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Статті в журналах з теми "BIOAVAILABILITY TEST"

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Shkolnikova, Marina Nikolaevna, and Elena Vladimirovna Voronova. "FLAVONOIDS BIOAVAILABILITY ASSESSMENT USING THE DISSOLUTION TEST." Bulletin of KSAU, no. 6 (2022): 194–203. http://dx.doi.org/10.36718/1819-4036-2022-6-194-203.

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Skogley, Earl O. "The universal bioavailability environment/soil test unibest." Communications in Soil Science and Plant Analysis 23, no. 17-20 (November 1992): 2225–46. http://dx.doi.org/10.1080/00103629209368736.

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Sips, A. J., W. J. van der Vijgh, R. Barto, and J. C. Netelenbos. "Intestinal strontium absorption: from bioavailability to validation of a simple test representative for intestinal calcium absorption." Clinical Chemistry 41, no. 10 (October 1, 1995): 1446–50. http://dx.doi.org/10.1093/clinchem/41.10.1446.

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Abstract Calcium absorption tests have rarely been validated for being representative for absolute bioavailability (true absorption) or for intraindividual variation. Therefore, we investigated the reproducibility of the absolute bioavailability of strontium chloride, a marker for intestinal calcium absorption, in healthy male volunteers (n = 8) by measuring the area under the plasma strontium concentration-time curve after oral and intravenous administration of strontium. Subsequently, we selected a simple test variable as being representative of absolute bioavailability. The mean absolute bioavailability (+/- SD) was 25% +/- 7%. The best test variable appeared to be the fractional absorption at 240 min (Fc240) after oral intake, which demonstrated the highest correlation with absolute bioavailability (r = 0.66). The intraindividual variations of the data for this variable and for the absolute bioavailability are similar to those described for various absorption tests based on the use of calcium isotopes. Thus, the Fc240 of strontium offers the potential of a simple clinical test for use as a measure of intestinal calcium absorption and its modulation.
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Vergin, H., and V. Nitsche. "Oral Bioavailability of Atenolol." Journal of International Medical Research 17, no. 5 (September 1989): 417–25. http://dx.doi.org/10.1177/030006058901700503.

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The bioavailability of two formulations of atenolol was compared in an open, randomized crossover study. Each film-coated tablet contained 100 mg of active drug. The plasma concentrations of atenolol were determined using a newly developed and specific high-performance liquid chromatography procedure. The areas under the concentration – time curves (AUC) were calculated, as were pair differences and ratios for individual AUC values and for maximum plasma levels. The latter were determined (Cmax.(c)) and calculated (Cmax.(c)) at the corresponding time values ( tmax.) for test and reference formulations, and were then tested for statistical significance. The 95% confidence limits for both test and reference preparations, taken according to Westlake or Wilcoxon, were found to be 80.0 − 114.7% for AUC, 80.2 − 119.9% for Cmax. and 74.5 − 132.8% for tmax. In terms of pharmacokinetic target criteria, therefore, it can be seen that there were no substantial differences between the two film-coated tablets. The two atenolol preparations, therefore, may be classified as bioequivalent.
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Nelson, Colin. "Calcium Supplements Differ in Bioavailability, Simple Acid Test Shows." Internal Medicine News 38, no. 15 (August 2005): 15. http://dx.doi.org/10.1016/s1097-8690(05)71237-3.

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Allen, Lindsay Helen. "Bioavailability of Vitamin B12." International Journal for Vitamin and Nutrition Research 80, no. 45 (October 1, 2010): 330–35. http://dx.doi.org/10.1024/0300-9831/a000041.

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Vitamin B12 deficiency is common in people of all ages who consume a low intake of animal-source foods, including populations in developing countries. It is also prevalent among the elderly, even in wealthier countries, due to their malabsorption of B12 from food. Several methods have been applied to diagnose vitamin B12 malabsorption, including Schilling’s test, which is now used rarely, but these do not quantify percent bioavailability. Most of the information on B12 bioavailability from foods was collected 40 to 50 years ago, using radioactive isotopes of cobalt to label the corrinoid ring. The data are sparse, and the level of radioactivity required for in vivo labeling of animal tissues can be prohibitive. A newer method under development uses a low dose of radioactivity as 14C-labeled B12, with measurement of the isotope excreted in urine and feces by accelerator mass spectrometry. This test has revealed that the unabsorbed vitamin is degraded in the intestine. The percent bioavailability is inversely proportional to the dose consumed due to saturation of the active absorption process, even within the range of usual intake from foods. This has important implications for the assessment and interpretation of bioavailability values, setting dietary requirements, and interpreting relationships between intake and status of the vitamin.
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Bakasta, Deepu, and M. G. Shambhu. "The Development of Models Based on Linear and Nonlinear Multivariate Methods to Predict ADME/PK Properties Using Physicochemical Properties of Kinase, Protease Inhibitors, and GPCR Antagonists." International Journal of Medicinal Chemistry 2013 (March 19, 2013): 1–6. http://dx.doi.org/10.1155/2013/495134.

