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Preclinical models of idiosyncratic drug-induced liver injury(iDILI):Moving towards prediction

Acta Pharmaceutica Sinica b 2021年第12期11卷 3685-3726页

作者： Antonio Segovia-Zafra Daniel E.Di Zeo-Sanchez Carlos Lopez-Gomez Zeus Perez-Valdes Eduardo Garcıa-Fuentes Raul J.Andrade M.Isabel Lucena marina Villanueva-Paz Unidad de Gestio´n Clı´nica de Gastroenterologı´a Servicio de Farmacologıa ClınicaInstituto de Investigacio´n Biomedica de Malaga-IBIMAHospital Universitario Virgen de la VictoriaUniversidad de MalagaMalaga 29071Spain Centro de Investigacion biomedica en Red en el Area Tematica de Enfermedades Hepaticas y Digestivas(CIbERehd) Madrid 28029Spain Platform ISCIII de Ensayos Clınicos UICEC-IBIMAMalaga 29071Spain Unidad de Gestion Clınica de Aparato Digestivo Instituto de Investigacion Biomedica de Malaga(IBIMA)Hospital Universitario Virgen de la VictoriaMalaga 29010Spai

Idiosyncratic drug-induced liver injury(iDILI) encompasses the unexpected harms that prescription and non-prescription drugs,herbal and dietary supplements can cause to the *** remains a major public health problem and a major cause of drug *** the lack of biomarkers for iDILI prediction,diagnosis and prognosis,searching new models to predict and study mechanisms of iDILI is *** of the major limitations of iDILI preclinical assessment has been the lack of correlation between the markers of hepatotoxicity in animal toxicological studies and clinically significant ***,major advances in the understanding of iDILI susceptibility and pathogenesis have come from the study of well-phenotyped iDILI ***,there are many gaps for explaining all the complexity of iDILI susceptibility and ***,there is a need to optimize preclinical human in vitro models to reduce the risk of iDILI during drug ***,the current experimental models and the future directions in iDILI modelling are thoroughly discussed,focusing on the human cellular models available to study the pathophysiological mechanisms of the disease and the most used in vivo animal iDILI *** also comment about in silico approaches and the increasing relevance of patient-derived cellular models.

关键词： Drug-induced liver injury Preclinical models Mechanisms Oxidative stress Mitochondrial damage Immune response Personalized medicine

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Fine Tuning of Real Time PCR as a First Tool for the Detection of G143A Substitution in Venturia inaequalisSamples

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American Journal of Plant Sciences 2021年第6期12卷 960-974页

作者： Ceren Turan Irene Maja Nanni Lucia Landi Alessandro Pirondi marina Collina Department of Agricultural and Food Sciences University of Bologna Bologna Italy Department of Agricultural Food and Environmental Sciences Polytechnic University of Marche Ancona Italy

Apple scab caused by Venturia inaequalis (Cke.) Wint. is the most important disease of apple trees worldwide and requires a high number of fungicide applications. The G143A substitution in the inhibitor binding site of cytochrome b of V. inaequalis confers a high level of resistance to strobilurins targeting the bcb>1b> complex. The aim of this work was to substitute the labor intensive in vitro assays, with the faster quantitative PCR. An allele-specific qPCR method with a newly designed primer set was successfully developed to quantitatively determine the frequency of QoI-resistant A143 allele in populations of V. inaequalis. To be able to suggest that the molecular method could be applied as unique and robust technique, we carried out in vitro sensitivity test to trifloxystrobin;first testing the relative germination and subsequently confirmed with the quantification of mutated allele frequencies by qPCR on forty-nine Italian V. inaequalis populations. qPCR gave a similar pattern to that obtained using in vitro conidial germination test in predominantly sensitive and resistant populations, the variability betwee

关键词： Venturia inaequalis qPCR Strobilurin Cytochrome b

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Effect of Calcium Consumption on the Spasticity in the Spastic Rats

