231 research outputs found
Multicenter validation of spin-density projection-assisted R2-MRI for the noninvasive measurement of liver iron concentration
No full textPurpose: Magnetic resonance imaging (MRI)-based techniques for assessing liver iron concentration (LIC) have been limited by single scanner calibration against biopsy. Here, the calibration of spin-density projection-assisted (SDPA) R2-MRI (FerriScan®) in iron-overloaded β-thalassemia patients treated with the iron chelator, deferasirox, for 12 months is validated. Methods: SDPA R2-MRI measurements and percutaneous needle liver biopsy samples were obtained from a subgroup of patients (n=233) from the ESCALATOR trial. Five different makes and models of scanner were used in the study. Results LIC, derived from mean of MRI- and biopsy-derived values, ranged from 0.7 to 50.1 mg Fe-g dry weight. Mean fractional differences between SDPA R2-MRI- and biopsy-measured LIC were not significantly different from zero. They were also not significantly different from zero when categorized for each of the Ishak stages of fibrosis and grades of necroinflammation, for subjects aged 3 to 8 versus ≥8 years, or for each scanner model. Upper and lower 95percent limits of agreement between SDPA R2-MRI and biopsy LIC measurements were 74 and -71percent. Conclusion: The calibration curve appears independent of scanner type, patient age, stage of liver fibrosis, grade of necroinflammation, and use of deferasirox chelation therapy, confirming the clinical usefulness of SDPA R2-MRI for monitoring iron overload. © 2013 Wiley Periodicals, Inc.Anderson LJ, 2001, EUR HEART J, V22, P2171, DOI 10.1053-euhj.2001.2822; ANGELUCCI E, 1995, BRIT J HAEMATOL, V89, P757; Angelucci E, 2000, NEW ENGL J MED, V343, P327, DOI 10.1056-NEJM200008033430503; Bland JM, 1999, STAT METHODS MED RES, V8, P135, DOI 10.1191-096228099673819272; Bonkovsky HL, 1999, RADIOLOGY, V212, P227; Brittenham GM, 2001, SEMIN HEMATOL, V38, P37, DOI 10.1053-shem.2001.20143; BRITTENHAM GM, 1982, NEW ENGL J MED, V307, P1671, DOI 10.1056-NEJM198212303072703; BRITTENHAM GM, 1994, NEW ENGL J MED, V331, P567, DOI 10.1056-NEJM199409013310902; Christoforidis A, 2009, EUR J HAEMATOL, V82, P388, DOI 10.1111-j.1600-0609.2009.01223.x; Clark PR, 2003, MAGNET RESON MED, V49, P572, DOI 10.1002-mrm.10378; Emond MJ, 1999, CLIN CHEM, V45, P340; Fischer R, 2003, BRIT J HAEMATOL, V121, P938, DOI 10.1046-j.1365-2141.2003.04297.x; Fischer R, 1999, AM J HEMATOL, V60, P289, DOI 10.1002-(SICI)1096-8652(199904)60:4289::AID-AJH73.0.CO;2-W; Gandon Y, 2004, LANCET, V363, P357, DOI 10.1016-S0140-6736(04)15436-6; Garbowski MW, 2009, BLOOD, V114, P2004; Hankins JS, 2009, BLOOD, V113, P4853, DOI 10.1182-blood-2008-12-191643; Hershko C, 1998, ANN NY ACAD SCI, V850, P191, DOI 10.1111-j.1749-6632.1998.tb10475.x; ISHAK K, 1995, J HEPATOL, V22, P696, DOI 10.1016-0168-8278(95)80226-6; KREEFTENBERG HG, 1984, CLIN CHIM ACTA, V144, P255, DOI 10.1016-0009-8981(84)90061-5; NIELSEN P, 1995, BRIT J HAEMATOL, V91, P827, DOI 10.1111-j.1365-2141.1995.tb05396.x; Nielsen P., 2000, Transfusion Science, V23, P257, DOI 10.1016-S0955-3886(00)00101-6; Olivieri NF, 1997, BLOOD, V89, P739; Pavitt HL, 2011, MAGN RESON MED, V65, P1346, DOI 10.1002-mrm.22712; Sirlin CB, 2010, MAGN RESON IMAGING C, V18, P359, DOI 10.1016-j.mric.2010.08.014; Soriano-Cubells MJ, 1984, ATOM SPECTROSC, V5, P217; St Pierre TG, 