Macrophage Migration Inhibitory Factor Antagonist Blocks the Development of Endometriosis In Vivo

Endometriosis, a disease of reproductive age women, is a major cause of infertility, menstrual disorders and pelvic pain. Little is known about its etiopathology, but chronic pelvic inflammation is a common feature in affected women. Beside symptomatic treatment of endometriosis-associated pain, only two main suboptimal therapeutic approaches (hormonal and invasive surgery) are generally recommended to patients and no specific targeted treatment is available. Our studies led to the detection of a marked increase in the expression of macrophage migration inhibitory factor (MIF) in the eutopic endometrium, the peripheral blood and the peritoneal fluid of women with endometriosis, and in early, vascularized and active endometriotic lesions. Herein, we developed a treatment model of endometriosis, where human endometrial tissue was first allowed to implant into the peritoneal cavity of nude mice, to assess in vivo the effect of a specific antagonist of MIF (ISO-1) on the progression of endometriosis and evaluate its efficacy as a potential therapeutic tool. Administration of ISO-1 led to a significant decline of the number, size and in situ dissemination of endometriotic lesions. We further showed that ISO-1 may act by significantly inhibiting cell adhesion, tissue remodeling, angiogenesis and inflammation as well as by altering the balance of pro- and anti-apoptotic factors. Actually, mice treatment with ISO-1 significantly reduced the expression of cell adhesion receptors αv and ß3 integrins (P<0.05), matrix metalloproteinases (MMP) 2 and 9 (P<0.05), vascular endothelial cell growth factor (VEGF) (P<0.01), interleukin 8 (IL8) (P<0.05), cyclooxygenease (COX)2 (P<0.001) and the anti-apoptotic protein Bcl2 (P<0.01), but significantly induced the expression of Bax (P<0.05), a potent pro-apoptotic protein. These data provide evidence that specific inhibition of MIF alters endometriotic tissue growth and progression in vivo and may represent a promising potential therapeutic avenue

Neuroendocrine–immune disequilibrium and endometriosis: an interdisciplinary approach

Endometriosis, a chronic disease characterized by endometrial tissue located outside the uterine cavity, affects one fourth of young women and is associated with chronic pelvic pain and infertility. However, an in-depth understanding of the pathophysiology and effective treatment strategies of endometriosis is still largely elusive. Inadequate immune and neuroendocrine responses are significantly involved in the pathophysiology of endometriosis, and key findings are summarized in the present review. We discuss here the role of different immune mechanisms particularly adhesion molecules, protein–glycan interactions, and pro-angiogenic mediators in the development and progression of the disease. Finally, we introduce the concept of endometrial dissemination as result of a neuroendocrine-immune disequilibrium in response to high levels of perceived stress caused by cardinal clinical symptoms of endometriosis

Electrostatic interactions inside the aqueous core of spherical reversed micelles (L2 phase)

We propose a model for describing electrostatic interactions in the aqueous core of a spherical reversed micelle. Some counterions are located at the surface of the aqueous core, the others are distributed inside the core following a Boltzmann law. The nonlinearized Poisson-Boltzmann equation is solved in spherical geometry; an asymptotic expansion of its solution is found near a logarithmic divergence. We give an evaluation of the enthalpy of association of a counterion to the surface of the aqueous core. Assuming that the area by polar head remains constant, we obtain the electrostatic energy of the micelle and we show that the electrostatic energy by monomer is a function of the aggregation number.Nous proposons un modèle qui décrit les interactions électrostatiques dans le coeur aqueux d'une micelle inverse sphérique. Nous supposons que certains contre-ions sont situés à la surface du coeur aqueux, les autres étant répartis à l'intérieur suivant une loi de Boltzmann. L'équation de Poisson-Boltzmann non linéarisée est résolue et nous donnons un développement asymptotique de sa solution près d'une divergence logarithmique mise ici en évidence. L'enthalpie d'association d'un contre-ion, à la surface du cœur aqueux est évaluée. Quand la surface par tête polaire reste constante, l'énergie électrostatique par monomère est une fonction du nombre d'agrégation de la micelle

Treatment of dairy process waters modelled by diluted milk using dynamic nanofiltration with a rotating disk module

We have investigated the recovery by nanofiltration of lactose and milk proteins as well as carbon oxygen demand (COD) and ionic concentration reduction in dairy process waters simulated by UHT skim milk diluted 1:2 with an initial COD of 36,000 mgO2 L−1. The filtration system consisted in a 14.5 cm diameter metal disk (smooth or equipped with vanes) rotating near a circular Desal 5 DK membrane. At initial concentration, the permeate fluxes at a transmembrane pressure (TMP) of 4000 kPa and 45 °C ranged from 130 L h−1 m−2 for a smooth disk at 1000 rpm to 230 L h−1 m−2 using a disk with vanes at 2000 rpm. Permeate COD was minimum for this last case which gave the highest shear rates and decreased with increasing TMP from 60 mgO2 L−1 at 1400 kPa to 22 at 4000 kPa. In concentration tests at a TMP of 4000 kPa, at 2000 rpm with vanes, the permeate flux decayed with increasing volume reduction ratio (VRR) but was still 100 L h−1 m−2 at VRR = 7.5. The maximum VRR, reached using a disk with 6 mm vanes rotating at 2000 rpm, was 14.3, corresponding to 38% of dry matter. Permeate COD remained quasi independent of shear rate (rotation speed and disk type) until VRR = 5 but increased more rapidly at lower shear rates for higher VRR, to reach 350 mgO2 L−1 at 2000 rpm with vanes. Comparison with recent data using same fluid, and same membrane, but installed in a vibrating system (VSEP), showed that the rotating disk yields better performance than the VSEP, due to its higher membrane shear rate

Recovery of trypsin inhibitor and soy milk protein concentration by dynamic filtration

This paper investigates the feasibility of producing a soy milk fraction enriched in trypsin inhibitor (STI) which could serve as a feed material for chromatographic purification of STI. This STI is also a soy antinutritional factor which is valuable for its medical and scientific applications. We have used a shear-enhanced filtration system with a disk rotating at high speed near the membrane. Stabilized permeate fluxes at 2500 rpm, with a disk equipped with vanes and a transmembrane pressure (TMP) of 67 kPa were 92 L h-1 m-2 with a 50 kDa MWCO PES membrane against 60 L h-1 m-2 with a 300 kDa one, under the same conditions. STI rejection by the 50 kDa membrane was 98.6%. With a smooth disk at a TMP of 107 kPa, fluxes fell to 30 L h-1 m-2 for both membranes, and rejection remained close to 98% for the 50 kDa membrane. During concentration tests, the permeate flux obeyed the logarithmic decay with concentration factor (CF), with a theoretical maximum CF of 4.85. © 2006 Elsevier B.V. All rights reserved.Articl