Human Chorionic Gonadotropin: a hormone with immunological and angiogenic properties.
; Gridelet, Virginie ; Berndt, Sarah et al
in Journal of Reproductive Immunology (2010), 85(1), 93-8
The success of implantation depends on a receptive endometrium, a normal blastocyst and synchronized cross-talk at the maternal–fetal interface. The progression of pregnancy then requires immunological ... [more ▼]
The success of implantation depends on a receptive endometrium, a normal blastocyst and synchronized cross-talk at the maternal–fetal interface. The progression of pregnancy then requires immunological tolerance which allows conceptus survival. A cascade of cytokines mediates this dialogue and is crucial in the cross-talk between the immune and endocrine systems. The first known human embryo-derived signal is chorionic gonadotropin (hCG) by which the embryo profoundly influences immunological tolerance and angiogenesis at the maternal–fetal interface. hCG levels coincide with the development of trophoblast tolerance. Indeed, it increases the number of uterine natural killer cells that play a key role in the establishment of pregnancy. hCG also intervenes in the development of local immune tolerance through the cellular system of apoptosis via Fas/Fas-Ligand. It modulates the Th1/Th2 balance and acts on complement C3 and C4A/B factors modulating decidual immunity. The transient tolerance evident during gestation is at least partially achieved via the presence of regulatory T cells which are attracted by hCG at the fetal–maternal interface. Finally, hCG treatment of activated dendritic cells results in an up-regulation of MHC class II, IL-10 and IDO expression, reducing the ability to stimulate T cell proliferation. Successful implantation requires an extensive endometrial angiogenesis in the implantation site. Recent data demonstrate angiogenic effects of hCG via its interaction with endometrial and endothelial LH/hCG receptors. Our review focuses on these functions of hCG, giving new insight into the endocrine–immune dialogue that exists between the conceptus and immune cells within the receptive endometrium at the time of implantation. [less ▲]Detailed reference viewed: 67 (19 ULg)
Performance evaluation of microbead and ELISA assays for follicular G-CSF: a non-invasive biomarker of oocyte developmental competence for embryo implantation.
; Munaut, Carine ; et al
in Journal of Reproductive Immunology (2010), 86(2), 126-32
G-CSF in individual follicular fluids correlates with the potential of the corresponding embryo to result in a live birth after transfer in IVF. To evaluate the requirements for routine follicular fluid G ... [more ▼]
G-CSF in individual follicular fluids correlates with the potential of the corresponding embryo to result in a live birth after transfer in IVF. To evaluate the requirements for routine follicular fluid G-CSF quantification, we compared follicular fluid G-CSF measurements made with two multiplexed microbead assays purchased from Bio-Rad Laboratories and R&D Systems, and a commercial G-CSF ELISA (R&D Systems). Individual follicular fluids (n=139) associated with transferred embryos were analysed to determine cytokine profile and the fate of each transferred embryo was recorded. The effect of multiplexing as well as comparison of the respective performances of the microbead assay with a flow cytometry assay was explored. Multivariable logistic regression analysis was performed and receiver operating characteristic (ROC) analysis was used to determine the performance and sensitivity/specificity of each method for individual follicular fluids. Covariate factors known to influence IVF outcome such as age, serum oestradiol and embryo score were systematically integrated in each analysis. The quantification of follicular fluid G-CSF using microbead assay methodologies, but not ELISA, yielded results showing the utility of follicular fluid G-CSF as a biomarker predictive of a successful delivery (Au(roc): 0.77 [0.68-0.84] (p=0.003) and 0.75 [0.66-0.82] (p=0.004) for Bio-Rad and R&D Systems microbead assays respectively), whereas follicular fluid G-CSF values quantified by ELISA were not predictive (Au(roc):0.61 [0.52-0.70] p=0.84). Microbead assay and flow cytometry appeared similarly efficient for quantifying follicular fluid G-CSF and multiplex versus single-plex assays did not influence the reliability of quantification. [less ▲]Detailed reference viewed: 49 (16 ULg)
Maternal plasma soluble fms-like tyrosine kinase-1 and free vascular endothelial growth factor at 11 to 13 weeks of gestation in preeclampsia.
