Mascarillas: producto imprescindible en la pandemia COVID-19 / Masks: essential product in the pandemic COVID-19

Las mascarillas son un elemento básico de protección y limitación de la propagación de la infección por coronavirus. En concreto y en la situación de pandemia sanitaria mundial ante la que nos encontramos frente al COVID-19. Podemos diferenciar varios tipos de mascarillas (quirúrgicas, autofiltrantes, higiénicas, etc.), teniendo cada una de ellas una consideración diferente en cuanto a tipo de producto, requisitos normativos y protección que nos ofrecen. La situación de pandemia actual en la que nos encontramos, hace imprescindible el uso de las mismas para limitar la propagación de agentes infecciosos

Masks are a basic element of protection and limitation of the spread of coronavirus infection. We can distinguish several types of masks (surgical, auto filtering, hygienical, etc.), which have different considerations related to the type of product, regulatory requirements, and grade of protection. The current pandemic situation makes essential the use of masks to limit the spread of infectious agents

[Thrombosis in vascular accesses for haemodialysis: rescue treatment using invasive vascular radiological techniques]. / Accesos vasculares para hemodiálisis trombosados: rescate mediante técnicas de radiología vascular intervencionista.

BACKGROUND: The purpose of this paper is to communicate our experience in the salvage of thrombosed haemodialysis vascular accesses using interventional radiology techniques. METHODS: In the last four years, we have treated, by radiological means, 101 thrombosed haemodialysis vascular accesses. There were 44 autologous arteriovenous fistulas (43.56%) and 57 PTFE grafts (56.44%). There were 69 men (68.3%) and 32 women (31.7%). The mean age was 67.73 years (range 33-84). The mean vascular access age was 23.79 months (range 1-132). Manual catheter-directed aspiration was used. Fragmented, triturated or pushed the thrombus against the pulmonary circulation was avoided in all cases. RESULTS: 78 accesses were salvaged (77.2%). Autologous fistulas average and PTFE grafts success rate were 84.44% and 71.42% respectively. Angioplasty in one or more lesions after thromboaspiration was performed in all accesses, except six (5.9%). Metallic endoprostheses were implanted in 14 accesses (13.9%). Mean follow-up was 9 months (range 0-44). Primary patency was 42.3% +/- 5 at 6 months and 32% +/- 4 at one year. Autologous fistulas patency was better than PTFE grafts patency (p < or =0,05). CONCLUSIONS: Our results suggest thrombosed autologous arteriovenous fistulas salvage is better than PTFE grafts. This justifies interventional radiology techniques in these situations.

Accesos vasculares para hemodialisis trombosados: rescate mediante tecnicas de radiologia vascular intervencionista / No disponible

Introducción: el objetivo de este trabajo es comunicar nuestra experiencia en el rescate o salvación de los accesos vasculares para hemodiálisis trombosados (fístulas autólogas e injertos protésicos) mediante técnicas de radiología vascular intervencionista. Material y métodos: en los últimos cuatro años hemos tratado radiológicamente 101 accesos vasculares para hemodiálisis trombosados, 44 fístulas autólogas (43,56%) y 57 injertos protésicos (56,44%). La distribución por sexos fue de 69 hombres (68,3%) y 32 mujeres (31,7%), con una edad media de 67,63 años (r: 33-84). La antigüedad media del acceso desde su realización quirúrgica fue de 23,79 meses (r: 1-132). La técnica de rescate fue la tromboaspiración manual con catéter con presión negativa. En ningún caso se han fragmentado, triturado o empujado los trombos hacia la circulación. Resultados: en total, se rescataron con éxito 78 accesos (77,2%). El porcentaje de éxito en las fístulas nativas fue del 84,44%, y el de injertos protésicos, del 71,42%. En todos los accesos, menos en seis (5,9%), se hizo angioplastia en una o en más lesiones tras la trombectomía. En 14 accesos (13,9%), se implantaron una o más endoprótesis metálicas (stent). El seguimiento medio fue de nueve meses (rango: 0-44). La permeabilidad primaria global fue de 42,3% ± 5 a los seis meses, y de 32% ± 4 al año. Por grupos, en las fístulas nativas las permeabilidades primarias fueron mejores que en los injertos protésicos (p <0,05). Conclusiones: en nuestra opinión, y basándonos en nuestra experiencia, los resultados de rescate de accesos vasculares trombosados son mejores en las fístulas autólogas que en los injertos protésicos. Los buenos resultados obtenidos justifican el rescate mediante técnicas de radiología intervencionista, independientemente del tiempo transcurrido de la trombosis (AU)

