Pulmonary hypertension in chronic obstructive pulmonary disease

Pulmonary hypertension (PH) is a common complication of advanced chronic obstructive pulmonary disease (COPD) and is defined by a mean pulmonary artery pressure (PAP) ≥ 25 mm Hg at rest in the supine position. Owing to its frequency, COPD is a common cause of PH; in fact, it is the second most frequent cause of PH, just after left heart diseases. PH is due to the elevation of pulmonary vascular resistance, which is caused by functional and morphological factors, chronic alveolar hypoxia being the most important. In COPD PH is generally mild to moderate, PAP usually ranging between 25 and 35 mm Hg in a stable state of the disease. A small proportion of COPD patients may present a severe or “disproportionate” PH with a resting PAP > 35–40 mm Hg. The prognosis is particularly poor in these patients. In COPD PH worsens during exercise, sleep and severe exacerbations of the disease, and these acute increases in afterload may favour the development of right heart failure. The diagnosis of PH relies on Doppler echocardiography, and right heart catheterization is needed in a minority of patients. Treatment of PH in COPD relies on long-term oxygen therapy (≥ 16h/day) which generally stabilizes or at least attenuates the progression of PH. Vasodilator drugs, which are commonly used in idiopathic pulmonary arterial hypertension, have rarely been used in COPD, and we lack studies in this field. Patients with severe PH should be referred to a specialist PH centre where the possibility of inclusion in a controlled clinical trial should be considered.Pulmonary hypertension (PH) is a common complication of advanced chronic obstructive pulmonary disease (COPD) and is defined by a mean pulmonary artery pressure (PAP) ≥ 25 mm Hg at rest in the supine position. Owing to its frequency, COPD is a common cause of PH; in fact, it is the second most frequent cause of PH, just after left heart diseases. PH is due to the elevation of pulmonary vascular resistance, which is caused by functional and morphological factors, chronic alveolar hypoxia being the most important. In COPD PH is generally mild to moderate, PAP usually ranging between 25 and 35 mm Hg in a stable state of the disease. A small proportion of COPD patients may present a severe or “disproportionate” PH with a resting PAP > 35–40 mm Hg. The prognosis is particularly poor in these patients. In COPD PH worsens during exercise, sleep and severe exacerbations of the disease, and these acute increases in afterload may favour the development of right heart failure. The diagnosis of PH relies on Doppler echocardiography, and right heart catheterization is needed in a minority of patients. Treatment of PH in COPD relies on long-term oxygen therapy (≥ 16h/day) which generally stabilizes or at least attenuates the progression of PH. Vasodilator drugs, which are commonly used in idiopathic pulmonary arterial hypertension, have rarely been used in COPD, and we lack studies in this field. Patients with severe PH should be referred to a specialist PH centre where the possibility of inclusion in a controlled clinical trial should be considered

Magnetic resonance imaging in pulmonary hypertension: an overview of current applications and future perspectives.

Pulmonary hypertension is an heterogeneous group of diseases characterised by increased pulmonary arterial pressures which impact on the upstream right ventricle. Pulmonary hypertension can be challenging to diagnose, classify and monitor when specific therapies are applicable. Cardiac magnetic resonance (CMR) imaging has greatly evolved in the last decades and is a promising tool to non-invasively follow pulmonary hypertension patients. CMR provides a comprehensive evaluation of the heart and is therefore the gold standard for quantification of right ventricular volumes, mass and function, which are critical for pulmonary hypertension prognosis. In addition, innovative MR techniques allow an increasingly precise evaluation of pulmonary haemodynamics and lung perfusion. This review highlights the main advantages offered by CMR in pulmonary hypertension and gives an overview of putative future applications. Although right heart catheterisation remains mandatory in the diagnostic algorithm, CMR could play an increasingly important role in the coming years in monitoring pulmonary hypertension patients

Conception de nouveaux systèmes de formulation d'actifs dépigmentants, en vue de leur utilisation par voie cutanée

