourists contracted HBV while traveling, all by heterosexual contacts.
Conclusions. Dutch tourists who travel to HBV-endemic countries run a very low risk of contracting HBV. Vaccination of short-term Dutch tourists is not necessary. Immigrants run a higher risk irrespective of travel or duration of travel. This group should be advised vaccination. 相似文献
108.
Gerhild I B?ger Tanja K Rudolph Renke Maas Edzard Schwedhelm Ekaterina Dumbadze Anneke Bierend Ralf A Benndorf Rainer H B?ger 《Journal of the American College of Cardiology》2007,49(23):2274-2282
OBJECTIVES: We hypothesized that the level of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide (NO) synthase (eNOS), might determine the endothelial effects of statins. BACKGROUND: Endothelial NO synthase is up-regulated by statins. However, statins failed to improve endothelial function in some studies. Asymmetric dimethylarginine inhibits eNOS by a mechanism that is reversible by L-arginine. METHODS: Ninety-eight clinically asymptomatic elderly subjects had their plasma ADMA levels screened. Those in the highest (high ADMA, n = 15) and lowest quartiles of the ADMA distribution (low ADMA, n = 13) were eligible to receive, in a randomized order, simvastatin (40 mg/day), L-arginine (3 g/day), or a combination of both, each for 3 weeks. Endothelium-dependent vasodilation (EDD) was assessed by brachial artery ultrasound. RESULTS: Simvastatin had no effect on EDD in subjects with high ADMA (6.2 +/- 1.2% vs. 6.1 +/- 0.9%), whereas simvastatin plus L-arginine significantly improved EDD (9.8 +/- 1.5% vs. 5.3 +/- 0.8%; p < 0.01). In subjects with low ADMA, simvastatin improved endothelial function when given alone (9.5 +/- 3.2% vs. 6.1 +/- 3.8%; p < 0.001) or in combination with L-arginine (9.0 +/- 3.1% vs. 6.3 +/- 3.3%; p = 0.001). L-arginine alone improved endothelial function in both groups. Endothelium-independent vasodilation was not affected. CONCLUSIONS: Simvastatin does not enhance endothelial function in subjects with elevated ADMA, whereas it does so in patients with low ADMA. Combination of simvastatin with oral L-arginine improves endothelial function in subjects with high ADMA, but has no additional effect in subjects with low ADMA. As NO-mediated effects may play a major role in the therapeutic effects of statins, ADMA concentration is an important factor that influences the "pleiotropic" effects of simvastatin. 相似文献
109.
110.
Maas AP Didden R Bouts L Smits MG Curfs LM 《Research in developmental disabilities》2009,30(3):529-537
Individuals with Prader-Willi syndrome (PWS) are at risk for excessive daytime sleepiness (EDS) and disruptive behavior. This pilot study explores temporal characteristics of EDS and severe disruptive behavior across time of day and day of week in seven individuals with PWS (aged between 33 and 49 years) of whom five were matched to controls. Direct care staff and/or parents used a scatter plot (i.e., 2-h partial interval recording) to collect data during 28 successive days. Overall frequency of EDS and severe disruptive behavior was low in both groups. Individuals with PWS generally showed more EDS when there were no scheduled activities compared to when activities were scheduled, specifically in the afternoon and in the evening and during the weekend. Scatter plot methodology may be useful in identifying situations that evoke excessive sleepiness and severe disruptive behaviors in people with PWS. 相似文献