2005, BLOOD, V105, P855, DOI 10.1182-blood-2004-01-0177; St Pierre TG, 2004, NMR BIOMED, V17, P446, DOI 10.1002-nbm.905; Taher A, 2011, EUR J HAEMATOL, V87, P355, DOI 10.1111-j.1600-0609.2011.01662.x; Taher A, 2009, EUR J HAEMATOL, V82, P458, DOI 10.1111-j.1600-0609.2009.01228.x; Villeneuve JP, 1996, J HEPATOL, V25, P172, DOI 10.1016-S0168-8278(96)80070-5; Wood JC, 2008, HEMOGLOBIN, V32, P85, DOI 10.1080-03630260701699912; Wood JC, 2005, BLOOD, V106, P1460, DOI 10.1182-blood-2004-10-3982; Wood JC, 2008, MAGN RESON MED, V60, P82, DOI 10.1002-mrm.2166025
La stéatose hépatique et ses effets sur la régulation du métabolisme du cholestérol chez le rat
No full textCette maitrise a été fait en co-direction : Jean-Marc Lavoie (UdeM) et David St-Pierre (UQAM).Mise en contexte : La présente étude a pour but de tester l’hypothèse selon laquelle l’accumulation excessive de lipides au foie perturbe le métabolisme du cholestérol. La stéatose hépatique perturberait ainsi principalement les voies métaboliques qui impliquent les récepteurs de LDL au foie.
Méthodologie: Des rats Wistar (n/groupe = 10) ont été soumis soit à une diète standard (SD), une diète enrichie en lipides (HFD : High Fat Diet) ou à une diète occidentale (WD : Western Diet) pour une durée de 2 ou 6 semaines. Au niveau de la composition des diètes, 60% de l’apport calorique de la diète enrichie en lipides provient des lipides tandis que la diète occidentale est composée à 40% de lipides et 35% de sucrose dont 17,5% de fructose.
Résultats: Comparativement aux animaux traités pendant 2 semaines, le poids des tissus adipeux était environ trois fois plus élevé (~ 20 vs 7 g) chez les animaux soumis à 6 semaines de diètes obésogènes. Une augmentation significative du gain de poids (~ 40g) a été observée uniquement après 6 semaines chez les groupes soumis à la HFD ou la WD (P < 0.01). Comparativement aux animaux soumis à la diète conventionnelle, les niveaux de triglycérides (TG) hépatiques étaient significativement supérieurs chez les rats nourris avec la HFD et WD (P < 0.01) et ce, indépendamment de la durée du traitement. Après deux semaines, des concentrations de TG hépatiques significativement plus élevées (P < 0.05) ont été observés chez les animaux avec la WD comparativement à celles des rats avec la HFD. Des niveaux de cholestérol plasmatiques significativement plus élevés (P < 0.05) ont été mesurés chez les animaux avec la WD par rapport à la SD et la HFD et ce indépendamment de la durée. Après 2 et 6 semaines de diètes, l’expression génique au foie de LDL-R, PCSK9 et SREBP2, qui sont impliqués dans la captation des LDL-cholestérol, a significativement diminué chez les animaux soumis à la WD comparativement à ceux nourris avec la diète SD ou HFD (P < 0.01). De la même manière, des niveaux d’ARNm de LRP1 et ACAT2 significativement diminués (P < 0.01) ont été mesurés chez les animaux nourris avec WD comparativement ceux du groupe SD. L’expression de l’HMGCoAR, l’enzyme limitante impliquée dans la régulation de la synthèse endogène de cholestérol, a été significativement
6
diminuée chez les animaux soumis à la WD comparativement à ceux traités avec la SD ou la HFD après 2 (P < 0.001) et 6 semaines (P < 0.05). Dû au fait que la diète soit enrichie en sucrose et conséquemment en fructose, la WD a fortement favorisé l’expression de ChREBP et ACC, deux régulateurs majeurs dans la voie de la lipogenèse de novo.
