Differential Mobilization of the Phospholipid and Triacylglycerol Pools of Arachidonic Acid in Murine Macrophages.

Innate immune cells such as monocytes and macrophages contain high levels of arachidonic acid (AA), part of which can be mobilized during cellular activation for the formation of a vast array of bioactive oxygenated metabolites. Monocytes and macrophages present in inflammatory foci typically incorporate large amounts of AA, not only in membrane phospholipids, but also in neutral lipids such as triacylglycerol. Thus, it was of interest to investigate the metabolic fate of these two AA pools in macrophages. Utilizing a variety of radiolabeling techniques to distinguish the phospholipid and triacylglycerol pools, we show in this paper that during an acute stimulation of the macrophages with yeast-derived zymosan, the membrane phospholipid AA pool acts as the major, if not the only, source of releasable AA. On the contrary, the AA pool in triacylglycerol appears to be used at a later stage, when the zymosan-stimulated response has declined, as a source to replenish the phospholipid pools that were consumed during the activation process. Thus, phospholipids and triacylglycerol play different in roles AA metabolism and dynamics during macrophage activation.

Choline Glycerophospholipid-Derived Prostaglandins Attenuate TNFα Gene Expression in Macrophages via a cPLA2α/COX-1 Pathway.

Macrophages are professional antigen presenting cells with intense phagocytic activity, strategically distributed in tissues and cavities. These cells are capable of responding to a wide variety of innate inflammatory stimuli, many of which are signaled by lipid mediators. The distribution of arachidonic acid (AA) among glycerophospholipids and its subsequent release and conversion into eicosanoids in response to inflammatory stimuli such as zymosan, constitutes one of the most studied models. In this work, we used liquid and/or gas chromatography coupled to mass spectrometry to study the changes in the levels of membrane glycerophospholipids of mouse peritoneal macrophages and the implication of group IVA cytosolic phospholipase A2 (cPLA2α) in the process. In the experimental model used, we observed that the acute response of macrophages to zymosan stimulation involves solely the cyclooxygenase-1 (COX-1), which mediates the rapid synthesis of prostaglandins E2 and I2. Using pharmacological inhibition and antisense inhibition approaches, we established that cPLA2α is the enzyme responsible for AA mobilization. Zymosan stimulation strongly induced the hydrolysis of AA-containing choline glycerophospholipids (PC) and a unique phosphatidylinositol (PI) species, while the ethanolamine-containing glycerophospholipids remained constant or slightly increased. Double-labeling experiments with 3H- and 14C-labeled arachidonate unambiguously demonstrated that PC is the major, if not the exclusive source, of AA for prostaglandin E2 production, while both PC and PI appeared to contribute to prostaglandin I2 synthesis. Importantly, in this work we also show that the COX-1-derived prostaglandins produced during the early steps of macrophage activation restrict tumor necrosis factor-α production. Collectively, these findings suggest new approaches and targets to the selective inhibition of lipid mediator production in response to fungal infection.

The Contribution of Cytosolic Group IVA and Calcium-Independent Group VIA Phospholipase A2s to Adrenic Acid Mobilization in Murine Macrophages.

Adrenic acid (AA), the 2-carbon elongation product of arachidonic acid, is present at significant levels in membrane phospholipids of mouse peritoneal macrophages. Despite its abundance and structural similarity to arachidonic acid, very little is known about the molecular mechanisms governing adrenic acid mobilization in cells of the innate immune system. This contrasts with the wide availability of data on arachidonic acid mobilization. In this work, we used mass-spectrometry-based lipidomic procedures to define the profiles of macrophage phospholipids that contain adrenic acid and their behavior during receptor activation. We identified the phospholipid sources from which adrenic acid is mobilized, and compared the data with arachidonic acid mobilization. Taking advantage of the use of selective inhibitors, we also showed that cytosolic group IVA phospholipase A2 is involved in the release of both adrenic and arachidonic acids. Importantly, calcium independent group VIA phospholipase A2 spared arachidonate-containing phospholipids and hydrolyzed only those that contain adrenic acid. These results identify separate mechanisms for regulating the utilization of adrenic and arachidonic acids, and suggest that the two fatty acids may serve non-redundant functions in cells.

