Nanopartículas híbridas cargadas con un compuesto bioactivo y su efecto en biomarcadores neuroinflamatorios como potencial tratamiento de la enfermedad de Alzheimer

Hybrid nanoparticles loaded with a bioactive compound and their effect on neuroinflammatory biomarkers as a potential treatment for Alzheimer’s disease

Alondra Vargas Barona (2024, [Tesis de maestría])

La enfermedad de Alzheimer (EA) es una enfermedad neurodegenerativa progresiva caracterizada por el deterioro cognitivo asociado a la acumulación de la proteína beta amiloide (Aβ). La Aβ activa a las células gliales del cerebro, generando un aumento en la secreción de citocinas pro-inflamatorias que conducen a la neuroinflamación y muerte neuronal. Actualmente no existen tratamientos efectivos que curen o detengan su progresión, por ello, la EA se considera como una prioridad de salud mundial. Las principales limitaciones son la baja biodisponibilidad del fármaco y la impermeabilidad de la barrera hematoencefálica (BHE). Afortunadamente, la nanomedicina ha surgido como un campo prometedor para el desarrollo de nuevos sistemas para la entrega controlada y dirigida de fármacos hacia el cerebro. Por ello, en este trabajo se sintetizaron nanopartículas híbridas de polímeros y lípidos (NPsHPL) conjugadas con transferrina (Tf) para facilitar el cruce de la BHE, y cargadas con N-acetilcisteína (NAC) por su efecto anti-inflamatorio, y se llevó a cabo su caracterización fisicoquímica. Posteriormente se implementó un modelo in vitro con astrocitos humanos derivados de células pluripotentes inducidas (iPSC) provenientes de un paciente diagnosticado con la EA, las cuales se llevaron a un estado reactivo por la estimulación con lipopolisacárido (LPS). El cultivo de células fue tratado con las NPsHPL conjugadas con Tf y cargadas con NAC (NPsHPL-Tf-NAC) a 0.25 mg/mL y NAC libre a 5 mM. Los resultados mostraron que las NPsHPL-Tf-NAC modularon favorablemente la expresión de genes pro-inflamatorios, como la interleucina-1β (IL-1β), la proteína precursora de amiloide (APP) y la proteína ácida fibrilar glial (GFAP). Además, redujo la secreción de las citocinas pro-inflamatorias interleucina 6 (IL-6), IL-1β e interferóngamma (INF-γ), ambos casos respecto al grupo de células que no recibieron algún tratamiento. Por otra parte, la NAC libre sólo tuvo este efecto en la expresión de IL-1β y la secreción de las citocinas IL-6 e INF-γ. Estos resultados posicionan a las NPsHPL-Tf-NAC como un potencial tratamiento para la EA.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive impairment associated with the accumulation of beta-amyloid protein (Aβ). Aβ activates glial cells in the brain, increasing the secretion of pro-inflammatory cytokines that lead to neuroinflammation and neuronal death. Currently, there are no effective treatments that cure or stop its progression, therefore AD is considered a global health priority. The main limitations are the low drug bioavailability and impermeability of the blood-brain barrier (BBB). Fortunately, nanomedicine has emerged as a promising field for the development of new nanosystems for the controlled and targeted delivery of drugs to the brain. Therefore, in this work, lipid–polymer hybrid nanoparticles (LPHNPs) conjugated with transferrin (Tf) to facilitate crossing the BBB, and loaded with N-acetylcysteine (NAC) for its anti-inflammatory effect were synthesized, and their physicochemical characterization was carried out. Subsequently, an in vitro model with human astrocytes derived from induced pluripotent stem cells (iPSC) from an AD diagnosed patient was implemented, which were brought to a reactive state by stimulation with lipopolysaccharide (LPS). The cell culture was treated with Tf-conjugated LPHNPs loaded with NAC (LPHNPs-Tf-NAC) at 0.25 mg/mL and free NAC at 5 mM. The results showed that LPHNPs-Tf-NAC favorably modulated the expression of pro-inflammatory genes, such as interleukin-1β (IL-1β), amyloid precursor protein (APP) and glial fibrillary acidic protein (GFAP). In addition, they reduced the secretion of the pro-inflammatory cytokines interleukin 6 (IL-6), IL-1β and interferon-gamma (INF-γ), both cases compared to the group of cells that did not receive any treatment. On the other hand, free NAC only had this effect on the expression of IL-1β and the secretion of the cytokines IL-6 and INF-γ. These results position LPHNPs-Tf-NAC as a potential treatment for AD.

