Publications by authors named "Ana Belén García"

22 Publications

  • Page 1 of 1

Cardiac arrest following unsuspected self-poisoning with doxylamine.

Ther Drug Monit 2022 Jan 11. Epub 2022 Jan 11.

Clinical Toxicology Unit, Clinical Analysis Department. Hospital Universitari Son Llàtzer. Research Institute of Health Sciences (IdISBa). Palma de Mallorca, Spain. Intensive Care Department. Hospital Universitari Son Llàtzer. Research Institute of Health Sciences (IdISBa). Palma de Mallorca, Spain. Intensive Care Department. Hospital Universitari Son Llàtzer. Research Institute of Health Sciences (IdISBa). Palma de Mallorca, Spain. Intensive Care Department. Hospital Universitari Son Llàtzer. Research Institute of Health Sciences (IdISBa). Palma de Mallorca, Spain. Cardiology Department. Hospital Universitari Son Llàtzer. Department of Medicine, Faculty of Medicine, University of the Balearic Islands. Research Institute of Health Sciences (IdISBa). Palma de Mallorca, Spain. Institute of Legal Medicine of the Balearic Islands. Ministry of Justice. Department of Medicine, Faculty of Medicine, University of the Balearic Islands. Palma de Mallorca, Spain. Institute of Legal Medicine of the Balearic Islands. Ministry of Justice. Department of Medicine, Faculty of Medicine, University of the Balearic Islands. Palma de Mallorca, Spain.

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http://dx.doi.org/10.1097/FTD.0000000000000960DOI Listing
January 2022

Macrocyclization as a Source of Desired Polypharmacology. Discovery of Triple PI3K/mTOR/PIM Inhibitors.

ACS Med Chem Lett 2021 Nov 2;12(11):1794-1801. Epub 2021 Nov 2.

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

The PI3K/AKT/mTOR and PIM kinase pathways contribute to the development of several hallmarks of cancer. Cotargeting of these pathways has exhibited promising synergistic therapeutic effects in liquid and solid tumor types. To identify molecules with combined activities, we cross-screened our collection of PI3K/(±mTOR) macrocycles (MCXs) and identified the MCX thieno[3,2-]pyrimidine derivative as a moderate dual PI3K/PIM-1 inhibitor. We report the medicinal chemistry exploration and biological characterization of a series of thieno[3,2-]pyrimidine MCXs, which led to the discovery of IBL-302 (), a potent, selective, and orally bioavailable triple PI3K/mTOR/PIM inhibitor. IBL-302, currently in late preclinical development (AUM302), has recently demonstrated efficacy in neuroblastoma and breast cancer xenografts. Additionally, during the course of our experiments, we observed that macrocyclization was essential to obtain the desired multitarget profile. As a matter of example, the open precursors - were inactive against PIM whereas MCX displayed low nanomolar activity.
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http://dx.doi.org/10.1021/acsmedchemlett.1c00412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591745PMC
November 2021

Diagnostic Yield of Genetic Testing in Sudden Cardiac Death with Autopsy Findings of Uncertain Significance.

J Clin Med 2021 Apr 21;10(9). Epub 2021 Apr 21.

Department of Clinical Analysis and Toxicology, Son Espases University Hospital, IdISBa, 07120 Palma de Mallorca, Spain.

Background: Sudden death (SD) in the young usually has an underlying genetic cause. In many cases, autopsy reveals unspecific and inconclusive results, like idiopathic left ventricular hypertrophy (LVH), nonsignificant coronary atherosclerosis (CA), and primary myocardial fibrosis (PMF). Their pathogenicity and their relation to SD cause is unknown. This study aims to evaluate the diagnostic yield of genetic testing in these cases.

Methods: SD cases, between 1 and 50 years old, with findings of uncertain significance (idiopathic LVH, nonsignificant CA and PMF) on autopsy were evaluated prospectively, including information about medical and family history and circumstances of death. Genetic testing was performed.

Results: In a series of 195 SD cases, we selected 31 cases presenting idiopathic LVH ( = 16, 51.61%), nonsignificant CA ( = 17, 54.84%), and/or PMF ( = 24, 77.42%) in the autopsy. Mean age was 41 ± 7.2 years. Diagnostic yield of genetic test was 67.74%, considering variants of unknown significance (VUS), pathogenic variants (PV) and likely pathogenic variants (LPV); 6.45% including only PV and LPV. Structural genes represented 41,93% ( = 13) of cases, while 38,7% ( = 12) were related to channelopathies.