Cellular Plasmalogen Content Does Not Influence Arachidonic Acid Levels or Distribution in Macrophages: A Role for Cytosolic Phospholipase A2γ in Phospholipid Remodeling.

Availability of free arachidonic acid (AA) constitutes a rate limiting factor for cellular eicosanoid synthesis. AA distributes differentially across membrane phospholipids, which is largely due to the action of coenzyme A-independent transacylase (CoA-IT), an enzyme that moves the fatty acid primarily from diacyl phospholipid species to ether-containing species, particularly the ethanolamine plasmalogens. In this work, we examined the dependence of AA remodeling on plasmalogen content using the murine macrophage cell line RAW264.7 and its plasmalogen-deficient variants RAW.12 and RAW.108. All three strains remodeled AA between phospholipids with similar magnitude and kinetics, thus demonstrating that cellular plasmalogen content does not influence the process. Cell stimulation with yeast-derived zymosan also had no effect on AA remodeling, but incubating the cells in AA-rich media markedly slowed down the process. Further, knockdown of cytosolic-group IVC phospholipase A2γ (cPLA2γ) by RNA silencing significantly reduced AA remodeling, while inhibition of other major phospholipase A2 forms such as cytosolic phospholipase A2α, calcium-independent phospholipase A2ß, or secreted phospholipase A2 had no effect. These results uncover new regulatory features of CoA-IT-mediated transacylation reactions in cellular AA homeostasis and suggest a hitherto unrecognized role for cPLA2γ in maintaining membrane phospholipid composition via regulation of AA remodeling.

Sequestration of 9-Hydroxystearic Acid in FAHFA (Fatty Acid Esters of Hydroxy Fatty Acids) as a Protective Mechanism for Colon Carcinoma Cells to Avoid Apoptotic Cell Death.

Hydroxy fatty acids are known to cause cell cycle arrest and apoptosis. The best studied of them, 9-hydroxystearic acid (9-HSA), induces apoptosis in cell lines by acting through mechanisms involving different targets. Using mass spectrometry-based lipidomic approaches, we show in this study that 9-HSA levels in human colorectal tumors are diminished when compared with normal adjacent tissue. Since this decrease could be compatible with an escape mechanism of tumors from 9-HSA-induced apoptosis, we investigated different features of the utilization of this hydroxyfatty acid in colon. We show that in colorectal tumors and related cell lines such as HT-29 and HCT-116, 9-HSA is the only hydroxyfatty acid constituent of branched fatty acid esters of hydroxyfatty acids (FAHFA), a novel family of lipids with anti-inflammatory properties. Importantly, FAHFA levels in tumors are elevated compared with normal tissue and, unlike 9-HSA, they do not induce apoptosis of colorectal cell lines over a wide range of concentrations. Further, the addition of 9-HSA to colon cancer cell lines augments the synthesis of different FAHFA before the cells commit to apoptosis, suggesting that FAHFA formation may function as a buffer system that sequesters the hydroxyacid into an inactive form, thereby restricting apoptosis.

Medicina y Cirugía sin Sangre La Experiencia de Solca Guayaquil / Medicine and Surgery without Blood The Experience of Solca Guayaquil