L'encapsulation de molécules actives est au centre de la boîte à outils du formulateur du troisième millénaire. Le recours à cette technique est de plus en plus employée car cette dernière présente de nombreux avantages ; libération contrôlée de molécules actives de leur environnement, diminution de la toxicité des actifs ou encore véhiculer le principe actif jusqu'à sa cible. La peau qui constitue une barrière physiologique a pour fonction d'assurer une protection biologique et physiologique en empêchant la pénétration d'agents pathogènes et de xénobiotiques. L'industrie ne développant pas de nouvelles molécules actives spécialement destinée à la voie topique, l'enjeu majeur de ce mode d'administration est de trouver des techniques pour parer aux inconvénients de cette voie d'administration. Ce travail réalisé en collaboration avec les laboratoires Pierre Fabre consiste en la mise au point de nouveaux systèmes d'actifs dépigmentants, en vue de leur utilisation par voie topique. Pour ce faire nous avons voulu exploité les nombreuses propriétés du chitosan, polysaccharide biocompatible, biodégradable, afin d'inscrire ce travail dans une démarche de développement durable. Il s'agit alors, dans ce travail, de mettre au point de systèmes associant actifs dépigmentants et promoteur de pénétration cutanée, encapsulés par un sel de chitosan, afin de former des complexes aux propriétés dépigmentantes. Les complexes formés, pourront grâce au promoteur de pénétration faciliter le passage de la molécule active à travers les différentes couches de l'épiderme, afin de favoriser l'acheminement de l'actif jusqu'à son site d'action, c'est-à-dire, le mélanocyte. Ces systèmes originaux sont alors mis à profit pour l'élaboration de nouvelles formulations bioactives qui pourront être utilisés dans le cadre de thérapies des hyperpigmentations.The encapsulation of active molecules is central to the toolbox of the formulator of the third millennium. The use of this technique is increasingly used because it has many advantages; controlled release of active molecules in their environment, decrease the toxicity of assets or carry the active ingredient to the target. The skin which is a physiological barrier function is to protect biological and physiological preventing the penetration of pathogens and xenobiotics. The industry does not develop new active molecules specifically designed to topically; the major challenge of this mode of administration is to find techniques to counter the disadvantages of this route of administration. This work done in collaboration with Pierre Fabre Laboratories consists in developing new systems depigmenting agents, to use topically. To do this we wanted to operate numerous properties of chitosan, polysaccharide biocompatible, biodegradable, to place this work in a sustainable development approach. It is then, in this work, to develop systems combining active depigmenting skin penetration enhancer, salt encapsulated chitosan to form complexes with depigmenting properties. Complexes formed, may through penetration enhancer facilitate the passage of the active molecule through the different layers of the epidermis, to facilitate the delivery of the asset to its site of action, ie ie, the melanocyte. These original systems are then used to develop new bioactive formulations that can be used in therapy hyperpigmentation

Simulation of turbulent flows out of spectral equilibrium using the PITM method

The two main approaches to numerical prediction of turbulent flows that are the RANS method and the LES method have long been developed independently from each other and there is a need in practice to bridge these apparently different approaches. Relying upon the spectral theory background, it has been possible to develop continuous hybrid methods that allow seamless coupling between RANS and LES. The derivation of the PITM method is based on the dynamic equation of the two-point fluctuating velocity correlations with extension to nonhomogeneous turbulence. Indeed, the two-point velocity correlation equation embodies a detailed description of the turbulence field. Then, using Fourier transform and performing averaging on spherical shells on the dynamic equation, leads formally to the evolution equation of the one-dimensional spectral velocity correlation tensor. Exiled in one-dimensional space, the turbulence quantities are represented by functions of the scalar wave number rather than the wave vector. These spectral equations have also been the basis for developing one-dimensional non-isotropic spectral models [1, 2]. A partial integration over a split spectrum, with a given partitioning understood as spectral filtering, yields the partial integrated transport modeling (PITM) method that can be used for practical simulations of turbulent flows [3, 4]. As a result, new transport equations for the subfilter scale stresses and dissipation-rate have been obtained. In this formulation, the model is governed by a dimensionless parameter which involves the cutoff wave number and the turbulence length-scale. Previous simulations have shown that the PITM method is able to reproduce fairly well a large variety of internal and external flows out of spectral equilibrium in the energetic sense and spectral anisotropy sense. Because advanced closures can be used to model the subfilter range, then, large filter widths can be used without prejudice and as a result the computing time can be fairly reduced. The present paper considers various applications such as rotating flows encountered in turbomachinery [6], pulsed turbulent flows [3], flows with wall mass injection [4], flows with separation and reattachment of the boundary layer [7, 8] a mixing of two turbulent flows of different scales [9], airfoil flows [10], and a flow in a small axisymmetric contraction [11], while allowing a drastic reduction of the computational resources in comparison with the one required for highly resolved LES. [1] Cambon, C., Jeandel, D., Mathieu, J. 104, 247-262 (1981). [2] Chaouat, B., Schiestel, R. Theor. Comput. Fluid Dyn. 21, 201-229 (2007). [3] Schiestel, R., Dejoan, A. Theor. Comput. Fluid Dyn. 18, 443-468 (2005). [4] Chaouat, B., Schiestel, R. Phys. Fluids 17, 065106, 1-19 (2005). [5] Chaouat, B., Schiestel, R. Phys. Fluids 24, 085106, 1-34 (2012). [6] Chaouat, B. Phys. Fluids 24, 045108,1-35 (2012). [7] Chaouat, B. J. Turbul. 11, 1-30 (2010). [8] Chaouat, B., Schiestel, R. Computers and Fluids 84, 279-300 (2013). [9] Befeno, I., Schiestel, R. Flow, Turbul. Combust. 78, 129-151 (2007). [10] Stoellinger, M., Roy, R., Heinz, S. in Proceedings of the 9th Symposium on Turbulence Shear Flow Phenomena, edited by the University of Melbourne, 7B5, 1-6 (2015). [11] B. Chaouat. Flow, Turbul. Combust. In press (2016). [12] Uberoi M.S., Wallis, S. J. Fluid Mech. 24, 539-543 (1966)