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Oral bioavailability of a drug compound is the significant property for potential drug candidates. Measuring this property can be costly and time-consuming. Quantitative structure-property relationships (QSPRs) are used to estimate the percentage of oral bioavailability, and they are an attractive alternative to experimental measurements. A data set of 217 drug and drug-like compounds with measured values of the percentage of oral bioavailability taken from the small molecule ChemBioBase database was used to develop and test a QSPR model. Descriptors were calculated for the compounds using Codessa 2.1 tool. Nonlinear general regression neural network model was generated using the DTREG predictive modeling program software. The calculated percentage of oral bioavailability model performs well, with root-mean-square (rms) errors of 4.55% oral bioavailability units for the training set, 14.32% oral bioavailability units for the test set, and 19.12% oral bioavailability units for the external prediction set. Given the structural diversity and bias of the data set, this is a good first attempt at modeling oral bioavailability using QSPR methods. The model can be used as a potential virtual screen or property estimator. With a larger data supply less biased toward the high end values of the percentage of oral bioavailability, a more successful model could likely be developed.
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Yudanti, Gendis Purno, Ilham Kuncahyo, and Endang Diyah Ikasari. "In vitro Naringenin SNEDDS Release Test by Dissolution." Natural Sciences Engineering and Technology Journal 3, no. 2 (June 22, 2022): 179–85. http://dx.doi.org/10.37275/nasetjournal.v3i2.29.

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Naringenin is the main flavanone in grapefruit which has anti-inflammatory, anti-cancer, hepatoprotective and antilipid peroxidation effects. Its low solubility in water causes dissolution and low bioavailability when taken orally. This study aims to increase the solubility and bioavailability of naringenin by using the SNEDDS technique. Initial characterization to determine the optimum formula was carried out using the D-optimal mixture design method, namely by optimizing the composition of SNEDDS which consisted of triacetin as the oil phase, tween 80 as surfactant and transcutol P as cosurfactant as an independent factor and SNEDDS characterization included emulsification time, drug loading, size globules and percent transmittance in response. The optimization results showed that the optimum formula was obtained at the composition of 10% triacetin, 70% tween 80 and 20% transcutol P. The dissolution test showed that the SNEDDS of naringenin was capable of dissolution (Q30) of 87,50% ±1,73 at the 30th minute and the f2 value of 28,93 so it can be concluded that the dissolution profile between the SNEDDS of naringenin and the naringenin capsules is not identical.
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Schweiggert, Ralf M., Rachel E. Kopec, Maria G. Villalobos-Gutierrez, Josef Högel, Silvia Quesada, Patricia Esquivel, Steven J. Schwartz, and Reinhold Carle. "Carotenoids are more bioavailable from papaya than from tomato and carrot in humans: a randomised cross-over study." British Journal of Nutrition 111, no. 3 (August 12, 2013): 490–98. http://dx.doi.org/10.1017/s0007114513002596.

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Carrot, tomato and papaya represent important dietary sources of β-carotene and lycopene. The main objective of the present study was to compare the bioavailability of carotenoids from these food sources in healthy human subjects. A total of sixteen participants were recruited for a randomised cross-over study. Test meals containing raw carrots, tomatoes and papayas were adjusted to deliver an equal amount of β-carotene and lycopene. For the evaluation of bioavailability, TAG-rich lipoprotein (TRL) fractions containing newly absorbed carotenoids were analysed over 9·5 h after test meal consumption. The bioavailability of β-carotene from papayas was approximately three times higher than that from carrots and tomatoes, whereas differences in the bioavailability of β-carotene from carrots and tomatoes were insignificant. Retinyl esters appeared in the TRL fractions at a significantly higher concentration after the consumption of the papaya test meal. Similarly, lycopene was approximately 2·6 times more bioavailable from papayas than from tomatoes. Furthermore, the bioavailability of β-cryptoxanthin from papayas was shown to be 2·9 and 2·3 times higher than that of the other papaya carotenoids β-carotene and lycopene, respectively. The morphology of chromoplasts and the physical deposition form of carotenoids were hypothesised to play a major role in the differences observed in the bioavailability of carotenoids from the foods investigated. Particularly, the liquid-crystalline deposition of β-carotene and the storage of lycopene in very small crystalloids in papayas were found to be associated with their high bioavailability. In conclusion, papaya was shown to provide highly bioavailable β-carotene, β-cryptoxanthin and lycopene and may represent a readily available dietary source of provitamin A for reducing the incidence of vitamin A deficiencies in many subtropical and tropical developing countries.
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Settineri, Robert, Jin Ji, Zenaida P. Shields, and Garth L. Nicolson. "The effects of Membrane Lipid Replacement with NTFactor® Lipids on increasing the bioavailability of three test nutrients." Bioactive Compounds in Health and Disease 5, no. 5 (May 10, 2022): 106. http://dx.doi.org/10.31989/bchd.v5i5.936.