Background: The purpose of this paper is to communicate our experience in the salvage of thrombosed haemodialysis vascular accesses using interventional radiology techniques. Methods: In the last four years, we have treated, by radiological means, 101 thrombosed haemodialysis vascular accesses. There were 44 autologous arteriovenous fistulas (43.56%) and 57 PTFE grafts (56.44%). There were 69 men (68.3%) and 32 women (31.7%). The mean age was 67.73 years (range 33-84). The mean vascular access age was 23.79 months (range 1-132). Manual catheter-directed aspiration was used. Fragmented, triturated or pushed the thrombus against the pulmonary circulation was avoided in all cases. Results: 78 accesses were salvaged (77.2%). Autologous fistulas average and PTFE grafts success rate were 84.44% and 71.42% respectively. Angioplasty in one or more lesions after thromboaspiration was performed in all accesses, except six (5.9%). Metallic endoprostheses were implanted in 14 accesses (13.9%). Mean follow-up was 9 months (range 0-44). Primary patency was 42.3% ± 5 at 6 months and 32% ± 4 at one year. Autologous fistulas patency was better than PTFE grafts patency (p ≤0,05). Conclusions: Our results suggest thrombosed autologous arteriovenous fistulas salvage is better than PTFE grafts. This justifies interventional radiology techniques in these situations (AU)

Cloning of DGAT2, a second mammalian diacylglycerol acyltransferase, and related family members.

Studies involving the cloning and disruption of the gene for acyl-CoA:diacylglycerol acyltransferase (DGAT) have shown that alternative mechanisms exist for triglyceride synthesis. In this study, we cloned and characterized a second mammalian DGAT, DGAT2, which was identified by its homology to a DGAT in the fungus Mortierella rammaniana. DGAT2 is a member of a gene family that has no homology with DGAT1 and includes several mouse and human homologues that are candidates for additional DGAT genes. The expression of DGAT2 in insect cells stimulated triglyceride synthesis 6-fold in assays with cellular membranes, and DGAT2 activity was dependent on the presence of fatty acyl-CoA and diacylglycerol, indicating that this protein is a DGAT. Activity was not observed for acyl acceptors other than diacylglycerol. DGAT2 activity was inhibited by a high concentration (100 mm) of MgCl(2) in an in vitro assay, a characteristic that distinguishes DGAT2 from DGAT1. DGAT2 is expressed in many tissues with high expression levels in the liver and white adipose tissue, suggesting that it may play a significant role in mammalian triglyceride metabolism.

Análisis y estudio comparativo de la producción científica de los servicios de farmacia de hospital de España y gran bretaña a través del medline (1966-1997) / Analysis and comparative study of the scientific production of the hospital pharmacy services of Spain and Great Britain through the Medline (1966-1997)

En un intento de conocer las aportaciones de los servicios de farmacia de hospital (SFH) localizados en España y Gran Bretaña que pueden favorecer el desarrollo de la práctica basada en la evidencia, se ha realizado un análisis y un estudio comparativo de las líneas de investigación desarrolladas en dichos servicios, a partir de las publicaciones que originan. La base de datos utilizada como fuente de información fue Medline y el período de estudio 1966-1997.Para ello se fijaron tres criterios de inclusión para la selección de un documento indizado en Medline: que se realizara en España o Gran Bretaña, que los autores estuvieran adscritos exclusivamente al SFH y que el tema científico no fuera el económico. El análisis y estudio comparativo se realizó en función del área temática, año y revista de publicación y lugar de realización de los artículos publicados durante el período de estudio. (AU)

Triglyceride synthesis: insights from the cloning of diacylglycerol acyltransferase.

