110 results on '"Largo C"'
Search Results
2. Protective effect of supercritical fluid rosemary extract, Rosmarinus officinalis, on antioxidants of major organs of aged rats
- Author
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Posadas, S.J., Caz, V., Largo, C., De la Gándara, B., Matallanas, B., Reglero, G., and De Miguel, E.
- Published
- 2009
- Full Text
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3. Array CGH and gene-expression profiling reveals distinct genomic instability patterns associated with DNA repair and cell-cycle checkpoint pathways in Ewing's sarcoma
- Author
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Ferreira, B I, Alonso, J, Carrillo, J, Acquadro, F, Largo, C, Suela, J, Teixeira, M R, Cerveira, N, Molares, A, Goméz-López, G, Pestaña, Á, Sastre, A, Garcia-Miguel, P, and Cigudosa, J C
- Published
- 2008
- Full Text
- View/download PDF
4. DNA profiling analysis of 100 consecutive de novo acute myeloid leukemia cases reveals patterns of genomic instability that affect all cytogenetic risk groups
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Suela, J, Álvarez, S, Cifuentes, F, Largo, C, Ferreira, B I, Blesa, D, Ardanaz, M, García, R, Marquez, J A, Odero, M D, Calasanz, M J, and Cigudosa, J C
- Published
- 2007
- Full Text
- View/download PDF
5. PRECLINICAL EVALUATION OF THE IMMUNOMODULATORY EFFECT OF Lactobacillus plantarum 3547 ON HUMAN MACROPHAGES AND OBESE WISTAR RATS.: O109
- Author
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Tabernero, M., Caz, J. V., Martínez-Gutiérrez, E., Plaz, López B., Candela, Gómez C., López-Collazo, E., and Largo, C.
- Published
- 2013
6. Systemic Glucose Administration Alters Water Diffusion and Microvascular Blood Flow in Mouse Hypothalamic Nuclei - An fMRI Study
- Author
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Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Comunidad de Madrid, Lizarbe, Blanca, Fernández-Pérez, Antonio, Caz, V., Largo, C., Vallejo, Mario, López-Larrubia, Pilar, Cerdán, Sebastián, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Comunidad de Madrid, Lizarbe, Blanca, Fernández-Pérez, Antonio, Caz, V., Largo, C., Vallejo, Mario, López-Larrubia, Pilar, and Cerdán, Sebastián
- Abstract
The hypothalamus is the principal regulator of global energy balance, enclosing additionally essential neuronal centers for glucose-sensing and osmoregulation. Disturbances in these tightly regulated neuronal networks are thought to underlie the development of severe pandemic syndromes, including obesity and diabetes. In this work, we investigate in vivo the response of individual hypothalamic nuclei to the i.p. administration of glucose or vehicle solutions, using two groups of adult male C57BL6/J fasted mice and a combination of non-invasive T2∗-weighted and diffusion-weighted functional magnetic resonance imaging (fMRI) approaches. MRI parameters were assessed in both groups of animals before, during and in a post-stimulus phase, following the administration of glucose or vehicle solutions. Hypothalamic nuclei depicted different patterns of activation characterized by: (i) generalized glucose-induced increases of neuronal activation and perfusion-markers in the lateral hypothalamus, arcuate and dorsomedial nuclei, (ii) cellular shrinking events and decreases in microvascular blood flow in the dorsomedial, ventromedial and lateral hypothalamus, following the administration of vehicle solutions and (iii) increased neuronal activity markers and decreased microperfusion parameters in the ARC nuclei of vehicle-administered animals. Immunohistochemical studies performed after the post-stimulus phase confirmed the presence of c-Fos immunoreactive neurons in the arcuate nucleus (ARC) from both animal groups, with significantly higher numbers in the glucose-treated animals. Together, our results reveal that fMRI methods are able to detect in vivo diverse patterns of glucose or vehicle-induced effects in the different hypothalamic nuclei.
- Published
- 2019
7. Abordaje combinado Kocher-Langenbeck y Stoppa en el tratamiento de fracturas complejas de acetábulo.
- Author
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Pinzon-Largo, C. Y. and Chávez-Ramírez, R. G.
- Abstract
Introduction: Complex acetabulum fractures are a challenge for orthopedic surgeons. An evaluation of the radiographic reduction and functional result of the patients with complex fracture of the acetabulum who underwent the combined Kocher- Langenbeck and Stoppa approach was carried out. Material and methods: Cross-sectional, descriptive, ambispective design. Patients with complex acetabulum fracture who underwent the combined Kocher-Langenbeck approach plus Stoppa between 2016 and 2020 were included. The clinical records were reviewed, and the quality of the radiographic reduction was evaluated according to Matta criteria. In addition, a functional evaluation was performed with the Merle d'Aubigne and Postel scale at least 12 months after the injury. Results: Of the 31 patients, the average time between the date of fractures and the surgical intervention was 13.7 days (3-38 days). In the radiographic evaluation according to Matta criteria, 21 anatomical patients (67.7%), 7 almost anatomical (22.5%), 3 imperfect (9.6%). Functional results according to the Merle d'Aubigne and Postel scale resulted in 8 (25.8%) with excellent results, 16 (51.6%) with good results, 5 (22.5%) moderate and 2 (16.1%) poor patients. There was a statistical correlation between the age of the patient and the functional result (p = 0.029), also between the body mass index and blood loss (p = 0.027). Conclusion: The combined Kocher-Langenbeck plus Stoppa approaches are a valid alternative in these lesions, mostly with anatomical and almost anatomical radiographic results according to the Matta radiographic scale, and with excellent and good functional results according to the Merle d'Aubigne and Postel scale. [ABSTRACT FROM AUTHOR]
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- 2021
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8. The effect of a novel intravenous fluid (Oxsealife®) on recovery from haemorrhagic shock in pigs
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Oller, L., primary, Dyer, W. B., additional, Santamaría, L., additional, Largo, C., additional, Javidroozi, M., additional, and Shander, A., additional
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- 2019
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9. fDWI predicts obesity development in rats
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Lizarbe, Blanca, López-Larrubia, Pilar, Cerdán, Sebastián, Caz, V., Tabernero, María, Miguel, Enrique de, and Largo, C.
- Abstract
Trabajo presentado al 29th Annual Scientific Meeting of European Society for Magnetic Resonance In Medicine and Biology, celebrado en Lisboa (Portugal) del 4 al 6 de Octubre de 2012.
- Published
- 2012
10. Potential of mesenchymal stem cell in stabilization of abdominal aortic aneurysm sac
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Riera del Moral, L., primary, Largo, C., additional, Ramirez, J.R., additional, Vega Clemente, L., additional, Fernández Heredero, A., additional, Riera de Cubas, L., additional, Garcia-Olmo, D., additional, and Garcia-Arranz, M., additional
- Published
- 2015
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11. Intragenic GNAS deletion involving exon A/B in pseudohypoparathyroidism type 1A resulting in an apparent loss of exon A/B methylation: potential for misdiagnosis of pseudohypoparathyroidism type 1B
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Fernandez-Rebollo E, García-Cuartero B, Garin I, Largo C, Martínez F, Garcia-Lacalle C, Castaño L, Bastepe M, and Pérez de Nanclares G
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musculoskeletal diseases ,natural sciences - Abstract
Several endocrine diseases that share resistance to PTH are grouped under the term pseudohypoparathyroidism (PHP). Patients with PHP type Ia show additional hormone resistance, defective erythrocyte G(s)alpha activity, and dysmorphic features termed Albright's hereditary osteodystrophy (AHO). Patients with PHP-Ib show less diverse hormone resistance and normal G(s)alpha activity; AHO features are typically absent in PHP-Ib. Mutations affecting G(s)alpha coding exons of GNAS and epigenetic alterations in the same gene are associated with PHP-Ia and -Ib, respectively. The epigenetic GNAS changes in familial PHP-Ib are caused by microdeletions near or within GNAS but without involving G(s)alpha coding exons.