Introducción: Los riesgos asociados con las Transfusiones de Sangre Alogénicas (TSA) son ampliamente conocidos y han contribuido a nuevos paradigmas de tratamiento para la medicina y cirugía sin sangre. Por tanto, es importante contar con estrategias terapéuticas efectivas y prácticas que sirvan como alternativas al uso de TSA. Este informe describirá las estrategias aplicadas a los pacientes de este reporte. Métodos: Estudio retrospectivo descriptivo de alternativas a la TSA utilizadas en SOLCA Guayaquil con pacientes que no aceptaron TSA bajo ninguna circunstancia, entre los años 2011 y 2017. La estrategia terapéutica se basó en un diagnóstico temprano y un tratamiento agresivo de la anemia y cualquier tipo de sangrado activo. Se utilizó eritropoyetina, hierro y folato, según requerimientos del paciente. Todos los pacientes quirúrgicos recibieron ácido tranexámico y otros hemostáticos tópicos según necesidad. Resultados: De 73 pacientes oncológicos, el 68.5 % eran no quirúrgicos, de este grupo el 62 % recibió quimioterapia. La hemoglobina aumentó hasta 12.6 g/dL. Por tratamiento global por paciente se administraron hasta 3000 mg de hierro, 140.000 unds de eritropoyetina y megadosis de vitamina C fue aplicada con una media de 24 gramos. Todos los pacientes aumentaron sus niveles de hemoglobina en un promedio de 25 días. Conclusión: Es esencial iniciar un tratamiento temprano, preventivo y coordinado con un equipo multidisciplinario comprometido a estos esquemas. Los pacientes respondieron bien a los medicamentos y las dosis recibidas y no se informaron efectos secundarios. También podemos ver que estas estrategias son efectivas y factibles de aplicar.

Introduction: Risks associated with the Allogeneic Blood Transfusions (ABT) are widely known and have contributed to new treatment paradigms for bloodless medicine and surgery. Therefore, it is essential to have effective therapeutic strategies that serve as alternatives to ABTs. This report describes the strategies applied to patients in this paper. Methods: A Retrospective descriptive study of ABT alternatives used in SOLCA Guayaquil with patients who did not accept ABTs under any circumstances, between 2011 and 2017. The therapeutic strategy was an early diagnosis and an aggressive treatment of anemia and any active bleeding. Erythropoietin, iron, and folate were applied, according to the patient's requirements. All surgical patients received tranexamic acid and other hemostatics as needed. Results: Of 73 cancer patients, 68.5% were non-surgical, 62% of the group received chemotherapy. For global treatment per patient, up to 3000 mg of iron was administered, 140,000 units of erythropoietin and megadoses of vitamin C were applied with an average of 24 grams. All patients increased their hemoglobin levels by an average of 25 days. All patients increased their hemoglobin levels by an average of 25 days. Conclusion: It is essential to start early treatment, prevent and coordinate with a multidisciplinary team committed to these schemes. The patients responded well to the medications, and the doses received, and no side effects were reported. We can also see that these strategies are practical and feasible to apply.

Automated Neuron Detection in High-Content Fluorescence Microscopy Images Using Machine Learning.

The study of neuronal morphology in relation to function, and the development of effective medicines to positively impact this relationship in patients suffering from neurodegenerative diseases, increasingly involves image-based high-content screening and analysis. The first critical step toward fully automated high-content image analyses in such studies is to detect all neuronal cells and distinguish them from possible non-neuronal cells or artifacts in the images. Here we investigate the performance of well-established machine learning techniques for this purpose. These include support vector machines, random forests, k-nearest neighbors, and generalized linear model classifiers, operating on an extensive set of image features extracted using the compound hierarchy of algorithms representing morphology, and the scale-invariant feature transform. We present experiments on a dataset of rat hippocampal neurons from our own studies to find the most suitable classifier(s) and subset(s) of features in the common practical setting where there is very limited annotated data for training. The results indicate that a random forests classifier using the right feature subset ranks best for the considered task, although its performance is not statistically significantly better than some support vector machine based classification models.

Regulation of Phagocytosis in Macrophages by Membrane Ethanolamine Plasmalogens.