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Introduction: Previous studies indicated that lipids and nanostructured materials may improve the uptake of nutrients with moderate bioabsorption properties. Objectives: This study evaluated the effects of Membrane Lipid Replacement with NTFactor® Lipids (NTFL) on bioabsorption of three poorly to moderately absorbed nutrients (quercetin, curcumin and coenzyme Q10) utilizing the Caco-2 epithelial cell permeability model. Methods: Transfer across a Caco-2 epithelial cell layer has become a reference standard in the pharmaceutical and nutraceutical industries for in vitro prediction of in vivo human intestinal absorption and bioavailability of orally administered substances. The degree of bioabsorption of the test materials was assessed by monitoring the concentrations of the test materials on each side of the Caco-2 monolayers by liquid chromatography and mass spectroscopy (LCMS/MS analysis).Results: When NTFL was added to each of the three test nutrients, there was increased absorption and transfer across a Caco-2 cell layer in a dose-dependent manner for the three nutrients. When compared individually, CoQ10 with NTFL showed the most significant increase in absorption (2.01-times more compared to controls without NTFL, p=0.0011) at a concentration of NTFL of 10 mg/mL. NTFL also increased absorption and transfer across a Caco-2 cell layer of the other test nutrients, but these results did not achieve the same level of significance. Discussion: A variety of Oral membrane lipid replacement supplements with NTFL, such as various vitamins, minerals and nutrients, have been designed to reduce fatigue, improve health conditions, and protect cellular and especially mitochondrial membranes from damage. Here we used NTFL to demonstrate improvements in absorption and bioavailability of three nutrients. Conclusion: Using the Caco-2 bioabsorption and bioavailability in vitro model we found that NTFL could enhance absorption, bioavailability and uptake of nutrients while providing its own clinically demonstrated health benefits. Keywords: Phospholipids, Membrane Lipid Replacement, CoQ10, curcumin, quercetin, bioavailability, absorption, permeability, Caco2, bio-uptake, bioabsorption, glycerolphospholipids, intestinal absorption
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Дисертації з теми "BIOAVAILABILITY TEST"

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Peck, Mika Robert. "A site-specific tropical sediment toxicity test using Chironomus crassiforceps to investigate metal bioavailability in acid-sulphate sediments." Thesis, University of Stirling, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341247.

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Mochan, Daria Galina. "Evaluation of a Rapid-screening Toxicity Test Using the Ciliate, Colpoda inflata (Stokes): Sensitivity and Bioavailability to Model Compounds." PDXScholar, 1996. https://pdxscholar.library.pdx.edu/open_access_etds/5165.

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Standard toxicity tests often require high costs for maintaining healthy cultures, so few test species are employed in routine ecotoxicological analysis. An alternative is the "battery of tests" approach involving using rapid toxicity tests for screening. Rapid-screening toxicity tests must display organism sensitivity, similarity in responses to other test organisms, relevancy to many circumstances, and repeatability. Protozoa are ideal candidates for rapid-screening bioassays. They are cosmopolitan, play important roles in ecosystems, and have high reproductive rates. Many protozoa can form a resting stage (cyst) that remains viable during adverse conditions, eliminating the need for maintaining continuous cultures for testing. The main objective of this research was to evaluate the soil ciliate, Colpoda inflata (Stokes), as a bioassay organism in rapid-screening tests by determining its sensitivity to a variety of model compounds. These tests were based on the principle that exposure to a toxic compound would negatively affect population growth. To test for sensitivity, C. inflata was exposed to different levels of dissolved organic carbon in test media for each compound tested. C. inflata was expected to be more sensitive to toxicants in an inorganic medium than in media with high organic carbon content. Data were analyzed by determining the median tolerance limit for inhibition of population growth (IG50) relative to controls. IG50 values of the eight model compounds tested varied considerably. C. inflata growth was not significantly affected by 2,4-D or malathion. C. inflata showed differences in sensitivity between organic and inorganic media for the toxic metals tested and the order of toxicity corresponded to those found in standard tests. A significant difference occurred between the test media and the pesticide PCP, where growth was not inhibited in the organic medium; in the inorganic medium the IG50 was 0.269 mg/L. No significant effect of test media was found for ammonia or SDS. Compared to several published toxicity results, C. inflata proved more sensitive overall than other rapid-screening tests and many standard acute toxicity tests. Results of this study show that this rapid-screening toxicity test is sensitive, repeatable, and provides information similar to traditional standard toxicity tests.
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Pyle, Gregory G. "The toxicity and bioavailability of nickel and molybdenum to standard toxicity-test fish species and fish species found in northern Canadian lakes." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/NQ63914.pdf.

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Caboche, Julien. "Validation d'un test de mesure de bioaccessibilité : application à quatre éléments traces métalliques dans les sols : as, Cd, Pb et Sb." Thesis, Vandoeuvre-les-Nancy, INPL, 2009. http://www.theses.fr/2009INPL049N/document.