- Published
- 2010
12. Simultaneous translocations of FGFR3/MMSET and CCND1 into two different IGH alleles in multiple myeloma: lack of concurrent activation of both proto-oncogenes
- Author
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Saez, B. (Borja), Martin-Subero, J.I. (Jose Ignacio), Lahortiga, I. (Idoya), Largo, C. (Cristina), Larrayoz, M.J. (María J.), Odero, M.D. (Maria Dolores), Prosper, F. (Felipe), Cigudosa, J.C. (Juan Cruz), Siebert, R. (Reiner), and Calasanz-Abinzano, M.J. (Maria Jose)
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hemic and lymphatic diseases ,Ciencias de la Salud::Oncología [Materias Investigacion] - Abstract
The simultaneous occurrence of two different translocations affecting both alleles of the IGH gene has rarely been reported in multiple myeloma. In such a case, two different oncogenes might become transcriptionally deregulated. To investigate this hypothesis, we have characterized the plasma cell leukemia cell line SK-MM2 and a primary myeloma both carrying simultaneous IGHeFGFR3/MMSET and IGHeCCND1 fusions as shown by multicolor fluorescence in situ hybridization. Remarkably, quantitative real-time polymerase chain reaction demonstrated that only one of the oncogene loci was transcriptionally upregulated in both instances. Moreover, the upregulated oncogenes differed between both samples. Thus, biallelic IGH translocations might exert different pathogenetic effects in plasma cell disorders.
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- 2007
13. Genomic and expression profiling identifies the B-cell associated tyrosine kinase Syk as a possible therapeutic target in mantle cell lymphoma
- Author
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Rinaldi, A, Kwee, I, Taborelli, M, Largo, C, Uccella, Silvia, Martin, V, Poretti, G, Gaidano, G, Calabrese, G, Martinelli, G, Baldini, L, Pruneri, G, Capella, CARLO RENATO, Zucca, E, Cotter, Fe, Cigudosa, Jc, Catapano, Cv, Tibiletti, Mg, and Bertoni, F.
- Published
- 2006
14. Identification of recurrent chromosomal breakpoints in multiple myeloma with complex karyotypes by combined G-banding, spectral karyotyping, and fluorescence in situ hybridization analyses
- Author
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Saez, B. (Borja), Martin-Subero, J.I. (Jose Ignacio), Largo, C. (Cristina), Martin, M.C. (María C.), Odero, M.D. (Maria Dolores), Prosper, F. (Felipe), Siebert, R. (Reiner), Calasanz-Abinzano, M.J. (Maria Jose), and Cigudosa, J.C. (Juan Cruz)
- Subjects
Ciencias de la Salud::Oncología [Materias Investigacion] - Abstract
The description of novel chromosomal aberrations in multiple myeloma (MM) remains necessary to fully understand the pathogenesis of this heterogeneous disease. Therefore, we have used spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) with locus-specific probes to characterize the chromosomal abnormalities in 11 MM cases in which G-banding revealed a complex karyotype. SKY refined G-banding karyotypes in all cases. Recurrent breakpoints involved bands Xp11, 8q24, 11q13, 12q13, 13q21, and 14q32. In addition, combined SKY and FISH analyses permitted us to identify a subset of patients harboring 22q11.2 rearrangements not involving the IGL locus. This finding suggests the presence of other gene(s) in band 22q11 that might be implicated in MM pathogenesis. Moreover, band 1p13 was identified as a novel partner of immunoglobulin (IG) translocations in MM. Finally, using interphase FISH, we have detected interstitial deletions in 13q14 and 17p13, as well as cryptic translocations affecting IGH, which were neither detected by G-banding nor by SKY. The results of the present study suggest the existence of hitherto unknown nonrandom chromosomal changes that may play a role in the pathogenesis of MM. Our findings underline the importance of the combination of banding, SKY, and FISH analyses to increase the accuracy of karyotype interpretation in plasma cell neoplasias.
- Published
- 2006
15. The SRY-HMG box gene, SOX4, is a target of gene amplification at chromosome 6p in lung cancer
- Author
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Medina, P.P., Castillo, S.D., Blanco, S., Sanz-Garcia, M., Largo, C., Alvarez, S., Yokota, J., Gonzalez-Neira, A., Benitez, J., Clevers, H., Cigudosa, J.C., Lazo, P.A., Sanchez-Cespedes, M., Medina, P.P., Castillo, S.D., Blanco, S., Sanz-Garcia, M., Largo, C., Alvarez, S., Yokota, J., Gonzalez-Neira, A., Benitez, J., Clevers, H., Cigudosa, J.C., Lazo, P.A., and Sanchez-Cespedes, M.
- Abstract
The search for oncogenes is becoming increasingly important in cancer genetics because they are suitable targets for therapeutic intervention. To identify novel oncogenes, activated by gene amplification, we analyzed cDNA microarrays by high-resolution comparative genome hybridization and compared DNA copy number and mRNA expression levels in lung cancer cell lines. We identified several amplicons (5p13, 6p22-21, 11q13, 17q21 and 19q13) that had a concomitant increase in gene expression. These regions were also found to be amplified in lung primary tumours. We mapped the boundaries and measured expression levels of genes within the chromosome 6p amplicon. The Sry-HMG box gene SOX4 (sex-determining region Y box 4), which encodes a transcription factor involved in embryonic cell differentiation, was overexpressed by a factor of 10 in cells with amplification relative to normal cells. SOX4 expression was also stronger in a fraction of lung primary tumours and lung cancer cell lines and was associated with the presence of gene amplification. We also found variants of SOX4 in lung primary tumours and cancer cell lines, including a somatic mutation that introduced a premature stop codon (S395X) at the serine-rich C-terminal domain. Although none of the variants increased the transactivation ability of SOX4, overexpression of the wildtype and of the non-truncated variants in NIH3T3 cells significantly increased the transforming ability of the weakly oncogenic RHOA-Q63L. In conclusion, our results show that, in lung cancer, SOX4 is overexpressed due to gene amplification and provide evidence of oncogenic properties of SOX4., The search for oncogenes is becoming increasingly important in cancer genetics because they are suitable targets for therapeutic intervention. To identify novel oncogenes, activated by gene amplification, we analyzed cDNA microarrays by high-resolution comparative genome hybridization and compared DNA copy number and mRNA expression levels in lung cancer cell lines. We identified several amplicons (5p13, 6p22-21, 11q13, 17q21 and 19q13) that had a concomitant increase in gene expression. These regions were also found to be amplified in lung primary tumours. We mapped the boundaries and measured expression levels of genes within the chromosome 6p amplicon. The Sry-HMG box gene SOX4 (sex-determining region Y box 4), which encodes a transcription factor involved in embryonic cell differentiation, was overexpressed by a factor of 10 in cells with amplification relative to normal cells. SOX4 expression was also stronger in a fraction of lung primary tumours and lung cancer cell lines and was associated with the presence of gene amplification. We also found variants of SOX4 in lung primary tumours and cancer cell lines, including a somatic mutation that introduced a premature stop codon (S395X) at the serine-rich C-terminal domain. Although none of the variants increased the transactivation ability of SOX4, overexpression of the wildtype and of the non-truncated variants in NIH3T3 cells significantly increased the transforming ability of the weakly oncogenic RHOA-Q63L. In conclusion, our results show that, in lung cancer, SOX4 is overexpressed due to gene amplification and provide evidence of oncogenic properties of SOX4.
- Published
- 2009
16. Effects of radiation on human mesenchymal stem cells
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Glaria Enríquez, L., primary, Huerga Cabrerizo, C., additional, García Olmo, D., additional, García Arranz, M., additional, and Largo, C., additional
- Published
- 2013
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17. Neurotensin increases intestinal adaptation and reduces enteroglucagon-like immunoreactivity after large bowel resection in rats
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Mata A, Ignacio Gomez de Segura, Largo C, Codesal J, and De Miguel E
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Male ,Jejunum ,Proliferating Cell Nuclear Antigen ,Animals ,Female ,Intestinal Mucosa ,Rats, Wistar ,Adaptation, Physiological ,Sensitivity and Specificity ,Cell Division ,Colectomy ,Neurotensin ,Rats - Abstract
To assess the effects of giving neurotensin on intestinal adaptation after colectomy and their relation to enteroglucagon-like immunoreactivity.Laboratory experiment.Teaching hospital, Spain.55 Male Wistar rats.All animals were anaesthetised before undergoing laparotomy; 24 animals had 75% of their colon resected. Half of the animals (12 in each group) were treated with neurotensin (600 micrograms/kg body wt/day) for 14 days.Differences in the number of mitoses and in nuclear antigen staining of proliferating cells in the intestinal mucosal crypts; plasma enteroglucagon-like immunoreactivity.After colon resection, the proliferative status, number of mitoses (p0.01), and nuclear antigen staining of proliferating cells (p0.001) increased significantly in the jejunum of animals treated with neurotensin (p0.05). Less pronounced effects were observed in colon and ileum. Plasma enteroglucagon-like immunoreactivity levels fell significantly in all animals given neurotensin (p0.05).Neurotensin increases the adaptive intestinal process after colon resection and reduces plasma enteroglucagon-like immunoreactivity in rats.