Conclusion: Molecular autopsy in SD cases between 1 and 50 years old, with findings of uncertain significance, has a low diagnostic yield, being VUS the most frequent variant observed.
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http://dx.doi.org/10.3390/jcm10091806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122344PMC
April 2021

Using a B-Phycoerythrin Extract as a Natural Colorant: Application in Milk-Based Products.

Molecules 2021 Jan 8;26(2). Epub 2021 Jan 8.

Department of Physical and Analytical Chemistry, High Engineering Polytechnic School of Linares, University of Jaen, 23700 Linares, Spain.

Nowadays, there is a growing interest in finding new coloring molecules of natural origin that can increase and diversify the offer of natural food dyes already present in the market. In the present work, a B-phycoerythrin extract from the microalgae was tested as a food colorant in milk-based products. Using spectroscopy and colorimetry, the extract was characterized and gave evidence of good properties and good stability in the pH range between 4.0 and 9.0. Coloring studies were conducted to demonstrate that samples carrying the pink extract could be used for simulating the pink color of marketed milk-based products. The staining factors, representing the amount of pink protein to be added to reproduce the color of strawberry commercial products, ranged between 1.6 mg/L and 49.5 mg/L, being sufficiently low in all samples. Additionally, color stability during a short period of cold storage was studied: it demonstrated that the three tested types of dairy products remained stable throughout the 11-day analysis period with no significant changes. These results prove the potential of the B-phycoerythrin extract as a natural colorant and alternative ingredient to synthetic coloring molecules.
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http://dx.doi.org/10.3390/molecules26020297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826896PMC
January 2021

Omipalisib inspired macrocycles as dual PI3K/mTOR inhibitors.

Eur J Med Chem 2021 Feb 18;211:113109. Epub 2020 Dec 18.

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/ Melchor Fernández Almagro 3, E-28029, Madrid, Spain. Electronic address:

Activation of the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway occurs frequently in a wide range of human cancers and is a main driver of cell growth, proliferation, survival, and chemoresistance of cancer cells. Compounds targeting this pathway are under active development as anticancer therapeutics and some of them have reached advanced clinical trials or been approved by the FDA. Dual PI3K/mTOR inhibitors combine multiple therapeutic efficacies in a single molecule by inhibiting the pathway both upstream and downstream of AKT. Herein, we report our efforts on the exploration of novel small molecule macrocycles (MCXs) as dual PI3K/mTOR inhibitors. Macrocyclization is an attractive approach used in drug discovery, as the semi-rigid character of these structures could provide improved potency, selectivity and favorable pharmacokinetic properties. Importantly, this strategy allows access to new chemical space thus obtaining a better intellectual property position. A series of MCXs based on GSK-2126458, a known clinical PI3K/mTOR inhibitor is described. These molecules showed potent biochemical and cellular dual PI3K/mTOR inhibition, demonstrated strong antitumoral effects in human cancer cell lines, and displayed good drug-like properties. Among them, MCX 83 presented remarkable selectivity against a panel of 468 kinases, high in vitro metabolic stability, and favorable pharmacokinetic parameters without significant CYP450 and h-ERG binding inhibition. This profile qualified this compound as a suitable candidate for future in vivo PK-PD and efficacy studies in mouse cancer models.
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http://dx.doi.org/10.1016/j.ejmech.2020.113109DOI Listing
February 2021

Spiropiperidyl rifabutins: expanded in vitro testing against ESKAPE pathogens and select bacterial biofilms.

J Antibiot (Tokyo) 2020 12 10;73(12):868-872. Epub 2020 Jul 10.

Center for Drug Discovery and Innovation, University of South Florida, Tampa, FL, USA.