Although the biochemistry of triglyceride synthesis has been studied for decades, an understanding of the molecular processes involved has been lacking. The recent cloning of a gene encoding acyl coenzyme A : diacylglycerol acyltransferase, an enzyme that catalyses the final step in triglyceride synthesis, has opened this area to molecular investigation and has begun to provide new insights into triglyceride metabolism.

Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat.

Triglycerides (or triacylglycerols) represent the major form of stored energy in eukaryotes. Triglyceride synthesis has been assumed to occur primarily through acyl CoA:diacylglycerol transferase (Dgat), a microsomal enzyme that catalyses the final and only committed step in the glycerol phosphate pathway. Therefore, Dgat has been considered necessary for adipose tissue formation and essential for survival. Here we show that Dgat-deficient (Dgat-/-) mice are viable and can still synthesize triglycerides. Moreover, these mice are lean and resistant to diet-induced obesity. The obesity resistance involves increased energy expenditure and increased activity. Dgat deficiency also alters triglyceride metabolism in other tissues, including the mammary gland, where lactation is defective in Dgat-/- females. Our findings indicate that multiple mechanisms exist for triglyceride synthesis and suggest that the selective inhibition of Dgat-mediated triglyceride synthesis may be useful for treating obesity.

Apolipoprotein B-related gene expression and ultrastructural characteristics of lipoprotein secretion in mouse yolk sac during embryonic development.

In mice, the yolk sac appears to play a crucial role in nourishing the developing embryo, especially during embryonic days (E) 7;-10. Lipoprotein synthesis and secretion may be essential for this function: embryos lacking apolipoprotein (apo) B or microsomal triglyceride transfer protein (MTP), both of which participate in the assembly of triglyceride-rich lipoproteins, are apparently defective in their ability to export lipoproteins from yolk sac endoderm cells and die during mid-gestation. We therefore analyzed the embryonic expression of apoB, MTP, and alpha-tocopherol transfer protein (alpha-TTP), which have been associated with the assembly and secretion of apoB-containing lipoproteins in the adult liver, at different developmental time points. MTP expression or activity was found in the yolk sac and fetal liver, and low levels of activity were detected in E18.5 placentas. alpha-TTP mRNA and protein were detectable in the fetal liver, but not in the yolk sac or placenta. Ultrastructural analysis of yolk sac visceral endoderm cells demonstrated nascent VLDL within the luminal spaces of the rough endoplasmic reticulum and Golgi apparatus at E7.5 and E8.5. The particles were reduced in diameter at E13.5 and reduced in number at E18.5;-19. The data support the hypothesis that the yolk sac plays a vital role in providing lipids and lipid-soluble nutrients to embryos during the early phases (E7;-10) of mouse development. secretion in mouse yolk sac during embryonic development.

Identification of a gene encoding an acyl CoA:diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis.

Triacylglycerols are quantitatively the most important storage form of energy for eukaryotic cells. Acyl CoA:diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) catalyzes the terminal and only committed step in triacylglycerol synthesis, by using diacylglycerol and fatty acyl CoA as substrates. DGAT plays a fundamental role in the metabolism of cellular diacylglycerol and is important in higher eukaryotes for physiologic processes involving triacylglycerol metabolism such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, and lactation. DGAT is an integral membrane protein that has never been purified to homogeneity, nor has its gene been cloned. We identified an expressed sequence tag clone that shared regions of similarity with acyl CoA:cholesterol acyltransferase, an enzyme that also uses fatty acyl CoA as a substrate. Expression of a mouse cDNA for this expressed sequence tag in insect cells resulted in high levels of DGAT activity in cell membranes. No other acyltransferase activity was detected when a variety of substrates, including cholesterol, were used as acyl acceptors. The gene was expressed in all tissues examined; during differentiation of NIH 3T3-L1 cells into adipocytes, its expression increased markedly in parallel with increases in DGAT activity. The identification of this cDNA encoding a DGAT will greatly facilitate studies of cellular glycerolipid metabolism and its regulation.

ACAT-2, a second mammalian acyl-CoA:cholesterol acyltransferase. Its cloning, expression, and characterization.