- Published
- 1997
18. Array CGH and gene-expression profiling reveals distinct genomic instability patterns associated with DNA repair and cell-cycle checkpoint pathways in Ewing's sarcoma
- Author
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Ferreira, B I, primary, Alonso, J, additional, Carrillo, J, additional, Acquadro, F, additional, Largo, C, additional, Suela, J, additional, Teixeira, M R, additional, Cerveira, N, additional, Molares, A, additional, Goméz-López, G, additional, Pestaña, Á, additional, Sastre, A, additional, Garcia-Miguel, P, additional, and Cigudosa, J C, additional
- Published
- 2007
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19. Multiple myeloma primary cells show a highly rearranged unbalanced genome with amplifications and homozygous deletions irrespective of the presence of immunoglobulin-related chromosome translocations
- Author
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Largo, C., primary, Saez, B., additional, Alvarez, S., additional, Suela, J., additional, Ferreira, B., additional, Blesa, D., additional, Prosper, F., additional, Calasanz, M. J., additional, and Cigudosa, J. C., additional
- Published
- 2007
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20. Longitudinal Depolarization Gradients Along the Somatodendritic Axis of CA1 Pyramidal Cells: A Novel Feature of Spreading Depression
- Author
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Canals, S., primary, Makarova, I., additional, López-Aguado, L., additional, Largo, C., additional, Ibarz, J. M., additional, and Herreras, O., additional
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- 2005
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21. Las huellas eléctricas en el camino hacia la muerte neuronal isquémica
- Author
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Largo C and Herreras O
- Subjects
Nervous tissue ,Ischemia ,nutritional and metabolic diseases ,Depolarization ,General Medicine ,Biology ,medicine.disease ,eye diseases ,Neuron types ,Functional integrity ,Neurochemical ,medicine.anatomical_structure ,Membrane integrity ,Cortical spreading depression ,medicine ,Neurology (clinical) ,Neuroscience - Abstract
Introduction and development. During episodes of ischemia/anoxia, the neurochemical and environmental changes considered toxic for nervous tissue lie behind the characteristic abrupt massive cell depolarization (MCD). A strong resemblance with otherpathologic events enable us to postulate thatMCD is a different state of the tissue that includes among others the anoxic depolarization and Leao's spreading depression. MCD is an active event. Neurons enter and leave MCD suddenly and synchronously, and contrary to current belief, their membrane integrity is preserved and ion gradients are only reduced. Biophysical membrane properties are not compatible with some postulates based on endotoxines. There is a direct relation between MCD susceptibility of the different neuron types/nuclei and their vulnerability to ischemia/anoxia. Two different substates can be distinguished in the associated interstitial potentials that are likely related to neuronal and glial dysfunction, respectively. The different modes and timings of anoxic neuronal death depend on the duration of MCD, the functional integrity of the glial network and the history ofprevious insults. Conclusions. MCD is a cellular state of risk bridging life and death. Neurons die if they cannot exit, but may recover if they do promptly, although still have to face subtle changes -as well initiated during MCD- that will eventually lead them to a delayed death. A voiding MCD is escaping death. From a clinical point of view, the relevant point is that manipulating MCD entails the simultaneous control of all 'toxic' neurochemical concomitants. Reinforcing vulnerable neurons to avoid their falling into MCD is possible.
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- 2002
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22. The effect of depressing glial function in rat brain in situ on ion homeostasis, synaptic transmission, and neuron survival
- Author
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Largo, C, primary, Cuevas, P, additional, Somjen, GG, additional, Martin del Rio, R, additional, and Herreras, O, additional
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- 1996
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23. Role of neuronal synchronizing mechanisms in the propagation of spreading depression in the in vivo hippocampus
- Author
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Herreras, O, primary, Largo, C, additional, Ibarz, JM, additional, Somjen, GG, additional, and Martin del Rio, R, additional
- Published
- 1994
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24. Unusual organization of the ilvIH promoter of Escherichia coli
- Author
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Haughn, G W, Squires, C H, De Felice, M, Largo, C T, and Calvo, J M
- Abstract
Analysis of plasmids containing ilvIH-galK fusions indicated that the Escherichia coli ilvIH promoter and sequences sufficient to cause leucine repression lie within 363 base pairs (bp) of ilvI. Experiments designed to locate the promoter and regulatory sequences more precisely gave the following results. The positions of the 5' endpoints of both unlabeled and pulse-labeled ilvIH mRNAs transcribed in vivo lie 30 bp upstream of ilvI. By contrast, the major in vitro RNA endpoints lie at positions further upstream. Several mutations which increase the expression of ilvIH lie 40 to 50 bp upstream of ilvI, within a putative promoter termed P1. Deletion of a 50-bp region immediately upstream of ilvI, which includes P1, resulted in the loss of all ilvIH promoter activity. Deletion of sequences more than 200 bp upstream of ilvI reduced ilvIH promoter activity by more than 80%. These results suggest that transcription of the ilvIH operon is initiated from promoter P1 but that sequences more than 200 bp upstream are required for optimal transcription of the operon.
- Published
- 1985
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25. Blood lipid biomarkers after consumption of a commercial reduced milk fat cheese naturally-enriched in CLA
- Author
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Calvo, M., Rodriguez-Alcala, L., Maria Tabernero, Kives, J., Romero, J., Gomez-Candela, C., Largo, C., and Fontecha, J.
26. [Technical aspects of experimental intestinal transplant].,Aspectos técnicos del trasplante intestinal experimental
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López-Fernández, S., Hernández, F., Hernández-Martín, S., Barrena, S., Wang, Z., Zou, W., Andrés, A. M., Encinas, J. L., Massimo Garriboli, Largo, C., López-Santamaría, M., and Tovar, J. A.
27. Identification of overexpressed genes in frequently gained/amplified chromosome regions in multiple myeloma
- Author
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Largo, C., Alvarez, S., Saez, B., Blesa, D., Jose Ignacio Martin-Subero, González-García, I., Brieva, J. A., Dopazo, J., Siebert, R., Calasanz, M. J., and Cigudosa, J. C.
28. Combination of different genomic approaches to define a candidate deleted gene in AML
- Author
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Suela, J., Largo, C., Ferreira, B., Alvarez, S., Robledo, M., Anna Gonzalez-Neira, Calasanz, M. J., and Cigudosa, J. C.
29. OREXIGENIC HYPOTHALAMYC ACTIVATION DETERMINED WITH FUNCTIONAL DIFFUSION WEIGHTED IMAGING (FDWI) DIFFERS AMONG OBESE AND LEAN ANIMALS DURING FASTING
- Author
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Maria Tabernero, Lizarbe, B., Caz, V., Lopez-Larrubia, P., Cerdan, S., and Largo, C.
30. Effects of mannoprotein E1 in liquid diet on inflammatory response and TLR5 expression in the gut of rats infected by Salmonella typhimurium
- Author
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Largo Carlota, Quilez Immaculada, Cendejas Emilio, Caballero Isabel, Caz Victor, Posadas Sinforiano J, Elvira Marcos, and De Miguel Enrique
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background Mannoproteins are yeast cell wall componend, and rich in mannose. The use of foods rich in mannose as carbohydrate, could have a bioprotective effect against entrobacteria intestinal infection. Nothing is known about mannoproteins' activity in inflammatory bowel processes induced by entrobacteria. This study investigates the effects of mannoprotein administration via a liquid diet on inflammatory response and TLR5 expression during intestinal tissue injury in a rat model of infection with Salmonella typhimurium. Methods Adult Wistar male rats were divided into three groups: control, and mannoprotein E1 at 10 or 15%. Animals were fed with a liquid diet supplemented or not with mannoprotein E1. Groups were infected by intragastrical administration of S. typhimurium. 24 h post-inoculation samples of spleen, ileum and liver were collected for microbiological studies. Gut samples were processed to determine levels of proinflammatory cytokines (mRNA) and TLR5 (mRNA and protein) by quantitative PCR and Western-blot, and the number of proliferative and apoptotic cells determined by immunohistochemistry. Results Ininfected levels of proinflammatory cytokines and TLR5 were higher in untreated controls than in the animals receiving mannoprotein. Proliferation was similar in both groups, whereas apoptosis was higher in controls. Curiosly, the mannoprotein effect was dose dependent. Conclusions Mannoprotein administration in a liquid diet seems to protect intestinal tissue against S. typhimurium infection. This protection seems to expressed as a lower pro-inflammatory response and TLR5 downregulation in gut epithelium, as well as by an inhibition of apoptosis. Nevertheless, the molecular mechanism by which mannoprotein is able to regulate these responses remain unclear. These results could open up new avenues in the use of mannoproteins as prebiotics in the therapeutic strategy for treatment of inflammatory gut processes induced by microbia.
