Inactive matrix gla-protein is associated with arterial atiffness in an adult population-based study

La vitesse de l'onde de pouls (VOP) est la méthode pour mesurer la rigidité artérielle la plus répandue et la plus validée. C'est aussi un prédicteur indépendant de la mortalité. La Matrix Gla- protein (MGP) est une protein qui inhibe les calcifications vasculaires. MGP nécessite une enzyme dérivée de la vitamine K pour être activée, à l'instar de certains facteurs de coagulation. La forme inactive de MGP, connue sous le terme de « desphospho-uncarboxylated MGP » (dp-ucMGP), peut-être mesurée dans le plasma. Plus les apports de vitamine K sont importants plus les taux de dp-ucMGP diminue. Les taux de dp-ucMGP ont déjà été étudiés et associés à différents marqueurs cardiovasculaires (CV), aux événements CV et à la mortalité. Dans notre travail de recherche nous avons émis l'hypothèse que des taux élevés de dp-ucMGP seraient associés à une VOP élevée. Nous avons recruté les participants à travers une étude multicentrique suisse (SKIPOGH). Le processus de recrutement ciblait des familles dans lesquelles plusieurs membres étaient d'accord de participer. Nous avons mesuré la dp-ucMGP plasmatique grâce à la méthode immuno-enzymatique « ELISA ». Concernant la VOP, nous avons mesuré les ondes de pression au niveau carotidien et fémorale grâce à un tonomètre et calculer la vitesse de leurs propagations. Par la suite nous avons utilisé un modèle de régression linéaire multiple afin de déterminer le lien entre la VOP et dp- ucMGP. Le modèle était ajusté pour l'âge, la fonction rénale et les risques CV classiques. Nous avons inclut 1001 participants dans les analyses (475 hommes et 526 femmes). La valeur moyenne de la VOP était de 7.87 ± 2.10 (m/s) et celle de dp-ucMGP de 0.43 ± 0.20 (nmol/L). La VOP était positivement et significativement associée à dp-ucMGP avant comme après ajustement pour le sexe, l'âge, l'indice de masse corporel, la taille, la pression artérielle systolique et diastolique, la fréquence cardiaque, la fonction rénale, les taux de cholestérol (LDL, HDL), la glycémie, la consommation de tabac, la présence d'un diabète, l'utilisation de médicaments antihypertenseurs ou hypolipémiants et la présence d'antécédents CV (P<0.01). En conclusion, des taux élevés de dp-ucMGP sont positivement et indépendamment associés à la rigidité artérielle après ajustement pour les facteurs de risques CV traditionnels, la fonction rénale et l'âge. Des études expérimentales sont nécessaires afin de déterminer si une supplémentation en vitamine K permet de ralentir l'avancement de la rigidité artérielle grâce à son activation de la MGP.

Embolização arterial no tratamento de hemobilia pós-trauma hepático: relato de caso

Hemobilia é causa rara de hemorragia digestiva e complicação incomum no trauma hepático. Ocorre devido à comunicação entre ductos biliares e vasos intra-hepáticos. Os autores relatam um caso de paciente vítima de ferimento penetrante abdominal que evoluiu, após três meses da hepatorrafia, com dor, icterícia e hemorragia digestiva. Foi realizada angiografia, que demonstrou pseudoaneurisma de artéria hepática direita, e efetuada embolização com sucesso.

Arterial Therapies of Non-Colorectal Liver Metastases.