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La gestion des sites et sols pollués repose sur l’évaluation des expositions aux contaminants. Le retour d’expérience montre que les voies d’exposition directe, et notamment l’ingestion de terre pour les enfants, engendrent les niveaux de risque les plus élevés. Actuellement, en se basant sur la concentration totale d’un polluant dans le sol, l’évaluation des risques tend à être surprotectrice dans la mesure où seule une fraction de la substance peut pénétrer à l’intérieur de l’organisme. L’objectif de l’étude est de mettre en évidence que le test in vitro UBM (Unified Barge Method) de bioaccessibilité est pertinent pour estimer la fraction biodisponible des ETM dans les sols. Pour cela, il est nécessaire de démontrer que la solubilisation des contaminants dans le tractus gastro-intestinal est une étape limitante dans le processus de biodisponibilité et d’autre part que les mesures de bioaccessibilité sont corrélées aux mesures de biodisponibilité. Pour 15 sols sélectionnés sur trois sites contaminés différents, l’étude montre que la biodisponibilité est très variable pour le plomb (8% à 82%), le cadmium (12% à 91%) et l’arsenic (3% à 78%). Pour l’antimoine, les valeurs de biodisponibilité relative et de bioaccessibilité sont très faibles indépendamment des caractéristiques contrastées des sols (valeurs < 20%). De ce fait, ces conditions ne permettent pas de valider le test in vitro pour l’antimoine. Les résultats des corrélations, pour les trois autres contaminants, démontrent que la bioaccessibilité est l’étape limitante de la biodisponibilité et que le test UBM est pertinent pour estimer la bioaccessibilité de ces éléments dans les sols. Notre étude met également en évidence l’impact de la matrice sol sur les variations des valeurs de bioaccessibilité. Ainsi, il a été montré que la distribution des contaminants sur les différentes phases porteuses du sol est un paramètre majeur et robuste pour expliquer les variations de la bioaccessibilité pour l’ensemble des sols étudiés. Les résultats de l’étude mettent en lumière que le test in vitro UBM peut fournir une alternative possible aux investigations in vivo afin d’affiner les niveaux d’exposition des ETM suite à l’ingestion de sol
The management of contaminated soil is based on the assessment of exposure of pollutants. The review shows that the direct routes of exposure, including soil ingestion for children, generate the highest risk levels. Currently, based on the total pollutant concentration in soil, risk assessment tends to be overestimate because only a fraction of the substance may penetrate into the body. The aim of the study is to demonstrate that in vitro UBM test (Unified Method Barge) is relevant to estimate the bioavailable fraction of metals in the soil by estimating the bioaccessible fraction. For this, it is necessary to show that the solubilization of contaminants in the gastrointestinal tract is a limiting step in oral bioavailability process and that bioaccessibility is correlated to bioavailability. For 15 soils selected on three different sites, the study shows that bioavailability is highly variable for lead (8% to 82%), cadmium (12% to 91%) and arsenic (3 % to 78%). For antimony, the relative bioavailability and bioaccessibility values are very low independently of the different soil characteristics (values <20%). Thus, these conditions do not allow to validate in vitro test for antimony. The results of correlations, for the three other contaminants, show that bioaccessibility is the limiting step in the bioavailability process and that UBM test is relevant to estimate the bioaccessibility. Our study also highlights the impact of the soil matrix on the variation of bioaccessibility values. Thus, it was shown that the distribution of contaminants in the different bearing phases of soil is a major and robust parameter to explain the variations of bioaccessibility for all soils studied. The results of the study highlight that the in vitro UBM test is a promising alternative to in vivo investigations to measure the exposure levels of metals after soil ingestion
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Mézin, Laurent C. "Effects of humic acids and salinity on pesticide bioavailability and toxicity as estimated by SPME and toxicity tests." W&M ScholarWorks, 2001. https://scholarworks.wm.edu/etd/1539616775.

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The interactive effects of humic acids (HAs) and salinity on the bioavailability and toxicity of the pesticides chlorpyrifos and 4,4'-dichlorodiphenyltrichloroethane (DDT) were investigated. The effects of various HAs on the toxicity of chlorpyrifos were initially assessed with the chronic MicrotoxRTM test. Environmentally relevant concentrations of Aldrich, Peat, Leonardite and Suwannee River HAs had no significant effect on the toxicity of either chlorpyrifos or copper (Cu), the test's positive control. as reductions in contaminant toxicity had previously been reported for some contaminants by HAs, it appeared that salinity might be a mitigating factor. Thus salinity effects were further investigated with Aldrich HA only, in freshwater and at lower salinities. HA-pesticide associations were assessed through the pesticides' relative uptake by solid-phase microextraction (SPME) in the presence of Aldrich HA. Such binding has been hypothesized to reduce contaminant bioavailability. Increasing salinity (0--20 ppt) had no effect on the uptake of DDT by SPME, but generally enhanced that of chlorpyrifos. Aldrich HA alone greatly decreased the relative uptake of both pesticides at environmentally relevant DOM concentrations (∼0--20 mg C/l), and the effect was more pronounced for DDT. Increases in salinity reduced the effects of HA on uptake by SPME, and seemed to have an "effect threshold" between 1 and 5 ppt. to examine the biological consequences of possible HA-salinity interactions, the acute toxicities of chlorpyrifos and DDT were assessed using both freshwater (Ceriodaphnia dubia) and saltwater (Americamysis bahia) crustaceans. The DDT 24 hour LC50 for C. dubia was 1050 ng/l. No definitive value was obtained for A. bahia. CPF was more acutely toxic, with LC50s of 326 ng/l for A. bahia and 78.8 ng/l for C. dubia. Results of the acute toxicity experiments were in good agreement with the SPME data; i.e. while pesticide toxicities were reduced by HAs in freshwater, no reductions were seen in saline water (20 ppt). The toxicity reduction in freshwater was proportional to the HA concentration. The difference in toxicity mitigation is believed to be a function of salinity effects on HA-pesticide binding, likely due to conformational changes in the HA molecules, rather than organismal effects.
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Brumbaugh, William G. "Development of an integrative sampler for bioavailable metals in water /." free to MU campus, to others for purchase, 1997. http://wwwlib.umi.com/cr/mo/fullcit?p9842510.