- Published
- 2010
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31. Multiple myeloma primary cells show a highly rearranged unbalanced genome with amplifications and homozygous deletions irrespective of the presence of immunoglobulin-related chromosome translocations
- Author
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Largo, C. (Cristina)
- Subjects
- Multiple myeloma, ArrayCGH, Hyperdiploid, Amplification, Homozygous deletion
- Abstract
Background and Objectives Multiple myeloma (MM) is a malignant plasma cell neoplasia in which genetic studies have shown that genomic changes may affect almost all chromosomes, as shown by fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH). Our objective was the genomic characterization of CD 138 positive primary MM samples by means of a high resolution array CGH platform. Design and Methods For the first time, a high resolution array CGH with more than 40,000 probes, has been used to analyze 26 primary MM samples after the enrichment of CD138-positive plasma cells. Results This approach identified copy number imbalances in all cases. Bioinformatics strategies were optimized to perform data analysis allowing the segregation of hyperdiploid and non-hyperdiploid cases by array CGH. Additional analysis showed that structural chromosome rearrangements were more frequently seen in hyperdiploid cases. We also identified the same Xq21 duplication in nearly 20% of the cases, which originated through unbalanced chromosome translocations. High level amplifications and homozygous deletions were recurrently observed in our series and involved genes with meaningful function in cancer biology. Interpretation and Conclusions High resolution array CGH allowed us to identify copy number changes in 100% of the primary MM samples. We segregated different MM subgroups based on their genomic profiles which made it possible to identify homozygous deletions and amplifications of great genetic relevance in MM.
- Published
- 2007
32. ROX Index Variation as a Predictor of Outcomes in COVID-19 Patients.
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Maldonado A, Endara P, Abril P, Carrión H, Largo C, and Benavides P
- Abstract
Background: During the COVID-19 pandemic, emergency departments were overcrowded with critically ill patients, and many providers were confronted with ethical dilemmas in assigning respiratory support to them due to scarce resources. Quick tools for evaluating patients upon admission were necessary, as many existing scores proved inaccurate in predicting outcomes. The ROX Index (RI), a rapid and straightforward scoring system reflecting respiratory status in acute respiratory failure patients, has shown promise in predicting outcomes for COVID-19 patients. The 24 h difference in the RI accurately gauges mortality and the need for invasive mechanical ventilation (IMV) among patients with COVID-19. Methods: Study design: Prospective cohort study. A total of 204 patients were admitted to the emergency department from May to August 2020. Data were collected from the clinical records. The RI was calculated at admission and 24 h later, and the difference was used to predict the association with mortality and the need for IMV, a logistic regression model was used to adjust for age, sex, presence of comorbidities, and disease severity. Finally, the data were analyzed using ROC. Results: The difference in respiratory RI between admission and 24 h is a good predictor for death (AUC 0.92) and for mechanic ventilation (AUC: 0.75). Each one-unit decrease in the RI difference at 24 h was associated with an odds ratio of 1.48 for the risk of death (95%CI: 1.31-1.67) and an odds ratio of 1.16 for IMV (95% IC: 1.1-1.23). Conclusions: The 24 h variation of RI is a good prediction tool to allow healthcare professionals to identify the patients who will benefit from invasive treatment, especially in low-resource settings.
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- 2024
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33. Preclinical Study of DCD and Normothermic Perfusion for Visceral Transplantation.
- Author
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Serradilla J, Andrés Moreno AM, Talayero P, Burgos P, Machuca M, Camps Ortega O, Vallejo MT, Rubio Bolívar FJ, Bueno A, Sánchez A, Zambrano C, De la Torre Ramos CA, Rodríguez O, Largo C, Serrano P, Prieto Bozano G, Ramos E, López Santamaría M, Stringa P, and Hernández F
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- Animals, Swine, Humans, Perfusion, Reperfusion, Graft Rejection, Tissue Donors, Reperfusion Injury
- Abstract
Considering recent clinical and experimental evidence, expectations for using DCD-derived intestines have increased considerably. However, more knowledge about DCD procedure and long-term results after intestinal transplantation (ITx) is needed. We aimed to describe in detail a DCD procedure for ITx using normothermic regional perfusion (NRP) in a preclinical model. Small bowel was obtained from pigs donors after 1 h of NRP and transplanted to the recipients. Graft Intestinal samples were obtained during the procedure and after transplantation. Ischemia-reperfusion injury (Park-Chiu score), graft rejection and transplanted intestines absorptive function were evaluated. Seven of 8 DCD procedures with NRP and ITx were successful (87.5%), with a good graft reperfusion and an excellent recovery of the recipient. The architecture of grafts was well conserved during NRP. After an initial damage of Park-chiu score of 4, all grafts recovered from ischemia-reperfusion, with no or very subtle alterations 2 days after ITx. Most recipients (71.5%) did not show signs of rejection. Only two cases demonstrated histologic signs of mild rejection 7 days after ITx. Interestingly intestinal grafts showed good absorptive capacity. The study's results support the viability of intestinal grafts from DCD using NRP, contributing more evidence for the use of DCD for ITx., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Serradilla, Andrés Moreno, Talayero, Burgos, Machuca, Camps Ortega, Vallejo, Rubio Bolívar, Bueno, Sánchez, Zambrano, De la Torre Ramos, Rodríguez, Largo, Serrano, Prieto Bozano, Ramos, López Santamaría, Stringa and Hernández.)
- Published
- 2023
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34. When less is more: Experimental Bishop-Koop technique for reduction in the use of laboratory animals for intestinal pathophysiological studies.
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Abate JC, Lausada N, Vecchio Dezillio L, Moreira J, Marinoff II, Ferreyra Compagnucci MM, Andrés Moreno AM, Largo C, Rumbo M, Hernández Oliveros F, Romanin D, and Stringa P
- Subjects
- Animals, Rats, Research Design, Reproducibility of Results, Animals, Laboratory, Inflammation, Colitis, Reperfusion Injury
- Abstract
The use of animals to gain knowledge and understanding of diseases needs to be reduced and refined. In the field of intestinal research, because of the complexity of the gut immune system, living models testing is mandatory. Based on the 3Rs (replacement, reduction and refinement) principles, we aimed to developed and apply the derived-intestinal surgical procedure described by Bishop and Koop (BK) in rats to refine experimental gastrointestinal procedures and reduce the number of animals used for research employing two models of intestinal inflammation: intestinal ischemia-reperfusion injury and chemical-induced colitis. Our results show the feasibility of the application of the BK technique in rodents, with good success after surgical procedure in both small and large intestine (100% survival, clinical recovery and weight regain). A considerable reduction in the use of the number of rats in both intestinal inflammation models (80% in case of intestinal ischemia-reperfusion damage and 66.6% in chemical-induced colitis in our experimental design) was achieved. Compared with conventional experimental models described by various research groups, we report excellent reproducibility of intestinal damage and functionality, survival rate and clinical status of the animals when BK is applied.
- Published
- 2023
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35. Effect of convalescent plasma as complementary treatment in patients with moderate COVID-19 infection.