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Food and Nutrition Sciences 2019年第1期10卷 37-50页

作者： marina Indriasari &nbsp Hardinsyah Lilik Kustiyah bambang Pontjo Priosoeryanto Ferial Hadipoetro Idris Department of Community Nutrition Faculty of Human Ecology Bogor Agricultural University Bogor Indonesia Department of Histopathology Faculty of Veterinary Medicine Bogor Agricultural University Bogor Indonesia Faculty of Medicine and Health University of Muhammadiyah Jakarta Indonesia

Spasticity is a stiff muscle condition because the muscles receive impulses continuously. Calcium ions play a role in the ability of nerves to stimulate muscle contraction. This study aimed to analyze the effect of calcium consumption on the changes of spasticity and the relation of calcium levels in the blood and muscle to the spasticity. The experimental study was conducted on 42 male Sprague-Dawley rats aged 12 - 14 weeks. The 15-d intervention was conducted on six groups of spastic rats by administering 20 g of feed containing 50 mg, 100 mg, and 200 mg of calcium, it also received 100 mg, 200 mg, and 300 mg of calcium lactate supplementation. The experimental rats were induced with 80 mg/kg bW of Erythrocin b through the tail vein to make them spastic. This study showed a tendency of increased spasticity along with the increased dose of calcium given to the subjects. There were significant differences (p = 0.007) in changes in spasticity between groups. The significant differences (p = 0.02) in changes in blood calcium levels. The Spearman’s correlations test on the changes in blood calcium levels and changes in spasticity showed a positive coefficient correlation (r = 0.097) with a p-value of 0.54. An increase in blood calcium levels and a large decrease in spasticity were found in the group receiving 100 mg calcium intake in 20 g of feed. The calcium levels in muscles had a significant correlation with spasticity (p = 0.038, r = 0.810). The calcium levels in the muscle had a strong correlation with blood calcium levels (p = 0.041, r = 0.748). The biggest decrease in spasticity occurred after 100 mg of calcium were given to the rats for 15 days, and it was considered as an optimal dose. The calcium levels in the muscles had a strong correlation with blood calcium levels and the spasticity of the spastic rats.

关键词： Calcium Consumption Spasticity

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Rooting of Stem Cuttings of Jatropha platyphylla(Euphorbiaceae) in the Obtaining of Axillary buds for Grafting

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American Journal of Plant Sciences 2021年第12期12卷 1880-1893页

作者： Edith Salazar-Villa Miguel Angel Angulo-Escalante Jesús Diego Castro-Valenzuela Karla marina báez-Parra Lluvia de Abril Alexandra Soriano-Melgar Federico Soto-Landeros Centro de Investigación en Alimentación y Desarrollo A.C. Culiacán México Universidad Autónoma de Occidente Guasave México Facultad de Ciencias Químico biológicas Universidad Autónoma de Sinaloa Culiacán México Centro de Investigación en Química Aplicada Saltillo México Instituto Tecnológico Superior de Guasave Guasave México

Jatropha platyphylla is considered as a potential source of edible protein, oil, and phenolic compounds with anti-inflammatory activity. The use of stem cutting in vegetative propagation and grafting is as indispensable tools for mass multiplication of superior genotypes and helps in improve planting yield and quality. The study was aimed to investigate the effect of different diameters (10 - 15, 16 - 25 and 26 - 35 mm) and different hormone concentrations of indo-butyric acid (0, 1.5, 3, 6 and 10 g/L), in the rooting of Jatropha platyphylla and to obtain axillary buds to performed grafts. Rooting efficiency was 80% in greenhouse conditions. Hormone concentration and diameter significantly affected the rooting and shooting ability of Jatropha platyphylla stem cuttings. Stem cuttings of 26 - 35 mm have the greatest number, length and dry root weight. 76% survival of the grafted plants was obtained. This demonstrates the necessity to improve the conventional propagation methods with appropriate scientific inputs for more economical and time efficient techniques for standard propagation protocols.