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Junqueira, Marcelo de Souza. "Influencia do diclofenaco sodico na absorção, concentração serica e excreção da amoxicilina : estudos em ratos." [s.n.], 2006. http://repositorio.unicamp.br/jspui/handle/REPOSIP/290191.

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Анотація:
Orientadores : Thales Rocha de Mattos Filho, Francisco Carlos Groppo
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
Made available in DSpace on 2018-08-06T06:37:26Z (GMT). No. of bitstreams: 1 Junqueira_MarcelodeSouza_D.pdf: 648615 bytes, checksum: 3b46ad75b56af2255d981b942d82fa8f (MD5) Previous issue date: 2006
Resumo: O uso de antimicrobianos e de antiinflamatórios é prática comum na odontologia, embora haja escassez de trabalhos sobre seu uso simultâneo. Portanto, o objetivo deste trabalho foi avaliar, em ratos, os efeitos do diclofenaco sódico na absorção, concentração sérica e excreção da amoxicilina utilizando a técnica de perfusão tecidual e o método microbiológico. Foram utilizados 108 ratos Wistar machos (12 grupos, n= 9), com peso entre 150 e 200 g. Foram administrados aos animais: amoxicilina 25 mg/Kg (grupos: G1, D1, S1 e R1), diclofenaco sódico 2,5 mg/Kg + amoxicilina 25 mg/Kg (grupos: G2, D2, S2 e R2) e 1,0 mL de solução de cloreto de sódio a 0,9% (grupos: G3, D3, S3 e R3). As drogas foram administradas por injeção intraluminal aos animais dos grupos G1, G2, G3, D1, D2 e D3 e por via oral aos animais dos grupos S1, S2, S3, R1, R2 e R3. Foram avaliadas nos tempos de 15, 30, 45, 60, 120, 180, 240, 300 e 360 minutos as concentrações plasmáticas e urinárias de amoxicilina e a absorção gastrintestinal ¿in vitro¿ do antimicrobiano. O diclofenaco sódico causou uma redução significativa na absorção intestinal e um aumento na excreção renal do antimicrobiano em ratos, com conseqüente diminuição da sua concentração sérica. Portanto, em algumas situações clínicas, a eficácia da amoxicilina poderia ser prejudicada pela sua co-administração com o diclofenaco sódico
Abstract: The prescription of antibiotics associated to anti-inflammatory drugs is common in dentistry; however its effects have not been studied enough. Thus, the aim of this work was to evaluate the influence of sodium diclofenac on absorption, serum concentration and excretion of amoxicillin, in rats, by the microbiologic and tissue perfusion methods. The sample consisted of 108 male Wistar rats (12 groups, 9 rats each), weighing 150¿200 g. The animals were given: amoxicillin 25 mg/Kg (groups G1, D1, S1 and R1), sodium diclofenac 2.5 mg/Kg plus amoxicillin 25 mg/Kg (groups G2, D2, S2 and R2) and 1.0 mL of solution of sodium chloride 0.9% (groups G3, D3, S3 and R3). The animals in the groups G1, G2, G3, D1, D2 and D3 were administered drugs by intra-luminal injection and the animals in the groups S1, S2, S3, R1, R2 and R3 were administered drugs p.o. After 15, 30, 45, 60, 120, 180, 240, 300 and 360 minutes, were evaluated the blood and urine concentrations of amoxicillin and the ¿in vitro¿ absorption of the antibiotic. Sodium diclofenac had decreased the intestinal absorption, increased renal excretion and, consequently, decreased the serum concentration of the amoxicillin. Thus, sodium diclofenac could decrease the efficacy of amoxicillin under some clinical situations
Doutorado
Farmacologia, Anestesiologia e Terapeutica
Doutor em Odontologia
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Lin, Chia-Yu, and 林家玉. "Quality control criteria and test method for the gastrointestinal in-vitro bioavailability test using arsenic-contaminated soils." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/79466744598160168834.

