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1.
J Biochem Mol Toxicol ; 38(1): e23611, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38084605

RESUMEN

BACKGROUND: Nanotechnology and its application to manipulate herbal compounds to design new neuroprotective agents to manage neurotoxicity has recently increased. Cur-ZnO conjugated nanoparticles were synthesized and used in an experimental model of ketamine-induced neurotoxicity. METHODS: Cur-ZnO conjugated nanoparticles were chemically characterized, and the average crystalline size was determined. Forty-nine adult mice were divided into seven groups of seven animals each. Normal saline was given to control mice (group 1). Ketamine (25 mg/kg) was given to a second group. A third group of mice was given ketamine (25 mg/kg) in combination with curcumin (40 mg/kg), while mice in groups 4, 5, and 6 received ketamine (25 mg/kg) plus Cur-ZnO nanoparticles (10, 20, and 40 mg/kg). Group 7 received only ZnO (5 mg/kg). All doses were ip for 14 days. Hippocampal mitochondrial quadruple complex enzymes, oxidative stress, inflammation, and apoptotic characteristics were assessed. RESULTS: Cur-ZnO nanoparticles and curcumin decreased lipid peroxidation, GSSG content, IL-1ß, TNF-α, and Bax levels while increasing GSH and antioxidant enzymes like GPx, GR, and SOD while increasing Bcl-2 level and mitochondrial quadruple complex enzymes in ketamine treatment groups. CONCLUSION: The neuroprotective properties of Cur-ZnO nanoparticles were efficient in preventing ketamine-induced neurotoxicity in the mouse brain. The nanoparticle form of curcumin (Cur-ZnO) required lower doses to produce neuroprotective effects against ketamine-induced toxicity than conventional curcumin.


Asunto(s)
Curcumina , Ketamina , Nanopartículas , Fármacos Neuroprotectores , Síndromes de Neurotoxicidad , Óxido de Zinc , Ratones , Animales , Curcumina/farmacología , Neuroprotección , Óxido de Zinc/toxicidad , Ketamina/toxicidad , Estrés Oxidativo , Fármacos Neuroprotectores/farmacología , Síndromes de Neurotoxicidad/tratamiento farmacológico , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/prevención & control
2.
Naunyn Schmiedebergs Arch Pharmacol ; 397(4): 1971-1984, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-37812241

RESUMEN

Doxorubicin is a potent chemotherapeutic agent that can cause cardiotoxicity. Many documents (more than 14,000) have been published in the area of doxorubicin-induced cardiotoxicity (DIC) since 1970. A comprehensive bibliographic analysis of author keywords was used to describe better and understand the molecular mechanisms involved in DIC. The objective was to consider the state of the author keywords of research on the molecular mechanisms involved in DIC based on a bibliometrics study of articles published over the past fifty years. A bibliometrics analysis was conducted using VOSviewer with data collected from the Web of Science Core Collection database of over 14,000 documents (from 1970 to July 19, 2023). Using scientific publications retrieved about DIC, author keywords were assessed at the scientific field level. The current study showed that the annual number of DIC-related publications has increased over the past 50 years. The Journal of Clinical Oncology is the leading journal in this field. The top cited DIC document was published in 2004. The top keywords with high frequency were "doxorubicin," "cardiotoxicity," and "adriamycin." According to the results of this study, the most common mechanisms involved in DIC were as follows oxidative stress, apoptosis, inflammation, autophagy, mitophagy, endoplasmic reticulum stress, pyroptosis, and ferroptosis. The highest occurrences of regulators-related author keywords were "AKT," "Sirt1," and "AMPK." Based on the findings, oxidative stress, apoptosis, inflammation, autophagy, mitophagy, endoplasmic reticulum stress, pyroptosis, and ferroptosis were hot research mechanisms of DIC from 1970 to July 19, 2023.