Conclusion: Ces résultats suggèrent que la diète de type occidentale augmenterait les niveaux de TG en favorisant simultanément la captation exogène de lipides ainsi que leur production endogène par l’activation de la lipogenèse de novo. L’altération de la voie de la captation du cholestérol par les LDL-R favoriserait une augmentation rapide des taux plasmatiques de cholestérol.Background: The present study was designed to test the hypothesis that excessive fat accumulations impair cholesterol metabolism mainly through alterations in the LDL-receptor (LDL-R) pathway in liver.
Method: Rats were either submitted to standard (SD), high fat (HFD; 60% kcal) or western (WD; 40% fat + 35% sucrose (17.5% fructose)) diets for 2 or 6 weeks.
Results: Weight gain (~ 40g) was observed only following 6 weeks of the obesogenic diets (P < 0.01). Compared to the 2-week treatment, obesogenic diets tripled fat pad weight (~ 20 vs 7 g) after 6 weeks. Hepatic triglyceride (TG) levels were greater in response to both the WD and HFD compared to the SD (P < 0.01) at 2 and 6 weeks and their concentrations were greater (P < 0.05) in WD than HFD at 2 weeks. Plasma cholesterol levels were higher (P < 0.05) in animals submitted to WD compare to SD and HFD. After 2 and 6 weeks, liver expression of LDL-R, PCSK9 and SREBP2, involved in LDL-cholesterol uptake, was lower in animals submitted to WD than in others treated with HFD or SD (P < 0.01). Similarly, LRP1 and ACAT2 mRNA levels were lower (P < 0.01) among WD compared to SD-fed rats. Expression of the gene coding the main regulator of endogenous cholesterol synthesis, HMGCoAR was reduced in response to WD compared to SD and HFD at 2 (P < 0.001) and 6 (P < 0.05) weeks. Being enriched in fructose, the WD strongly promoted the expression of ChREBP and ACC, two key regulators of de novo lipogenesis.
Conclusion: These results show that the WD promptly increased TG levels in the liver by potentiating dietary fat storage and de novo lipogenesis. This effect impaired hepatic cholesterol uptake via the LDL-R axis and promoted a rapid increase in plasma cholesterol levels
Correlation of liver iron concentration determined by R2 magnetic resonance imaging with serum ferritin in patients with thalassemia intermedia
No full text[No abstract available]BRITTENHAM GM, 1993, AM J HEMATOL, V42, P81, DOI 10.1002-ajh.2830420116; BUONANNO G, 1984, SCAND J HAEMATOL, V32, P83; FIORELLI G, 1990, HAEMATOLOGICA, V75, P89; OLIVIERI NF, 1995, NEW ENGL J MED, V332, P918, DOI 10.1056-NEJM199504063321404; Origa R, 2007, HAEMATOL-HEMATOL J, V92, P583, DOI 10.3324-haematol.10842; Pakbaz Z, 2007, PEDIATR BLOOD CANCER, V49, P329, DOI 10.1002-pbc.21275; PIPPARD MJ, 1979, LANCET, V2, P819; St Pierre TG, 2005, ANN NY ACAD SCI, V1054, P379, DOI 10.1196-annals.1345.046; St Pierre TG, 2005, BLOOD, V105, P855, DOI 10.1182-blood-2004-01-0177; Taher A, 2006, BLOOD CELL MOL DIS, V37, P12, DOI 10.1016-j.bcmd.2006.04.005; Wood JC, 2007, CURR OPIN HEMATOL, V14, P183, DOI 10.1097-MOH.0b013e3280d2b76b36414
Calibration of myocardial T2 and T1 against iron concentration.
No full textBACKGROUND: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron.
METHODS: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy.
RESULTS: From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (± SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe] = 5081•(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3 ± 25.8 ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12 months. In the remaining hearts stored for <10 weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001).