nanopartículas híbridas; enfermedad de Alzheimer; neuroinflamación; astrocitos; iPSC; nanomedicina hybrid nanoparticles, Alzheimer’s disease, neuroinflammation; astrocytes; iPSC; nanomedicine BIOLOGÍA Y QUÍMICA CIENCIAS DE LA VIDA OTRAS ESPECIALIDADES DE LA BIOLOGÍA OTRAS OTRAS

Discovery of genomic regions associated with grain yield and agronomic traits in Bi-parental populations of maize (Zea mays. L) under optimum and low nitrogen conditions

Noel Ndlovu Vijay Chaikam Berhanu Tadesse Ertiro Biswanath Das Yoseph Beyene Charles Spillane Prasanna Boddupalli Manje Gowda (2023, [Artículo])

Grain Yield Low Soil Nitrogen CIENCIAS AGROPECUARIAS Y BIOTECNOLOGÍA GRAIN NITROGEN SOIL CHEMICOPHYSICAL PROPERTIES MAIZE QUANTITATIVE TRAIT LOCI

PROPUESTA DE MANEJO DE LA PESQUERÍA EMERGENTE DE MERLUZA DEL PACÍFICO NORTE Merluccius productus EN EL GOLFO DE ULLOA, BAJA CALIFORNIA SUR

PABLO MORA ZAMACONA (2023, [Tesis de doctorado])

"La merluza del Pacífico Merluccius productus se distribuye desde Alaska hasta el sur de México, con una población particular descrita al sur de la península de Baja California conocida como merluza enana, de la que poco se sabe. Dicha población actualmente no es pescada comercialmente, por lo que representa un recurso con potencial de explotación. Las pesquerías potenciales y emergentes crean desafíos y oportunidades para los administradores pesqueros que necesitan tomar decisiones sobre cómo gestionar de forma sostenible una pesquería previa a su inicio. Este trabajo propone y analiza posibles medidas alternativas de gestión pesquera para esta potencial pesquería, bajo incertidumbre biológica y de mercado. Debido al desconocimiento de diversos aspectos de la biología del recurso primeramente se analizó el crecimiento individual del stock y posteriormente se realizó un análisis bioeconómico de la potencial pesquería.

Para el análisis del crecimiento individual se utilizó un total de 240 otolitos y datos de longitud patrón de 932 especímenes muestreados de mayo a diciembre de 2015. La formación anual de incrementos en los otolitos se verificó mediante la relación de incremento marginal y el análisis de borde. La edad se estimó a partir de recuentos de anillos en secciones sagitales de otolitos y el crecimiento se analizó mediante un enfoque de inferencia multimodelo. Se consideraron los modelos de crecimiento de von Bertalanffy (VBGM), VBGM generalizado, Gompertz, Logístico y Johnson, los cuales se ajustaron a conjuntos de datos de talla a la edad observados y retrocalculados agrupados por sexo. Según el criterio de información de Akaike, el VBGM generalizado fue el más apropiado para las hembras (L∞= 31.36 cm, k= 0.15 cm año-1), mientras que el VBGM proporcionó el mejor ajuste para los machos (L∞= 25.35 cm, k= 0.28 cm año-1).

El análisis bioeconómico de alternativas de manejo para una potencial pesquería de merluza enana indicó que una nueva pesquería de dicho stock podría ser biológicamente sostenible y económicamente rentable, bajo un conjunto de estrategias de gestión y reglas de control. Se recomienda un acceso limitado con bajo esfuerzo pesquero ya que resulta más redituable por barco y biológicamente precautorio, considerando la alta incertidumbre asociada con la explotación de una población virgen..."

"The Pacific hake Merluccius productus is distributed from Alaska to southern Mexico, with a particular population described south of the Baja California peninsula known as dwarf hake, about which little is known. This population is not currently commercially fished; hence it represents a resource with potential for exploitation. Potential and emerging fisheries create challenges and opportunities for fishery managers who need to make decisions about how to sustainably manage a fishery prior to its initiation. This work proposes and analyzes possible alternative fishery management measures for this potential fishery, under biological and market uncertainty. Due to the lack of knowledge of various aspects of the biology of the resource, the individual growth of the stock was first analyzed and subsequently a bioeconomic analysis of the potential fishery was carried out.