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Baldeón ME, Maldonado A, Ochoa-Andrade M, Largo C, Pesantez M, Herdoiza M, Granja G, Bonifaz M, Espejo H, Mora F, Abril-López P, Armijo LKR, Pacheco V, Salazar R, Reinthaller S, Zertuche F, and Fornasini M
- Subjects
- Humans, Pandemics, SARS-CoV-2, COVID-19 Serotherapy, COVID-19 therapy, Immunization, Passive methods
- Abstract
Introduction: South America is one of the regions most affected by the COVID-19 pandemic. Specific and affordable treatments are needed to treat SARS-CoV-2 infection. Evidence regarding the use of convalescent plasma in COVID-19 patients is still limited. We compared the safety and efficacy of COVID-19-convalescent plasma administration as a complement to standard treatment in the early management of patients with moderate SARS-CoV-2 infection., Methods: We carried out a random double blinded, placebo-controlled trial that compared standard treatment plus convalescent plasma (CP) or plus non-convalescent plasma in the management of COVID-19 patients. The main outcome was survival and secondary endpoints included: length of hospitalisation (LOH), days from treatment to discharge, time to clinical improvement or death within a 28-day period, and adverse reactions to treatment., Results: Administration of CP with antibodies against SARS-CoV-2 did not affect patient survival, RR = 1.003, 95% CI (0.3938, 2.555). These results led to terminate the RCT prematurely. However, early treatment of COVID-19 patients with CP tended to decrease the LOH while the delay in CP treatment was associated with longer hospitalisation. In addition, delay in CP treatment negatively affected the recovery of the respiratory rate., Conclusion: Use of CP for the treatment of COVID-19 patients is safe and its early use can decrease the LOH and improve respiratory function. Early administration of antibody-rich CP could contribute to decrease the negative impact of COVID-19 pandemic in patients with impaired immune response., (© 2022 British Blood Transfusion Society.)
- Published
- 2022
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36. [Combined Kocher-Langenbeck and Stoppa approach in the treatment of complex acetabulum fractures].
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Pinzon-Largo CY and Chávez-Ramírez RG
- Subjects
- Acetabulum surgery, Body Mass Index, Cross-Sectional Studies, Humans, Hip Fractures, Spinal Fractures
- Abstract
Introduction: Complex acetabulum fractures are a challenge for orthopedic surgeons. An evaluation of the radiographic reduction and functional result of the patients with complex fracture of the acetabulum who underwent the combined Kocher-Langenbeck and Stoppa approach was carried out., Material and Methods: Cross-sectional, descriptive, ambispective design. Patients with complex acetabulum fracture who underwent the combined Kocher-Langenbeck approach plus Stoppa between 2016 and 2020 were included. The clinical records were reviewed, and the quality of the radiographic reduction was evaluated according to Matta criteria. In addition, a functional evaluation was performed with the Merle d'Aubigne and Postel scale at least 12 months after the injury., Results: Of the 31 patients, the average time between the date of fractures and the surgical intervention was 13.7 days (3-38 days). In the radiographic evaluation according to Matta criteria, 21 anatomical patients (67.7%), 7 almost anatomical (22.5%), 3 imperfect (9.6%). Functional results according to the Merle d'Aubigne and Postel scale resulted in 8 (25.8%) with excellent results, 16 (51.6%) with good results, 5 (22.5%) moderate and 2 (16.1%) poor patients. There was a statistical correlation between the age of the patient and the functional result (p = 0.029), also between the body mass index and blood loss (p = 0.027)., Conclusion: The combined Kocher-Langenbeck plus Stoppa approaches are a valid alternative in these lesions, mostly with anatomical and almost anatomical radiographic results according to the Matta radiographic scale, and with excellent and good functional results according to the Merle d'Aubigne and Postel scale.
- Published
- 2021
37. Prevalence of metabolic syndrome and diabetes mellitus type-2 and their association with intake of dairy and legume in Andean communities of Ecuador.
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Baldeón ME, Felix C, Fornasini M, Zertuche F, Largo C, Paucar MJ, Ponce L, Rangarajan S, Yusuf S, and López-Jaramillo P
- Subjects
- Adult, Aged, Dairy Products statistics & numerical data, Diet adverse effects, Dietary Fiber statistics & numerical data, Ecuador, Fabaceae, Female, Humans, Male, Meat Products statistics & numerical data, Middle Aged, Socioeconomic Factors, Diabetes Mellitus, Type 2 epidemiology, Diet statistics & numerical data, Metabolic Syndrome epidemiology
- Abstract
Metabolic syndrome (MetS) and type 2 diabetes (T2D) are metabolic alterations associated with high morbidity and mortality, particularly in low and middle-income countries. Diet has a significant impact on the risk to develop MetS and T2D; in this regard, consumption of fruits, vegetables, and protein rich foods (from plant and animals) are important to prevent and manage these pathologies. There are limited studies regarding the potential association between Andean foods rich in proteins and the presence of cardio-metabolic conditions in Ecuador. It is necessary to develop new low-cost, local-culturally acceptable strategies to reduce the burden of cardio-metabolic diseases. We describe the prevalence (baseline data) of MetS and T2D in the Ecuadorian cohort of the Prospective Urban and Rural Epidemiology (PURE) study and their potential association with the consumption of protein rich foods, including beef, white meat, dairy and legumes. In this cross-sectional study, we assessed 1,997 individuals aged 35-70 years (mean age 51 years, 72% women), included in the Ecuadorian cohort of the PURE study, from February to December 2018. The prevalence of MetS was 42% for male and 44% for female participants; the prevalence of T2D was 9% for male and 10% for female. Metabolic syndrome and T2D were more common in women older than 50 years of age with primary education or less, low economic income, and with obesity; MetS was more frequent in the rural area while T2D was more frequent in the urban area. Using logistic regression analysis, we observed a significant protective effect of higher consumption of dairy and legumes in the prevalence of MetS and T2D compared with low consumption. It will be important to develop policies for ample production and consumption of protein rich foods such as legumes and dairy, part of traditional diets, to reduce the burden of cardio-metabolic diseases., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2021
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38. Galactomannan as a Potential Modulator of Intestinal Ischemia-Reperfusion Injury.
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Stringa P, Toledano V, Papa-Gobbi R, Arreola M, Largo C, Machuca M, Aguirre LA, Rumbo M, López-Collazo E, and Hernández Oliveros F
- Subjects
- Animals, Disease Models, Animal, Galactose analogs & derivatives, Humans, Intestinal Mucosa blood supply, Intestinal Mucosa pathology, Jejunum blood supply, Jejunum drug effects, Jejunum pathology, Male, Mice, Reperfusion Injury etiology, Reperfusion Injury pathology, Intestinal Mucosa drug effects, Ischemia complications, Mannans administration & dosage, Reperfusion Injury prevention & control
- Abstract
Background: Galactomannan (GAL), a polysaccharide present on the cell wall of several fungi, has shown an ability to modulate inflammatory responses through the dectin-1 receptor in human macrophages. However, studies evaluating the modulatory properties of this polysaccharide in in vivo inflammatory scenarios are scarce. We hypothesized that GAL pretreatment would modulate local and remote damage related to intestinal reperfusion after an ischemic insult., Materials and Methods: Adult male Balb/c mice were subjected to intestinal ischemia-reperfusion injury by reversible occlusion of the superior mesenteric artery, consisting of 45 min of ischemia followed by 3 or 24 h of reperfusion. Intragastric GAL (70 mg/kg) was administered 12 h before ischemia, and saline solution was used in the control animals. Jejunum, lung, and blood samples were taken for the analysis of histology, gene expression, plasma cytokine levels, and nitrosative stress., Results: Intestinal and lung histologic alterations were attenuated by GAL pretreatment, showing significant differences compared with nontreated animals. Interleukin 1β, monocyte chemoattractant protein 1, and IL-6 messenger RNA expression were considerably downregulated in the small intestine of the GAL group. In addition, GAL treatment significantly prevented plasma interleukin 6 and monocyte chemoattractant protein 1 upregulation and diminished nitrate and nitrite levels after 3 h of intestinal reperfusion., Conclusions: GAL pretreatment constitutes a novel and promising therapy to reduce local and remote damage triggered by intestinal ischemia-reperfusion injury. Further in vivo and in vitro studies to understand GAL's modulatory effects are warranted., (Copyright © 2019 Elsevier Inc. All rights reserved.)
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- 2020
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39. In vitro and in vivo testing of the hypocholesterolemic activity of ergosterol- and β-glucan-enriched extracts obtained from shiitake mushrooms (Lentinula edodes).
