Revistas
Revista:
NANOMATERIALS
ISSN:
2079-4991
Año:
2023
Vol.:
13
N°:
1
Págs.:
3
A new material composed of a kaolin base with silver nanoparticles (AgNPs) attached to its surface was developed, as an alternative to antibiotics used as supplements in animal feed. As part of its safety assessment, an in vivo geno-toxicological evaluation of this material was conducted in rats. First, a preliminary dose finding study was carried out to decide the doses to be tested in the main study: 50, 300 and 2000 mg/kg b.w. For the main study, a combined strategy composed of the MN test (TG 474) and the comet assay (TG 489), integrated in a repeated dose 28-day oral toxicity study (TG 407), was performed. A No Observed Adverse Effect Level (NOAEL) of 2000 mg of the silver-kaolin formulation/kg b.w. by oral route, for 28 days, was determined. The silver-kaolin formulation did not induce micronuclei in bone marrow, or DNA strand breaks (SBs) or alkali labile sites (ALS) in liver, spleen, kidney or duodenum at any dose. The modified Fpg comet assay did not reveal oxidized bases in the same tissues at the dose of 2000 mg/kg b.w. Silver was quantified by ICP-MS in all the target organs, confirming the negative results obtained under these conditions.
Revista:
TOXINS
ISSN:
2072-6651
Año:
2023
Vol.:
15
N°:
8
Págs.:
491
Mycotoxins are natural food and feed contaminants produced by several molds. The primary mode of exposure in humans and animals is through mixtures. Aflatoxin B1 (AFB1) and sterigmatocystin (STER) are structurally related mycotoxins that share the same biosynthetic route. Few in vivo genotoxicity assays have been performed with STER. In the present genotoxicity study, Wistar rats were dosed orally with STER (20 mg/kg b.w.), AFB1 (0.25 mg/kg b.w.) or a mixture of both in an integrated micronucleus (bone marrow) and comet study (liver and kidney). STER was dosed at the highest feasible dose in corn oil. No increase in the percentage of micronuclei in bone marrow was observed at any condition. Slight DNA damage was detected in the livers of animals treated with AFB1 or the mixture (DNA strand breaks and Fpg (Formamidopyrimidine DNA glycosylase)-sensitive sites, respectively). Plasma, liver, and kidney samples were analyzed with LC-MS/MS demonstrating exposure to both mycotoxins. General toxicity parameters (organs absolute weight, biochemistry, and histopathology) were not altered either individually or in the mixture. The overall absence of individual genotoxicity did not allow us to set any type of interaction in the mixture. However, a possible toxicokinetic interaction was observed.
Revista:
PHARMACEUTICS
ISSN:
1999-4923
Año:
2021
Vol.:
13
N°:
8
Págs.:
1269
The use of allogeneic adipose-derived mesenchymal stromal cells (alloADSCs) represents an attractive approach for treating myocardial infarction (MI). Furthermore, adding a natural support improves alloADSCs engraftment and survival in heart tissues, leading to a greater therapeutic effect. We aimed to examine the safety and immunological reaction induced by epicardial implantation of a clinical-grade collagen scaffold (CS) seeded with alloADSCs for its future application in humans. Thus, cellularized scaffolds were myocardially or subcutaneously implanted in immunosuppressed rodent models. The toxicological parameters were not significantly altered, and tumor formation was not found over the short or long term. Furthermore, biodistribution analyses in the infarcted immunocompetent rats displayed cell engraftment in the myocardium but no migration to other organs. The immunogenicity of alloADSC-CS was also evaluated in a preclinical porcine model of chronic MI; no significant humoral or cellular alloreactive responses were found. Moreover, CS cellularized with human ADSCs cocultured with human allogeneic immune cells produced no alloreactive response. Interestingly, alloADSC-CS significantly inhibited lymphocyte responses, confirming its immunomodulatory action. Thus, alloADSC-CS is likely safe and does not elicit any alloreactive immunological response in the host. Moreover, it exerts an immunomodulatory action, which supports its translation to a clinical setting.
Revista:
PHARMACEUTICS
ISSN:
1999-4923
Año:
2021
Vol.:
13
N°:
3
Págs.:
361
Curcumin is a natural compound obtained from turmeric root with high antioxidant and anti-inflammatory activities. However, clinical application of curcumin has been limited due to its low solubility and bioavailability and rapid metabolism and degradation. This study was conducted to evaluate the effect of curcumin incorporation in zein nanoparticles on the pharmacokinetic parameters of systemic curcumin in plasma. Wistar rats were administered a single oral dose of 250 mg/kg of standard curcumin (control) or nanocurcumin (zein-based nanoparticles, Nucaps). The proposed new formulation was also compared with two commercially available curcumin complexes. Blood samples were collected at different times, and plasma levels were determined using HPLC-MS/MS. Overall, nanocurcumin (Nucaps) formulation was well tolerated and showed a 9-fold increase in oral bioavailability when compared to the standard curcumin natural extract. In addition, the nanoparticles prepared in this study demonstrated a bioavailability profile superior to that of other bioavailability-enhanced curcumin complexes currently available in the marketplace. Thus, our nanoparticle-based formulation has shown great potential as a nutraceutical for the oral administration of curcumin.