The expanded microbiological evaluation of a series of rifastures, novel spiropiperidyl rifamycin derivatives, against clinically relevant ESKAPE bacteria has identified several analogs with promising in vitro bioactivities against antibiotic-resistant strains of Enterococcus faecium and Staphylococcus aureus. Thirteen of the rifastures displayed minimum inhibitory concentrations (MICs) below 1 µg/ml against the methicillin- and vancomycin-resistant forms of S. aureus and E. faecium (MRSA, VRSA, VRE). Aryl-substituted rifastures 1, 11, and 12 offered the greatest bioactivity, with MICs reaching ≤0.063 µg ml for these human pathogens. Further analysis indicates that diphenyl rifasture 1 had greater antibiofilm activity against S. aureus and lower cytotoxicity in mammalian HEK cells than rifabutin.
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http://dx.doi.org/10.1038/s41429-020-0346-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928017PMC
December 2020

Pyrido[2,3-b][1,5]benzoxazepin-5(6H)-one derivatives as CDK8 inhibitors.

Eur J Med Chem 2020 Sep 20;201:112443. Epub 2020 Jun 20.

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/ Melchor Fernández Almagro 3, E-28029, Madrid, Spain. Electronic address:

CDK8 is a cyclin-dependent kinase that forms part of the mediator complex, and modulates the transcriptional output from distinct transcription factors involved in oncogenic control. Overexpression of CDK8 has been observed in various cancers, representing a potential target for developing novel CDK8 inhibitors in cancer therapeutics. In the course of our investigations to discover new CDK8 inhibitors, we designed and synthesized tricyclic pyrido[2,3-b][1,5]benzoxazepin-5(6H)-one derivatives, by introduction of chemical complexity in the multi-kinase inhibitor Sorafenib taking into account the flexibility of the P-loop motif of CDK8 protein observed after analysis of structural information of co-crystallized CDK8 inhibitors. In vitro evaluation of the inhibitory activity of the prepared compounds against CDK8 led us to identify compound 2 as the most potent inhibitor of the series (IC = 8.25 nM). Co-crystal studies and the remarkable selectivity profile of compound 2 are presented. Compound 2 showed moderate reduction of phosphorylation of CDK8 substrate STAT1 in cells, in line with other reported Type II CDK8 inhibitors. We propose herein an alternative to find a potential therapeutic use for this chemical series.
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http://dx.doi.org/10.1016/j.ejmech.2020.112443DOI Listing
September 2020

Efficacy of methyl ester of conjugated linoleic acid (t10,c12 isomer) for sows and cows for reproduction.

EFSA J 2019 Mar 5;17(3):e05614. Epub 2019 Mar 5.

A mixture of methylated conjugated linoleic acid (CLA) isomers (t10,c12 and c9,t11) in equal proportions is the subject of this assessment. The active substance is considered to be CLA (t10,c12) methyl ester (ME). The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) of EFSA previously issued an opinion on the safety and efficacy of the product, in which it could not conclude on the efficacy of this additive for sows for reproduction and for cows for reproduction. The European Commission asked EFSA to deliver an opinion on the efficacy of this additive for sows and cows for reproduction, based on additional data submitted by the applicant. The FEEDAP Panel has performed the assessment of the new data following an approach in line with the principles laid down in Regulation (EC) No 429/2008 and the relevant guidance documents. In relation to the data on efficacy in sows for reproduction, owing to methodological shortcomings of the study submitted, including the duration of the study and the limited biological relevance of the effect observed, the FEEDAP Panel cannot conclude on the efficacy of CLA (t10,c12)-ME for sows for reproduction. The data related to dairy cows indicate that dietary CLA (t10,c12)-ME supplementation in the late dry period and/or lactation period showed an increase of the probability of pregnancy and a reduction of time to conception in the same reproductive cycle. However, considering that the minimum duration of efficacy studies for reproductive parameters is of at least two reproductive cycles, the FEEDAP Panel is not in a position to conclude on the efficacy of the additive for cows for reproduction.
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http://dx.doi.org/10.2903/j.efsa.2019.5614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009295PMC
March 2019

Discovery of novel triazolo[4,3-b]pyridazin-3-yl-quinoline derivatives as PIM inhibitors.

Eur J Med Chem 2019 Apr 19;168:87-109. Epub 2019 Feb 19.

