La mortalidad por cáncer en las comarcas de cataluña (1983–1989)

ResumenObjectivosComparar la mortalidad intercomarcal de Cataluña para algunos de los tumores malignos más frecuentes.MetodologíaSe han analizado los datos globales y de cinco localizaciones tumorales específicas relativos a la mortalidad por cáncer de un período de siete años (1983-1989). Se han obtenido las tasas brutas de mortalidad y las específicas para cada localización analizada. La comparación intercomarcal se ha realizado ajustando las tasas por edad mediante el método directo, tomando como referencia la población de Cataluña de 1986. Se han calculado las razones comparativas de mortalidad (RCM) de cada comarca respecto a Cataluña.ResultadosLa mortalidad global por cáncer es más alta en la comarca del Barcelonés para los hombres y en la de Osona para las mujeres. La RCM de los hombres del Barcelonés es la más alta para el cáncer de tráquea, bronquios y pulmón; la de la comarca del Solsonés es la más alta para el cáncer de estómago, y la de la Cerdanya es la más alta para el cáncer de colon y recto. Entre las mujeres, la RCM más alta para el cáncer de tráquea, bronquios y pulmón la presenta la comarca del Montsiá, para el cáncer de mama la del Baix Empordá y para el cáncer de estómago la del Alt Urgell.ConclusionesEl análisis comparativo de la mortalidad por cáncer, por comarcas y por sexos, permite observar importantes diferencias en la manifestación del fenómeno, lo cual puede orientar de manera más específica las políticas de control del cáncer y de investigación a desarrollar en cada territorio.SummaryObjectivesTo compare mortality among counties (comarques) in Catalonia, Spain for the most frequent malignant tumors.MethodsOverall mortality data and for five specific tumor sites were analyzed for a five-year period (1983-1989). Crude and site-specific mortality rates were computed. The comparison between counties was adjusted for the 1986 population of Catalonia using the direct method. Comparative mortality ratios (CMR) were obtained for each county with respect to Catalonia.ResultsOverall cancer mortality was higher in the Barcelonés for men and in Osona form women. The CMR for men in the Barcelonés was the highest for cancer of the trachea, bronchi and lungs; the CMR in Solsonés was the highest for stomach cancer, while in Cerdanya it was the highest for colorectal cancer. Among women, the highest CMR for cancer of the trachea, bronchi and lungs was in Montsiá, whereas for breast cancer it was Baix Empordá, and Alt Urgell for stomach cancer.ConclusionsComparative analyses of cancer mortality by county in Catalonia and sex underscores differences in its distribution, allowing the orientation of cancer control policies and research to be developed in each geographical area

Plant cell and organ cultures as a source of phytochemicals

Podeu consultar el llibre complet a: http://hdl.handle.net/2445/67430Plant cell and organ cultures constitute a promising platform for the production of numerous valuable secondary compounds. Currently, in vitro culture techniques involve both empirical and rational approaches as suitable strategies to condition high metabolite production and establish competitive plant cell-based bioprocesses. In this context, we have developed hairy root cultures of Panax ginseng, and engineered hairy root cultures of Duboisia, Datura metel and Hyoscyamus spp and plant cell cultures of Centella asiatica and Taxus spp. This chapter describes our work on the development of two different biotechnological systems to improve taxol production in cell suspension cultures of Taxus spp and ginsenoside production in hairy root cultures of Panax ginseng

Destination Sustainability and Memorable Tourism Experiences

The objective of this paper is to study the relationship between memorable tourism experiences and destination sustainability. Three hypotheses that relate dimensions of sustainability (economic, socio-cultural, and environmental) to memorable tourism experience are considered, based on a review of the literature. A questionnaire designed for that purpose was administered to 1034 tourists who stayed at five rural and sun and beach destinations in Spain. A multigroup analysis with a structural equation model was conducted to establish the differences between both destination types. The results show that destination environmental sustainability influences the memorable tourism experience, though significant differences between rural and sun and beach destinations have been detected. Age plays a moderating role: the younger the tourist the greater the influence of sustainability on memorable tourism experiences

Genetic transformation of Artemisia carvifolia Buch with rol genes enhances artemisinin accumulation