Revista:
SCIENTIFIC REPORTS
ISSN:
2045-2322
Año:
2020
Vol.:
10
N°:
1
Págs.:
17073
Ivermectin is a widely used antiparasitic drug with known efficacy against several single-strain RNA viruses. Recent data shows significant reduction of SARS-CoV-2 replication in vitro by ivermectin concentrations not achievable with safe doses orally. Inhaled therapy has been used with success for other antiparasitics. An ethanol-based ivermectin formulation was administered once to 14 rats using a nebulizer capable of delivering particles with alveolar deposition. Rats were randomly assigned into three target dosing groups, lower dose (80-90 mg/kg), higher dose (110-140 mg/kg) or ethanol vehicle only. A toxicology profile including behavioral and weight monitoring, full blood count, biochemistry, necropsy and histological examination of the lungs was conducted. The pharmacokinetic profile of ivermectin in plasma and lungs was determined in all animals. There were no relevant changes in behavior or body weight. There was a delayed elevation in muscle enzymes compatible with rhabdomyolysis, that was also seen in the control group and has been attributed to the ethanol dose which was up to 11 g/kg in some animals. There were no histological anomalies in the lungs of any rat. Male animals received a higher ivermectin dose adjusted by adipose weight and reached higher plasma concentrations than females in the same dosing group (mean Cmax 86.2 ng/ml vs. 26.2 ng/ml in the lower dose group and 152 ng/ml vs. 51.8 ng/ml in the higher dose group). All subjects had detectable ivermectin concentrations in the lungs at seven days post intervention, up to 524.3 ng/g for high-dose male and 27.3 ng/g for low-dose females. nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats, additional experiments are required to assess the safety of this formulation in larger animals.
Revista:
JOURNAL OF FUNCTIONAL FOODS
ISSN:
1756-4646
Año:
2019
Vol.:
59
Págs.:
319 - 328
Brassicaceae contain bioactive compounds with potential positive effects on metabolic syndrome. Here, we evaluated the eventual anti-obesity properties of an ethanolic broccoli extract (BE), selected by a tested ability to reduce Caenorhabditis elegans fat content. Two doses (14 and 140 mg/kg animal) of BE were evaluated in a diet-induced obesity (DIO) Wistar rat model.
After 10 weeks of BE supplementation, animals exhibited reduced body weight gain and food efficiency, decreased atherogenic index of plasma and improved glucose tolerance in comparison with non-supplemented rats. BE also reduced the retroperitoneal fat mass and adipocyte size, all associated to down-regulation of Cebpa, Srebp1, Fasn and Adipoq expression in adipocytes. Finally, BE significantly decreased liver steatosis, accompanied by the up-regulation of Acot8 and Acox1, and the down-regulation of Fasn, Fatp4 and Srebf1 expression in hepatocytes. Our data provides new knowledge about the potential role of broccoli components in the prevention of metabolic syndrome.
Revista:
FOOD & FUNCTION
ISSN:
2042-6496
Año:
2019
Vol.:
10
N°:
8
Págs.:
4811 - 4822
Cocoa polyphenols exhibit high antioxidant activity and have been proposed as a potential adjuvant for the treatment of metabolic disturbances. Here, we demonstrate that supplementation with low doses (14 and 140 mg per kg per rat) of a complete cocoa extract induces metabolic benefits in a diet-induced obesity (DIO) model of Wistar rats. After 10 weeks, cocoa extract-supplemented animals exhibited significantly lower body weight gain and food efficiency, with no differences in energy intake. Cocoa significantly reduced visceral (epididymal and retroperitoneal) and subcutaneous fat accumulation accompanied by a significant reduction in the adipocyte size, which was mediated by downregulation of the adipocyte-specific genes Cebpa, Fasn and Adipoq. Additionally, cocoa extract supplementation reduced the triacylglycerol/high density lipoprotein (TAG/HDL) ratio, decreased hepatic triglyceride accumulation, improved insulin sensitivity by reducing HOMA-IR, and significantly ameliorated glucose tolerance after an intraperitoneal glucose tolerance test. Finally, no adverse effect was observed in an in vivo toxicity evaluation of our cocoa extract at doses up to 500 mg kg -1 day -1. Our data demonstrate that low doses of cocoa extract supplementation (14 and 140 mg kg -1 day -1) are safe and sufficient to counteract obesity and type-2 diabetes in rats and provide new insights into the potential application of cocoa supplements in the management of the metabolic syndrome.
Revista:
EXPERIMENTAL AND MOLECULAR MEDICINE
ISSN:
1226-3613
Año:
2017
Vol.:
49
N°:
6
Págs.:
e345
Sepsis, which is induced by severe bacterial infections, is a major cause of death worldwide, and therapies combating the disease are urgently needed. Because many drugs have failed in clinical trials despite their efficacy in mouse models, the development of reliable animal models of sepsis is in great demand. Several studies have suggested that rabbits reflect sepsis-related symptoms more accurately than mice. In this study, we evaluated a rabbit model of acute sepsis caused by the intravenous inoculation of Salmonella enterica. The model reproduces numerous symptoms characteristic of human sepsis including hyperlactatemia, hyperglycemia, leukopenia, hypothermia and the hyperproduction of several pro-inflammatory cytokines. Hence, it was chosen to investigate the proposed ability of Pep19-2.5-an anti-endotoxic peptide with high affinity to lipopolysaccharide and lipoprotein-to attenuate sepsis-associated pathologies in combination with an antibiotic (ceftriaxone). We demonstrate that a combination of Pep19-2.5 and ceftriaxone administered intravenously to the rabbits (1) kills bacteria and eliminates bacteremia 30¿min post challenge; (2) inhibits Toll-like receptor 4 agonists in serum 90¿min post challenge; (3) reduces serum levels of pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor ¿); and (4) reverts to hypothermia and gives rise to temperature values indistinguishable from basal levels 330¿min post challenge. The two components of the combination displayed synergism in some of these activities, and Pep19-2.5 notably counteracted the endotoxin-inducing potential of ceftriaxone. Thus, the combination therapy of Pep19-2.5 and ceftriaxone holds promise as a candidate for human sepsis therapy.