Asunto(s)
Apoptosis , Cardiotoxicidad , Humanos , Bibliometría , Doxorrubicina , Inflamación
3.
Clin Pharmacol Ther ; 111(2): 391-403, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-33998672

RESUMEN

This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of BIA 10-2474, a fatty acid amide hydrolase (FAAH) inhibitor, after first administration to healthy male and female participants. Participants (n = 116) were recruited into this phase I, double-blind, randomized, placebo-controlled, single ascending dose and multiple ascending dose (10-day) study. The primary outcome was the safety and tolerability of BIA 10-2474. Secondary outcomes were pharmacokinetics of BIA 10-2474 and pharmacodynamics, considering plasma concentrations of anandamide and three other fatty acid amides (FAAs) and leukocyte FAAH activity. Single oral doses of 0.25-100 mg and repeated oral doses of 2.5-50 mg were evaluated. BIA 10-2474 was well tolerated up to 100 mg as a single dose and up to 20 mg once daily for 10 days. In the cohort receiving repeated administrations of 50 mg, there were central nervous system adverse events in five of six participants, one with fatal outcome, which led to early termination of the study. BIA 10-2474 showed a linear relationship between dose and area under plasma concentration-time curve (AUC) across the entire dose range and reached steady state within 5-6 days of administration, with an accumulation ratio, based on AUC0-24h , of <2 on Day 10. BIA 10-2474 was rapidly absorbed with a mean terminal elimination half-life of 8-10 hours (Day 10). BIA 10-2474 caused reversible, dose-related increases in plasma FAAs. In conclusion, we propose that these data, as well as the additional data generated since the clinical trial was stopped, do not provide a complete mechanistic explanation for the tragic fatality.


Asunto(s)
Amidohidrolasas/antagonistas & inhibidores , Sistema Nervioso Central/efectos de los fármacos , Óxidos N-Cíclicos/efectos adversos , Inhibidores Enzimáticos/efectos adversos , Piridinas/efectos adversos , Administración Oral , Sistema Nervioso Central/fisiopatología , Óxidos N-Cíclicos/administración & dosificación , Óxidos N-Cíclicos/farmacocinética , Método Doble Ciego , Esquema de Medicación , Cálculo de Dosificación de Drogas , Terminación Anticipada de los Ensayos Clínicos , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/farmacocinética , Femenino , Francia , Voluntarios Sanos , Humanos , Masculino , Seguridad del Paciente , Piridinas/administración & dosificación , Piridinas/farmacocinética , Medición de Riesgo , Factores de Riesgo
4.
J Biochem Mol Toxicol ; 34(12): e22605, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32830361

RESUMEN

Rotenone is a widely used organic pesticide; its serious side effect for off-target species is neurotoxicity. The primary mechanism of rotenone toxicity is inhibition of the mitochondrial complex I. Oxidative stress, apoptosis, and reduction of autophagy are key outcomes of the inhibition of complex I. Numerous in vitro and in vivo studies have shown antioxidant, anti-apoptotic, and autophagy enhancement of a variety of natural compounds (NCs). In this manuscript, we reviewed several NCs, which have protective effects against rotenone-induced neurotoxicity.


Asunto(s)
Productos Biológicos/farmacología , Sistema Nervioso/efectos de los fármacos , Rotenona/toxicidad , Animales
5.
J Transl Med ; 18(1): 205, 2020 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-32430070

RESUMEN

The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also affects society as a whole; so, it has also become the leading scientific concern. We discuss in this treatise the importance of bringing the world's scientists together to find effective solutions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemic's consequences and prevent recurrences of similar pandemics.