关键词： Axillary buds Graft Stem Cutting Plant breeding Varietal Selection

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Practical obstacles and their mitigation strategies in compressional optical coherence elastography of biological tissues

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Journal of Innovative Optical Health Sciences 2017年第6期10卷 51-63页

作者： Vladimir Y.Zaitsev Alexandr L.Matveyev Lev A.Matveev Ekaterina V.Gubarkova Alexandr A.Sovetsky marina A.Sirotkina Grigory V.Gelikonov Elena V.Zagaynova Natalia D.Gladkova Alex Vitkin Institute of Applied Physics Russian Academy of Sciences Ulyanova Street 46 Nizhny Novgorod 603950 Russia Nizhny Novgorod State Medical Academy 10/1 Minina Square Nizhny Novgorod 603005 Russia University of Toronto and University Health Network 610 University Avenue Toronto ON M5G 2M9Canada

In this paper,we point out some practical obstacles arising in realization of compressional optical coherence elastography(OCE)that have not attracted sufficient attention ***-cally,we discuss(i)complications in quantification of the Young modulus of tissues related to partial adhesion between the OCE probe and soft intervening reference layer sensor,(i)distorting influence of tisue suface curvature/corrugation on the subsurface strain distri-bution mapping,(ii)ways of signal-to-noise mtio(SNR)enhancement in OCE strain mapping when periodic averaging is not realized,and(iv)potentially significant infuence of tissue elastic nonlinearity on quantification of its *** pnactical approaches to mitigate the effects of these complications are also described.

关键词： Optical coherence elastography optical coherence tomography phase-resolved methods strain mapping stiffness characterization

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Antioxidative Effect of Fermented Soybeans Extract in beef Patties with and without n-3 Fatty Acids

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Journal of Life Sciences 2010年第4期4卷 11-16页

作者： Ana Maria Romero Mirtha marina Doval Mario Anibal Sturla Maria Alicia Judis Faculty of Agroindustry National University of the Northeast Cdte. Fernandez 755 Saenz Peha Chaco Argentina

The objectives of the study were： a） to determine the optimal concentration of the extract that should be incorporated in meat products to maintain the lipid oxidative stability, and b） to verify if the extract exerted antioxidant activity even when these products were enriched with soybean oil （with fatty acids omega 3）. To carry out these aims, in the first instance the additive was incorporated into meat patties （elaborated with 80% beef and 20% fat plus 2% salt over total mass） at 0, 0.5, 1, 5 and 10 g/kg, respectively. The lipid oxidation was evaluated by measurement of peroxide value during 15 days at 8 ℃ and the results were expressed as reduction percentage of peroxidation （RP）. RP obtained were 55, 49, 73 and 59 respectively. As 5 g/kg was the optimum concentration of antioxidant, this was chosen to add to meat products enriched with soybean oil. In this case the RP obtained was 78%, indicating that the extract decreased lipid oxidation effectively.

关键词： Natural antioxidants peroxide value meat quality n-3 PUFAs lipid oxidation.

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Management of Congenital Malformations of the Face in the GbèkèRegion (Côte d’Ivoire)

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Open Journal of Stomatology 2022年第5期12卷 166-174页

作者： Eric Kouassi Zegbeh-N’Guessan Rokiatou Kone Pornan Issa Jules berete Ernest Martial Djemi Affoué ba Diane marina Amenou Tuo Karna Drissa Grébéret Emmanuel Crezoit Department of Odontology and Maxillofacial Surgery Bouaké University Hospital Bouaké C&ocirc te d’Ivoire Department of Stomatology and Maxillofacial Surgery Bamako University Hospital National Center of Odonto-Stomatology Bamako Mali