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/ Melchor Fernández Almagro 3, E-28029 Madrid, Spain. Electronic address:

PIM kinase family (PIM-1, PIM-2 and PIM-3) is an appealing target for the discovery and development of selective inhibitors, useful in various disease conditions in which these proteins are highly expressed, such as cancer. The significant effort put, in the recent years, towards the development of small molecules exhibiting inhibitory activity against this protein family has ended up with several molecules entering clinical trials. As part of our ongoing exploration for potential drug candidates that exhibit affinity towards this protein family, we have generated a novel chemical series of triazolo[4,3-b]pyridazine based tricycles by applying a scaffold hopping strategy over our previously reported potent pan-PIM inhibitor ETP-47453 (compound 2). The structure-activity relationship studies presented herein demonstrate a rather selective PIM-1/PIM-3 biochemical profile for this novel series of tricycles, although pan-PIM and PIM-1 inhibitors have also been identified. Selected examples show significant inhibition of the phosphorylation of BAD protein in a cell-based assay. Moreover, optimized and highly selective compounds, such as 42, did not show significant hERG inhibition at 20 μM concentration, and proved its antiproliferative activity and utility in combination with particular antitumoral agents in several tumor cell lines.
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http://dx.doi.org/10.1016/j.ejmech.2019.02.022DOI Listing
April 2019

Modulation of telomere protection by the PI3K/AKT pathway.

Nat Commun 2017 11 2;8(1):1278. Epub 2017 Nov 2.

Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, Madrid, E-28029, Spain.

Telomeres and the insulin/PI3K pathway are considered hallmarks of aging and cancer. Here, we describe a role for PI3K/AKT in the regulation of TRF1, an essential component of the shelterin complex. PI3K and AKT chemical inhibitors reduce TRF1 telomeric foci and lead to increased telomeric DNA damage and fragility. We identify the PI3Kα isoform as responsible for this TRF1 inhibition. TRF1 is phosphorylated at different residues by AKT and these modifications regulate TRF1 protein stability and TRF1 binding to telomeric DNA in vitro and are important for in vivo TRF1 telomere location and cell viability. Patient-derived breast cancer PDX mouse models that effectively respond to a PI3Kα specific inhibitor, BYL719, show decreased TRF1 levels and increased DNA damage. These findings functionally connect two of the major pathways for cancer and aging, telomeres and the PI3K pathway, and pinpoint PI3K and AKT as novel targets for chemical modulation of telomere protection.
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http://dx.doi.org/10.1038/s41467-017-01329-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668434PMC
November 2017

Correlation between resistance mechanisms in and cell wall and septum thickening.

Infect Drug Resist 2017 17;10:353-356. Epub 2017 Oct 17.

Department of Clinical Microbiology, Hospital Clínico San Carlos, Complutense University, Madrid, Spain.

Purpose: The aim of the present study is to examine cell wall and septum thickening of methicillin-sensitive (MSSA), methicillin-resistant (MRSA), and methicillin- and linezolid-resistant (MLRSA) isolates by transmission electron microscopy to correlate the association of resistance mechanisms with major changes in the morphology of membrane or septum.

Materials And Methods: MSSA, MRSA, and MLRSA strains obtained from clinical samples of an outbreak that occurred in 2010 at the Intensive Care Unit of our Hospital were thawed and sown at 37°C in blood agar overnight. After that, they were washed, pelleted, and treated with a fixer solution. Pellets were dehydrated and finally embedded in resin. Transmission electron microscopy was used to characterize cell wall and septum thickening in all isolates. The comparison between the measurements obtained for each group was performed by a Kruskal-Wallis test and a post hoc Dunn-Bonferroni's pairwise comparison method.

Results: Differences in cell wall and septum thickness were statistically significant (<0.001 and <0.001, respectively) between the three groups. Moreover, significant differences were detected in wall and septum thickness between the MSSA and MRSA strains (<0.001 and <0.001, respectively) and between the MSSA and MLRSA strains (<0.001 and <0.001, respectively) but not between the MRSA and MLRSA strains (=0.386 and =0.117).

Conclusion: In this analysis, we correlate the resistance mediated by alterations in the cell membrane of (methicillin-resistant, for example) with a greater thickness of the wall or septum. The resistance added to linezolid did not determine significant changes in the characteristics of the wall or septum with respect to those strains resistant only to methicillin.
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http://dx.doi.org/10.2147/IDR.S146748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655128PMC
October 2017

In vitro ceftaroline combinations against meticillin-resistant Staphylococcus aureus.

J Med Microbiol 2016 Oct 22;65(10):1119-1122. Epub 2016 Aug 22.