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Анотація:
碩士
中國醫藥大學
環境醫學研究所
96
In order to preserve underground water resource for sustainable use, most countries in the world have promulgated heavy metal standards for soil. Recently Taiwan and many other countries have proposed a variety of risk assessment meth-ods for site remediation. But most of the methods normally assume 100% bioavail-ability for contaminated soils. The US Environmental Protection Agency (USEPA) allows for a modification of bioavailability in the Superfund Program. The absolute bioavailability factor (ABF) is defined as the dose percentage of contaminant in soil entering the blood circulation system, while relative bioavailability factor (RBF) is defined as the ABF ratio in percentage between soil samples to the standard sample. Various in-vitro bioavailability test methods based on gastrointestinal physiology have been proposed since 1992. The aim of this study is to propose a standard test procedure for bioavailability focusing on establishing quality control (QC) criteria and simplifying test procedure and apparatus. This study refers to the physiologically based extraction test (PBET) developed by USEPA Region VIII and the method developed in the early study by our group. The first phase of this method simulates stomach condition (pH 1.8) and the second phase simulates intestinal condition (pH 7.0). Many test parameters proposed in these methods have widely accepted in the literature for sample pretreatment, tem-perature, enzyme dose, pH, and reaction time. This study used sodium arsenate (Na2HAsO4•7H2O) and NIST 2710 soil as the standards to investigate the effect of mixing intensity, liquid to solid (L/S) ratio, extraction time, and extract pretreatment methods for the determination of bioavailability. Testing at a constant L/S ratio of 1000:1 mL/gm, all the ABFs (n = 5) obtained for the 2 phases from the 3 velocity gradients (G) of 0, 470, and 1000 1/sec had no significant difference (95 % CI) for both standards. The ABFs (n = 5) from both phases were 82-96 % for sodium arsenate and were 26-35% for the NIST soil. When the test was conducted at a constant G of 470 1/sec with 3 L/S ratios of 200:1, 1000:1, and 5000:1 mL/gm, only the ABFs obtained from the intestinal phase for the standard soil resulted in significant difference (p =0.02). The ABFs (n= 5) ob-tained from both phases were 85-101 % for sodium arsenate and were 25-33 % for the standard soil. The As concentrations extracted for both standards from the intes-tinal phase were within 10% of difference for 2-11 hours of extraction time based on the first hour of extraction. Thus 1 hour of extraction appears to be appropriate. Sample pretreatment using centrifugation with or without a follow-up filtration yielded no significant difference. In conclusion, we propose 3 types of QC criteria: (1) a concentration less than the method detection limit (MDL) for the reagent blank; (2) a ABFG and ABFI of 90±8 % and 90±5 % for sodium arsenate, respectively, (3) a RBFG and RBFI of 35±2 % and 30±3 % for NIST 7210 soil, respectively. Based on the test results, this study proposes a standard procedure for the two-phase bioavailability test. The soil sample is first dried by air and sieved for the particle size of 250 μm or less. A 0.5 gram of sample is fed into a serum bottle with a liquid volume of 500 mL at a liquid to solid (L/S) ratio of 1000:1 mL/gm in the stomach phase. A velocity gradient (G) of 500 1/sec is provided using magnetic stir-ring and a temperature of 37±0.5 oC is maintained in a air-circulated incubator. The extraction liquid contains 0.15 M of NaCl and 1% of porcine pepsin and the pH is adjusted to 1.8±0.1 by HCl stock solution. After 1 hour of extraction, a sample of extract is taken and centrifuged to remove particulate matters. The supernatant is determined for total arsenic. In the intestinal phase, pancreatin and bile are added to the extract liquid and is adjusted to pH 7.0±0.1 by NaHCO3 stock solution. After I hour of extraction, a sample extract is taken and centrifuged for the measurement of arsenic. In order to simply the method, we further propose using magnetic stirring with weighted ring in stead of argon sparging; using air-circulated incubator in stead of water bath for better observation and sample collection; using centrifuging in stead of filtration for extract pretreatment; using one phase of simplified bioaccessibility extraction (SBET) method instead of the two-phase method for a better estimate to the in-vivo method.
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9

Fang-Hua, Chang, and 張芳華. "Risk assessment by gastrointestinal bioavailability in-vitro test of heavy metals for waste-transformed soil conditionals." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/81606886094797761836.