Macrophages, as professional phagocytes of the immune system, possess the ability to detect and clear invading pathogens and apoptotic cells through phagocytosis. Phagocytosis involves membrane reorganization and remodeling events on the cell surface, which play an essential role in innate immunity and tissue homeostasis and the control of inflammation. In this work, we report that cells deficient in membrane ethanolamine plasmalogen demonstrate a reduced capacity to phagocytize opsonized zymosan particles. Amelioration of plasmalogen deficiency in these cells by incubation with lysoplasmalogen results in a significant augmentation of the phagocytic capacity of the cells. In parallel with these increases, restoration of plasmalogen levels in the cells also increases the number and size of lipid rafts in the membrane, reduces membrane fluidity down to levels found in cells containing normal plasmalogen levels, and improves receptor-mediated signaling. Collectively, these results suggest that membrane plasmalogen level determines characteristics of the plasma membrane such as fluidity and the formation of microdomains that are necessary for efficient signal transduction leading to optimal phagocytosis by macrophages.

Enfermedad cardiovascular y renta individual: un factor que se debe tener en cuenta / Cardiovascular disease and individual income: A factor not to be overlooked

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Group V secreted phospholipase A2 is upregulated by IL-4 in human macrophages and mediates phagocytosis via hydrolysis of ethanolamine phospholipids.

Studies on the heterogeneity and plasticity of macrophage populations led to the identification of two major polarization states: classically activated macrophages or M1, induced by IFN-γ plus LPS, and alternatively activated macrophages, induced by IL-4. We studied the expression of multiple phospholipase A2 enzymes in human macrophages and the effect that polarization of the cells has on their levels. At least 11 phospholipase A2 genes were found at significant levels in human macrophages, as detected by quantitative PCR. None of these exhibited marked changes after treating the cells with IFN-γ plus LPS. However, macrophage treatment with IL-4 led to strong upregulation of the secreted group V phospholipase A2 (sPLA2-V), both at the mRNA and protein levels. In parallel with increasing sPLA2-V expression levels, IL-4-treated macrophages exhibited increased phagocytosis of yeast-derived zymosan and bacteria, and we show that both events are causally related, because cells deficient in sPLA2-V exhibited decreased phagocytosis, and cells overexpressing the enzyme manifested higher rates of phagocytosis. Mass spectrometry analyses of lipid changes in the IL-4-treated macrophages suggest that ethanolamine lysophospholipid (LPE) is an sPLA2-V-derived product that may be involved in regulating phagocytosis. Cellular levels of LPE are selectively maintained by sPLA2-V. By supplementing sPLA2-V-deficient cells with LPE, phagocytosis of zymosan or bacteria was fully restored in IL-4-treated cells. Collectively, our results show that sPLA2-V is required for efficient phagocytosis by IL-4-treated human macrophages and provide evidence that sPLA2-V-derived LPE is involved in the process.

Phospholipase A2 regulation of lipid droplet formation.

The classical regard of lipid droplets as mere static energy-storage organelles has evolved dramatically. Nowadays these organelles are known to participate in key processes of cell homeostasis, and their abnormal regulation is linked to several disorders including metabolic diseases (diabetes, obesity, atherosclerosis or hepatic steatosis), inflammatory responses in leukocytes, cancer development and neurodegenerative diseases. Hence, the importance of unraveling the cell mechanisms controlling lipid droplet biosynthesis, homeostasis and degradation seems evident Phospholipase A2s, a family of enzymes whose common feature is to hydrolyze the fatty acid present at the sn-2 position of phospholipids, play pivotal roles in cell signaling and inflammation. These enzymes have recently emerged as key regulators of lipid droplet homeostasis, regulating their formation at different levels. This review summarizes recent results on the roles that various phospholipase A2 forms play in the regulation of lipid droplet biogenesis under different conditions. These roles expand the already wide range of functions that these enzymes play in cell physiology and pathophysiology.