Department of Clinical Microbiology and Infectious Diseases, Hospital Clinico San Carlos, Universidad Complutense, Madrid, Spain.

We studied in vitro ceftaroline combinations against 61 meticillin-resistant Staphylococcus aureus isolates; 18 of them were also resistant to linezolid, using overlapping E-test method. Daptomycin-ceftaroline combination obtained lower fractional inhibitory concentration values, in comparison with those including vancomycin or linezolid against meticillin-resistant S. aureus (P<0.05). All meticillin- and linezolid-resistant S. aureus strains were resistant to ceftaroline; nevertheless, combinations with vancomycin or daptomycin showed higher synergy or addition rates than those with linezolid.
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http://dx.doi.org/10.1099/jmm.0.000341DOI Listing
October 2016

[Isolation of Pasteurella dagmatis after a tiger bite].

Rev Esp Quimioter 2014 Dec;27(4):269-70

Ana Belén García, Servicio de Microbiología Clínica, Hospital Clínico San Carlos. Madrid, Spain.

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December 2014

Examining the benefits of learning based on an audience response system when confronting emergency situations.

Comput Inform Nurs 2014 May;32(5):207-13

Author Affiliations: Department of Informatics and Systems, Faculty of Computer Science (Dr Fernández-Alemán and Mr Jiménez), and Department of Nursing, Faculty of Nursing (Ms García and Dr Montesinos), University of Murcia; and Reina Sofía University General Hospital of Murcia (Ms García), Spain.

This article presents an empirical study on the effectiveness of the use of an audience response system called SIstema De Respuesta inmediata de la Audiencia on a nursing course. A total of 130 students of mixed gender, age, and computer experience and educational background on a third-year course in nursing administration and management participated in the study. The benefits of an audience response system as regards learning how to confront emergency situations were studied. The innovative aspect of the proposal is twofold: (1) the use of a smartphone to respond to the questions and (2) the analysis of the students' response time when confronting critical situations while managing nursing resources. A positive impact on the students' performance was revealed in their final assessments. Our findings show that SIstema De Respuesta inmediata de la Audiencia increases student participation and aids in identifying and correcting misconceptions. The students found SIstema De Respuesta inmediata de la Audiencia to be very motivating and wanted it to be used in additional lectures. Further research is required to study the effectiveness of SIstema De Respuesta inmediata de la Audiencia for it to be widely used in other disciplines.
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http://dx.doi.org/10.1097/CIN.0000000000000053DOI Listing
May 2014

Validation of the Quality of Life Questionnaire of the European Foundation for Osteoporosis-31 in Spanish postmenopausal women.

Menopause 2014 May;21(5):469-76

From the 1Department of Health Sciences, Faculty of Health Sciences, University of Jaén, Jaén, Spain; 2Institute of Biopathology and Regenerative Medicine (IBIMER), Department of Human Anatomy and Embryology, and 3Department of Obstetrics and Gynecology, Faculty of Medicine, University of Granada, Granada, Spain; 4Faculty of Nursing, Physiotherapy, Podology, and Occupational Therapy, University of Málaga, Málaga, Spain; 5Department of Music, Plastical Expression, and Body Language, University of Jaén, Jaén, Spain; and 6Department of Personality, Evaluation, and Psychological Treatment, University of Granada, Granada, Spain.

Objective: The Quality of Life Questionnaire of the European Foundation for Osteoporosis-31 (QUALEFFO-31) is a reliable and validated questionnaire that assesses quality of life in osteoporotic women. Our objective was to analyze the reliability and validity of the Spanish version of QUALEFFO-31 and its ability to discriminate between women with osteoporosis and women without osteoporosis in a Spanish postmenopausal population.

Methods: One hundred eighteen women (aged 50-65 y) completed the Spanish version of QUALEFFO-31. Bone mineral density was measured by dual-energy x-ray densitometry. Internal consistency and test-retest reliability were analyzed. Concurrent validity of QUALEFFO-31 was evaluated using Spearman's rank correlation coefficient with the 36-item Short-Form Health Survey (SF-36). To determined responsiveness, we analyzed mean differences between osteoporotic and nonosteoporotic women and performed receiver operating characteristic curve analysis.