A total of 240 otoliths and standard-length data from 932 specimens sampled from May to December 2015 were used for the analysis of individual growth. The annual formation of otolith increments was verified using the marginal increment analysis and the edge analysis. Age was estimated from annuli counts in sagittal sections of otoliths and growth was analyzed using a multi-model inference approach. The von Bertalanffy growth models (VBGM), generalized VBGM, Gompertz, Logistic and Johnson growth models were considered, which were fitted to observed and back calculated length-at-age data sets grouped by sex. According to Akaike's information criterion, the generalized VBGM was the most appropriate for females (L∞= 31.36 cm, k= 0.15 cm year-1), while the VBGM provided the best fit for males (L∞= 25.35 cm, k= 0.28 cm year-1).

The bioeconomic analysis of management alternatives for a potential dwarf hake fishery indicated that a new fishery for said stock could be biologically sustainable and economically profitable, under a set of management strategies and control rules. Limited access with low fishing effort is recommended as it is more profitable by boat and biologically precautionary, considering the high uncertainty associated with the exploitation of an unfished stock. Despite the combination of high fishing costs and low prices, the fishery could still be profitable in the long term, although there is risk of overexploitation if high fishing effort is allowed..."

Merluza enana, stock no explotado, crecimiento individual, análisis bioeconómico, pesquería potencial Dwarf hake, unexploited stock, individual growth, bioeconomic analysis, potential fishery CIENCIAS AGROPECUARIAS Y BIOTECNOLOGÍA CIENCIAS AGRARIAS PECES Y FAUNA SILVESTRE REGLAMENTACIÓN Y CONTROL REGLAMENTACIÓN Y CONTROL

Bundling subsurface drip irrigation with no-till provides a window to integrate mung bean with intensive cereal systems for improving resource use efficiency

Manish Kakraliya madhu choudhary Mahesh Gathala Parbodh Chander Sharma ML JAT (2024, [Artículo])

The future of South Asia’s major production system (rice–wheat rotation) is at stake due to continuously aggravating pressure on groundwater aquifers and other natural resources which will further intensify with climate change. Traditional practices, conventional tillage (CT) residue burning, and indiscriminate use of groundwater with flood irrigation are the major drivers of the non-sustainability of rice–wheat (RW) system in northwest (NW) India. For designing sustainable practices in intensive cereal systems, we conducted a study on bundled practices (zero tillage, residue mulch, precise irrigation, and mung bean integration) based on multi-indicator (system productivity, profitability, and efficiency of water, nitrogen, and energy) analysis in RW system. The study showed that bundling conservation agriculture (CA) practices with subsurface drip irrigation (SDI) saved ~70 and 45% (3-year mean) of irrigation water in rice and wheat, respectively, compared to farmers’ practice/CT practice (pooled data of Sc1 and Sc2; 1,035 and 318 mm ha−1). On a 3-year system basis, CA with SDI scenarios (mean of Sc5–Sc8) saved 35.4% irrigation water under RW systems compared to their respective CA with flood irrigation (FI) scenarios (mean of Sc3 and Sc4) during the investigation irrespective of residue management. CA with FI system increased the water productivity (WPi) and its use efficiency (WUE) by ~52 and 12.3% (3-year mean), whereas SDI improved by 221.2 and 39.2% compared to farmers practice (Sc1; 0.69 kg grain m−3 and 21.39 kg grain ha−1 cm−1), respectively. Based on the 3-year mean, CA with SDI (mean of Sc5–Sc8) recorded −2.5% rice yield, whereas wheat yield was +25% compared to farmers practice (Sc1; 5.44 and 3.79 Mg ha−1) and rice and wheat yield under CA with flood irrigation were increased by +7 and + 11%, compared to their respective CT practices. Mung bean integration in Sc7 and Sc8 contributed to ~26% in crop productivity and profitability compared to farmers’ practice (Sc1) as SDI facilitated advancing the sowing time by 1 week. On a system basis, CA with SDI improved energy use efficiency (EUE) by ~70% and partial factor productivity of N by 18.4% compared to CT practices. In the RW system of NW India, CA with SDI for precise water and N management proved to be a profitable solution to address the problems of groundwater, residue burning, sustainable intensification, and input (water and energy) use with the potential for replication in large areas in NW India.