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Анотація:
碩士
中國醫藥大學
環境醫學研究所
93
Bioavailability is an important concept in toxicology. The absolute bioavailability factor (ABF) is defined as the portion of a target toxicant entering the blood circulation system via a specific pathway in a certain period of time after exposure. To avoid inaccurate measurement, the relative bioavailability factor (RBF) is normally used in practice and is defined as the ratio of the ABF of the test material to the ABFof a surrogate reference material (SRM). Theoretically, a low level of RBF characterizes a high degree of encapsulation of the material being evaluated with a low level of the target toxicant being extracted in the gastrointestinal digestion environment. In reference of USEPA Region VIII’s method, this study proposed a two-step in-vitro bioavailability test for soil materials and the like. In the first step, 0.15 M NaCl and 1% porcine were used as the stomach liquid at a pH of 1.8 for 1 hour of extraction, while in the second step, 3.5gm/L bile and 0.35gm/L pancreatin were used as the intestinal liquid at a pH of 5.5 for 1 hr. Sodium arsenate (Na2HAsO4‧7H2O) and NIST 2710 Montana soil were used as the SRM and matrix standard, respectively, for developing test criteria of oxidation reduction potential (ORP), peristalsis intensity, liquid to solid (L/S) ratio, and extraction period. The in-vitro test was first continuously monitored in a sealed vessel after feeding for ORP during the extraction. ORPs were obtained from the tests on the two standard materials were 220 and 265 mv for the stomach phase and 46 and 80 mv for the intestinal phase, respectively. Comparing with the ORP data (150 and -50 mv) reported for the human gastrointestinal system, the ORP values appeared to be overestimated for no control of oxygen from air in test preparation. The two-step procedure was evaluated at three levels of mixing intensity (G = 0, 470, 1006 sec-1) using a dosage of 0.5 gm (1.0 mg/L) and a L/S ratio of 1000 mL/gm for the two standard materials. The ABF obtained from both phases of the test ranged 95 ~ 102 % for the SRM; and the RBFG and RBFI ranged 39 ~ 58 % and 29 ~ 55 %, respectively, for the standard soil materials. At a confidence level of 95 %, only the ABF obtained from the stomach phase for the SRM was significantly different (p = 0.004) at the three G values under study. However, this difference was inexplicable because the dosages administered were well below the solubility (5.46 gm/100 mL at 0 oC) and there was little encapsulation for the SRM. This fact suggested that mixing intensity was not a key parameter under the test conditions in this study. This study proposed to use the a G value at 500 sec-1 for the mixing intensity. Three L/S ratios (200, 1000, 5000 mL/gm) were also evaluated at a constant G value of 470 sec-1. The ABF obtained from both test phases ranged 98 ~ 102 % for the SRM; and the RBFG and RBFI ranged 28 ~ 39 % and 27 ~ 32 %, respectively, for the standard soil material. The three RBFI values were significantly different (p < 0.001) with respect to the L/S values, and the RBF was linearly associated with the L/S ratios (R2 = 0.84). However there was no significant difference in RBF for the stomach phase. It was speculated that the low pH in stomach reduces the degree of encapsulation and consequently resulted in little difference in RBF for the NIST soil. The RBFG obtained from this study appears to be significantly lower that reported by Hamel et al. (46 ~ 56 %); and the cause of the discrepancy could not be analyzed due to the difference in testing conditions between the two studies. This study suggests an L/S ratio of 1000 mL/gm for the in-vitro test. The concentrations obtained from the intestinal phase at 1 hour of extraction were 253 and 0.19 mg/L for the SRM and NIST soil, respectively. For the extended extraction of 2 ~ 10 hr, the concentration increased only marginally to 259 and 0.30 mg/L, by 2.3 and 4.7 %, respectively. An extraction time of 1hour for both phases is therefore suggested. Based on the results of this study, a set of quality control (QC) criteria were proposed for the in-vitro test: the concentration of the target toxicant extracted from the reagent blank should bower than the method detection limit (MDL), an average ABF of 100 ± 10 % for SRM for both phases, and an average RBFG of 40 ± 10 % and RBFI of 36 ± 10 % for the NIST soil. Using the RBFG values obtained from this study and literatures (calcine, slag, soil), a lifetime cumulative risks (ELCR) was computed to be 1.3 ~ 26.7×10 -4 at an IRIS’s slope factor of 1.5 (mg/kg-d)-1 for the carcinogenicity of arsenic assuming a default intake value of 0.1 gm/day and a body weight of 70 kg. The calculated ELCR was much higher than the risk level normally mandated for regulation at 10-6 ~ 10 -4. The health risk posed by contaminated soils and soils conditionals transformed from wastes may be an important issue deserved for further attention.
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10

Lin, Pei Jin, and 林佩錦. "Estimation of iron bioavailability from laver (parphyra laciniata) using an in vitro method and a hemoglobin regeneration test." Thesis, 1995. http://ndltd.ncl.edu.tw/handle/41431581979823021924.

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Анотація:
碩士
國立臺灣大學
農業化學研究所
83
World Health Organization (WHO) has reportered iron deficiency is the most common nutritional disorder in the world. Nevertheless, the problems are also common- although to a lesser extent- in certain regions in developed countries. The main causes of this disorder is poor bioavailability of dietary iron. Two possible ways to controling iron deficiency: there are increasing iron intake and bioavailability. The iron content is high in Parphyra laciniata (Laver), almost 900 ppm or 438 mg/1000 kcal. Our objectives were to determine the Relative Biological Value (RBV) of laver''s iron using a hemoglobin regeneration method and to determine the effect of ascorbic acid and heating processed on iron dissociation of laver using an in vitro method Laver purchased from supermarket is treated with 65 ℃ hot drying, 6 hours,then cut to 1.5 cm2 and milling. Iron dialyzability (ID) served as an index of the in vitro method. Our results show that ascorbic acid and citrate can increase the ID of laver, acetate can''t. The enhancing effect was the highest when the ratio of ascorbic acid to iron is five. Enhancing effect of citrate is dose - related. Fruit juice can increase ID of laver and is more effective than the same amount of ascorbic acid. The increasing effect is lemon> kiwi, orange. About 100 ℃, heating 30 minutes, the processing neither changes ID of laver nor reduces the enhancing effect of ascorbic aicd. The RBV of iron from laver with or without was 32 % and 24.6 %, respectively. The enhancing effect of ascorbic acid was abserved in in vitro system, but was not significant in rats.
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Книги з теми "BIOAVAILABILITY TEST"

1

Martirosyan, Danik. BCHD : Bioactive Compounds in Health and Disease: The Effects of Membrane Lipid Replacement with NTFactor® Lipids on Increasing the Bioavailability of Three Test Nutrients. Independently Published, 2022.