BACKGROUND: The unique situation of the liver with arterial and venous blood supply and the dependency of the tumor on the arterial blood flow make this organ an ideal target for intrahepatic catheter-based therapies. Main forms of treatment are classical bland embolization (TAE) cutting the blood flow to the tumors, chemoembolization (TACE) inducing high chemotherapy concentration in tumors, and radioembolization (TARE) without embolizing effect but very high local radiation. These different forms of therapies are used in different centers with different protocols. This overview summarizes the different forms of treatment, their indications and protocols, possible side effects, and available data in patients with non-colorectal liver tumors. METHODS: A research in PubMed was performed. Mainly clinical controlled trials were reviewed. The search terms were 'embolization liver', 'TAE', 'chemoembolization liver', 'TACE', 'radioembolization liver', and 'TARE' as well as 'chemosaturation' and 'TACP' in the indications 'breast cancer', 'neuroendocrine', and 'melanoma'. All reported studies were analyzed for impact and reported according to their clinical relevance. RESULTS: The main search criteria revealed the following results: 'embolization liver + breast cancer', 122 results, subgroup clinical trials 16; 'chemoembolization liver + breast cancer', 62 results, subgroup clinical trials 11; 'radioembolization liver + breast cancer', 37 results, subgroup clinical trials 3; 'embolization liver + neuroendocrine', 283 results, subgroup clinical trials 20; 'chemoembolization liver + neuroendocrine', 202 results, subgroup clinical trials 9; 'radioembolization liver + neuroendocrine', 64 results, subgroup clinical trials 9; 'embolization liver + melanoma', 79 results, subgroup clinical trials 15; 'chemoembolization liver + melanoma', 60 results, subgroup clinical trials 14; 'radioembolization liver + melanoma', 18 results, subgroup clinical trials 3. The term 'chemosaturation liver' was tested without indication since only few publications exist and provided us with five results and only one clinical trial. CONCLUSION: Despite many years of clinical use and documented efficacy on intra-arterial treatments of the liver, there are still only a few prospective multicenter trials with many different protocols. To guarantee the future use of these efficacious therapies, especially in the light of many systemic or surgical therapies in the treatment of non-colorectal liver metastases, further large randomized trials and transparent guidelines need to be established.

Resultate und ausser- gewöhnliche Komplikationen der Chirurgie der Gehörgangexostosen [Results and extraordinary complications of surgery for exostoses of the external auditory canal].

We present a retrospective study on 22 operations of exostosis of the external auditory canal in 20 patients. 8 patients were passionated by water sports. The most frequent indication for surgery (13 operations) was recurrent external otitis or ceruminal obstruction. In 7 cases the need for a wider access to the middle ear indicated surgery. Surgery was usually performed as an outpatient procedure, maximum hospitalization was 3 days. The mean healing period was 6 (3-10) weeks. Mean follow up was 43 (3-110) months. There were no severe intraoperative complications such as facial paresis, lesions of the ossicles or of the inner ear. As intraoperative complications we found 2 perforations of the tympanic membrane, 2 expositions of the capsule of the mandibular joint, one of which was followed by chronic pain. As postoperative complications we found an early soft tissue stenosis of the external auditory canal and one late soft tissue stenosis which recurred after revision surgery. No recurrence of exostosis was seen. We describe an up to now unknown complication: the appearance of bilateral petrositis caused by staphylococcus epidermidis after bilateral surgery in an otherwise healthy patient. This study confirms that severe complications are rare, minor ones however relatively common. And that also minor complications may have a troublesome follow. Therefore and because of the potential of severe complications indication for surgery must be made cautiously and risks of the operation must not be underestimated.

Transcatheter arterial embolization for unresectable symptomatic giant hepatic hemangiomas: single-center experience using a lipiodol-ethanol mixture

AbstractObjective:The present article is aimed at reporting the author’s experience with transcatheter arterial embolization using a lipiodol-ethanol mixture in three cases of unresectable symptomatic giant hepatic hemangiomas.Materials and Methods:The cases of three patients with giant unresectable symptomatic hepatic hemangiomas embolized in the period 2009–2010 were retrospectively reviewed. In all the cases, transarterial embolization was performed with an ethanol-lipiodol mixture.Results:Symptoms regression and quality of life improvement were observed in all the cases. No complications were observed and all the patients were discharged within 12 hours after the procedure.Conclusion:Transcatheter arterial embolization using ethanol mixed with lipiodol was a safe and effective treatment for symptomatic giant hepatic hemangiomas in this small series of patients.

Anatomical variations of the celiac trunk and hepatic arterial system: an analysis using multidetector computed tomography angiography

Abstract Objective: To analyze the prevalence of anatomical variations of celiac arterial trunk (CAT) branches and hepatic arterial system (HAS), as well as the CAT diameter, length and distance to the superior mesenteric artery. Materials and Methods: Retrospective, cross-sectional and predominantly descriptive study based on the analysis of multidetector computed tomography images of 60 patients. Results: The celiac trunk anatomy was normal in 90% of cases. Hepatosplenic trunk was found in 8.3% of patients, and hepatogastric trunk in 1.7%. Variation of the HAS was observed in 21.7% of cases, including anomalous location of the right hepatic artery in 8.3% of cases, and of the left hepatic artery, in 5%. Also, cases of joint relocation of right and left hepatic arteries, and trifurcation of the proper hepatic artery were observed, respectively, in 3 (5%) and 2 (3.3%) patients. Mean length and caliber of the CAT were 2.3 cm and 0.8 cm, respectively. Mean distance between CAT and superior mesenteric artery was 1.2 cm (standard deviation = 4.08). A significant correlation was observed between CAT diameter and length, and CAT diameter and distance to superior mesenteric artery. Conclusion: The pattern of CAT variations and diameter corroborate the majority of the literature data. However, this does not happen in relation to the HAS.