The synthesis of cholesterol esters by acyl-CoA:cholesterol acyltransferase (ACAT, EC 2.3.1.26) is an important component of cellular cholesterol homeostasis. Cholesterol ester formation also is hypothesized to be important in several physiologic processes, including intestinal cholesterol absorption, hepatic lipoprotein production, and macrophage foam cell formation in atherosclerotic lesions. Mouse tissue expression studies and the disruption of the mouse ACAT gene (Acact) have indicated that more than one ACAT exists in mammals and specifically that another enzyme is important in mouse liver and intestine. We now describe a second mammalian ACAT enzyme, designated ACAT-2, that is 44% identical to the first cloned mouse ACAT (henceforth designated ACAT-1). Infection of H5 insect cells with an ACAT-2 recombinant baculovirus resulted in expression of a approximately 46-kDa protein in cell membranes that was associated with high levels of cholesterol esterification activity. Both ACAT-1 and ACAT-2 also catalyzed the esterification of the 3beta-hydroxyl group of a variety of oxysterols. Cholesterol esterification activities for ACAT-1 and ACAT-2 exhibited different IC50 values when assayed in the presence of several ACAT-specific inhibitors, demonstrating that ACAT inhibitors can selectively target specific forms of ACAT. ACAT-2 was expressed primarily in mouse liver and small intestine, supporting the hypothesis that ACAT-2 contributes to cholesterol esterification in these tissues. The mouse ACAT-2 gene (Acact2) maps to chromosome 15 in a region containing a quantitative trait locus influencing plasma cholesterol levels. The identification and cloning of ACAT-2 will facilitate molecular approaches to understanding the role of ACAT enzymes in mammalian biology.

Adrenocortical lipid depletion gene (ald) in AKR mice is associated with an acyl-CoA:cholesterol acyltransferase (ACAT) mutation.

ald, a recessive allele in AKR inbred mice, is responsible for complete adrenocortical lipid depletion in postpubertal males, which appears to be androgen dependent. Two recent observations (adrenocortical lipid depletion in acyl-CoA:cholesterol acyltransferase-deficient (Acact-/-) mice and the mapping of Acact to a region of chromosome 1 containing the ald locus) prompted us to ask whether adrenocortical lipid depletion in AKR mice results from an Acact mutation. Refined genetic mapping of Acact and ald was consistent with colocalization of these loci. Crossing Acact-/- with AKR (ald/ald) mice yielded postpubertal male offspring characterized by adrenocortical lipid depletion, indicating that these loci are not complementational and are therefore allelic. Immunoblotting of preputial gland homogenates demonstrated that AKR mice had an ACAT protein with a lower molecular mass than other mouse strains. Analysis of Acact cDNA from AKR mice revealed a deletion of the first coding exon and two missense mutations. Despite these coding sequence differences, the ACAT protein from the ald allele catalyzed cholesterol esterification activity at levels similar to that of wild-type protein. We speculate that the adrenocortical lipid depletion resulting from the ald mutation is caused by an altered susceptibility of the mutant protein to modifying factors, such as androgen production at puberty, in an as yet undetermined manner.

Mice heterozygous for a deletion of the tumor necrosis factor-alpha and lymphotoxin-alpha genes: biological importance of a nonlinear response of tumor necrosis factor-alpha to gene dosage.

The tumor necrosis factors (TNF-alpha and lymphotoxin, or LT-alpha) are important mediators of the immune and inflammatory responses, and it has been proposed that a positive feedback loop could boost the expression of the TNF to sufficiently high levels to fend off infections. To investigate this phenomenon and its biological consequences, we have generated LT-alpha/TNF-alpha knockout mice and compared mice having one or two functional LT-alpha/TNF-alpha alleles. In response to lipopolysaccharide (LPS) stimulation, TNF-alpha levels in the circulation or in the supernatant of macrophage cultures were 20- to 100-fold lower in heterozygous samples than in their wild-type counterparts. This differential increased with the intensity of stimulation and throughout the response, supporting the involvement of a positive feedback loop. Moreover, the heterozygous mice had an increased bacterial load following Listeria monocytogenes infection and exhibited a bimodal response to the association of D-galactosamine and LPS which was similar to that of wild-type mice at low doses of LPS and more like that of homozygous mutants at high doses. These results therefore establish the biological importance of the nonlinear response of TNF-alpha levels to gene dosage, and these mice provide a unique tool to study how the propensity to produce TNF can determine the immunological fitness of individuals.