Direct Seeded Rice Subsurface Drip Irrigation Economic Profitability Energy and Nitrogen Efficiency CIENCIAS AGROPECUARIAS Y BIOTECNOLOGÍA CONSERVATION AGRICULTURE RICE SUBSURFACE IRRIGATION IRRIGATION SYSTEMS WATER PRODUCTIVITY ECONOMIC VIABILITY ENERGY EFFICIENCY NITROGEN-USE EFFICIENCY

Dual function of EDTA with silver nanoparticles for root canal treatment–A novel modification

JUAN MANUEL MARTINEZ ANDRADE (2018, [Artículo])

The chelating and antimicrobial capacity of a novel modification of 17% EDTA with silver nanoparticles (AgNPs) (EDTA-AgNPs) was evaluated in-vitro for root canal treatment (RCT). The EDTA-AgNPs solution was characterized by UV-Vis spectroscopy, ?-potential and high-resolution transmission electron microscopy (HRTEM). Antimicrobial capacity was evaluated against Candida albicans and Staphylococcus aureus in planktonic and biofilm cells by broth macrodilution (24 h) and XTT assays, (1, 10 and 30 min) respectively. The chelating capacity of EDTA-AgNPs was assessed indirectly (smear layer removal) and directly (demineralizing effect) in bovine dentin at two silver concentrations, 16 and 512 ?g/ ml at 1 and 10 minutes of exposure time. Smear layer removal was evaluated by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The demineralizing effect was determined by atomic absorption spectroscopy (AAS), microhardness test (MH) and X-ray diffractometer (XRD). Synthesized AgNPs were quasi-spherical in shape with an average size of 13.09 ± 8.05 nm. 17% EDTA-AgNPs was effective to inhibit C. albicans and S. aureus in planktonic and biofilm cultures. The smear layer removal and demineralizing effect were similar between 17% EDTA-AgNPs and 17% EDTA treatments. The 17% EDTA-AgNPs solution proved to be an effective antimicrobial agent, and has a similar chelating capacity to 17% EDTA alone. These in-vitro studies strongly suggest that EDTA-AgNPs could be used for effective smear layer removal, having an antimicrobial effect at the same time during RCT. © 2018 Martinez-Andrade et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

edetic acid, silver nanoparticle, edetic acid, metal nanoparticle, silver, antibacterial activity, antibiotic sensitivity, antifungal activity, antimicrobial activity, Article, atomic absorption spectrometry, atomic force microscopy, biofilm, bovine, BIOLOGÍA Y QUÍMICA CIENCIAS DE LA VIDA MICROBIOLOGÍA MICROBIOLOGÍA

Nitrogen deficiency tolerance and responsiveness of durum wheat genotypes in Ethiopia

Tesfaye Geleta Aga Kebebew Assefa Bekele Abeyo (2022, [Artículo])

Low-Nitrogen Tolerance Yield Reduction Tolerant Genotypes Parental Donors CIENCIAS AGROPECUARIAS Y BIOTECNOLOGÍA NITROGEN HARD WHEAT GENOTYPES

Tecnologías para la remoción de contaminantes emergentes, nutrientes y producción de energía en aguas y lodos residuales para cuencas hidrográficas del estado de Morelos

PETIA MIJAYLOVA NACHEVA EDSON BALTAZAR ESTRADA ARRIAGA MERCEDES ESPERANZA RAMIREZ CAMPEROS (2014, [Documento de trabajo])

El objetivo de este proyecto fue desarrollar sistemas avanzados y adaptar sistemas ya existentes para remover nutrientes y compuestos emergentes presentes en las aguas y lodos residuales de las cuencas hidrográficas del Estado de Morelos, implementando dispositivos de ahorro y/o producción de energía.

Se realizaron experimentos en laboratorio en las tres líneas de investigación: Sistemas de tratamiento de las aguas residuales que remueven compuestos emergentes. Sistemas de tratamiento biológico avanzado para remoción de nutrientes. Generación de energía mediante celdas de combustible microbianas. Los resultados se presentan en forma detallada en este informa.