CONCLUSION: Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies
Characterization of an organic anion-transporting polypeptide (OATP-B) in human placenta
No full textOrganic anion-transporting polypeptides (OATPs) are a family of multispecific carriers that mediate the sodium-independent transport of steroid hormone and conjugates, drugs, and numerous anionic endogenous substrates. We investigated whether members of the OATP gene family could mediate fetal-maternal transfer of anionic steroid conjugates in the human placenta. OATP-B (gene symbol SLC21A9) was isolated from a placenta cDNA library. An antiserum to OATP-B detected an 85-kDa protein in basal but not apical syncytiotrophoblast membranes. Immunohistochemistry of first-, second-, and third-trimester placenta showed staining in the cytotrophoblast membranes and at the basal surface of the syncytiotrophoblast. Trophoblasts that reacted with an antibody to Ki-67, a proliferation-associated antigen, expressed lower levels of OATP-B. OATP-B mRNA levels were measured in isolated trophoblasts under culture conditions that promoted syncytia formation. Real-time quantitative PCR estimated an 8-fold increase in OATP-B expression on differentiation to syncytia. The uptake of [(3)H]estrone-3-sulfate, a substrate for OATP-B, was measured in basal syncytiotrophoblast membrane vesicles. Transport was saturable and partially inhibited by pregnenolone sulfate, a progesterone precursor. Pregnenolone sulfate also partially inhibited OATP-B-mediated transport of estrone-3-sulfate in an oocyte expression system. These findings suggest a physiological role for OATP-B in the placental uptake of fetal-derived sulfated steroids
Figure 4 from: Brousseau P-M, Giroux M, Handa IT (2020) First record on the biology of Sarcophaga (Bulbostyla) (Diptera, Sarcophagidae). ZooKeys 909: 59-66. https://doi.org/10.3897/zookeys.909.46488
No full textFigure 4 Sarcophaga (Bulbostyla) cadyiA female external terminalia, dorsoventral B female external terminalia, dorsoventral (from Giroux and Wheeler 2010). Abbreviations: cerc, cerci; st, sternite; tg, tergite. Scale bars: 0.5 mm (A–B)
Iron overload indices rise linearly with transfusion rate in patients with sickle cell disease
No full text[No abstract available]Adamkiewicz TV, 2009, BLOOD, V114, P4632, DOI 10.1182-blood-2009-02-203323; Anderson GJ, 2007, AM J HEMATOL, V82, P1128, DOI 10.1002-ajh.21075; Cohen AR, 2008, BLOOD, V111, P583, DOI 10.1182-blood-2007-08-109306; SEARS DA, 1966, BLOOD-J HEMATOL, V28, P708; St Pierre TG, 2005, ANN NY ACAD SCI, V1054, P379, DOI 10.1196-annals.1345.046; Vichinsky E, 2005, AM J HEMATOL, V80, P70, DOI 10.1002-ajh.20402; WHITTEN CF, 1962, NEW ENGL J MED, V266, P529, DOI 10.1056-NEJM19620315266110211121
A comparison of the sensitivities of detection of <it>Plasmodium falciparum </it>gametocytes by magnetic fractionation, thick blood film microscopy, and RT-PCR
No full textAbstract Background The magnetic properties of Plasmodium-infected erythrocytes have been exploited for different clinical and research purposes. A recent study in a rural clinical setting in Papua New Guinea has demonstrated that Plasmodium falciparum gametocyte detection is facilitated by magnetic deposition microscopy but no study has yet determined the relative sensitivity and limit of detection of a magnetic fractionation technique. The present study compares the detection limit and sensitivity of a technique based on the use of commercially available magnetic fractionation columns with those for thick blood film microscopy and reverse transcriptase polymerase chain reaction (RT-PCR) methods. Methods Gametocyte detection in six series of dilutions of cultured P. falciparum parasites with known gametocytaemia was conducted using magnetic fractionation, thick blood film, and RT-PCR techniques. Results The preparations obtained by the magnetic fractionation method were of thin film quality allowing easy gametocyte identification by light microscopy. Magnetic fractionation had a higher sensitivity and approximately two orders of magnitude better limit of detection than thick blood film microscopy. Gametocytes were also more readily detectable on the magnetically fractionated preparations. Magnetic fractionation had a similar limit of detection to that of RT-PCR. Conclusion Magnetic fractionation is a highly sensitive and convenient method for gametocyte detection in comparison with the standard thick blood film and RT-PCR methods, and could readily be adapted to field application.</p