Asunto(s)
Investigación Biomédica/organización & administración , Infecciones por Coronavirus/epidemiología , Prestación Integrada de Atención de Salud/organización & administración , Urgencias Médicas , Necesidades y Demandas de Servicios de Salud , Pandemias , Neumonía Viral/epidemiología , Betacoronavirus/patogenicidad , Investigación Biomédica/métodos , COVID-19 , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/virología , Prestación Integrada de Atención de Salud/métodos , Historia del Siglo XXI , Humanos , Comunicación Interdisciplinaria , Estudios Interdisciplinarios , Neumonía Viral/terapia , Neumonía Viral/virología , Salud Pública/historia , Salud Pública/normas , SARS-CoV-2
6.
Int J Toxicol ; 39(2): 165-172, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32066298

RESUMEN

Risk assessment of chemical mixtures has emerged as a focus of research efforts, but traditional toxicology testing in mammals is costly, time-consuming, and subject to ethical scrutiny in the context of recent trends to reduce reliance on animal testing. In this review, which is a summary of presentations given at a workshop in Havana, Cuba, in April 2019, we survey the utility of zebra fish as an alternative laboratory model in whole-mixture and component-based testing, as well as in vitro modeling in 3-dimensional organotypic cultures from primary human cells cultured at the air-liquid interface and organ-on-a-chip platforms. Finally, we discuss the complexities of assessing the dynamics and delivery of multispecies liquid aerosol mixtures along the human respiratory tract, with examples of alternative and computational approaches to aerosol dosimetry. The workshop contributed to the professional development of Cuban toxicologists, an underserved segment of the global scientific community, delivering a set of tools and recommendations that could potentially provide cost-effective solutions for scientists with limited research resources.


Asunto(s)
Alternativas a las Pruebas en Animales , Interacciones Farmacológicas , Medición de Riesgo , Aerosoles , Animales , Cuba , Humanos , Sistema Respiratorio/efectos de los fármacos , Productos de Tabaco/toxicidad
7.
Pharmacol Res ; 150: 104516, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31698066

RESUMEN

The endoplasmic reticulum (ER) is the site of production and folding of secreted, membrane bound and some organelle targeted proteins. Accumulation of misfolded or unfolded proteins in the ER makes cells undergo a stress response known as the unfolded protein response (UPR). UPR is initially protective. However, prolonged and severe ER stress can lead to the induction of apoptosis in stressed cells. Cardiac hypertrophy and myocardial ischemia accounts for substantial morbidity and mortality worldwide. Accumulating evidence suggests that aberrant cardiac cell death caused by ER stress is often associated with structural or functional cardiac abnormalities. MicroRNAs (miRNAs) are a class of small non-coding RNAs that mediate posttranscriptional gene silencing. The miRNAs play important roles in regulating cardiac physiological and pathological events such as hypertrophy, apoptosis, and heart failure. In this review, we discussed the role of microRNAs on Endoplasmic Reticulum Stress in myocardial ischemia and cardiac hypertrophy to demonstrate the relation between microRNAs and the ER in cardiac cells providing potential new treatment strategies and improvement of survival.


Asunto(s)
Cardiomegalia/genética , Estrés del Retículo Endoplásmico/genética , MicroARNs , Isquemia Miocárdica/genética , Animales , Retículo Endoplásmico/metabolismo , Humanos
8.
Pharmacol Res ; 146: 104335, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31265891

RESUMEN

The endoplasmic reticulum (ER), a cellular organelle with multiple functions, plays an important role in several biological processes including protein folding, secretion, lipid biosynthesis, calcium homeostasis, and cellular stress. Accumulation of misfolded or unfolded proteins in the ER makes cells undergo a stress response known as the unfolded protein response (UPR). UPR is initially protective. However, prolonged and severe ER stress can lead to autophagy and/or the induction of apoptosis in stressed cell. Many studies have demonstrated that ER stress and the UPR are involved in different diseases such as neurodegenerative diseases, cancer, osteoporosis, diabetes, and inflammatory diseases. Curcumin, a natural polyphenol, has well documented evidence supporting its numerous biological properties including antioxidant, anti-inflammatory, immune-modulatory, anti-microbial, anti-ischemic, anti-angiogenesis, neuroprotective, hepatoprotective, nephroprotective, anti-atherogenic and anti-diabetic activities. In this review, the role of ER stress in several pathological condition and the potential protective effects of curcumin are discussed.