Results: The Spanish version of QUALEFFO-31 has shown excellent test-retest reliability with a high intraclass correlation coefficient for all its domains, especially for the total score (0.988; P < 0.001), and good internal consistency with optimal Cronbach α values in all scales (0.70-0.90). In concurrent validity analysis, QUALEFFO-31 total score showed a high and negative correlation with several scales of the SF-36 (P < 0.001). In responsiveness analysis, significant differences in the pain (P = 0.002) and QUALEFFO-31 total score (P = 0.004) scales were found between osteoporotic and nonosteoporotic women. No differences in areas under the receiver operating characteristic curve were found between the QUALEFFO-31 and the SF-36 scales.

Conclusions: The Spanish version of QUALEFFO-31 has good internal consistency, concurrent validity, and test-retest reliability, with satisfactory general psychometric properties, and is a valid tool for discriminating between osteoporotic and nonosteoporotic postmenopausal women aged 50 to 65 years.
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http://dx.doi.org/10.1097/GME.0b013e3182a6cc64DOI Listing
May 2014

Imidazo[1,2-a]pyrazines as novel PI3K inhibitors.

Bioorg Med Chem Lett 2012 Mar 28;22(5):1874-8. Epub 2012 Jan 28.

Experimental Therapeutics Program, Spanish National Cancer Research Centre (CNIO). C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

Phosphoinositide-3-kinase (PI3K) is an important target for cancer therapeutics due to the deregulation of its signaling pathway in a wide variety of human cancers. We describe herein a novel series of imidazo[1,2-a]pyrazines as PI3K inhibitors.
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http://dx.doi.org/10.1016/j.bmcl.2012.01.074DOI Listing
March 2012

Optimisation of the operational conditions of trichloroethylene degradation using Trametes versicolor under quinone redox cycling conditions using central composite design methodology.

Biodegradation 2012 Apr 6;23(2):333-41. Epub 2011 Sep 6.

Departament d'Enginyeria Química and Institut de Ciència i Tecnologia Ambientals, Universitat Autònoma de Barcelona (UAB), Escola d'Enginyeria, 08193, Bellaterra, Barcelona, Spain.

Extracellular radicals produced by Trametes versicolor under quinone redox cycling conditions can degrade a large variety of pollutant compounds, including trichloroethylene (TCE). This study investigated the effect of the agitation speed and the gas-liquid phase volume ratio on TCE degradation using central composite design (CCD) methodology for a future scale-up to a reactor system. The agitation speed ranged from 90 to 200 rpm, and the volume ratio ranged from 0.5 to 4.4. The results demonstrated the important and positive effect of the agitation speed and an interaction between the two factors on TCE degradation. Although the volume ratio did not have a significant effect if the agitation speed value was between 160 and 200 rpm, at lower speed values, the specific pollutant degradation was clearly more extensive at low volume ratios than at high volume ratios. The fitted response surface was validated by performing an experiment using the parameter combination in the model that maximised TCE degradation. The results of the experiments carried out using different biomass concentrations demonstrated that the biomass concentration had a positive effect on pollutant degradation if the amount of biomass present was lower than 1.6 g dry weight l(-1). The results show that the maximum TCE degradation was obtained at the highest speed (200 rpm), gas-liquid phase volume ratio (4.4), and a biomass concentration of 1.6 g dry weight l(-1).
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http://dx.doi.org/10.1007/s10532-011-9513-xDOI Listing
April 2012

Strong in vitro activities of two new rifabutin analogs against multidrug-resistant Mycobacterium tuberculosis.

Antimicrob Agents Chemother 2010 Dec 20;54(12):5363-5. Epub 2010 Sep 20.

Instituto Universitario de Química Organometálica Enrique Moles, Unidad Asociada al C.S.I.C., Universidad de Oviedo, c/ Julián Clavería 8, 33006 Oviedo, Spain.

Two new rifabutin analogs, RFA-1 and RFA-2, show high in vitro antimycobacterial activities against Mycobacterium tuberculosis. MIC values of RFA-1 and RFA-2 were ≤0.02 μg/ml against rifamycin-susceptible strains and 0.5 μg/ml against a wide selection of multidrug-resistant strains, compared to ≥50 μg/ml for rifampin and 10 μg/ml for rifabutin. Molecular dynamic studies indicate that the compounds may exert tighter binding to mutants of RNA polymerase that have adapted to the rifamycins.
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http://dx.doi.org/10.1128/AAC.00149-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981290PMC
December 2010

The Galpha12/13 family of heterotrimeric G proteins and the small GTPase RhoA link the Kaposi sarcoma-associated herpes virus G protein-coupled receptor to heme oxygenase-1 expression and tumorigenesis.