Efecto de la maca roja (Lepidium meyenii) sobre los niveles de IFN-y en ratas ovariectomizadas / Effect of red maca (Lepidium meyenii) on IFN-y levels in ovariectomized rats

Objetivos. Comparar el efecto de diferentes dosis de maca roja sobre los niveles de interferón gamma (IFN-y) en ratas ovariectomizadas (OVX). Materiales y métodos. Ratas hembras adultas fueron divididas al azar en los siguientes seis grupos: Grupo 1: ratas pesudo-ovariectomizadas (PO); Grupo 2: ratas OVX; Grupo 3: ratas OVX tratadas con 4 ug/kg de estradiol, y Grupo 4, 5 y 6: ratas OVX tratadas con extractos de maca con 2,15, 4,3 y 8,6 mg polifenoles/kilogramo de peso corporal, respectivamente. Resultados. Las ratas OVX mostraron niveles bajos de IFN-y en comparación con las ratas PO. El estradiol y la maca roja revirtieron el efecto de la ovariectomía sobre los niveles de IFN-y. La maca roja presenta un incremento dosis-respuesta de los niveles de IFN-y (r=0,57, p<0,05). Conclusiones. La administración de la maca roja incrementa los niveles de IFN-y en ratas ovariectomizadas.

Objectives. Compare the effect of different doses of red maca on gamma interferon (IFN-y) levels in ovariectomized rats (OVX). Materials and methods. Adult female rats were randomly divided into the following six groups: Group 1: pseudo-ovariectomized rats (PO); Group 2: OVX rats; Group 3: OVX rats treated with 4 ug/kg estradiol; and Group 4, 5 and 6: OVX rats treated with red maca extracts with 2.15, 4.3 and 8.6 mg polyphenols/body weight kilogram, respectively. Results. OVX rats showed low levels of IFN-y compared to PO rats. Estradiol and red maca reversed the effect of ovariectomy on the IFN-y levels. A positive dose-response effect of red maca on IFN-y levels was shown (r = 0.57, p <0.05). Conclusions. Red maca administration increases levels of IFN-y in ovariectomized rats.

[Maca (Lepidium meyenii Walp), a review of its biological properties]. / Maca (Lepidium meyenii Walp), una revisión sobre sus propiedades biológicas.

Maca (Lepidium meyenii) is a plant that grows above 4000 altitude meters in Peru's Central Andes; it has different varieties according to the color of the hypocotyl. This review summarizes the results of studies about the effects of maca on sexual function, spermatogenesis, female reproductive function, memory, depression and anxiety, and energy as well as effects on benign prostatic hyperplasia, osteoporosis and metabolic syndrome. Its anti-aging effect is also discussed as well as safety in consumption. Differences have been shown between the effects of the black, yellow and red maca varieties. Black maca shows the best results on spermatogenesis, memory and fatigue, while red maca is the variety that reverses the benign prostatic hyperplasia and experimentally induced osteoporosis. In addition, maca reduces the glucose levels, and its consumption is related to the lowering of blood pressure and an improved health score. Experimental studies have proven that short and long term consumption don't show in vivo and in vitro toxicity. Although experimental studies have shown that maca has diverse beneficial effects, more clinical studies are needed to confirm these results.

Activation and identification of five clusters for secondary metabolites in Streptomyces albus J1074.

Streptomyces albus J1074 is a streptomycete strain widely used as a host for expression of secondary metabolite gene clusters. Bioinformatic analysis of the genome of this organism predicts the presence of 27 gene clusters for secondary metabolites. We have used three different strategies for the activation of some of these silent/cryptic gene clusters in S. albus J1074: two hybrid polyketide-non-ribosomal peptides (PK-NRP) (antimycin and 6-epi-alteramides), a type I PK (candicidin), a non-ribosomal peptides (NRP) (indigoidine) and glycosylated compounds (paulomycins). By insertion of a strong and constitutive promoter in front of selected genes of two clusters, production of the blue pigment indigoidine and of two novel members of the polycyclic tetramate macrolactam family (6-epi-alteramides A and B) was activated. Overexpression of positive regulatory genes from the same organism also activated the biosynthesis of 6-epi-alteramides and heterologous expression of the regulatory gene pimM of the pimaricin cluster activated the simultaneous production of candicidins and antimycins, suggesting some kind of cross-regulation between both clusters. A cluster for glycosylated compounds (paulomycins) was also identified by comparison of the high-performance liquid chromatography profiles of the wild-type strain with that of a mutant in which two key enzymes of the cluster were simultaneously deleted.