Revista:
JOURNAL OF MEDICAL MICROBIOLOGY
ISSN:
0022-2615
Año:
2017
Vol.:
66
N°:
7
Págs.:
946 - 958
Purpose. The aim of this study was to develop an immunogenic protective product against Shigella flexneri by employing a simple and safe heat treatment-based strategy. Methodology. The physicochemical characteristics of naturally produced (OMV) and heat-induced (HT) outer-membrane vesicles from S. flexneri were examined, including a comparison of the protein content of the products. Toxicological and biodistribution studies, and a preliminary experiment to examine the protective effectiveness of HT in a murine model of S. flexneri infection, were also included. Results. This method simultaneously achieves complete bacterial inactivation and the production of the HT vaccine product, leading to a safe working process. The obtained HT complex presented a similar morphology (electron microscopy) and chemical composition to the classical OMV, although it was enriched in some immunogens, such as lipoproteins, OmpA or OmpC, among others. The HT formulation was not toxic and biodistribution studies performed in mice demonstrated that the vaccine product remained in the small intestine after nasal administration. Finally, a single dose of HT administered nasally was able to protect mice against S. flexneri 2a. Conclusion. The convenient and safe manufacturing process, and the preliminary biological evaluation, support the use of the self-adjuvanted HT complex as a new vaccine candidate to face shigellosis. Further development is required, such as additional immune analyses, to evaluate whether this new subunit vaccine can be useful in achieving full protection against Shigella.
Revista:
FOOD & FUNCTION
ISSN:
2042-6496
Obesity and type 2-diabetes are becoming a worldwide health problem, remarking the importance of alternative therapies to tackle their progression. Here, we hypothesized that supplementation of diet with 6 % w/w of a freeze-dried strawberry-blueberry (5:1) powder (FDSB) could exert beneficial metabolic effects in Wistar rats. FDSB-supplemented animals experienced significantly reduced body weight gain, food efficiency and visceral adiposity accumulation in two independent experiments. FDSB supplementation also contributed to lower area under the curve after an intraperitoneal GTT and reduced serum insulin levels and insulin resistance index (IR-HOMA) in HFS diet-fed animals, together with reduced plasma MCP-1 inflammation marker concentrations. Gene expression analysis in retroperitoneal adipocytes from experiment 1 and 3T3-L1 cells showed that FDSB inhibited adipogenesis and lipogenesis through down-regulation of Pparg, Cebpa, Lep, Fasn, Scd-1 and Lpl gene expression. Untargeted metabolomics identified the cis isomer ofresveratrol-3-glucoside-sulphate as a metabolite differentially increased in FDSB-treated serum samples, which corresponds to a strawberry metabolite that could be considered a serum biomarker of FDSB-intake. Our results suggest that FDSB powder might be useful for treatment/prevention of obesity-related diseases.
Revista:
FOOD AND CHEMICAL TOXICOLOGY
ISSN:
0278-6915
Año:
2017
Vol.:
106
Págs.:
477 - 486
In the last years, casein nanoparticles have been proposed as carriers for the oral delivery of biologically active compounds. However, till now, no information about their possible specific hazards in vivo was available. The aim of this work was to assess the safety of casein nanoparticles when administered orally to animals through a 90 days dose-repeated toxicity study (OECD guideline 408), that was performed in Wistar rats under GLP conditions. After 90 days, no evidences of significant alterations in animals treated daily with 50,150 or 500 mg/kg bw of nanoparticles were found. This safety agrees well with the fact that nanoparticles were not absorbed and remained within the gut as observed by radiolabelling in the biodistribution study. After 28 days, there was a generalized hyperchloremia in males and females treated with the highest dose of 500 mg/kg bw, that was coupled with hypernatremia in the females. These effects were related to the presence of mannitol which was used as excipient in the formulation of casein nanoparticles. According to these results, the No Observed Adverse Effect Level (NOAEL) could be established in 150 mg/kg bw/day and the Lowest Observed Effect Level (LOEL) could be established in 500 mg/kg bw/day. (C) 2017 Published by Elsevier Ltd.
Revista:
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
ISSN:
0939-6411
Año:
2016
Vol.:
101
Págs.:
112 - 118
The pharmacodynamic effect and the safety of cyclosporine A lipid nanoparticles (CsA LN) for oral administration were investigated using Sandimmune Neoral as reference. First, the biocompatibility of the unloaded LN on Caco-2 cells was demonstrated. The pharmacodynamic response and blood levels of CsA were studied in Balb/c mice after 5 and 10days of daily oral administration equivalent to 5 and 15mg/kg of CsA in different formulations. The in vivo nephrotoxicity after 15days of treatment at the high dose was also evaluated. The results showed a significant decrease in lymphocyte count (indicator of immunosuppression) for the CsA LN groups which was not observed with Sandimmune Neoral. CsA blood levels remained constant over the time after treatment with LN, whereas a proportional increase in drug blood concentration was observed with Sandimmune Neoral. Therefore, CsA LN exhibited a better pharmacological response along with more predictable pharmacokinetic information, diminishing the risk of toxicity. Moreover, a nephroprotective effect against CsA related toxicity was observed in the histopathological evaluation when LN containing Tween 80 were administered. Therefore, our preliminary findings suggest LN formulations would be a good alternative for CsA oral delivery, enhancing efficacy and reducing the risk of nephrotoxicity.