; ; Foidart, Jean-Michel et al
in Prenatal Diagnosis (2010), 30(3), 191-7
Objective To investigate the maternal plasma concentration of soluble fms-like tyrosine kinase-1 (sFlt-1) and free vascular endothelial growth factor (free-VEGF) at 11 to 13 weeks of gestation in patients ... [more ▼]
Objective To investigate the maternal plasma concentration of soluble fms-like tyrosine kinase-1 (sFlt-1) and free vascular endothelial growth factor (free-VEGF) at 11 to 13 weeks of gestation in patients destined to develop preeclampsia (PE) and to examine whether any possible differences in maternal plasma levels are related to uterine artery pulsatility index (PI) and maternal serum placental growth factor (PlGF). Methods Plasma free-VEGF, plasma sFlt-1, serum PlGF and uterine artery PI were measured at 11 to 13 weeks in 90 cases that subsequently developed PE and in 180 unaffected controls. Results In the majority of cases of PE and controls the levels of free-VEGF were undetectable. In the pregnancies that developed PE, compared to unaffected controls, uterine artery PI was higher, serum PlGF was lower but there was no significant difference in levels of sFlt-1. Conclusion Measurement of free-VEGF and sFlt-1 in maternal blood at 11 to 13 weeks of gestation is not useful in the prediction of pregnancies destined to develop PE [less ▲]Detailed reference viewed: 27 (5 ULg)
Management of severe preeclampsia
Brichant, Géraldine ; Dewandre, Pierre-Yves ; Foidart, Jean-Michel et al
in Acta Clinica Belgica (2010), 65(3), 163-169
Features of severe preeclampsia include severe proteinuric hypertension and symptoms of central nervous system dysfunction, hepatocellular injury, thrombocytopenia, oliguria, pulmonary oedema ... [more ▼]
Features of severe preeclampsia include severe proteinuric hypertension and symptoms of central nervous system dysfunction, hepatocellular injury, thrombocytopenia, oliguria, pulmonary oedema, cerebrovascular accident and severe intrauterine growth restriction. Women with severe preeclampsia must be hospitalized to confirm the diagnosis, to assess the severity of the disease, to monitor the progression of the disease and to try to stabilize the disease. Severe preeclampsia may be managed expectantly, in selected cases. The objective of expectant management in these patients is to improve neonatal outcome. Expectant management is based on antihypertensive treatment and prevention of end organ dysfunction. Antihypertensive treatment improves maternal outcome but has the potential to be deleterious for the foetus. Plasma volume expansion has been suggested for severe preeclampsia but trials failed to show any benefit. Magnesium sulfate is the anticonvulsivant of choice to treat or prevent eclampsia when indicated. Antenatal corticosteroids are recommended in severely preeclamptic women with 26-34 weeks gestation. Timing of delivery is based upon gestational age, severity of preeclampsia, maternal and foetal risks. [less ▲]Detailed reference viewed: 79 (21 ULg)
Membrane type 1 matrix metalloproteinase detection in tumors, using the iodinated endogenous [123I]-tissue inhibitor 2 of metalloproteinases as imaging agent.
; ; et al
in Cancer Biotherapy & Radiopharmaceuticals (2010), 25(5), 511-20
Matrix metalloproteinases (MMPs) are principal participants in tumor development. In addition to serve as a useful biochemical marker, MMP expression may also provide a target for the diagnostic in vivo ... [more ▼]
Matrix metalloproteinases (MMPs) are principal participants in tumor development. In addition to serve as a useful biochemical marker, MMP expression may also provide a target for the diagnostic in vivo imaging of tumors, using a radiolabeled inhibitor. This study investigates the use of membrane type 1 (MT1)-MMP as target for in vivo tumor diagnosis. Specific binding of the endogenous tissue inhibitor of metalloproteinase-2 (TIMP-2) to MT1-MMP has been previously described. In this study, biodistribution and imaging experiments were performed on MT1-MMP-overexpressing (S.1.5) and control (C.IV.3) tumor-inoculated mice using [(123)I]-recombinant human TIMP-2 (rhTIMP-2) as radioligand and [(123)I]-rhTIMP-1 as control. The expression profile was controlled in vitro and on tumor extracts. rhTIMP-2 as well as rhTIMP-1 were labeled using the Iodogen method and characterized. Biodistribution of [(123)I]-rhTIMP-2 showed a tumor uptake of 2.87% +/- 1.58% ID/g at 3 hours postinjection in S.1.5. Tumor values of [(123)I]-rhTIMP-1 and [(123)I]-rhTIMP-2 evaluated in S.1.5 and C.IV.3, respectively, were significantly lower. Planar imaging revealed significant uptake of [(123)I]-rhTIMP-2 in S.1.5 compared with contralateral background areas. This could not be observed in C.IV.3 and with [(123)I]-rhTIMP-1 in S.1.5. All tumors were well established (200-800 mg). These results suggest that rhTIMP-2 holds potential for development of radiotracers for in vivo imaging in overexpressing MT1-MMP but not in similar tumors that do not express this protease. [less ▲]Detailed reference viewed: 20 (5 ULg)
Manifestations hemodynamiques et respiratoires de la preeclampsie.