background: Congenital malformations of the face are relatively frequent in the Gbèke region (Côte d’Ivoire). Objectives: Identify the epidemiological aspects, describe the management method, distinguish the anatomical-clinical aspects and identify the therapeutic methods and their results. Material and methods: A retrospective and descriptive study was carried out over a period of 8 years (2012-2019) in the Odontostomatology and Maxillofacial Surgery Department of the University Hospital Centre (bouaké) and in the “Jean baptiste Vatelot” religious hospital of bouaké. The study concerned patients whose congenital malformations of the face had undergone primary surgery. Results: 439 patients were collected, i.e. an annual frequency of 54.88 cases per year. The sex ratio was 1.07 and the mean age was 6.82 years (range 5 months to 48 years). There were 434 (98.86%) cleft lips and palates and 5 (1.14%) Tessier’s clefts. Among the cleft lip and palate, there were 214 (49.31%) cleft lip, 127 (29.26%) cleft palate and 93 (21.43%) combined cleft lip and cleft palate. Surgical treatments numbered 532 and included 293 (55.08%) cheiloplasties, 113 (21.24%) pushback uranostaphyloraphies and 90 (16.92%) double flap palatoplasties. Complications were noted in 43 cases. Conclusion: Congenital malformations of the face were managed relatively late in the Gbèkè region with satisfactory results. Ante-natal diagnosis, early psychotherapy and a better screening system should allow an improvement of the management.

关键词： Congenital Malformation Face

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Morphological Characterization and Phenological Modeling of Jatropha platyphylla(Euphorbiaceae) Muell. Arg. Genotypes

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American Journal of Plant Sciences 2022年第1期13卷 23-35页

作者： Edith Salazar-Villa Martha Lidia Gutiérrez-Pérez Federico Soto-Landeros Karla marina báez-Parra María de la Paz Sosa-Segura Miguel Angel Angulo-Escalante Centro de Investigación en Alimentación y Desarrollo AC Culiacán México Facultad de Agronomía Universidad Autónoma de Sinaloa Culiacán México Instituto Tecnológico Superior de Guasave Guasave México Facultad de Ciencias Químico biológicas Universidad Autónoma de Sinaloa Culiacán México Colegio de bachilleres del Estado de Sinaloa Culiacán México

Morphological characterization and phenological modeling were carried out on genotypes of Jatropha platyphylla collected from the states of Sinaloa and Durango, Mexico. The morphological characterization evidenced the existence of monoecious plants, finding individuals with male and female flowers in the same inflorescence. Fruit with four seeds was also found. The phenological study was divided into two phases and calculated in thermal requirement (°D): Vegetative [seedtime (0), germination (24), emergence (98), cotyledons (87), second (302) and fourth (524) true leaves, end of vegetative growth (302)] and reproductive [flowering (303), fructification (342), maturation (126), defoliation and senescence (450)]. The thermal constant (2558) was similar in all eight genotypes. The phenological stages and the accumulated degree days were adjusted with a third-degree polynomial (Stage = -0.0041x3 + 0.7446x2 - 8.6808x + 6.2448) (R2 = 0.99%) stage. The development of phenological models facilitates the prediction of the flowering date for the selection of varieties with high oil and protein content.

关键词： Degree-Days Monoecious Phenological Modeling Plant breeding Varietal Selection

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Determination of ETM, Histamine and Mycotoxins in Garba, a Traditional Ivoirian Meal

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American Journal of Analytical Chemistry 2018年第4期9卷 245-256页

作者： Adjo Thérèse Anoman Kouamé Mathias Koffi Kouassi Narcisse Aboua marina Koussemon Laboratoire Central pour l’Hygiène Alimentaire et l’Agro-industrie LANADA Ministère de l’Agriculture Abidjan C&ocirc te d’Ivoire Laboratoire de biochimie et Sciences des Aliments Université Félix Houphou&euml t boigny Abidjan C&ocirc te d’Ivoire Laboratoire des Sciences de l’Environnement Université Nangui Abrogoua Abidjan C&ocirc te d’Ivoire UFR Sciences et Technologie des Aliments Université Nangui Abrogoua Abidjan C&ocirc te d’Ivoire