Cuencas hidrográficas Tratamiento de aguas residuales Contaminantes emergentes Remoción de nutrientes Energía no convencional Informes de proyectos Morelos INGENIERÍA Y TECNOLOGÍA

Environmental Nanoparticles Reach Human Fetal Brains

LILIAN OFELIA CALDERON GARCIDUEÑAS ANGEL AUGUSTO PEREZ CALATAYUD ANGELICA GONZALEZ MACIEL RAFAEL REYNOSO ROBLES Héctor Gabriel Silva Pereyra Andrea Ramos Morales RICARDO TORRES JARDON Candelario de Jesús Soberanes Cerino Raúl Carrillo Esper JESÚS CARLOS BRIONES GARDUÑO Yazmin del Socorro Conde Gutiérrez (2022, [Artículo])

"Anthropogenic ultrafine particulate matter (UFPM) and industrial and natural nanoparticles (NPs) are ubiquitous. Normal term, preeclamptic, and postconceptional weeks(PCW) 8–15 human placentas and brains from polluted Mexican cities were analyzed by TEM and energy-dispersive X-ray spectroscopy. We documented NPs in maternal erythrocytes, early syncytiotrophoblast, Hofbauer cells, and fetal endothelium (ECs). Fetal ECs exhibited caveolar NP activity and widespread erythroblast contact. Brain ECs displayed micropodial extensions reaching luminal NP-loaded erythroblasts. Neurons and primitive glia displayed nuclear, organelle, and cytoplasmic NPs in both singles and conglomerates. Nanoscale Fe, Ti, and Al alloys, Hg, Cu, Ca, Sn, and Si were detected in placentas and fetal brains. Preeclamptic fetal blood NP vesicles are prospective neonate UFPM exposure biomarkers. NPs are reaching brain tissues at the early developmental PCW 8–15 stage, and NPs in maternal and fetal placental tissue compartments strongly suggests the placental barrier is not limiting the access of environmental NPs. Erythroblasts are the main early NP carriers to fetal tissues. The passage of UFPM/NPs from mothers to fetuses is documented and fingerprinting placental single particle composition could be useful for postnatal risk assessments. Fetal brain combustion and industrial NPs raise medical concerns about prenatal and postnatal health, including neurological and neurodegenerative lifelong consequences."

Environmental medicine Placental impairment Neurodevelopmental disorders Fetal brains Erythroblasts Preeclampsia Nanoparticles NPs extracellular vesicles Petrochemical pollution Villahermosa Tabasco BIOLOGÍA Y QUÍMICA QUÍMICA BIOQUÍMICA BIOQUÍMICA

Nanovacunas que valen oro

Carlos Eliud Angulo Valadez LUIS HERNANDEZ ADAME Ana Aguilera-Juarez (2022, [Artículo])

nanopartículas de oro BIOLOGÍA Y QUÍMICA CIENCIAS DE LA VIDA INMUNOLOGÍA VACUNAS VACUNAS

Effects of Paralytic Shellfish Toxins on marine mammals, seabirds and geoduck fisheriesin the Northern Gulf of California during 2015-2019

Efectos de las toxinas paralizantes en mamíferos y aves marinas, y en las pesqueríasde almeja generosa del Norte del Golfo de California durante 2015-2019

Jennifer Medina Elizalde (2021, [Tesis de doctorado])