Brichant, Jean-François ; Brichant, Géraldine ; Dewandre, Pierre-Yves et al
in Annales Françaises d'Anesthésie et de Réanimation (2010), 29
The hemodynamic and cardiovascular changes seen during PE vary according to the natural history of the disease, its severity and eventual therapeutic measures taken. In the early stages of pregnancy ... [more ▼]
The hemodynamic and cardiovascular changes seen during PE vary according to the natural history of the disease, its severity and eventual therapeutic measures taken. In the early stages of pregnancy, patients who will eventually develop PE, present with a blood pressure which even though within normal limits, is higher than in other women. Similarly, their cardiac output is higher with a normal or decreased peripheral vascular resistance. As soon as the clinical signs of the disease appear, the hemodynamic picture usually shifts toward that of a high peripheral resistance with low cardiac output. Sometimes however, a clinically hyperkinetic circulation may be demonstrated. In PE patients, cardiac preload pressures are usually normal even though the circulatory volumes are lower by 600 to 800ml when compared to those found in normal pregnancy. The cardiac function is however usually preserved during PE. PE induces an exaggerated capillary permeability. This results in the worsening of the airway edema which may render the intubation very difficult. The increased capillary permeability contributes, among other factors, to the heightened risk of acute pulmonary edema. It is not justified to administer an anti-hypertensive treatment to PE women presenting with only moderate hypertension. An anti-hypertensive treatment must only be initiated whenever the hypertension is severe (i.e. SBP>/=160mmHg and/or DBP>/=110mmHg) in order to reduce the risk of maternal complications. In the absence of objective comparative data assessing anti-hypertensive agents for the PE patient, the choice of therapy relies predominantly on the practitioners' own experience. Systematic circulatory volume expansion has not been proven to improve the maternal nor the neonatal prognosis. Such treatment is to be reserved solely for situations in which correcting a hypo-volemia is absolutely necessary. The treatment of acute pulmonary edema in a PE patient is symptomatic and includes the administration of vasodilating agents and of diuretics. A benefit in setting-up an invasive monitoring of the pulmonary artery occlusive pressure has not been demonstrated. The sonographic surveillance of the hemodynamic state can however be useful in these circumstances. [less ▲]Detailed reference viewed: 45 (6 ULg)
Management of recurrent or persistent stress urinary incontinence after TVT-O by mesh readjustment
De Landsheere, Laurent ; ; Foidart, Jean-Michel et al
in International Urogynecology Journal & Pelvic Floor Dysfunction (2010), 21(11), 1347-51
Introduction and hypothesis The aim of this study was to evaluate, retrospectively, the place of sub-urethral mesh readjustment when treating recurrent stress urinary incontinence (SUI) after TVT-O ... [more ▼]
Introduction and hypothesis The aim of this study was to evaluate, retrospectively, the place of sub-urethral mesh readjustment when treating recurrent stress urinary incontinence (SUI) after TVT-O. Methods Between August 2006 and August 2008, eight patients had recurrent or persistent SUI. They were treated surgically by tightening the pre-implanted sling. Results Medium delay between first surgery and mesh adjustment was 6 months. One patient needed a second TVT-O for rupture of the pre-implanted mesh during adjustment. Among the seven patients who underwent a mesh readjustment, three were cured, three improved, there was one failure. Mean follow-up was 25 months. Conclusions The sub-urethral mesh readjustment is a simple and safe procedure for patients with recurrent SIU after TVT-O procedure. Success rates are high, surgery minimally invasive but long-term follow-up is needed to evaluate efficiency. [less ▲]Detailed reference viewed: 52 (3 ULg)
Further pharmacological and genetic evidence for the efficacy of PlGF inhibition in cancer and eye disease.