Transcription of unr (upstream of N-ras) down-modulates N-ras expression in vivo.

The ras proteins (Harvey, Kirsten and N-ras) are key regulators of signal transduction and a perturbation of their GDP/GTP cycle is frequently observed in tumors. In mammals, N-ras constitutes with unr (upstream of N-ras) a tightly linked tandem of ubiquitously expressed genes. Although unr and N-ras appear to be involved in distinct functions, this unusual genetic organization could be important for the regulation of N-ras expression. Specifically, transcription of unr could negatively regulate that of N-ras by transcriptional interference. To investigate this possibility, we have deleted the unr promoter by homologous recombination in murine embryonic stem cells. Analysis of tissues of heterozygous mice revealed an increase in N-ras mRNA accumulation ranging between 20 and 65%, in agreement with the suppression of a transcriptional interference.

Disruption of the acyl-CoA:cholesterol acyltransferase gene in mice: evidence suggesting multiple cholesterol esterification enzymes in mammals.

The microsomal enzyme acyl-CoA:cholesterol acyltransferase (ACAT; EC 2.3.1.26) catalyzes the esterification of cellular cholesterol with fatty acids to form cholesterol esters. ACAT activity is found in many tissues, including macrophages, the adrenal glands, and the liver. In macrophages, ACAT is thought to participate in foam cell formation and thereby to contribute to atherosclerotic lesion development. Disruption of the gene for ACAT (Acact) in mice resulted in decreased cholesterol esterification in ACAT-deficient fibroblasts and adrenal membranes, and markedly reduced cholesterol ester levels in adrenal glands and peritoneal macrophages; the latter finding will be useful in testing the role of ACAT and macrophage foam cell formation in atherosclerosis. In contrast, the livers of ACAT-deficient mice contained substantial amounts of cholesterol esters and exhibited no reduction in cholesterol esterification activity. These tissue-specific reductions in cholesterol esterification provide evidence that in mammals this process involves more than one form of esterification enzyme.

A novel function for apolipoprotein B: lipoprotein synthesis in the yolk sac is critical for maternal-fetal lipid transport in mice.

Apolipoprotein (apo) B, the principal structural component necessary for the synthesis and secretion of triglyceride-rich lipoproteins by the intestine and liver, is highly expressed in the yolk sac visceral endoderm of mammals, although its function in this tissue has been hitherto unclear. Disruption of the apoB gene in mice results in embryonic lethality (approximately 9.5 - 10.5 d). Here we demonstrate that apoB is normally expressed at early time points in embryonic development in yolk sac visceral endodermal cells, and that this expression is associated with the synthesis and secretion of apoB-containing lipoproteins. The lack of apoB in the visceral endoderm resulted in an accumulation of intracellular lipid droplets, an absence of lipoproteins from the secretory pathway, and reduced concentrations of cholesterol and alpha-tocopherol in tissues of apoB-/- embryos. Visceral endoderm of apoB+/- embryos exhibited an intermediate phenotype. Our results suggest that apoB plays an essential role in the transport of lipid nutrients to the developing mouse embryo via the yolk sac-mediated synthesis and secretion of apoB-containing lipoproteins.

Inactivation of the murine N-ras gene by gene targeting.

The mammalian ras genes have been implicated in the genesis of a wide variety of tumors. Although it is likely that they play an essential role in signal transduction, their specific function is still unknown. To initiate a genetic analysis of the ras genes in mammals we inactivated the N-ras gene in murine embryonic stem cells by gene targeting. The frequency of integration at the N-ras locus of our targeting vector being low (of the order of 1/5000 transfectants), we used a positive/negative selection followed by an analysis of individual colonies in order to minimize the in vitro manipulation of the embryonic stem cells. Using this approach, we isolated two clones of ES cells with one inactivated N-ras allele. These cells have no distinctive phenotype either in vitro or in vivo in chimeric mice.