Asunto(s)
Curcumina/farmacología , Curcumina/uso terapéutico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Animales , Retículo Endoplásmico/efectos de los fármacos , Humanos , Transducción de Señal/efectos de los fármacos
9.
Biofactors ; 45(1): 5-23, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30339717

RESUMEN

People are exposed to a number of environmental, occupational, and therapeutic toxic agents which may be natural or man made. These hazardous substances may manifest as direct side effects on the function of organs or indirectly induced alteration of gene expression, cancer-associated metabolic pathways, and/or alter homeostasis. Lycopene, as a one of the most potent antioxidant, is found in fruits and vegetables. High-intake of lycopene has been shown to be effective in decreasing the risk of both natural toxins including mycotoxins, bacterial toxins, and chemical toxins including heavy metals, pesticides as well as herbicides. Recently, there is growing attention in understanding the mechanisms of the phytochemicals and carotenoids as antioxidative, antiapoptotic, radical scavenging, and chelating agents and their roles in the modulation of inflammatory pathways. This review summarizes available data from several recent studies about lycopene and its role against chemical and natural toxicants. © 2018 BioFactors, 45(1):5-23, 2019.


Asunto(s)
Antioxidantes/farmacología , Toxinas Bacterianas/antagonistas & inhibidores , Quelantes/farmacología , Licopeno/farmacología , Micotoxinas/antagonistas & inhibidores , Plaguicidas/antagonistas & inhibidores , Animales , Antioxidantes/metabolismo , Toxinas Bacterianas/toxicidad , Quelantes/metabolismo , Fluoruros/antagonistas & inhibidores , Fluoruros/toxicidad , Contaminación de Alimentos/análisis , Humanos , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/toxicidad , Licopeno/metabolismo , Redes y Vías Metabólicas/efectos de los fármacos , Redes y Vías Metabólicas/genética , Metales Pesados/antagonistas & inhibidores , Metales Pesados/toxicidad , Micotoxinas/toxicidad , Plaguicidas/toxicidad , Ratas , Pruebas de Toxicidad Crónica
11.
Int J Environ Health Res ; 24(1): 56-62, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-23544435

RESUMEN

We assessed the acute effects of a 1-h exposure to second-hand smoke (SHS) on complete blood count (CBC) markers in a controlled simulated bar/restaurant environment. Nineteen adult never-smokers completed a 1-h .exposure to SHS at bar/restaurant levels, and a 1-h exposure to normal room air. Blood samples were collected at the baseline at 30 min during each exposure, and at 0, 0.5, 1, 2, 3, and 4 h after each exposure. The values of white blood cells (WBC) at 1 h (p = 0.010), 3 h (p = 0.040), and 4 h (p = 0.008) following SHS were significantly increased compared with the baseline values. Also, there was a positive association between the WBC and cotinine levels (r = 0.28, p = 0.007). A 1-h exposure to SHS at bar/restaurant levels significantly increased the WBC for at least 4 h following the exposure time. This effect of SHS on WBC has dose-response characteristics and should be considered to prescribing CBC.


Asunto(s)
Cotinina/sangre , Exposición a Riesgos Ambientales , Contaminación por Humo de Tabaco/efectos adversos , Adulto , Biomarcadores/sangre , Recuento de Células Sanguíneas , Cromatografía Liquida , Estudios Cruzados , Monitoreo del Ambiente , Femenino , Humanos , Masculino , Espectrometría de Masas , Restaurantes , Factores de Tiempo , Adulto Joven
14.
Food Chem Toxicol ; 61: 60-8, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23380202