; ; et al
in Cell (2010), 141(1), 178-90
Our findings that PlGF is a cancer target and anti-PlGF is useful for anticancer treatment have been challenged by Bais et al. Here we take advantage of carcinogen-induced and transgenic tumor models as ... [more ▼]
Our findings that PlGF is a cancer target and anti-PlGF is useful for anticancer treatment have been challenged by Bais et al. Here we take advantage of carcinogen-induced and transgenic tumor models as well as ocular neovascularization to report further evidence in support of our original findings of PlGF as a promising target for anticancer therapies. We present evidence for the efficacy of additional anti-PlGF antibodies and their ability to phenocopy genetic deficiency or silencing of PlGF in cancer and ocular disease but also show that not all anti-PlGF antibodies are effective. We also provide additional evidence for the specificity of our anti-PlGF antibody and experiments to suggest that anti-PlGF treatment will not be effective for all tumors and why. Further, we show that PlGF blockage inhibits vessel abnormalization rather than density in certain tumors while enhancing VEGF-targeted inhibition in ocular disease. Our findings warrant further testing of anti-PlGF therapies. [less ▲]Detailed reference viewed: 128 (11 ULg)
New Biological Investigations on 3-Bromophenyl 6-Acetoxymethyl-2-oxo-2H-1-Benzopyran-3-Carboxylate as Anti-angiogenic Agent
; ; De Tullio, Pascal et al
in Drug Development Research (2010), 71
The development of blood vessels inside tumors is required to provide the nutrients and oxygen needed for tumor growth and to allow the spread of cancer cells at a distance to form metastasis ... [more ▼]
The development of blood vessels inside tumors is required to provide the nutrients and oxygen needed for tumor growth and to allow the spread of cancer cells at a distance to form metastasis. Angiogenesis is also implicated in ocular diseases like age-related macular degeneration. The present work describes the potential anti-angiogenic properties of a coumarinic derivative, 3-bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate (IK9), previously described as a potent inhibitor of HT 1080 fibrosarcoma cell invasion in vitro and tumor growth in vivo. In vivo, ex vivo, and in vitro models were used to delineate the anti-angiogenic properties of IK9. The anti-angiogenic effect of IK9 was demonstrated in vivo in a choroidal neovascularization mice model and additionally ex vivo in a rat aortic ring assay where it was more active than the known matrix metalloproteinase inhibitor Ro 28-2653. IK9 did not affect apoptosis, proliferation, or endothelial cell invasiveness in vitro. These findings suggest a complex mechanism of action of the compound via direct or indirect effects on endothelial cell properties. This study identifies IK9 as a new potent inhibitor of angiogenesis and suggests its potential use as a therapeutic agent. [less ▲]Detailed reference viewed: 81 (14 ULg)
MMP-19 Deficiency Promotes Tenascin-C Accumulation and Allergen-induced Airway Inflammation.