Revista:
FOOD AND CHEMICAL TOXICOLOGY
ISSN:
0278-6915
Año:
2015
Vol.:
76
Págs.:
116 - 124
Aflatoxin B1 (AFB1) and Ochratoxin A (OTA) are genotoxic mycotoxins that can contaminate a variety of foodstuffs, the liver and the kidney being their target organs, respectively. The micronucleus (MN) assay (bone marrow) and the comet assay (liver and kidney) were performed simultaneously in F344 rats, treated with AFB1 (0.25 mg/kg b.w.), OTA (0.5 mg/kg b.w.) or both mycotoxins. After AFB1 treatment, histopathology and biochemistry analysis showed liver necrosis, focal inflammation and an increase in Alanine Aminotransferase and Aspartate Aminotransferase. OTA alone did not cause any alteration. The acute hepatotmdc effects caused by AFB1 were less pronounced in animals treated with both mycotoxins. With regard to the MN assay, after 24 h, positive results were obtained for AFB1 and negative results were obtained for OTA, although both toxins caused bone marrow toxicity. In the combined treatment, OTA reduced the toxicity and the number of MN produced by AFB1. In the comet assay, after 3 h, positive results were obtained for AFB1 in the liver and for OTA in the kidney. The combined treatment reduced DNA damage in the liver and had no influence in the kidney. Altogether, these results may be indicative of an antagonistic relationship regarding the genotoxicity of both mycotoxins
Revista:
INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION
ISSN:
0963-7486
Año:
2015
Vol.:
66
N°:
Supl. 1
Págs.:
S13 - S21
The growing presence of products on the market with added value in terms of health makes essential their regulation and harmonization in critical aspects such as safety. The toxicology applied to the bioactive compounds should demonstrate the absence of toxic effects at doses advised for consumption, as well as evaluate the potential toxic effects in the assumption that the products are used in quantities superior to those recommended. The specific strategy should be defined case by case; therefore, prior to any toxicological development, it is essential to study all the information regarding the bioactive compounds (BACs) characterization, nutridynamics and nutrikinetics, that is available. In this guideline, a general strategy to be applied in the development of BACs is proposed. It includes a first in vitro phase to discard genotoxicity and endocrine effects and a second in vivo phase with different possibilities regarding the duration and the extension of the studies.
Revista:
MALARIA JOURNAL
ISSN:
1475-2875
Año:
2015
Vol.:
14
Págs.:
102
Background: The prospect of eliminating malaria is challenged by emerging insecticide resistance and vectors with outdoor and/or crepuscular activity. Ivermectin can simultaneously tackle these issues by killing mosquitoes feeding on treated animals and humans. A single oral dose, however, confers only short-lived mosquitocidal plasma levels.
Methods: Three different slow-release formulations of ivermectin were screened for their capacity to sustain mosquito-killing levels of ivermectin for months. Thirty rabbits received a dose of one, two or three silicone implants containing different proportions of ivermectin, deoxycholate and sucrose. Animals were checked for toxicity and ivermectin was quantified periodically in blood. Potential impact of corresponding long-lasting formulation was mathematically modelled.
Results: All combinations of formulation and dose released ivermectin for more than 12 weeks; four combinations sustained plasma levels capable of killing 50% of Anopheles gambiae feeding on a treated subject for up to 24 weeks. No major adverse effects attributable to the drug were found. Modelling predicts a 98% reduction in infectious vector density by using an ivermectin formulation with a 12-week duration.
Conclusions: These results indicate that relatively stable mosquitocidal plasma levels of ivermectin can be safely sustained in rabbits for up to six months using a silicone-based subcutaneous formulation. Modifying the formulation of ivermectin promises to be a suitable strategy for malaria vector control.
Revista:
INTERNATIONAL JOURNAL OF PHARMACEUTICS
ISSN:
0378-5173
Año:
2014
Vol.:
474
N°:
1 - 2
Págs.:
1 - 5
Edelfosine, an alkyl-lysophospholipid antitumor drug with severe side-effects, has previously been encapsulated into lipid nanoparticles (LN) with the purpose of improving their toxicity profile. LN are made of lipids recognized as safe by the Food and Drug Administration (FDA) and, therefore, these systems are generally considered as nontoxic vehicles. However, toxicity studies regarding the use of LN as vehicles for drug administration are limited. In the present study, we investigated the in vivo toxicity of free edelfosine, and the protection conferred by LN. The free drug, non-loaded LN and edelfosine-loaded LN were orally administered to mice. Our results show that the oral administration of the free drug at 4 times higher than the therapeutic dose caused the death of the animals within 72 h. Moreover, histopathology revealed gastrointestinal toxicity and an immunosuppressive effect. In contrast, LN showed a protective effect against edelfosine toxicity even at the higher dose and were completely safe. LN are, therefore, a safe vehicle for the administration of edelfosine by the oral route. The nanosystems developed could be further used for the administration of other drugs.