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Morales D, Tejedor-Calvo E, Jurado-Chivato N, Polo G, Tabernero M, Ruiz-Rodríguez A, Largo C, and Soler-Rivas C
- Subjects
- Animals, Ergosterol chemistry, Fruiting Bodies, Fungal chemistry, Male, Mice, Mice, Inbred C57BL, beta-Glucans chemistry, Cholesterol blood, Ergosterol pharmacology, Shiitake Mushrooms, beta-Glucans pharmacology
- Abstract
Herein, a supercritical extraction plant (with a 6 L extraction cell) was successfully used to obtain ergosterol-enriched extracts from Lentinula edodes under the following conditions: a temperature of 40 °C, pressure of 225 bar, reaction time of 1-5 h, and the flow rate of 20 L h
-1 for recirculated CO2 . Moreover, ergosterol (ERG) and the SFE extract (SFE) with highest ergosterol concentration were microemulsified and submitted to in vitro digestion to study their ability to displace cholesterol from dietary mixed micelles (DMMs). ERG was also mixed with a β-glucan-enriched (33.5%) extract (BGE) obtained from L. edodes to investigate the synergies between them; the results indicated that all these extracts (including BGE without ERG) could reduce the cholesterol levels in the DMMs. However, when ERG and SFE were simultaneously administered to mice with a hypercholesterolemic diet, no significant differences in the serum cholesterol levels were detected as compared to the case of the control. However, when only BGE was administrated to another mice model previously induced with hypercholesterolemia, significant reduction in the cholesterol levels was noticed.- Published
- 2019
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40. Systemic Glucose Administration Alters Water Diffusion and Microvascular Blood Flow in Mouse Hypothalamic Nuclei - An fMRI Study.
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Lizarbe B, Fernández-Pérez A, Caz V, Largo C, Vallejo M, López-Larrubia P, and Cerdán S
- Abstract
The hypothalamus is the principal regulator of global energy balance, enclosing additionally essential neuronal centers for glucose-sensing and osmoregulation. Disturbances in these tightly regulated neuronal networks are thought to underlie the development of severe pandemic syndromes, including obesity and diabetes. In this work, we investigate in vivo the response of individual hypothalamic nuclei to the i.p. administration of glucose or vehicle solutions, using two groups of adult male C57BL6/J fasted mice and a combination of non-invasive T
2 ∗ -weighted and diffusion-weighted functional magnetic resonance imaging (fMRI) approaches. MRI parameters were assessed in both groups of animals before, during and in a post-stimulus phase, following the administration of glucose or vehicle solutions. Hypothalamic nuclei depicted different patterns of activation characterized by: (i) generalized glucose-induced increases of neuronal activation and perfusion-markers in the lateral hypothalamus, arcuate and dorsomedial nuclei, (ii) cellular shrinking events and decreases in microvascular blood flow in the dorsomedial, ventromedial and lateral hypothalamus, following the administration of vehicle solutions and (iii) increased neuronal activity markers and decreased microperfusion parameters in the ARC nuclei of vehicle-administered animals. Immunohistochemical studies performed after the post-stimulus phase confirmed the presence of c-Fos immunoreactive neurons in the arcuate nucleus (ARC) from both animal groups, with significantly higher numbers in the glucose-treated animals. Together, our results reveal that fMRI methods are able to detect in vivo diverse patterns of glucose or vehicle-induced effects in the different hypothalamic nuclei.- Published
- 2019
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41. Main histological parameters to be evaluated in an experimental model of myocardial infarct treated by stem cells on pigs.
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García Gómez-Heras S, Largo C, Larrea JL, Vega-Clemente L, Calderón Flores M, Ruiz-Pérez D, García-Olmo D, and García-Arranz M
- Abstract
Myocardial infarction has been carefully studied in numerous experimental models. Most of these models are based on electrophysiological and functional data, and pay less attention to histological discoveries. During the last decade, treatment using advanced therapies, mainly cell therapy, has prevailed from among all the options to be studied for treating myocardial infarction. In our study we wanted to show the fundamental histological parameters to be evaluated during the development of an infarction on an experimental model as well as treatment with mesenchymal stem cells derived from adipose tissue applied intra-lesionally. The fundamental parameters to study in infarcted tissue at the histological level are the cells involved in the inflammatory process (lymphocytes, macrophages and M2, neutrophils, mast cells and plasma cells), neovascularization processes (capillaries and arterioles) and cardiac cells (cardiomyocytes and Purkinje fibers). In our study, we used intramyocardial injection of mesenchymal stem cells into the myocardial infarction area 1 hour after arterial occlusion and allowed 1 month of evolution before analyzing the modifications on the normal tissue inflammatory infiltrate. Acute inflammation was shortened, leading to chronic inflammation with abundant plasma cells and mast cells and complete disappearance of neutrophils. Another benefit was an increase in the number of vessels formed. Cardiomyocytes and Purkinje fibers were better conserved, both from a structural and metabolic point of view, possibly leading to reduced morbidity in the long term. With this study we present the main histological aspects to be evaluated in future assays, complementing or explaining the electrophysiological and functional findings., Competing Interests: Authors Damián García Olmo is a member of the Advisory Board of Tigenix S. A. U. and collaborates with TAKEDA; Damián García Olmo and Mariano García Arranz have applied for two patents related to Cx401 and Cx601 titled “Identification and Isolation of Multipotent Cells from Non-Osteochondral Mesenchymal Tissue” (WO 2006/057649) and “Use of Adipose Tissue-Derived Stromal Stem Cells in Treating Fistula” (WO 2006/136244). The other authors indicated no potential conflicts of interest.
- Published
- 2019
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42. Modified Multivisceral Transplantation with Native Spleen Removal in Rats.
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Stringa P, Arreola NM, Moreno AMA, Largo C, Rumbo M, and Hernandez F
- Subjects
- Animals, Male, Outcome Assessment, Health Care, Pancreas Transplantation mortality, Rats, Rats, Inbred Lew, Survival Rate, Transplantation, Heterotopic, Vascularized Composite Allotransplantation mortality, Intestine, Small transplantation, Pancreas Transplantation methods, Spleen transplantation, Stomach transplantation, Vascularized Composite Allotransplantation methods
- Abstract
Background: Modified multivisceral transplantation (MMVTx) refers to the use of a graft that includes all abdominal organs except the liver. The use of this type of transplant in children and adults expanded over the last years with good results. However, long-term survival in experimental models has not been reported. Our aim is to describe in detail some technical modifications of MMVTx to obtain long-term survival., Materials and Methods: Syngeneic (Lewis-Lewis) heterotopic MMVTx was performed in 16 male rats (180-250 g). All procedures were performed under isoflurane anesthesia. The graft consisted of stomach, duodenopancreatic axis, spleen, and small bowel. The vascular pedicle consisted of a conduit of aorta, including the celiac trunk and the superior mesenteric artery (SMA), and the portal vein (PV). The engraftment was performed by end-to-side anastomosis to the infra-renal cava vein and aorta. After reperfusion, the graft was accommodated in the right side of the abdomen, and a terminal ileostomy performed. The native spleen was removed., Results: Donor and recipient time was 39 ± 4.4 minutes and 69 ± 7 minutes, respectively; venous and arterial anastomosis time was 14 ± 1 minutes and 12.3 ± 1 minutes, respectively. Total ischemia time was 77.2 ± 7.9 minutes. Survival was 75% (12/16), six were sacrificed after 2 hours, and six were kept alive for long-term evaluation (more than 1 week)., Conclusion: Long-term survival is reported after heterotopic MMVTx in rats. The heterotopic MMVTx with native spleen removal would potentially improve the existent models for transplant research. The usefulness of this model warrants further confirmation in allogeneic experiments., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)
- Published
- 2019
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43. Effect of traditional and modern culinary processing, bioaccessibility, biosafety and bioavailability of eritadenine, a hypocholesterolemic compound from edible mushrooms.