Guéders, Maud ; ; Quesada Calvo, Florence et al
in American Journal of Respiratory Cell and Molecular Biology (2010), 43(3), 286-95
Matrix metalloproteinases (MMPs) recently appeared as key regulators of inflammation, allowing recruitment and clearance of inflammatory cells and modifying the biological activity of many peptidic ... [more ▼]
Matrix metalloproteinases (MMPs) recently appeared as key regulators of inflammation, allowing recruitment and clearance of inflammatory cells and modifying the biological activity of many peptidic mediators by cleavage. MMP-19 is a newly described MMP and preferentially cleaves matrix proteins such as collagens and tenascin-C. The role of MMP-19 in asthma has not been described to date. The purpose of the present study was to assess MMP-19 expression in a murine asthma model and to address biological effects of MMP-19 deficiency in mice. Allergenexposed wild-type (WT) mice displayed an increased expression of MMP-19 mRNA and an increased number of MMP-19-positive cells in the lungs detected by immunohistochemistry. After allergen challenge of MMP-19 knockout (MMP-19-/-) mice, an exacerbated eosinophilic inflammation was detected in bronchoalveolar lavage fluid and bronchial tissue along with an increased airway responsiveness to methacholine. A shift towards increased Th2-driven inflammation in MMP-19-/- mice was demonstrated by 1) increased numbers of cells expressing the IL-33 receptor T1/ST2 in lung parenchyma, 2) increased IgG1 levels in serum and 3) higher levels of IL-13 and CCL11 in lung extracts. Tenascin-C was found accumulated in peribronchial areas of MMP-19-/- after allergen challenges as assessed by Western blot and immunohistochemistry analysis. We conclude that MMP-19 is a new mediator in asthma, preventing tenascin-C accumulation and directly or indirectly controlling Th2-driven airway eosinophilia and airway hyperreactivity. Our data suggest that MMP-19 might act on Th2 inflammation homeostasis through preventing tenascin protein accumulation. [less ▲]Detailed reference viewed: 85 (20 ULg)
Métaplasie osseuse de l'endomètre: deux cas rapportés
Mutsers, Emilie ; Chantraine, Frédéric ; Delbecque, Katty et al
in Gunaïkeia (2010), 15(4),Detailed reference viewed: 336 (9 ULg)
Diabete et grossesse: impact de l'inertie medicale et de l'observance therapeutique.
Pintiaux, Axelle ; ; Philips, Jean-Christophe et al
in Revue Médicale de Liège (2010), 65(5-6), 399-404
Pregnancy and infant outcomes are related to maternal blood glucose profile. Managing preexisting diabetes and achieving euglycaemia before and during the pregnancy reduce the risk for complications ... [more ▼]
Pregnancy and infant outcomes are related to maternal blood glucose profile. Managing preexisting diabetes and achieving euglycaemia before and during the pregnancy reduce the risk for complications. Screening, diagnosis and treatment of gestational diabetes are important issues from a public health point of view, more particularly because of the progression of this disease due to obesity epidemics among young people. Pregnancy in a diabetic woman is a critical situation where neither clinical inertia nor patient's non-compliance could be accepted. [less ▲]Detailed reference viewed: 240 (4 ULg)
L'entretien prénatal : de la rencontre des parents à l'organisation de la communication entre les professionnels
Absil, Gaëtan ; Vandoorne, Chantal ; Masson, Véronique et al
Poster (2009, October)Detailed reference viewed: 136 (55 ULg)
Les indications de l'androgénothérapie chez la femme
DE GOTTAL, Emilie ; PINTIAUX, Axelle ; BELIARD, Aude et al
in Réalités en Gynécologie-Obstétrique (2009), 138
Les taux d’androgènes peuvent être diminués dans de nombreuses situations pathologiques et iatrogènes, mais également physiologiquement chez la femme âgée. La déficience androgénique affecte de nombreux ... [more ▼]
Les taux d’androgènes peuvent être diminués dans de nombreuses situations pathologiques et iatrogènes, mais également physiologiquement chez la femme âgée. La déficience androgénique affecte de nombreux systèmes. La supplémentation androgénique améliorerait les fonctions cognitives, l’humeur, la libido, la qualité osseuse, la force et la fonction musculaire. Toutefois, ce traitement, n’est actuellement pas recommandé en routine par les Guidelines de l’Endocrine Society. Les androgènes peuvent entraîner de l’acné, une augmentation de la pilosité, une raucité de la voix et une clitorimégalie, ces deux derniers effets indésirables étant rares. Ils influencent également le système cardiovasculaire en modifiant le profil lipidique, mais les données restent controversées. La supplémentation par DHEA a été étudiée chez des femmes atteintes d’insuffisance surrénalienne. Il semblerait que 50 mg/j de DHEA soit la dose adéquate pour restaurer des taux d’androgènes physiologiques et améliorer ainsi les symptômes sans observer d’effets secondaires majeurs. Il est toutefois recommandé de poursuivre les recherches parmi les groupes de patientes atteintes de déficience androgénique afin d’en définir précisément le syndrome clinique et d’étudier les effets de l’androgénothérapie. [less ▲]Detailed reference viewed: 230 (1 ULg)
La psychosociologie : un cadre interprétatif de la fonction du tuteur dans un dispositif d'apprentissage par problèmes
VIERSET, Viviane ; ; Foidart, Jean-Michel
in Pédagogie Médicale (2009)Detailed reference viewed: 19 (4 ULg)
Conception, synthèse et évaluation biologique de dérivés coumariniques en tant qu’agents anti-cancéreux potentiels
Hemmer, Marc ; Bambi Nyanguile, Sylvie-Mireille ; De Tullio, Pascal et al
Poster (2009, May)Detailed reference viewed: 48 (20 ULg)
Conception, synthèse et évaluation biologique de dérivés coumariniques en tant qu’agents anti-cancéreux potentiels
; De Tullio, Pascal ; Konradowski, Erika et al
Conference (2009, February 03)Detailed reference viewed: 14 (6 ULg)
New asthma biomarkers: lessons from murine models of acute and chronic asthma.