Revista:
MOLECULES
ISSN:
1420-3049
Año:
2014
Vol.:
19
N°:
2
Págs.:
2166 - 2180
We report the synthesis and antimalarial activities of eighteen quinoxaline and quinoxaline 1,4-di-N-oxide derivatives, eight of which are completely novel. Compounds 1a and 2a were the most active against Plasmodium falciparum strains. Structure-activity relationships demonstrated the importance of an enone moiety linked to the quinoxaline ring.
Revista:
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
ISSN:
0066-4804
Año:
2013
Vol.:
57
N°:
7
Págs.:
3326 - 3333
The clinical management of human brucellosis is still challenging and demands in vitro active antibiotics capable of targeting the pathogen-harboring intracellular compartments. A sustained release of the antibiotic at the site of infection would make it possible to reduce the number of required doses and thus the treatment-associated toxicity. In this study, a hydrophobically modified gentamicin, gentamicin-AOT [AOT is bis(2-ethylhexyl) sulfosuccinate sodium salt], was either microstructured or encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles. The efficacy of the formulations developed was studied both in vitro and in vivo. Gentamicin formulations reduced Brucella infection in experimentally infected THP-1 monocytes (>2-log10 unit reduction) when using clinically relevant concentrations (18 mg/liter). Moreover, in vivo studies demonstrated that gentamicin-AOT-loaded nanoparticles efficiently targeted the drug both to the liver and the spleen and maintained an antibiotic therapeutic concentration for up to 4 days in both organs. This resulted in an improved efficacy of the antibiotic in experimentally infected mice. Thus, while 14 doses of free gentamicin did not alter the course of the infection, only 4 doses of gentamicin-AOT-loaded nanoparticles reduced the splenic infection by 3.23 logs and eliminated it from 50% of the infected mice with no evidence of adverse toxic effects. These results strongly suggest that PLGA nanoparticles containing chemically modified hydrophobic gentamicin may be a promising alternative for the treatment of human brucellosis.
Revista:
HUMAN GENE THERAPY
ISSN:
1043-0342
Año:
2013
Vol.:
24
N°:
12
Págs.:
1007 - 1017
Acute intermittent porphyria (AIP) results from haplo-insufficient activity of porphobilinogen deaminase (PBGD) and is characterized clinically by life-threatening, acute neurovisceral attacks. To date, liver transplantation is the only curative option for AIP. The aim of the present preclinical nonhuman primate study was to determine the safety and transduction efficacy of an adeno-associated viral vector encoding PBGD (recombinant AAV serotype 5-codon-optimized human porphobilinogen deaminase, rAAV5-cohPBGD) administered intravenously as part of a safety program to start a clinical study in patients with AIP. Macaques injected with either 1 × 10(13) or 5 × 10(13) vector genomes/kg of clinical-grade rAAV5-cohPBGD were monitored by standardized clinical parameters, and vector shedding was analyzed. Liver transduction efficacy, biodistribution, vector integration, and histopathology at day 30 postvector administration were determined. There was no evidence of acute toxicity, and no adverse effects were observed. The vector achieved efficient and homogenous hepatocellular transduction, reaching transgenic PBGD expression levels equivalent to 50% of the naturally expressed PBGD mRNA. No cellular immune response was detected against the human PBGD or AAV capsid proteins. Integration site analysis in transduced liver cells revealed an almost random integration pattern supporting the good safety profile of rAAV5-cohPBGD. Together, data obtained in nonhuman primates indicate that rAAV5-cohPBGD represents a safe therapy to correct the metabolic defect present in AIP patients.
Revista:
BIOANALYSIS
ISSN:
1757-6180
Año:
2013
Vol.:
5
N°:
3
Págs.:
289 - 305
Background: IFN-alpha 5 has been demonstrated to induce stronger signaling and higher expression of antiviral genes than IFN-alpha 2, which is the current treatment in chronic viral hepatitis. However, there is no specific and validated quantification method in order to conduct kinetic studies as part of the preclinical and clinical evaluation for regulatory purposes. Results: A novel integration of an antiviral assay against the cytopathic effect of the encephalomyocarditis virus in HeLa cells with a very sensitive method for assay processing - the Vialight (R) Plus assay - is presented for IFN-alpha 5 activity quantification. The bioassay has been validated in macaque and human serum and it has been demonstrated to be selective, precise and accurate. Conclusion: The validated bioassay meets suitable acceptance criteria for these types of biological assays.
Revista:
FOOD AND CHEMICAL TOXICOLOGY
ISSN:
0278-6915
Año:
2011
Vol.:
49
N°:
9
Págs.:
1935 - 1942
The impact of age and gender on Ochratoxin A (OTA) distribution in kidney and liver were studied. OTA was quantified in kidney and liver of young and mature rats of both sexes. Data was fit simultaneously using the population approach with NONMEM program. Fed and fasted mature males showed a 30% decrease and an 11% increase in relative bioavailability, respectively, in comparison with the rest of the groups. The OTA concentrations reached in kidney and liver were very similar between both organs. The models that best fit to data were the ones that considered that distribution of OTA to kidney and liver occurs from the central compartment and that elimination occurs mainly from the liver compartment. The kinetic analysis revealed that both, the apparent volume of distribution of the central compartment (V/F) and the apparent volume of distribution of the liver and kidney compartments (V(L,K)/F) increased significantly with body weight. Thus, the sex differences observed in organs distribution are a reflection of the differences in relative bioavailability observed in adult males, as a consequence of the fed and fasted conditions and to the significant higher body weight of mature males which directly affected the V/F and V(L,K)/F.