The methods of preparation, conservation and sale of Garba, the traditional Ivorian street meal, abundantly consumed in Côte d’Ivoire, can be exposed to various infections resulting in the poisoning of consumers. The aim of this study was to evaluate the hygienic quality of Garba through the analysis and the determination of certain toxic chemicals. In three hundred (300) samples of Garba collected in four districts in Abidjan, toxic metals (cadmium, mercury, lead), biogenic amine (histamine) and mycotoxins (aflatoxins and ochratoxin A) were detected and quantified using official standardized methods. Different toxics analyzed were present at various levels in the Garba. The mercury, lead, cadmium and histamine levels in the Garba were respectively 0.19 mg/kg, 0.19 mg/kg, 0.03 mg/kg and 32.69 mg/kg. The detected mycotoxins included aflatoxins b1, b2, G1, G2 and ochratoxin A, with respective average proportions of 3.44 μg/kg, 1.90 μg/kg, 8.07 μg/kg, 0.56 μg/kg and 0.42 μg/kg. The mycotoxins levels in the Garba are higher than the recommended toxic levels, particularly the ones in aflatoxin b1 and G1. This suggests a sanitary risk associated with the consumption of this meal. Consequently, awareness campaigns and training of the Garba sellers in hygiene and a better regulation of this sector by the competent authorities are required.

关键词： Garba Toxic Metals biogenic Amine Mycotoxins

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Magnetic Particle Imaging for Magnetic Hyperthermia Treatment: Visualization and Quantification of the Intratumoral Distribution and Temporal Change of Magnetic Nanoparticles in Vivo

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Open Journal of Medical Imaging 2016年第1期6卷 1-15页

作者： Tomomi Kuboyabu Isamu Yabata marina Aoki Natsuo banura Kohei Nishimoto Atsushi Mimura Kenya Murase Department of Medical Physics and Engineering Division of Medical Technology and Science Faculty of Health Science Graduate School of Medicine Osaka University Osaka Japan

Purpose: Magnetic hyperthermia treatment (MHT) is a strategy for cancer therapy using the tem-perature rise of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF). Re-cently, a new imaging method called magnetic particle imaging (MPI) has been introduced. MPI allows imaging of the spatial distribution of MNPs. The purpose of this study was to investigate the feasibility of visualizing and quantifying the intratumoral distribution and temporal change of MNPs and predicting the therapeutic effect of MHT using MPI. Materials and Methods: Colon-26 cells (1 × 106 cells) were implanted into the backs of eight-week-old male bALb/c mice. When the tumor volume reached approximately 100 mm3, mice were divided into untreated (n = 10) and treated groups (n = 27). The tumors in the treated group were directly injected with MNPs (Resovist?) with iron concentrations of 500 mM (A, n = 9), 400 mM (b, n = 8), and 250 mM (C, n = 10), respectively, and MHT was performed using an AMF with a frequency of 600 kHz and a peak amplitude of 3.5 kA/m. The mice in the treated group were scanned using our MPI scanner immediately before, immediately after, 7 days, and 14 days after MHT. We drew a region of interest (ROI) on the tumor in the MPI image and calculated the average, maximum, and total MPI values and the number of pixels by taking the threshold value for extracting the contour as 40% of the maximum MPI value (pixel value) within the ROI. These parameters in the untreated group were taken as zero. We also measured the relative tumor volume growth (RTVG) defined by (V-V0)/V0, where V0 and V are the tumor volumes immediately before and after MHT, respectively. Results: The average, maximum, and total MPI values decreased up to 7 days after MHT and remained almost constant thereafter in all groups, whereas the number of pixels tended to increase with time. The RTVG values in Groups A and b were significantly lower than those in the control group 3 days or more and 5 day

关键词： Magnetic Particle Imaging Magnetic Hyperthermia Treatment Magnetic Nanoparticles Intratumoral Distribution Temporal Change

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