Effects of Cocaine on c-Fos and NGFI-B mRNA Expression in Transgenic Mice Underexpressing Glucocorticoid Receptors
No full textNumerous evidences suggest that stress and stress-related hormones can modulate the activity of the brain reward pathway and thus may account for individual vulnerability towards the reinforcing effects of drugs of abuse. Transgenic (TG) mice expressing an antisense mRNA against the glucocorticoid receptor (GR), which partially blocks GR expression, were used to assess the role of GR dysfunction on cocaine (COC)-induced c-fos and Nerve-Growth Factor Inducible-B (NGFI-B, or Nur77) gene expression. These two genes belong to different families of transcription factors and have been shown to be modulated by various dopaminergic drugs. TG and wild-type (WT) mice were both acutely and repeatedly treated with COC (20 mg/kg, i.p.). In the chronic experiment, mice received a 5-day treatment of COC and were challenged 5 days later with COC or vehicle. Locomotor activity was assessed during the entire chronic experiment in the mouse home cages. Animals were sacrificed 1 h after the last injection and NGFI-B and c-fos mRNA levels in the prefrontal cortex, the nucleus accumbens and the striatum were measured by in situ hybridization. Acute COC administration led to significantly smaller c-fos increases in TG mice compared to WT, whereas repeated COC treatment potentiated c-fos induction both in TG and WT mice to equivalent levels. TG mice displayed higher basal NGFI-B expression in the nucleus accumbens and the level of NGFI-B mRNA was differently modulated by COC in TG mice compared to WT mice. In accordance with data on c-fos expression, behavioral data indicate a blunted locomotor effect on the first COC injection in TG mice, a phenomenon corrected by the repeated COC treatment. These results suggest that an alteration of the hypothalamus-pituitary-adrenal axis can modify COC-induced regulation of the transcription factors c-fos and NGFI-B, and that these changes parallel those seen at the behavioral level. It also demonstrates that the differences at the behavioral and molecular levels noted between TG and WT mice after acute COC injection disappear following repeated COC administration, suggesting that repeated COC has a greater impact in TG mice underexpressing GRs
Genetic epistasis in the VLDL catabolic pathway is associated with deleterious variations on triglyceridemia in obese subjects
No full textBackground :
Abdominal obesity and hypertriglyceridemia (the hypertriglyceridemic-waist phenotype) increase cardiovascular risk. The very low-density lipoprotein (VLDL) is a triglyceride (TG)-rich particle. Frequent variations in the genes coding for enzymes and proteins involved in the VLDL catabolism have already been documented. The epistatic effect of such variants on the risk profile associated with abdominal obesity remains to be elucidated.
Objective :
This study aims to assess the effect of combinations of frequent single-nucleotide polymorphisms (SNPs) in the VLDL catabolic pathway on the relation between abdominal obesity and fasting TG.
Method :
Only gene variants in the lipoprotein lipase, apolipoprotein (apo) CIII, hepatic lipase and apo E genes known to be frequent in the general population (allele frequency>5%) were included in this study. The presence of selected SNPs was detected by polymerase chain reaction-restriction fragment length polymorphisn in a sample of 640 non-diabetic French Canadians at high cardiovascular risk (405 obese, 235 non-obese).
Results :
Carrying more than two frequent gene variants involved in the VLDL catabolic pathway significantly increased the risk of hyperTG (odds ratio of TG>1.7 mmol/l=4.15; P=0.001). This effect was proportional to the number of SNPs and genes involved and was significantly amplified by the presence of abdominal obesity defined on the basis of waist circumference.
Conclusion :
When combined with abdominal obesity, epistasis in the VLDL pathway has a deleterious effect on fasting TG and coronary artery disease risk profile according to the TG threshold (1.7 mmol/l) used in medical guidelines for the assessment of the metabolic syndrome and associated risk
- …