- Author
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Morales D, Tabernero M, Largo C, Polo G, Piris AJ, and Soler-Rivas C
- Subjects
- Adenine chemistry, Adenine metabolism, Agaricales metabolism, Animals, Anticholesteremic Agents chemistry, Biological Availability, Containment of Biohazards, Cooking, Female, Humans, Hypercholesterolemia metabolism, Male, Plant Extracts chemistry, Rats, Rats, Sprague-Dawley, Adenine analogs & derivatives, Agaricales chemistry, Anticholesteremic Agents metabolism, Hypercholesterolemia diet therapy, Plant Extracts metabolism
- Abstract
Eritadenine is a hypocholesterolemic compound that is found in several mushroom species such as Lentinula edodes, Marasmius oreades, and Amanita caesarea (1.4, 0.7 and 0.6 mg per g dry weight, respectively). It was synthesized during all developmental stages, being present in higher concentrations in the skin of shiitake fruiting bodies. When subjected to traditional cooking, grilling followed by frying were more adequate methodologies than boiling or microwaving to maintain its levels. Modern culinary processes such as texturization (with agar-agar) and spherification (with alginate) also interfered with its release. Grilling and gelling using gelatin enhanced eritadenine's bioaccessibility in an in vitro digestion model. An animal model (where male and female rats were administered 21 and 10 mg per kg animal per day of eritadenine) indicated that intake of the compound was safe under these concentrations; it reached the liver and reduced the atherogenic index (TC/HDL) in rat sera. Thus, it might be used to design a functional food.
- Published
- 2018
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44. The effects of allogenic stem cells in a murine model of hind limb diabetic ischemic tissue.
- Author
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Álvarez García J, García Gómez-Heras S, Riera Del Moral L, Largo C, García-Olmo D, and García-Arranz M
- Abstract
Background: Diabetes is one of the major risk factors for peripheral arterial disease. In patients in whom surgery cannot be performed, cell therapy may be an alternative treatment. Since time is crucial for these patients, we propose the use of allogenic mesenchymal cells., Methods: We obtained mesenchymal cells derived from the fat tissue of a healthy Sprague-Dawley rat. Previous diabetic induction with streptozotocin in 40 male Sprague-Dawley rats, ligation plus left iliac and femoral artery sections were performed as a previously described model of ischemia. After 10 days of follow-up, macroscopic and histo-pathological analysis was performed to evaluate angiogenic and inflammatory parameters in the repair of the injured limb. All samples were evaluated by the same blind researcher. Statistical analysis was performed using the SPSS v.11.5 program ( P < 0.05)., Results: Seventy percent of the rats treated with streptozotocin met the criteria for diabetes. Macroscopically, cell-treated rats presented better general and lower ischemic clinical status, and histologically, a better trend towards angiogenesis, greater infiltration of type 2 macrophages and a shortening of the inflammatory process. However, only the inflammatory variables were statistically significant. No immunological reaction was observed with the use of allogeneic cells., Discussion: The application of allogeneic ASCs in a hind limb ischemic model in diabetic animals shows no rejection reactions and a reduction in inflammatory parameters in favor of better repair of damaged tissue. These results are consistent with other lines of research in allogeneic cell therapy. This approach might be a safe, effective treatment option that makes it feasible to avoid the time involved in the process of isolation, expansion and production of the use of autologous cells., Competing Interests: Prof. D. García Olmo and Dr. M. García Arranz have applied for two patents related to Adipose Derived Mesenchymal Stem Cells titled “Identification and Isolation of Multipotent Cells from Non-Osteochondral Mesenchymal Tissue” (WO 2006/057649) and “Use of Adipose Tissue-Derived Stromal Stem Cells in Treating Fistula” (WO 2006/136244). The remaining authors have no other financial or competing interests to declare.
- Published
- 2017
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45. Metamizole (dipyrone) effects on sevoflurane requirements and postoperative hyperalgesia in rats.
- Author
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Ruiz-Pérez D, Benito J, Largo C, Polo G, Canfrán S, and Gómez de Segura IA
- Subjects
- Animals, Hyperalgesia drug therapy, Male, Nociception drug effects, Pain Threshold drug effects, Prospective Studies, Pulmonary Alveoli metabolism, Random Allocation, Rats, Rats, Wistar, Sevoflurane, Dipyrone pharmacology, Hyperalgesia veterinary, Methyl Ethers pharmacokinetics
- Abstract
Unlike non-steroidal anti-inflammatory drugs (NSAIDs), metamizole has poor anti-inflammatory effects; and is suitable for models where analgesia, but not anti-inflammatory effects, is desirable. Like opioids, these drugs produce perioperative analgesia while reducing anaesthetic requirements, but it remains unclear whether they may develop tolerance or hyperalgesia, and thus decrease in analgesic efficacy. The aim was to determine whether tolerance or hyperalgesia to metamizole occurred in rats, and whether the sevoflurane minimum alveolar concentration (MAC) was affected. In a randomized, prospective, controlled study, male Wistar rats ( n = 8 per group) were administered metamizole (300 mg/kg, day 4). Previously, the following treatments were provided: daily metamizole for four days (0-3), morphine (10 mg/kg; positive control, day 0 only) or saline (negative control). The main outcome measures were mechanical (MNT) and warm thermal (WNT) nociceptive quantitative sensory thresholds. The baseline sevoflurane MAC and the reduction produced by the treatments were also determined. The mean (SD) baseline MAC [2.4(0.2)%vol] was decreased by morphine and metamizole by 45(11)% and 33(7)% ( P = 0.000, both), respectively. Baseline MNT [35.4(4.5) g] and WNT [13.2(2.4) s] were decreased by morphine and metamizole: MNT reduction of 22(6)% ( P = 0.000) and 22(7)% ( P = 0.001), respectively and WNT reduction of 34(14)% ( P = 0.000) and 24(13)% ( P = 0.001). The baseline MAC on day 4 was neither modified by treatments nor the MAC reduction produced by metamizole (days 0 and 4; P > 0.05). In conclusion, repeated metamizole administration may produce hyperalgesia, although it may not modify its anaesthetic sparing effect. The clinical relevance of this effect in painful research models requiring prolonged analgesic therapy warrants further investigation.
- Published
- 2017
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46. Docosahexaenoic Acid Supplemented Diet Influences the Orchidectomy-Induced Vascular Dysfunction in Rat Mesenteric Arteries.
- Author
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Villalpando DM, Navarro R, Del Campo L, Largo C, Muñoz D, Tabernero M, Baeza R, Otero C, García HS, and Ferrer M
- Subjects
- Acetylcholine pharmacology, Animals, Blood Pressure, Docosahexaenoic Acids pharmacology, Male, Nitric Oxide biosynthesis, Prostaglandins metabolism, Rats, Superoxides metabolism, Vasodilator Agents pharmacology, Dietary Supplements, Mesenteric Arteries drug effects, Mesenteric Arteries physiopathology, Orchiectomy
- Abstract
Over the past few decades, the cardiovascular benefits of a high dietary intake of long-chain polyunsaturated fatty acids (PUFAs), like docosahexaenoic acid (DHA), have been extensively studied. However, many of the molecular mechanisms and effects exerted by PUFAs have yet to be well explained. The lack of sex hormones alters vascular tone, and we have described that a DHA-supplemented diet to orchidectomized rats improve vascular function of the aorta. Based on these data and since the mesenteric artery importantly controls the systemic vascular resistance, the objective of this study was to analyze the effect of a DHA-supplemented diet on the mesenteric vascular function from orchidectomized rats. For this purpose mesenteric artery segments obtained from control, orchidectomized or orchidectomized plus DHA-supplemented diet were utilized to analyze: (1) the release of prostanoids, (2) formation of NO and ROS, (3) the vasodilator response to acetylcholine (ACh), as well as the involvement of prostanoids and NO in this response, and (4) the vasoconstrictor response to electrical field stimulation (EFS), analyzing also the effect of exogenous noradrenaline (NA), and the NO donor, sodium nitroprusside (SNP). The results demonstrate beneficial effects of DHA on the vascular function in orchidectomized rats, which include a decrease in the prostanoids release and superoxide formation that were previously augmented by orchidectomy. Additionally, there was an increase in endothelial NO formation and the response to ACh, in which NO involvement and the participation of vasodilator prostanoids were increased. DHA also reversed the decrease in EFS-induced response caused by orchidectomy. All of these findings suggest beneficial effects of DHA on vascular function by reversing the neurogenic response and the endothelial dysfunction caused by orchidectomy., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2017
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47. Technical Aspects and Benefits of Experimental Mouse Lung Transplantation.