Multidetector computed tomography angiography of the celiac trunk and hepatic arterial system: normal anatomy and main variants

Abstract Although digital angiography remains as the gold standard for imaging the celiac arterial trunk and hepatic arteries, multidetector computed tomography in association with digital images processing by software resources represents a useful tool particularly attractive for its non invasiveness. Knowledge of normal anatomy as well as of its variations is helpful in images interpretation and to address surgical planning on a case-by-case basis. The present essay illustrates several types of anatomical variations of celiac trunk, hepatic artery and its main branches, by means of digitally reconstructed computed tomography images, correlating their prevalence in the population with surgical implications.

Les WNK kinases et les effets de WNK3 sur l'activité du canal ENaC

Les WNK kinases sont une famille de sérine/thréonine protéines kinases, des enzymes capables de phosphoryler le résidu OH de sérine ou thréonine. Quatre membres (WNK 1-4) ont été identifiés, largement distribués dans les cellules et tissus des mammifères et dont les fonctions sont de réguler des canaux ioniques et cotransporteurs. Leur particularité se situe au niveau de leur structure puisque une lysine a été substituée par une cystéine dans le domaine catalytique, d'où leur nom « with-no-lysine kinase » (McCormick and Ellison, 2011). Leur rôle dans le bon fonctionnement du rein et plus particulièrement dans le contrôle et maintien du bilan hydro-sodé n'est plus à vérifier puisque des mutations dans WNK 1 et WNK 4 sont connues pour causer la maladie de l'hypertension familiale ou syndrome de pseudohypoaldostéronisme de type 2, aussi appelé syndrome de Gordon (ou Fhht = Familial hyperkalaemic hypertension) (Furgeson and Linas, 2010). Le syndrome de Gordon est une maladie génétique autosomale dominante caractérisée par une hypertension, une hyperkaliémie et une acidose métabolique. Les WNKs contrôlent de nombreux canaux et transporteurs dans le rein, devenant des acteurs importants dans la régulation du bilan sodique et potassique. Leurs effets sont nombreux et variables et les canaux jouant un rôle clé dans cette régulation sont ENaC, NCC et ROMK (Kahle et al., 2008). Dans ce travail, nous commencerons par une partie théorique faisant le point sur l'organisation des néphrons et la régulation du bilan sodique et les différents mécanismes entrant en jeu. Nous intégrerons des informations générales concernant les WNKs ainsi qu'une revue plus détaillée de leurs effets respectifs dans le néphron. Pour terminer, nous aborderons les résultats d'une expérience qui a été réalisée en laboratoire sur des oocytes de Xenopus laevis. L'implication de WNK1 et WNK4 dans le contrôle du sodium ayant déjà été prouvée à de nombreuses reprises, nous nous sommes intéressés ici aux effets de WNK3 sur le canal ENaC ainsi que l'implication de Nedd4-2 dans ce procédé.