Di Valentin, Emmanuel ; ; Garbacki, Nancy et al
in American Journal of Physiology - Lung Cellular and Molecular Physiology (2009), 296(2), 185-97
Many patients suffering from asthma are not fully controlled by currently available treatments, and some of them display an airway remodeling leading to exaggerated lung function decline. The aim of the ... [more ▼]
Many patients suffering from asthma are not fully controlled by currently available treatments, and some of them display an airway remodeling leading to exaggerated lung function decline. The aim of the present study was to unveil new mediators in asthma to better understand pathophysiology and propose or validate new potential therapeutic targets. A mouse model of asthma mimicking acute or chronic asthma disease was used to select genes undergoing a modulation in both acute and chronic conditions. Mice were exposed to ovalbumin or PBS for 1, 5, and 10 wk [short-, intermediate-, and long-term model (ST, IT, and LT)], and gene expression in the lung was studied using an Affymetrix 430 2.0 genome-wide microarray and further confirmed by RT-PCR and immunohistochemistry for selected targets. We report that 598, 1,406, and 117 genes were upregulated and 490, 153, 321 downregulated at ST, IT, and LT, respectively. Genes related to mucous secretion displayed a progressively amplified expression during the allergen exposure protocol, whereas genes corresponding to growth and differentiation factors, matrix metalloproteinases, and collagens were mainly upregulated at IT. By contrast, genes related to cell division were upregulated at ST and IT and were downregulated at LT. In this study, besides confirming that Arg1, Slc26a4, Ear11, and Mmp12 genes are highly modulated throughout the asthma pathology, we show for the first time that Agr2, Scin, and Cd209e genes are overexpressed throughout the allergen exposure and might therefore be considered as suitable new potential targets for the treatment of asthma. [less ▲]Detailed reference viewed: 167 (37 ULg)
USE OF CYCLODEXTRIN FOR TREATMENT AND PREVENTION OF BRONCHIAL INFLAMMATORY DISEASES.
Cataldo, Didier ; Evrard, Brigitte ; Foidart, Jean-Michel et al
Patent (2009)Detailed reference viewed: 68 (17 ULg)
Biomarker discovery in asthma-related inflammation and remodeling.
Quesada Calvo, Florence ; Fillet, Marianne ; De Seny, Dominique et al
in Proteomics (2009), 9(8), 2163-2170
Asthma is a complex inflammatory disease of airways. A network of reciprocal interactions between inflammatory cells, peptidic mediators, extracellular matrix components, and proteases is thought to be ... [more ▼]
Asthma is a complex inflammatory disease of airways. A network of reciprocal interactions between inflammatory cells, peptidic mediators, extracellular matrix components, and proteases is thought to be involved in the installation and maintenance of asthma-related airway inflammation and remodeling. To date, new proteic mediators displaying significant activity in the pathophysiology of asthma are still to be unveiled. The main objective of this study was to uncover potential target proteins by using surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) on lung samples from mouse models of allergen-induced airway inflammation and remodeling. In this model, we pointed out several protein or peptide peaks that were preferentially expressed in diseased mice as compared to controls. We report the identification of different five proteins: found inflammatory zone 1 or RELM (FIZZ-1), calcyclin (S100A6), clara cell secretory protein 10 (CC10), Ubiquitin, and Histone H4. [less ▲]Detailed reference viewed: 257 (71 ULg)