J Biol Chem 2007 Nov 19;282(47):34510-24. Epub 2007 Sep 19.

Instituto de Investigaciones Biomédicas A. Sols, Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid, Arzobispo Morcillo 4, Madrid, Spain.

Heme oxygenase-1 (HO-1), an inducible enzyme that metabolizes the heme group, is highly expressed in human Kaposi sarcoma lesions. Its expression is up-regulated by the G protein-coupled receptor from the Kaposi sarcoma-associated herpes virus (vGPCR). Although recent evidence shows that HO-1 contributes to vGPCR-induced tumorigenesis and vascular endothelial growth factor (VEGF) expression, the molecular steps that link vGPCR to HO-1 remain unknown. Here we show that vGPCR induces HO-1 expression and transformation through the Galpha(12/13) family of heterotrimeric G proteins and the small GTPase RhoA. Targeted small hairpin RNA knockdown expression of Galpha(12), Galpha(13), or RhoA and inhibition of RhoA activity impair vGPCR-induced transformation and ho-1 promoter activity. Knockdown expression of RhoA also reduces vGPCR-induced VEFG-A secretion and blocks tumor growth in a murine allograft tumor model. NIH-3T3 cells expressing constitutively activated Galpha(13) or RhoA implanted in nude mice develop tumors displaying spindle-shaped cells that express HO-1 and VEGF-A, similarly to vGPCR-derived tumors. RhoAQL-induced tumor growth is reduced 80% by small hairpin RNA-mediated knockdown expression of HO-1 in the implanted cells. Likewise, inhibition of HO-1 activity by chronic administration of the HO-1 inhibitor tin protoporphyrin IX to mice reduces RhoAQL-induced tumor growth by 70%. Our study shows that vGPCR induces HO-1 expression through the Galpha(12/13)/RhoA axes and shows for the first time a potential role for HO-1 as a therapeutic target in tumors where RhoA has oncogenic activity.
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http://dx.doi.org/10.1074/jbc.M703043200DOI Listing
November 2007

New rifabutin analogs: synthesis and biological activity against Mycobacterium tuberculosis.

Bioorg Med Chem Lett 2006 Nov 20;16(22):5717-22. Epub 2006 Sep 20.

Instituto Universitario de Química Organometálica Enrique Moles, Unidad Asociada al CSIC, Universidad de Oviedo, C/ Julián Clavería, 8, 33006 Oviedo, Spain.

The synthesis, structure, and biological evaluation of a series of novel rifamycin derivatives, Rifastures (RFA) with potent anti-tuberculosis activity are presented. Some of these derivatives showed higher in vitro activity than rifabutin and rifampicin against not only Mycobacterium tuberculosis strains but also against MAC and Mycobacterium kansasii.
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http://dx.doi.org/10.1016/j.bmcl.2006.08.090DOI Listing
November 2006

NMR spectroscopic analysis of new spiro-piperidylrifamycins.

Magn Reson Chem 2005 Apr;43(4):269-82

Instituto Universitario de Química Organometálica Enrique Moles, Unidad Asociada al CSIC, Universidad de Oviedo, C/Julián Clavería 8, 33006 Oviedo, Spain.

New spiro-piperidylrifamycin derivatives are presented. These compounds were synthesized from the reaction of 3-amino-4-iminorifamycin S and enantiomerically pure 4-piperidones, which generate diasteroisomeric rifabutin analogues with a new stereocentre at the spiranic carbon. The (1)H and (13)C NMR spectra of these new compounds, and also the configuration of the new stereogenic centres, were assigned using 2D NMR spectroscopic techniques. A preliminary study of the (1)H and (13)C NMR spectra of the starting compounds rifamycin S, 3-amino-4-iminorifamycin S and the related rifabutin was also carried out and as a result, their previously published (13)C NMR data were corrected.
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http://dx.doi.org/10.1002/mrc.1545DOI Listing
April 2005
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