Revista:
Food and Chemical Toxicology
ISSN:
0278-6915
Año:
2010
Vol.:
48
N°:
11
Págs.:
3159 - 3166
Nacionales y Regionales
Título:
Desarrollo de nuevas terapias antitumorales de elevada eficacia y especificidad y baja toxicidad para administración oral
Código de expediente:
RTC-2014-2589-1
Investigador principal:
José Ignacio Fernández de Trocóniz Fernández
Financiador:
MINISTERIO DE CIENCIA E INNOVACIÓN
Convocatoria:
2014 MINECO Retos Colaboración
Fecha de inicio:
29/01/2014
Fecha fin:
30/06/2018
Importe concedido:
202.435,00€
Otros fondos:
-
Título:
Desarrollo de formulaciones innovadoras con nanopartículas mucoadhesivas para el tratamiento de úlceras mucosales (NANOMUC)
Código de expediente:
RTC-2015-4437-1
Investigador principal:
Ana Gloria Gil Royo
Financiador:
MINISTERIO DE CIENCIA E INNOVACIÓN
Convocatoria:
2015 MINECORETOS-COLABORACION
Fecha de inicio:
24/02/2015
Fecha fin:
30/06/2018
Importe concedido:
159.264,00€
Otros fondos:
-
Título:
Desarrollo clínico de una vacuna terapéutica para el tratamiento de displasias cervicales
Código de expediente:
RTC-2015-3326-1
Investigador principal:
Ana Gloria Gil Royo
Financiador:
MINISTERIO DE CIENCIA E INNOVACIÓN
Convocatoria:
2015 MINECORETOS-COLABORACION
Fecha de inicio:
23/02/2015
Fecha fin:
31/05/2018
Importe concedido:
344.748,40€
Otros fondos:
-
Título:
Investigación de la eficacia farmacológica de ácidos grasos insaturados de diseño para el tratamiento de la enfermedad de Alzheimer (IGRALZHEIMER)
Código de expediente:
RTC-2015-3542-1
Financiador:
MINISTERIO DE CIENCIA E INNOVACIÓN
Convocatoria:
2015 MINECORETOS-COLABORACION
Fecha de inicio:
23/02/2015
Fecha fin:
31/05/2019
Importe concedido:
127.611,00€
Otros fondos:
-
Título:
Desarrollo clínico de una terapia celular para reparación cardíaca basada en ingeniería de tejidos-CARDIOMESH
Código de expediente:
RTC-2016-4911-1
Investigador principal:
Felipe Luis Prósper Cardoso
Financiador:
MINISTERIO DE CIENCIA E INNOVACIÓN
Convocatoria:
2016 MINECO RETOS-COLABORACION
Fecha de inicio:
09/03/2016
Fecha fin:
28/02/2019
Importe concedido:
222.982,00€
Otros fondos:
-
Título:
Desarrollo de inmunoterapia del cáncer basada en mRNA (ARNMUNE)
Código de expediente:
0011-1411-2023-000101
Investigador principal:
Ignacio Javier Melero Bermejo
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2023 GN PROYECTOS ESTRATEGICOS DE I+D 2023-2026
Fecha de inicio:
05/09/2023
Fecha fin:
31/12/2025
Importe concedido:
422.291,90€
Otros fondos:
Fondos FEDER
Título:
Aplicación de agentes paraprobióticos y postbióticos en la prevención y tratamiento de la obesidad. Mecanismos implicados.
Código de expediente:
0011-1383-2022-000015 (PC128-129 PARABIOTICS
Investigador principal:
Paula Aranaz Oroz
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2022 GN Proyectos Colaborativos
Fecha de inicio:
01/12/2022
Fecha fin:
30/11/2024
Importe concedido:
251.608,88€
Otros fondos:
-
Título:
Recubrimientos con propiedades antibacterianas y antiadherentes para instrumental quirúrgico reutilizable: apuesta por la seguridad y la sostenibilidad
Investigador principal:
Ana Gloria Gil Royo
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2022 GN Proyectos Colaborativos
Fecha de inicio:
01/09/2022
Fecha fin:
30/11/2024
Importe concedido:
0,00€
Otros fondos:
-
Título:
Modificaciones del ensayo del cometa para su aplicación en seguridad alimentaria; genotoxicidad de carnes cocinadas y digeridas in vitro
Código de expediente:
PID2020-115348RB-I00
Investigador principal:
Amaya Azqueta Oscoz, Diana María Ansorena Artieda
Financiador:
AGENCIA ESTATAL DE INVESTIGACION
Convocatoria:
2020 AEI PROYECTOS I+D+i (incluye Generación del conocimiento y Retos investigación)
Fecha de inicio:
01/09/2021
Fecha fin:
31/08/2024
Importe concedido:
173.030,00€
Otros fondos:
-
Título:
Identificación y desarrollo de candidato inhibidor de HDAC6 como tratamiento frente al cáncer de colon (COLON-HDAC6)
Código de expediente:
0011-1411-2021-000097
Investigador principal:
Ana Gloria Gil Royo
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2021 GN PROYECTOS ESTRATEGICOS DE I+D 2021-2024
Fecha de inicio:
01/07/2021
Fecha fin:
31/12/2023
Importe concedido:
412.467,21€
Otros fondos:
-
Título:
PREDISMET Estudio de la potencial aplicación de una combinación de probióticos, prebióticos y postibióticos para la prevención y tratamiento de la disbiosis intestintal caracterísstica del síndrome metabólico.