- Author
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Ruiz-Pérez D, Largo C, and García-Río F
- Subjects
- Analgesics therapeutic use, Anesthesia, General methods, Animals, Graft Rejection prevention & control, Microsurgery methods, Monitoring, Intraoperative methods, Pain, Postoperative drug therapy, Postoperative Care methods, Primary Graft Dysfunction etiology, Reperfusion Injury etiology, Respiration, Artificial, Species Specificity, Tissue Donors, Tissue and Organ Harvesting methods, Lung Transplantation methods, Mice surgery, Models, Animal, Rats surgery
- Abstract
In recent years, the number of lung transplantations performed as the last option for many respiratory diseases has grown considerably, both in adults and children. However, the causes for the relatively short survival of lungs compared to other organ transplants still need to be studied. Techniques have improved since the 1950s when experimental lung transplantation began, and the different animal species used now include rodents. The advantage of using these small species is that the surgical model has been expanded and standardized, and different respiratory problems can be studied. In this review we examine the different technical strategies used in experimental transplantation in rats and mice, focusing on surgical techniques and anesthesia and monitoring methods, and highlighting the major contributions of mouse lung transplantation to the field., (Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)
- Published
- 2016
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48. The Effects of the Toll-Like Receptor 4 Antagonist, Ibudilast, on Sevoflurane's Minimum Alveolar Concentration and the Delayed Remifentanil-Induced Increase in the Minimum Alveolar Concentration in Rats.
- Author
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Ruiz-Pérez D, Benito J, Polo G, Largo C, Aguado D, Sanz L, and Gómez de Segura IA
- Subjects
- Administration, Inhalation, Analgesics, Opioid administration & dosage, Analgesics, Opioid toxicity, Anesthetics, Inhalation administration & dosage, Animals, Drug Interactions, Drug Tolerance, Injections, Intraperitoneal, Injections, Intravenous, Male, Methyl Ethers administration & dosage, Naloxone pharmacology, Narcotic Antagonists pharmacology, Piperidines administration & dosage, Piperidines toxicity, Pyridines administration & dosage, Rats, Wistar, Remifentanil, Sevoflurane, Time Factors, Analgesics, Opioid pharmacology, Anesthetics, Inhalation pharmacology, Behavior, Animal drug effects, Methyl Ethers pharmacology, Pain Threshold drug effects, Piperidines pharmacology, Pyridines pharmacology, Toll-Like Receptor 4 antagonists & inhibitors
- Abstract
Background: Ultralow doses of naloxone, an opioid and toll-like receptor 4 antagonist, blocked remifentanil-induced hyperalgesia and the associated increase in the minimum alveolar concentration (MAC), but not tolerance. The aim was to determine the effects of the toll-like receptor 4 antagonist, ibudilast, on the MAC in the rat and how it might prevent the effects of remifentanil., Methods: Male Wistar rats were randomly allocated to 5 treatment groups (n = 7 per group): 10 mg/kg ibudilast intraperitoneally, 240 µg/kg/h remifentanil IV, ibudilast plus remifentanil, remifentanil plus naloxone IV, or saline. The sevoflurane MAC was determined 3 times in every rat and every day (days 0, 2, and 4): baseline (MAC-A) and 2 further determinations were made after treatments, 1.5 hours apart (MAC-B and MAC-C)., Results: A reduction in baseline MAC was produced on day 0 by ibudilast, remifentanil, remifentanil plus ibudilast, remifentanil plus naloxone (P < 0.01), but not saline. Similar effects were found on days 2 and 4. A tolerance to remifentanil was found on days 0, 2, and 4, which neither ibudilast nor naloxone prevented. The MAC increase produced by remifentanil on day 4 (P = 0.001) was prevented by either ibudilast or naloxone., Conclusions: Ibudilast, besides reducing the MAC, prevented the delayed increase in baseline MAC produced by remifentanil but not the increase in MAC caused by tolerance to remifentanil.
- Published
- 2016
- Full Text
- View/download PDF
49. Difficulties, guidelines and review of developing an acute rejection model after rat intestinal transplantation.
- Author
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Andres AM, Santamaria M, Hernandez-Oliveros F, Guerra L, Lopez S, Stringa P, Vallejo MT, Largo C, Encinas JL, Garcia de Las Heras MS, Lopez-Santamaria M, and Tovar JA
- Subjects
- Animals, Graft Survival, Guidelines as Topic, Humans, Intestine, Small surgery, Male, Models, Animal, Rats, Rats, Inbred Strains, Transplantation, Heterotopic, Graft Rejection immunology, Intestine, Small transplantation, Microsurgery methods, Organ Transplantation methods, Reperfusion Injury immunology
- Abstract
Experimental small bowel transplantation (SBT) in rats has been proven to be a useful tool for the study of ischemia-reperfusion and immunological aspects related to solid organ transplantation. However, the model is not completely refined, specialized literature is scarce and complex technical details are typically omitted or confusing. Most studies related to acute rejection (AR) use the orthotopic standard, with small sample sizes due to its high mortality, whereas those studying chronic rejection (CR) use the heterotopic standard, which allows longer term survival but does not exactly reflect the human clinical scenario. Various animal strains have been used, and the type of rejection and the timing of its analysis differ among authors. The double purpose of this study was to develop an improved unusual AR model of SBT using the heterotopic technique, and to elaborate a guide useful to implement experimental models for studying AR. We analyzed the model's technical details and expected difficulties in overcoming the learning curve for such a complex microsurgical model, identifying the potential problem areas and providing a step-by-step protocol and reference guide for future surgeons interested in the topic. We also discuss the historic and more recent options in the literature., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
50. Modulation of cholesterol-related gene expression by ergosterol and ergosterol-enriched extracts obtained from Agaricus bisporus.
- Author
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Gil-Ramírez A, Caz V, Martin-Hernandez R, Marín FR, Largo C, Rodríguez-Casado A, Tabernero M, Ruiz-Rodríguez A, Reglero G, and Soler-Rivas C
- Subjects
- Animals, Caco-2 Cells, Cholesterol, Dietary administration & dosage, Cholesterol, HDL blood, Cholesterol, LDL blood, Diacylglycerol O-Acyltransferase genetics, Diacylglycerol O-Acyltransferase metabolism, Diet, High-Fat, Down-Regulation, Ezetimibe pharmacology, Feces chemistry, Hep G2 Cells, Humans, Liver metabolism, Male, Mice, Mice, Inbred C57BL, RNA, Messenger genetics, RNA, Messenger metabolism, Receptors, Cytoplasmic and Nuclear genetics, Receptors, Cytoplasmic and Nuclear metabolism, Simvastatin pharmacology, Sterol Regulatory Element Binding Protein 2 genetics, Sterol Regulatory Element Binding Protein 2 metabolism, Sterols pharmacology, Triglycerides blood, Up-Regulation, beta-Glucans pharmacology, Agaricus chemistry, Ergosterol pharmacology, Gene Expression Regulation drug effects
- Abstract
Purpose: To investigate the effect of two extracts obtained from Agaricus bisporus on the mRNA expression of cholesterol-related genes. One of the extracts contained ergosterol and other fungal sterols (SFE) and the other contained β-glucans and fungal sterols (EβG)., Methods: Firstly, the dietary mixed micelles (DMMs) generated after in vitro digestion of standards and SFE were applied to Caco2 cells. Then, the lower compartment after a Caco2-transport experiment was applied to HepG2 cells. The mRNA expression was assessed in both cell lines by low-density arrays (LDA). Mice received the extracts, ergosterol or control drugs after 4 weeks of a high-cholesterol diet. The lipid profile of plasma, liver and feces was determined. LDA assays were performed in liver and intestines., Results: The DMM fraction of SFE up-regulated the LDLR mRNA expression in Caco2 cells. The lower compartment after Caco2-transport experiments up-regulated LDLR and modulated several other lipid-related genes in HepG2 cells. In mice, SFE decreased TC/HDL ratio and reduced hepatic triglycerides paralleled with down-regulation of Dgat1 expression, while EβG did it without transcriptional changes. Addition of SFE or ergosterol induced in jejunum a similar transcriptional response to simvastatin and ezetimibe; they all down-regulated Srebf2 and Nr1h4 (FXR) genes., Conclusion: Ergosterol-containing extracts from A. bisporus lowered hepatic triglyceride and modify the mRNA expression of cholesterol-related genes although the transcriptional regulation was unrelated to changes in plasma lipid profile. These extracts may be useful limiting hepatic steatosis and as bioactive ingredients to design novel functional foods preventing lifestyle-related diseases such as non-alcoholic fatty liver disease.
- Published
- 2016
- Full Text
- View/download PDF
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