Maca (Lepidium meyenii Walp), una revisión sobre sus propiedades biológicas / Maca (Lepidium meyenii Walp), a review of its biological properties

La maca (Lepidium meyenii) es una planta que crece sobre los 4000 metros de altitud en los Andes Centrales del Perú, presenta diferentes variedades de acuerdo al color de su hipocótilo. La presente revisión resume los resultados de estudios sobre los efectos de la maca en la función sexual, la espermatogénesis, la función reproductiva femenina, la memoria, la depresión y la ansiedad, como energizante y contra la hiperplasia benigna de próstata, osteoporosis y síndrome metabólico. Se discute también su efecto antienvejecimiento y la seguridad en su consumo. Se han demostrado diferencias en el efecto de las variedades negra, amarilla y roja de maca. La maca negra es la que mejores resultados presenta sobre la espermatogénesis, la memoria y contra la fatiga, mientras que la maca roja es la variedad que mejor revierte la hiperplasia benigna de próstata y la osteoporosis inducida experimentalmente. Además, la maca reduce los niveles de glucosa, y su consumo se relaciona con la reducción de la presión arterial y un mejor puntaje de salud. Estudios experimentales han demostrado que el consumo a corto como a largo plazo no muestra toxicidad tanto in vivo como in vitro. A pesar que los estudios experimentales han demostrado que la maca presenta diversos efectos benéficos, son necesarios más estudios clínicos para confirmar estos resultados.

Maca (Lepidium meyenii) is a plant that grows above 4000 altitude meters in Peru’s Central Andes; it has different varieties according to the color of the hypocotyl. This review summarizes the results of studies about the effects of maca on sexual function, spermatogenesis, female reproductive function, memory, depression and anxiety, and energy as well as effects on benign prostatic hyperplasia, osteoporosis and metabolic syndrome. Its anti-aging effect is also discussed as well as safety in consumption. Differences have been shown between the effects of the black, yellow and red maca varieties. Black maca shows the best results on spermatogenesis, memory and fatigue, while red maca is the variety that reverses the benign prostatic hyperplasia and experimentally induced osteoporosis. In addition, maca reduces the glucose levels, and its consumption is related to the lowering of blood pressure and an improved health score. Experimental studies have proven that short and long term consumption don’t show in vivo and in vitro toxicity. Although experimental studies have shown that maca has diverse beneficial effects, more clinical studies are needed to confirm these results.

[Effect of red maca (Lepidium meyenii) on INF-γ levels in ovariectomized rats]. / Efecto de la maca roja (Lepidium meyenii) sobre los niveles de IFN-γ en ratas ovariectomizadas.

OBJECTIVES: Compare the effect of different doses of red maca on gamma interferon (IFN-γ) levels in ovariectomized rats (OVX). MATERIALS AND METHODS: Adult female rats were randomly divided into the following six groups: Group 1: pseudo-ovariectomized rats (PO); Group 2: OVX rats; Group 3: OVX rats treated with 4 ug/kg estradiol; and Group 4, 5 and 6: OVX rats treated with red maca extracts with 2.15, 4.3 and 8.6 mg polyphenols/body weight kilogram, respectively. RESULTS: OVX rats showed low levels of IFN-γ compared to PO rats. Estradiol and red maca reversed the effect of ovariectomy on the IFN-γ levels. A positive dose-response effect of red maca on IFN-γ levels was shown (r = 0.57, p <0.05). CONCLUSIONS: Red maca administration increases levels of IFN-γ in ovariectomized rats.