The potent antimalarial drug artemisinin has a high cost, since its only viable source to date is Artemisia annua (0.010.8% DW). There is therefore an urgent need to design new strate- gies to increase its production or to find alternative sources. In the current study, Artemisia carvifolia Buch was selected with the aim of detecting artemisinin and then enhancing the production of the target compound and its derivatives. These metabolites were determined by LC-MS in the shoots of A. carvifolia wild type plants at the following concentrations: arte- misinin (8μg/g), artesunate (2.24μg/g), dihydroartemisinin (13.6μg/g) and artemether (12.8μg/g). Genetic transformation of A. carvifolia was carried out with Agrobacterium tumefaciens GV3101 harboring the rol B and rol C genes. Artemisinin content increased 3-7-fold in transgenics bearing the rol B gene, and 2.3-6-fold in those with the rol C gene. A similar pattern was observed for artemisinin analogues. The dynamics of artemisinin con- tent in transgenics and wild type A.carvifolia was also correlated with the expression of genes involved in its biosynthesis. Real time qPCR analysis revealed the differential expression of genes involved in artemisinin biosynthesis, i.e. those encoding amorpha-4, 11 diene synthase (ADS), cytochrome P450 (CYP71AV1), and aldehyde dehydrogenase 1 (ALDH1), with a relatively higher transcript level found in transgenics than in the wild type plant. Also, the gene related to trichome development and sesquiterpenoid biosynthesis (TFAR1) showed an altered expression in the transgenics compared to wild type A.carvifolia, which was in accordance with the trichome density of the respective plants. The trichome index was significantly higher in the rol B and rol C gene-expressing transgenics with an increased production of artemisinin, thereby demonstrating that the rol genes are effective inducers of plant secondary metabolism

Differential expression of E-type prostanoid receptors 2 and 4 in microglia stimulated with lipopolysaccharide

[Background] Cyclooxygenase-2 (COX-2) is induced under inflammatory conditions, and prostaglandin E2 (PGE2) is one of the products of COX activity. PGE2 has pleiotropic actions depending on the activation of specific E-type prostanoid EP1-4 receptors. We investigated the involvement of PGE2 and EP receptors in glial activation in response to an inflammatory challenge induced by LPS.[Methods] Cultures of mouse microglia or astroglia cells were treated with LPS in the presence or absence of COX-2 inhibitors, and the production of PGE2 was measured by ELISA. Cells were treated with PGE2, and the effect on LPS-induced expression of TNF-α messenger RNA (mRNA) and protein was studied in the presence or absence of drug antagonists of the four EP receptors. EP receptor expression and the effects of EP2 and EP4 agonists and antagonists were studied at different time points after LPS.[Results] PGE2 production after LPS was COX-2-dependent. PGE2 reduced the glial production of TNF-α after LPS. Microglia expressed higher levels of EP4 and EP2 mRNA than astroglia. Activation of EP4 or EP2 receptors with selective drug agonists attenuated LPS-induced TNF-α in microglia. However, only antagonizing EP4 prevented the PGE2 effect demonstrating that EP4 was the main target of PGE2 in naïve microglia. Moreover, the relative expression of EP receptors changed during the course of classical microglial activation since EP4 expression was strongly depressed while EP2 increased 24 h after LPS and was detected in nuclear/peri-nuclear locations. EP2 regulated the expression of iNOS, NADPH oxidase-2, and vascular endothelial growth factor. NADPH oxidase-2 and iNOS activities require the oxidation of NADPH, and the pentose phosphate pathway is a main source of NADPH. LPS increased the mRNA expression of the rate-limiting enzyme of the pentose pathway glucose-6-phosphate dehydrogenase, and EP2 activity was involved in this effect.[Conclusions] These results show that while selective activation of EP4 or EP2 exerts anti-inflammatory actions, EP4 is the main target of PGE2 in naïve microglia. The level of EP receptor expression changes from naïve to primed microglia where the COX-2/PGE2/EP2 axis modulates important adaptive metabolic changes.This work was supported by the Spanish Ministerio de Economia y Competitividad (MINECO) (SAF2014-56279R) and the European Community FP7 (InMiND project no. 278850). EBT had an FPU PhD fellowship of MINECO.Peer reviewe

Enhanced artemisinin yield by expression of rol genes in artemisia annua

Background: Despite of many advances in the treatment of malaria, it is still the fifth most prevalent disease worldwide and is one of the major causes of death in the developing countries which accounted for 584,000 deaths in 2013, as estimated by World Health Organization. Artemisinin from Artemisia annua is still one of the most effective treatments for malaria. Increasing the artemisinin content of A. annua plants by genetic engineering would improve the availability of this much-needed drug. Methods: In this regard, a high artemisinin-yielding hybrid of A. annua produced by the centre for novel agricultural products of the University of York, UK, was selected (artemisinin maximally 1.4 %). As rol genes are potential candidates of biochemical engineering, genetic transformation of A. annua with Agrobacterium tumefaciens GV3101 harbouring vectors with rol B and rol C genes was carried out with the objective of enhancement of artemisinin content. Transgenic lines produced were analysed by the LC-MS for quantitative analysis of artemisinin and analogues. These high artemisinin yielding transgenics were also analysed by real time quantitative PCR to find the molecular dynamics of artemisinin enhancement. Genes of artemisinin biosynthetic pathway were studied including amorphadiene synthase (ADS), cytochrome P450, (CYP71AV1) and aldehyde dehydrogenase 1 (ALDH1). Trichome-specific fatty acyl-CoA reductase 1(TAFR1) is an enzyme involved in both trichome development and sesquiterpenoid biosynthesis and both processes are important for artemisinin biosynthesis. Thus, real time qPCR analysis of the TAFR1 gene was carried out, and trichome density was determined. Results: Transgenics of rol B gene showed two- to ninefold (the decimal adds nothing in the abstract, please simplify to two- to ninefold) increase in artemisinin, 4-12-fold increase in artesunate and 1.2-3-fold increase in dihydroartemisinin. Whereas in the case of rol C gene transformants, a fourfold increase in artemisinin, four to ninefold increase in artesunate and one- to twofold increase in dihydroartemisinin concentration was observed. Transformants with the rol B gene had higher expression of these genes than rol C transformants. TAFR1 was also found to be more expressed in rol gene transgenics than wild type A. annua, which was also in accordance with the trichome density of the respective plant. Conclusion: Thus it was proved that rol B and rol C genes are effective in the enhancement of artemisinin content of A. annua, rol B gene being more active to play part in this enhancement than rol C gene