Código de expediente:
0011-1383-2020-000010 PC173 predismet
Investigador principal:
Paula Aranaz Oroz
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2020 GN Proyectos Colaborativos
Fecha de inicio:
01/06/2020
Fecha fin:
30/11/2022
Importe concedido:
296.051,13€
Otros fondos:
-
Título:
DISEÑO DE ALIMENTOS E INGREDIENTES SALUDABLES Y SOSTENIBLES A PARTIR DE LA APLICACIÓN DE ECONOMÍA CIRCULAR (ALISSEC)
Código de expediente:
0011-1411-2021-000100
Investigador principal:
Fermín Ignacio Milagro Yoldi
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2021 GN PROYECTOS ESTRATEGICOS DE I+D 2021-2024
Fecha de inicio:
01/05/2021
Fecha fin:
31/12/2023
Importe concedido:
372.686,84€
Otros fondos:
-
Título:
Nueva terapia fágica frente a infecciones de E. coli en humanos (ANTI-COLI)
Código de expediente:
0011-1365-2020-000279
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2020 GN I+D Transferencia del conocimiento (empresas)
Fecha de inicio:
01/04/2020
Fecha fin:
31/07/2022
Importe concedido:
224.058,73€
Otros fondos:
Fondos FEDER
Título:
Desarrollo y evaluación de procesos reuso de instrumental quirúrgico mediante el empleo de recubrimientos nanotecnológicos.
Código de expediente:
0011-1383-2018-000005 PC004 REUSECOV
Investigador principal:
Ana Gloria Gil Royo
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2018 GN Centros
Fecha de inicio:
01/03/2018
Fecha fin:
30/11/2018
Importe concedido:
36.342,63€
Otros fondos:
-
Título:
Desarrollo y evaluación de procesos de reúso de instrumental quirúrgico mediante al empleo de recubrimientos nanotecnológicos: Fase II
Código de expediente:
0011-1383-2019-00005 (PC028 REUSECOV 2)
Investigador principal:
Ana Gloria Gil Royo
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2019 GN Centros
Fecha de inicio:
01/02/2019
Fecha fin:
30/11/2019
Importe concedido:
64.009,65€
Otros fondos:
-
Título:
Fármacos innovadores para el tratamiento de la Enfermedad de Alzheimer: Estudios preclínicos de eficacia y toxicidad bajo condiciones BPL por vía oral.
Código de expediente:
RTC-2017-5994-1
Financiador:
MINISTERIO DE CIENCIA E INNOVACIÓN
Convocatoria:
2017 MINECO RETOS COLABORACIÓN
Fecha de inicio:
01/01/2018
Fecha fin:
31/12/2020
Importe concedido:
86.118,00€
Otros fondos:
Fondos FEDER
Título:
IDP4SCLC Optimización de fármacos en nuevas dianas terapéuticas IDP (ASCL1) para el tratamiento de cáncer microcítico de pulmón.
Código de expediente:
RTC-2017-6585-1
Financiador:
MINISTERIO DE CIENCIA E INNOVACIÓN
Convocatoria:
2017 MINECO RETOS COLABORACIÓN
Fecha de inicio:
01/01/2018
Fecha fin:
30/11/2021
Importe concedido:
133.489,47€
Otros fondos:
Fondos FEDER
Otros (PIUNA, fundaciones, contratos…)
Título:
Acuerdo UNIVERSIDAD DE NAVARRA-CASEN RECORDATI para el desar
Investigador principal:
Ángel María Irigoyen Barrio, Ana Gloria Gil Royo
Fecha de inicio:
30/12/2016
Fecha fin:
31/12/2019
Importe:
48.000,00€
Otros fondos:
-
Título:
CSIC 4 compuestos Toxicología
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
30/08/2021
Fecha fin:
30/11/2021
Importe:
48.998,40€
Otros fondos:
-
Título:
Desarrollo preclínico BPL de un producto para cancer
Fecha de inicio:
28/07/2020
Fecha fin:
31/12/2021
Importe:
195.414,50€
Otros fondos:
-
Título:
Extracción de plasma de mono
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
27/01/2022
Fecha fin:
01/04/2022
Importe:
430,00€
Otros fondos:
-
Título:
Extracción de muestra de Hígado
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
25/05/2019
Fecha fin:
30/06/2019
Importe:
120,00€
Otros fondos:
-
Título:
Hemocompatibilidad in vitro
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
23/07/2021
Fecha fin:
31/12/2021
Importe:
7.544,00€
Otros fondos:
-
Título:
BILASTINA Y BILASTINA/MOMETASONA: ESTUDIO DE TOXICIDAD Y TOL
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
23/05/2018
Fecha fin:
30/06/2019
Importe:
347.530,00€
Otros fondos:
-
Título:
Desarrollo Preclínico de un tratamiento COMBINADO
Investigador principal:
Ana Gloria Gil Royo, María Jesús Garrido Cid
Fecha de inicio:
23/05/2018
Fecha fin:
31/12/2018
Importe:
7.410,00€
Otros fondos:
-
Título:
Farmacocinética comparativa de 3 formulaciones
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
22/03/2018
Fecha fin:
28/02/2019
Importe:
20.346,00€
Otros fondos:
-
Título:
ESTUDIO ANTICUERPOS MACACOS
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
21/06/2021
Fecha fin:
31/12/2022
Importe:
186.025,00€
Otros fondos:
-
Título:
Extracción y procesamiento muestras tejido de macaco
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
21/04/2023