Reconstrucción de la vía biliar junto al tratamiento adyuvante con ácidoursodesoxicólico en lesiones/estenosisiatrogénicas posterior a colecistectomías. Resultados iniciales / Biliary reconstruction surgery follow by adju-vant therapy with ursodesoxicolcy acid in injury/stenosis after cholecistectomy. Prelimi-nary results

El tratamiento de la estenosis biliar benigna (EBB) constituye unreto médico, más del 70% de los casos son resueltos endoscópica-mente, reservando los más complejos para el abordaje quirúrgico,con una tasa éxito que ronda del 92 % al 60%. Una técnica qui-rúrgica impecable junto a factores favorables del paciente es la prin-cipal garantía de éxito. Objetivo: Mantener un adecuado flujo biliar es uno de los factoresprincipales para evitar inflamación y éstasis biliar, por lo que hemosemprendido el siguiente protocolo de estudio con terapia adyuvantecon ácido ursodesoxicólico posterior a la reconstrucción biliar.Métodos: Ensayo clínico prospectivo no aleatorizado, donde seincluyen pacientes con estenosis biliar benigna desde agosto 2012hasta agosto 2014.Resultados:Se han incluido 13 pacientes con preponderancia delsexo femenino con un 77 %, las estenosis tipo Bismuth 1 y 2 ocu-paron un 23 %, mientras que para Bismuth 4 y 5 un 15,38 % res-pectivamente, las EBB producto en anastomosis biliodigestiva ocu-rrió en un 23 %. El seguimiento promedio fue de 13,3 meses.Posterior al tratamiento, sólo 1 paciente experimentó colangitis enausencia de estenosis. Hasta la fecha de seguimiento ninguno hapresentado re-estenosis.Conclusión: Una técnica quirúrgica impecable junto al tratamientoadyuvante con ácido ursodesoxicólico pareciera ofrecer buenosresultados a fin de evitar la re-estenosis y la colangitis, por lo que suaplicación debe ser estudiada por periodos de tiempo prolongados(AU)

The benign biliary stenosis is a medical challenge; more than 70%of them are resulted endoscopically, leaving the most difficult casesfor surgical treatment, which can reach a success between 92% and60%. Meticulous surgical techniques with better patient prognosticfactors are guarantee of success. Objective:The adequate biliary flow is related with less inflationand less biliary stasis, that's why we decide to use ursodesoxicolicacid as an adjuvant treatment after biliary reconstruction surgery.Methods: Non randomized clinical trial, including patients betweenAugust 2012 to August 2014 with benign biliary stenosis.Results:Were included 13 patients, most of them women 77%.Type 1 and 2 Bismuth 23%, Bismuth 4 -5 15,38 % respectively, and23 % for stenosis of the biliodigestive anastomosis. The medianfollow up was 13,3 months. After surgical reconstruction there wereonly 1 patient who revealed cholangitis, and no restenosis in thefollow up period. Conclusion:A meticulous surgical technique and adjuvant treat-ment with ursobilanic acid seem to show good results avoiding re-stenosis and cholangitis, prolong study period is required(AU)

Chronic mountain sickness score was related with health status score but not with hemoglobin levels at high altitudes.

Chronic mountain sickness (CMS) or lack of adaptation to live in high altitudes is related to environmental hypoxia and excessive erythrocytosis (EE) (hemoglobin >21 and >19 g/dL for men and women, respectively). Diagnosis of CMS ("Qinghai CMS Score") is based on seven signs/symptoms (breathlessness and/or palpitations, sleep disturbance, cyanosis, dilatation of veins, paresthesia, headache, tinnitus) and the score for EE. The present study was designed to determine the association between hemoglobin, Qinghai CMS score, CMS clinical score (7 signs/symptoms) and Health Status using a health survey composed of 20 items. The rate of CMS (32.6%) was higher than the rate of EE (9.7%; P<0.002). A significant inverse relationship was observed between CMS clinical score and health status score (r=-0.56 for men, and r=-0.55 for women, P<0.01). However, CMS clinical score was not different in groups with different Hb levels. Health status score was significantly higher in subjects without CMS. In conclusion, elevated hemoglobin levels were not associated with elevated CMS clinical score.