RESUMEN

Grape extracts and wine have been studied widely due to their beneficial effects on human health. However, there are only few studies from grape stems extracts. Therefore, the main objective of the present study was the assessment in stem extracts from Greek Vitis vinifera varieties of the total polyphenolic content (TPC), the identification of the polyphenols present in them, and the evaluation of their antioxidant activity, protection against ROS-induced DNA damage and inhibition of liver (HepG2) and cervical (HeLa) cancer cell growth. The range of the TPC in grape stem extracts was from 345 to 584 mg GAE/g dry weight. Moreover, stem extracts contained different classes of polyphenols as flavonols, flavanols, procyanidins, phenolic acids and stilbenes. In DPPH and ABTS assays, the IC50 values of the stem extracts had an average of 7.8 ± 2.8 and 5.4 ± 2.6 µg/mL respectively. Also, all stem extracts inhibited OH- and ROO-induced DNA damage dose dependent with average IC50 values of 478 ± 217 and 1.15 ± 0.85 µg/mL respectively. Furthermore, stem extracts inhibited at low concentrations the growth of HepG2 and HeLa cancer cells with average IC50 values of 50 ± 12 and 32 ± 16 µg/mL respectively. The above activities of grape stem extracts were comparable to those of seed extracts.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Antioxidantes/farmacología , Daño del ADN/efectos de los fármacos , Extractos Vegetales/farmacología , Polifenoles/análisis , Vitis/química , Antineoplásicos Fitogénicos/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Radicales Libres/toxicidad , Células HeLa/efectos de los fármacos , Células Hep G2/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Extractos Vegetales/química , Tallos de la Planta/química , Especies Reactivas de Oxígeno/metabolismo
15.
Inhal Toxicol ; 25(2): 91-101, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23363041

RESUMEN

CONTEXT: Electronic cigarettes (e-cigarettes) are becoming increasingly popular yet their effects on health remain unknown. OBJECTIVE: To conduct the first comprehensive and standardized assessment of the acute impact of active and passive e-cigarette smoking on serum cotinine and lung function, as compared to active and passive tobacco cigarette smoking. MATERIALS AND METHODS: Fifteen smokers (≥15 cigarettes/day; seven females; eight males) and 15 never-smokers (seven females; eight males) completed this repeated-measures controlled study. Smokers underwent a control session, an active tobacco cigarette (their favorite brand) smoking session and an active e-cigarette smoking session. Never-smokers underwent a control session, a passive tobacco cigarette smoking session and a passive e-cigarette smoking session. Serum cotinine, lung function, exhaled carbon monoxide and nitric oxide were assessed. The level of significance was set at p ≤ 0.001 to adjust for multiple comparisons. RESULTS: e-Cigarettes and tobacco cigarettes generated similar (p > 0.001) effects on serum cotinine levels after active (60.6 ± 34.3 versus 61.3 ± 36.6 ng/ml) and passive (2.4 ± 0.9 versus 2.6 ± 0.6 ng/ml) smoking. Neither a brief session of active e-cigarette smoking (indicative: 3% reduction in FEV1/FVC) nor a 1 h passive e-cigarette smoking (indicative: 2.3% reduction in FEV1/FVC) significantly affected the lung function (p > 0.001). In contrast, active (indicative: 7.2% reduction in FEV1/FVC; p < 0.001) but not passive (indicative: 3.4% reduction in FEV1/FVC; p = 0.005) tobacco cigarette smoking undermined lung function. CONCLUSION: Regarding short-term usage, the studied e-cigarettes generate smaller changes in lung function but similar nicotinergic impact to tobacco cigarettes. Future research should target the health effects of long-term e-cigarette usage, including the effects of nicotine dosage.


Asunto(s)
Cotinina/sangre , Equipos y Suministros Eléctricos , Productos de Tabaco , Adolescente , Adulto , Monóxido de Carbono/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Fumar/efectos adversos , Fumar/sangre , Espirometría , Contaminación por Humo de Tabaco/efectos adversos , Adulto Joven
18.
Food Chem Toxicol ; 50(9): 3150-65, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22504784

RESUMEN

Assessment of safety for a food or dietary ingredient requires determination of a safe level of ingestion compared to the estimated daily intake from its proposed uses. The nature of the assessment may require the use of different approaches, determined on a case-by-case basis. Natural products are chemically complex and challenging to characterize for the purpose of carrying out a safety evaluation. For example, a botanical extract contains numerous compounds, many of which vary across batches due to changes in environmental conditions and handling. Key components integral to the safety evaluation must be identified and their variability established to assure that specifications are representative of a commercial product over time and protective of the consumer; one can then extrapolate the results of safety studies on a single batch of product to other batches that are produced under similar conditions. Safety of a well-characterized extract may be established based on the safety of its various components. When sufficient information is available from the public literature, additional toxicology testing is not necessary for a safety determination on the food or dietary ingredient. This approach is demonstrated in a case study of an aqueous extract of cranberry (Vaccinium macrocarpon Aiton) leaves.