Insights into the control of taxane metabolism: Molecular, cellular, and metabolic changes induced by elicitation in Taxus baccata cell suspensions

More knowledge is needed about the molecular/cellular control of paclitaxel (PTX) production in Taxus spp. cell cultures. In this study, the yield of this anticancer agent in Taxus baccata cell suspensions was improved 11-fold after elicitation with coronatine (COR) compared to the untreated cells, and 18-fold when co-supplemented with methyl-β-cyclodextrins (β-CDs). In the dual treatment, the release of taxanes from the producer cells was greatly enhanced, with 81.6% of the total taxane content being found in the medium at the end of the experiment. The experimental conditions that caused the highest PTX production also induced its maximum excretion, and increased the expression of taxane biosynthetic genes, especially the flux-limiting BAPT and DBTNBT. The application of COR, which activates PTX biosynthesis, together with β - CDs, which form inclusion complexes with PTX and related taxanes, is evidently an efficient strategy for enhancing PTX production and release to the culture medium. Due to the recently described role of lipid droplets (LDs) in the trafficking and accumulation of hydrophobic taxanes in Taxus spp. cell cultures, the structure, number and taxane storage capacity of these organelles was also studied. In elicited cultures, the number of LDs increased and they mainly accumulated taxanes with a side chain, especially PTX. Thus, PTX constituted up to 50-70% of the total taxanes found in LDs throughout the experiment in the COR + β - CD-treated cultures. These results confirm that LDs can store taxanes and distribute them inside and outside cells. Keywords: Taxus baccata; cell cultures; coronatine; gene expression; lipid droplets; paclitaxel; taxane accumulation

Randomized Double-Blind Multicentre Clinical Trial Comparing the Efficacy of Calcium dobesilate with placebo in the treatment of Chronic Venous Disease

Producción CientíficaObjective. To assess the efficacy of calcium dobesilate on the quality-of-life (QoL) of patients with chronic venous disease (CVD). Design. Randomised, parallel, double blind, placebo-controlled clinical trial. Methods. Patients were recruited from vascular surgery clinics and randomised to 500 mg capsules of calcium dobesilate twice a day for 3 months or placebo. The primary outcome measure was ‘QoL after 3 months’ treatment measured by the specific Chronic Insufficiency Venous International Questionnaire (CIVIQ). Secondary outcomes were QoL at 12 months and assessment of the CVD signs and symptoms. The principal analysis was undertaken on the intention-to-treat (ITT) data. Results. Five hundred and nine patients were recruited (246 to calcium dobesilate and 263 to placebo). The analysis of the ‘QoL after 3 months’ showed no significant differences between groups ( p ¼ 0.07). For secondary outcomes, oedema and symptoms of CVD, there were no significant differences between groups. In a multi-factorial analysis, the ‘QoL at 12 months’ was better in the calcium dobesilate group than in placebo group ( p ¼ 0.02). Conclusions. Treatment with calcium dobesilate was not found to be superior to placebo on the QoL of CVD patients. The sustained effect of calcium dobesilate observed after treatment should be confirmed in future studies. 2007 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved

Specialized Plant Metabolism Characteristics and Impact on Target Molecule Biotechnological Production.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI linkPlant secondary metabolism evolved in the context of highly organized and differentiated cells and tissues, featuring massive chemical complexity operating under tight environmental, developmental and genetic control. Biotechnological demand for natural products has been continuously increasing because of their significant value and new applications, mainly as pharmaceuticals. Aseptic production systems of plant secondary metabolites have improved considerably, constituting an attractive tool for increased, stable and large-scale supply of valuable molecules. Surprisingly, to date, only a few examples including taxol, shikonin, berberine and artemisinin have emerged as success cases of commercial production using this strategy. The present review focuses on the main characteristics of plant specialized metabolism and their implications for current strategies used to produce secondary compounds in axenic cultivation systems. The search for consonance between plant secondary metabolism unique features and various in vitro culture systems, including cell, tissue, organ, and engineered cultures, as well as heterologous expression in microbial platforms, is discussed. Data to date strongly suggest that attaining full potential of these biotechnology production strategies requires being able to take advantage of plant specialized metabolism singularities for improved target molecule yields and for bypassing inherent difficulties in its rational manipulation