Paralytic Shellfish Toxins (PSTs) are a group of neurotoxins produced by some marine dinoflagellates species. During the harmful algal blooms (HABs) of these species, PSTs accumulate in bivalves which become the main vector of the toxins to humans. Paralytic Shellfish Poisoning (PSP) is the most important shellfish toxin syndrome in Mexico related to HABs and the only one associated with human fatalities. At least four HABs of Gymnodinium catenatum occurred in the Northern Gulf of California (NGC) between 2015 and 2019. In 2015, a G. catenatum HAB caused multispecies mass mortalities of sea mammals and seabirds. More than 1,000 seabirds and 240 marine mammals were affected. Also, the intoxication of at least five people were associated with this HAB. The presence of G. catenatum was registered from January to May. The sardine “bocona” (Cetengraulis mysticetus) was the main vector of the PSTs to animals. Economic activities have been also impacted by HABs in the NGC. Multiple prohibitions (sanitary bans) to the harvesting and exportation of the geoduck clam Panopea globosa have been implemented in the region. The metabolism of the PSTs in the siphon and visceral mass was characterized, this information is necessary when creating management plans for this important fishery. A maximum toxicity of 16,740 µgSTX eq Kg-1 was detected on the visceral mass, with a depuration rate of 4.3% day-1. C1&2 were the most abundant analogues detected in geoduck samples collected during the HAB appearance. The concentration of these analogues decreased in the first weeks, and the more toxic analogues GTX5, dcGTX3 and dcSTX were detected. Five and seven months after the occurrence of the HAB, M-type analogues and STX were detected also in the visceral mass of the clams. This is the first description of the biotransformation of PST in P. globlosa. Monitoring of PSTs levels in bivalves, and particularly during HABs requires reliable results in a short period of time. To meet analytic demands, Mexican Health Authorities implemented the Scotia Rapid Testing (SRT). SRT and HPLC-PCOX, the reference methodology in the US and Canada, were compared with the mouse bioassay (MBA), the reference methodology in Mexico. The good correlation (R2=0.91) between HPLC-PCOX and MBA indicates that HPLC-PCOX is suitable for monitoring PSTs in P. globosa. However, it was found that STR was not an accurate methodology as more than 67% of false positives were registered. G. catenatum HABs have occurr

Las toxinas paralizantes (PST) son un grupo de neurotoxinas producidas por algunas especies de dinoflagelados marinos. Durante los Florecimientos Algales Nocivos (FAN) de estas especies, las PST se acumulan en bivalvos, que son el principal vector de las toxinas al hombre. La intoxicación paralizante por consumo de mariscos (PSP) es el síndrome asociado a toxinas en moluscos producidas por FAN más importante en México, y el único relacionado con muertes humanas. Al menos cuatro FANs de Gymnodinium catenatum ocurrieron en el norte del Golfo de California (NGC) entre 2015 y 2019. En 2015, el FAN provocó la mortalidad de más de 1,000 aves y 240 mamíferos marinos de distintas especies. Además, al menos 5 personas presentaron síntomas de intoxicación PSP. G. catenatum se registró de enero a mayo. La sardina “bocona” (Cetengraulis mysticetus) fue el principal vector de las PST hacia los animales. Las actividades económicas también se han visto afectadas por los FAN en el NGC debido a la implementación de vedas a la pesca y exportación de la almeja generosa Panopea globosa. En este trabajo, se caracterizó el metabolismo de las PST en el sifón y la masa visceral de la almeja, esta información es necesaria para la elaboración de planes de manejo para esta importante pesquería. La toxicidad máxima detectada fue 16,740 µg STXeq Kg-1 en la masa visceral, con una tasa de depuración de 4.3% día-1. C1&2 fueron los análogos más abundantes en muestras recolectadas al inicio del FAN, su concentración disminuyó en las primeras semanas y los análogos más tóxicos GTX5, dcGTX3 y dcSTX fueron detectados. Cinco y siete meses después de la aparición del FAN, se detectaron análogos de tipo M y STX. Esta es la primera descripción de la biotransformación de PSTs en P. globlosa. El monitoreo de las toxinas en bivalvos, particularmente durante un FAN, requiere la generación de resultados confiables en poco tiempo. Para satisfacer las demandas analíticas, las autoridades mexicanas implementaron el uso de Scotia Rapid Testing (SRT). En este trabajo, se compararon SRT y HPLC-PCOX, la metodología de referencia en EE.UU. y Canadá, con el bioensayo en ratón (MBA), la metodología de referencia en México. La buena correlación (R2 = 0.91) entre HPLC-PCOX y MBA indica que HPLC-PCOX es adecuado para monitorear PSTs en P. globosa, mientras que STR no es una metodología precisa ya que se registraron más de 67% de falsos positivos. Los FAN de G. catenatum se han producido en el NGC entre enero ...

Harmful Algae Bloom, Gymnodinium catenatum, Panopea globosa, HPLC-PCOX, Mousse Bioassay Florecimientos algales nocivos, Gymnodinium catenatum, Panopea globosa, HPLCPCOX, Bioensayo en ratón BIOLOGÍA Y QUÍMICA CIENCIAS DE LA VIDA CIENCIAS DE LA VIDA