Modeling the transport phenomena within arterial wall: porous media approach

The transport of macromolecules, such as low-density lipoprotein (LDL), and their accumulation in the layers of the arterial wall play a critical role in the creation and development of atherosclerosis. Atherosclerosis is a disease of large arteries e.g., the aorta, coronary, carotid, and other proximal arteries that involves a distinctive accumulation of LDL and other lipid-bearing materials in the arterial wall. Over time, plaque hardens and narrows the arteries. The flow of oxygen-rich blood to organs and other parts of the body is reduced. This can lead to serious problems, including heart attack, stroke, or even death. It has been proven that the accumulation of macromolecules in the arterial wall depends not only on the ease with which materials enter the wall, but also on the hindrance to the passage of materials out of the wall posed by underlying layers. Therefore, attention was drawn to the fact that the wall structure of large arteries is different than other vessels which are disease-resistant. Atherosclerosis tends to be localized in regions of curvature and branching in arteries where fluid shear stress (shear rate) and other fluid mechanical characteristics deviate from their normal spatial and temporal distribution patterns in straight vessels. On the other hand, the smooth muscle cells (SMCs) residing in the media layer of the arterial wall respond to mechanical stimuli, such as shear stress. Shear stress may affect SMC proliferation and migration from the media layer to intima. This occurs in atherosclerosis and intimal hyperplasia. The study of blood flow and other body fluids and of heat transport through the arterial wall is one of the advanced applications of porous media in recent years. The arterial wall may be modeled in both macroscopic (as a continuous porous medium) and microscopic scales (as a heterogeneous porous medium). In the present study, the governing equations of mass, heat and momentum transport have been solved for different species and interstitial fluid within the arterial wall by means of computational fluid dynamics (CFD). Simulation models are based on the finite element (FE) and finite volume (FV) methods. The wall structure has been modeled by assuming the wall layers as porous media with different properties. In order to study the heat transport through human tissues, the simulations have been carried out for a non-homogeneous model of porous media. The tissue is composed of blood vessels, cells, and an interstitium. The interstitium consists of interstitial fluid and extracellular fibers. Numerical simulations are performed in a two-dimensional (2D) model to realize the effect of the shape and configuration of the discrete phase on the convective and conductive features of heat transfer, e.g. the interstitium of biological tissues. On the other hand, the governing equations of momentum and mass transport have been solved in the heterogeneous porous media model of the media layer, which has a major role in the transport and accumulation of solutes across the arterial wall. The transport of Adenosine 5´-triphosphate (ATP) is simulated across the media layer as a benchmark to observe how SMCs affect on the species mass transport. In addition, the transport of interstitial fluid has been simulated while the deformation of the media layer (due to high blood pressure) and its constituents such as SMCs are also involved in the model. In this context, the effect of pressure variation on shear stress is investigated over SMCs induced by the interstitial flow both in 2D and three-dimensional (3D) geometries for the media layer. The influence of hypertension (high pressure) on the transport of lowdensity lipoprotein (LDL) through deformable arterial wall layers is also studied. This is due to the pressure-driven convective flow across the arterial wall. The intima and media layers are assumed as homogeneous porous media. The results of the present study reveal that ATP concentration over the surface of SMCs and within the bulk of the media layer is significantly dependent on the distribution of cells. Moreover, the shear stress magnitude and distribution over the SMC surface are affected by transmural pressure and the deformation of the media layer of the aorta wall. This work reflects the fact that the second or even subsequent layers of SMCs may bear shear stresses of the same order of magnitude as the first layer does if cells are arranged in an arbitrary manner. This study has brought new insights into the simulation of the arterial wall, as the previous simplifications have been ignored. The configurations of SMCs used here with elliptic cross sections of SMCs closely resemble the physiological conditions of cells. Moreover, the deformation of SMCs with high transmural pressure which follows the media layer compaction has been studied for the first time. On the other hand, results demonstrate that LDL concentration through the intima and media layers changes significantly as wall layers compress with transmural pressure. It was also noticed that the fraction of leaky junctions across the endothelial cells and the area fraction of fenestral pores over the internal elastic lamina affect the LDL distribution dramatically through the thoracic aorta wall. The simulation techniques introduced in this work can also trigger new ideas for simulating porous media involved in any biomedical, biomechanical, chemical, and environmental engineering applications.

Alternativa al poder; establecimiento de poder: el discurso en el canal en YouTube de Podemos

Peer-reviewed

Hipertensión arterial y enfermedad de Alzheimer

Hypertension (HT) is the most prevalent cardiovascular risk factor associated with dementia and Alzheimer disease (AD). The evidence about the association within hight blood pressure (BP) level in the middle age and dementia and Alzheimer’s disease incidence in the advanced age has increased. Longitudinal studies show that in the previous years of onset AD, BP is similar or lower in the patients who develop AD with regard to those who not develop. When patients has developed AD the case is the same that the previous one. Most studies show that BP reduction is beneficious to prevent cognitive impairment, dementia and AD. Is spite of some discordant studies, health authorities recommend to treat isolated systolic HT with an ‘A’ evidence degree, level 1, to prevent AD. Animal experimentation prove different ways to act of antihypertensive drugs in the AD prevention and has established the pathophysiological bases in this relation, until now only showed through various clinical studies

Anestésicos locais: interação com membranas biológicas e com o canal de sódio voltagem-dependente

Many theories about the mechanism of action of local anesthetics (LA) are described in the literature. Two types of theories can be distinguished: those that focus on the direct effects of LA on their target protein in the axon membranes, i.e. the voltage-gated sodium channel and the ones that take into account the interaction of anesthetic molecules with the lipid membrane phase for the reversible nerve blockage. Since there is a direct correlation between LA hydrophobicity and potency, it is crucial to take this physico-chemical property into account to understand the mechanism of action of LA, be it on the sodium channel protein, lipid(s), or on the whole membrane phase.