Cellular immune response to Plasmodium falciparum after pregnancy is related to previous placental infection and parity

BACKGROUND: Malaria in pregnancy is characterised by the sequestration of Plasmodium falciparum-infected erythrocytes in placental intervillous spaces. Placental parasites express a specific phenotype, which allows them to cytoadhere to chondroitin sulfate A expressed by syncytiotrophoblasts. Malaria infection during pregnancy allows the acquisition of antibodies against placental parasites, these antibodies are thought to be involved in protection during subsequent pregnancies. METHODS: To investigate the development of a cellular response to placental parasites during pregnancy, peripheral blood mononuclear cells were collected from women at the time of their confinement. The study was performed in Cameroon where malaria transmission is perennial. In vitro cell proliferation and cytokine production were measured in response to non-malarial activators (concanavalin A and PPD), a recombinant protein from P. falciparum MSP-1, and erythrocytes infected by two P. falciparum lines, RP5 and W2. Like placental parasites, the RP5 line, but not W2, adheres to chondroitin sulfate A and to syncytiotrophoblasts. RESULTS: The proliferative response to all antigens was lower for cells obtained at delivery than 3 months later. Most interestingly, the cellular response to the RP5 line of P. falciparum was closely related to parity. The prevalence rate and the levels of response gradually increased with the number of previous pregnancies. No such relationship was observed with W2 line, or MSP-1 antigen. CONCLUSIONS: This suggests the occurrence of an immune response more specific for the RP5 line in women having had multiple pregnancies, and who are likely to develop immunity to pregnancy-associated parasites. Both humoral and cellular mechanisms may account for the lower susceptibility of multigravidae to malaria

Critical role and therapeutic control of the lectin pathway of complement activation in an abortion-prone mouse mating

The abortion-prone mating combination CBA/J 7 DBA/2 has been recognized as a model of preeclampsia, and complement activation has been implicated in the high rate of pregnancy loss observed in CBA/J mice. We have analyzed the implantation sites collected from DBA/2-mated CBA/J mice for the deposition of the complement recognition molecules using CBA/J mated with BALB/c mice as a control group. MBL-A was observed in the implantation sites of CBA/J 7 DBA/2 combination in the absence of MBL-C and was undetectable in BALB/c-mated CBA/J mice. Conversely, C1q was present in both mating combinations. Searching for other complement components localized at the implantation sites of CBA/J 7 DBA/2, we found C4 and C3, but we failed to reveal C1r. These data suggest that complement is activated through the lectin pathway and proceeds to completion of the activation sequence as revealed by C9 deposition. MBL-A was detected as early as 3.5 d of pregnancy, and MBL-A deficiency prevented pregnancy loss in the abortion-prone mating combination. The contribution of the terminal complex to miscarriage was supported by the finding that pregnancy failure was largely inhibited by the administration of neutralizing Ab to C5. Treatment of DBA/2-mated CBA/J mice with Polyman2 that binds to MBL-A with high affinity proved to be highly effective in controlling the activation of the lectin pathway and in preventing fetal loss