Asunto(s)
Productos Biológicos/efectos adversos , Extractos Vegetales/efectos adversos , Hojas de la Planta/química , Vaccinium macrocarpon/química , Animales , Límite de Detección
19.
ALTEX ; 28(3): 183-209, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21993956

RESUMEN

The European cosmetics legislation foresees a review in 2011 and possible postponement of the 2013 marketing ban to enforce the testing ban for systemic and repeated-dose animal tests. For this purpose, a 119-page report commissioned by the European Commission was published recently. Here, a group of 17 independent experts from the US, Europe, and Japan was brought together to evaluate the report. The expert panel strongly endorsed the report and its conclusions. A number of important options not considered were identified; these do not, however, affect the overall conclusions regarding the current lack of availability of a full replacement, especially for the areas of repeated dose toxicity, carcinogenicity testing, and reproductive toxicity, though a roadmap for change is emerging. However, some of these options may provide adequate data for replacement of some animal studies in the near future pending validation. Various recommendations expand the original report. The reviewers agree with the report that there is greater promise in the short term for the areas of sensitization and toxicokinetics. Additional opportunities lie in more global collaborations and the inclusion of other industry sectors.


Asunto(s)
Alternativas a las Pruebas en Animales/métodos , Alternativas a las Pruebas en Animales/normas , Cosméticos/normas , Cosméticos/toxicidad , Pruebas de Toxicidad/métodos , Pruebas de Toxicidad/normas , Animales , Unión Europea , Testimonio de Experto
20.
Regul Toxicol Pharmacol ; 55(1): 6-12, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19567260

RESUMEN

A recent study in rats investigated the retail sweetener product, Granulated SPLENDA No Calorie Sweetener (Splenda) (Abou-Donia et al., 2008. Splenda alters gut microflora and increases intestinal P-glycoprotein and cytochrome P-450 in male rats. J. Toxicol. Environ. Health A, 71, 1415-1429), which is composed of (by dry weight) maltodextrin ( approximately 99%) and sucralose ( approximately 1%). The investigators reported that Splenda increased body weight, decreased beneficial intestinal bacteria, and increased the expression of certain cytochrome P450 (CYP450) enzymes and the transporter protein, P-glycoprotein (P-gp), the latter of which was considered evidence that Splenda or sucralose might interfere with the absorption of nutrients and drugs. The investigators indicated that the reported changes were attributable to the sucralose present in the product tested. An Expert Panel conducted a rigorous evaluation of this study. In arriving at its conclusions, the Expert Panel considered the design and conduct of the study, its outcomes and the outcomes reported in other data available publicly. The Expert Panel found that the study was deficient in several critical areas and that its results cannot be interpreted as evidence that either Splenda, or sucralose, produced adverse effects in male rats, including effects on gastrointestinal microflora, body weight, CYP450 and P-gp activity, and nutrient and drug absorption. The study conclusions are not consistent with published literature and not supported by the data presented.


Asunto(s)
Peso Corporal/efectos de los fármacos , Intestinos/efectos de los fármacos , Vigilancia de Productos Comercializados/normas , Sacarosa/análogos & derivados , Edulcorantes/farmacología , Animales , Interpretación Estadística de Datos , Estudios de Evaluación como Asunto , Intestinos/microbiología , Masculino , Ratas , Proyectos de Investigación/normas , Sacarosa/farmacología , Sacarosa/toxicidad , Edulcorantes/toxicidad
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