Fecha fin:
30/04/2023
Importe:
2.041,00€
Otros fondos:
-
Título:
Evaluation of the effect of a Lactoferricin derived peptide
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
20/05/2019
Fecha fin:
20/07/2019
Importe:
21.121,13€
Otros fondos:
-
Título:
Extracción muestras tejido de macaco
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
19/10/2022
Fecha fin:
15/11/2022
Importe:
942,00€
Otros fondos:
-
Título:
Informe del desarrollo de una formulación oral cominada
Fecha de inicio:
18/11/2019
Fecha fin:
20/05/2020
Importe:
4.150,00€
Otros fondos:
-
Título:
Orden de Trabajo 6: Toxicidad sistémica aguda/subaguda
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
18/08/2022
Fecha fin:
31/12/2022
Importe:
40.990,00€
Otros fondos:
-
Título:
Análisis certificado de micoplasma en 3 líneas celulares
Fecha de inicio:
18/02/2019
Fecha fin:
18/06/2019
Importe:
240,00€
Otros fondos:
-
Título:
Desarrollo preclínico de producto sanitario
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
17/10/2018
Fecha fin:
31/12/2019
Importe:
164.810,00€
Otros fondos:
-
Título:
Estudios preclínicos regulatorios
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
16/03/2023
Fecha fin:
31/12/2023
Importe:
77.295,00€
Otros fondos:
-
Título:
Tol. Local i.m y PK dos soluciones en conejo
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
15/07/2019
Fecha fin:
30/09/2019
Importe:
22.245,00€
Otros fondos:
-
Título:
Estudio de seguridad y eficacia de colirio
Fecha de inicio:
14/03/2023
Fecha fin:
15/11/2023
Importe:
140.235,00€
Otros fondos:
-
Título:
Estudio de seguridad y eficacia en colirio
Investigador principal:
Ana Gloria Gil Royo, María Jesús Garrido Cid
Fecha de inicio:
14/03/2023
Fecha fin:
30/09/2023
Importe:
130.145,00€
Otros fondos:
-
Título:
Orden de Trabajo 7: Toxicidad sistémica subcrónica/crónica
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
13/10/2022
Fecha fin:
30/04/2023
Importe:
57.900,00€
Otros fondos:
-
Título:
Estudios desarrollo preclínico Bilastina - Mometasona
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
13/10/2017
Fecha fin:
30/05/2018
Importe:
74.914,00€
Otros fondos:
-
Título:
Transferencia de material archivado
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
13/06/2022
Fecha fin:
30/06/2022
Importe:
2.740,00€
Otros fondos:
-
Título:
Redacción de protocolos del estudio de PK y de Toxicidad a 3
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
13/04/2018
Importe:
6.845,00€
Otros fondos:
-
Título:
Desarrollo toxicológico del producto en macaco
Fecha de inicio:
12/01/2021
Fecha fin:
31/08/2022
Importe:
115.775,00€
Otros fondos:
-
Título:
TOX 6 compuestos
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
11/05/2022
Fecha fin:
31/12/2022
Importe:
47.580,00€
Otros fondos:
-
Título:
Desarrollo preclínico CAPRICORN
Fecha de inicio:
09/11/2020
Fecha fin:
30/04/2024
Importe:
209.110,00€
Otros fondos:
-
Título:
Estudio PK bilastina perro: Generación de muestras - pk Bila
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
09/11/2017
Fecha fin:
15/10/2018
Importe:
9.500,00€
Otros fondos:
-
Título:
Estudio Bilastina Gotas oftálmicas
Fecha de inicio:
08/11/2016
Fecha fin:
18/01/2018
Importe:
106.541,00€
Otros fondos:
-
Título:
DRF en rata Glp Like, nueva molécula antitumoral
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
07/10/2020
Fecha fin:
31/12/2020
Importe:
13.140,00€
Otros fondos:
-
Título:
Evaluación farmacocinética del compuesta
Fecha de inicio:
07/06/2019
Fecha fin:
31/10/2019
Importe:
12.745,00€
Otros fondos:
-
Título:
Estudio I.m COnejo
Fecha de inicio:
05/10/2018
Fecha fin:
19/07/2019
Importe:
139.017,00€
Otros fondos:
-
Título:
BIoNanotecnologias para la prevención y Tratamiento de Enfer
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
05/06/2015
Fecha fin:
21/12/2018
Importe:
0,00€
Otros fondos:
-
Título:
BIoNanotecnologias para la prevención y Tratamiento de Enfer
Investigador principal:
Ana Gloria Gil Royo
Fecha de inicio:
05/05/2015
Fecha fin:
21/12/2018
Importe:
0,00€
Otros fondos:
-
Título:
Orden de Trabajo 4: Genotox
Investigador principal:
Adela María López de Cerain Salsamendi
Fecha de inicio:
01/11/2021
Fecha fin:
30/01/2022
Importe:
17.740,00€
Otros fondos:
-
Título:
ORDEN DE TRABAJO 3: Desarrollo Preclínico
Fecha de inicio:
01/09/2021
Fecha fin:
31/12/2023
Importe:
25.380,00€
Otros fondos:
-
Título:
¿Validation of bioanalútical method and Repeated dose
Investigador principal:
Ángel María Irigoyen Barrio, Ana Gloria Gil Royo
Fecha de inicio:
01/09/2019
Fecha fin:
30/03/2020
Importe:
36.380,00€
Otros fondos:
-