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2

Li, Jie Jack. Top Drugs. Oxford University Press, 2015. http://dx.doi.org/10.1093/oso/9780199362585.001.0001.

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Drugs like Lipitor, Plavix, Taxol, and Zoloft are integral in today's medicinal world. These widely used products save lives and improve the quality of lives, playing a crucial role in everything from cholesterol management to cancer treatment. These advances in medicine were brought into existence after nuanced process of creation, featuring a wide range of chemical and pharmacological experimentation and discovery. Top Drugs: Their History, Pharmacology, and Synthesis provides an in-depth study on ten prominent drugs, outlining the chemistry behind each one's creation. Jie Jack Li, a medicinal chemist and an expert on drug discovery, offers a thorough analysis of the landscape of current drug development. The comprehensive text is divided by health issues, including cardiovascular, cancer, metabolic diseases, and infectious diseases. Each section features individual chapters on significant drugs, outlining the chemistry and history of the drug's discovery. Li begins each chapter with the product's history, providing necessary context. Li then proceeds to describe the mechanism of action, structure-activity relationship (SAR), bioavailability, metabolism, toxicology, the discovery route, and the process route. Top Drugs: Their History, Pharmacology, and Synthesis will acclimate students, scientists, and interested laypersons to the world of chemistry and drug discovery.
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Частини книг з теми "BIOAVAILABILITY TEST"

1

Jenner, John. "OECD Test Guideline 428—A Method for In Vitro Percutaneous Absorption Measurement?" In Topical Drug Bioavailability, Bioequivalence, and Penetration, 381–87. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-1289-6_22.

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2

Kalimo, K., and K. Lammintausta. "Nickel Bioavailability from Patch Tests: Comparison Between Nickel Sulphate and Nickel Chloride Using TRUE Test." In Current Topics in Contact Dermatitis, 540–43. Berlin, Heidelberg: Springer Berlin Heidelberg, 1989. http://dx.doi.org/10.1007/978-3-642-74299-6_106.

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3

Louis Morel, Jean, Christian Hosy, and Gabriel Bitton. "Assessment of Bioavailability of Metals to Plants with Metplate, A Microbiological Test." In Soil & Environment, 527–28. Dordrecht: Springer Netherlands, 1995. http://dx.doi.org/10.1007/978-94-011-0415-9_144.

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4

Leopold, Kerstin, and Michael Schuster. "Pd Particles as Standardized Test Material for Bioavailability Studies of Traffic Related Pd Emissions to Barley Plants." In Urban Airborne Particulate Matter, 399–410. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-642-12278-1_20.

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5

Simmers, J. W., J. M. Marquenie, and R. G. Rhett. "A Test Procedure to Predict the Bioavailability of Heavy Metals, Polychlorinated Biphenyls and Polyaromatic Hydrocarbons to Animals Colonizing an Intertidal Wetland." In Contaminated Soil, 427–29. Dordrecht: Springer Netherlands, 1986. http://dx.doi.org/10.1007/978-94-009-5181-5_52.

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6

Yacobi, Avraham, Clarence T. Ueda, and Vinod P. Shah. "In Vitro Product Quality Tests and Product Performance Tests for Topical and Transdermal Drug Products." In Topical Drug Bioavailability, Bioequivalence, and Penetration, 81–89. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-1289-6_6.

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7

Li, Yi, Walelign Demisie, and Ming-kui Zhang. "Digestion Tests to Measure Heavy Metal Bioavailability in Soils." In Environmental Chemistry for a Sustainable World, 275–305. Cham: Springer International Publishing, 2015. http://dx.doi.org/10.1007/978-3-319-11906-9_7.

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8

Verma, Ravinder, Deepak Kaushik, Ritu Kaushik, and Vandana Singh. "Different Methodologies for Improving Solubility and Bioavailability." In A Comprehensive Text Book on Self-emulsifying Drug Delivery Systems, 1–29. BENTHAM SCIENCE PUBLISHERS, 2021. http://dx.doi.org/10.2174/9789814998000121010004.

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9

Chen, Yashu, Hongjian Chen, Qianchun Deng, Long Chen, and David Julian McClements. "Lipophilic Nutraceuticals." In Bioactive Delivery Systems for Lipophilic Nutraceuticals, 12–33. The Royal Society of Chemistry, 2023. http://dx.doi.org/10.1039/bk9781839165566-00012.

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Nutraceuticals are considered as components originating from foods, which are publicized to have health promoting effects beyond normal nutritional function due to their specific molecular structures. Certain therapeutic claims still lack further validation using controlled human trials or other long-term efficacy tests, which needs further research. Lipophilic nutraceuticals, which have poor water solubility, instability, etc., reveal the challenges of encapsulating them into the food matrix with improved bioavailability. Several kinds of delivery systems with delicate design can achieve controlled release with improved burst and sustained release of the encapsulated bioactive components. This chapter focuses on the characteristics of lipophilic nutraceuticals and possible challenges in their delivery process, which may contribute to the understanding of the design principle of protective and effective delivery systems for chemically labile lipophilic nutraceuticals.
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Rani, Sarita, Ankur Kaul, Anil Kumar Mishra, and Umesh Gupta. "Extra-Pulmonary TB." In Advances in Medical Diagnosis, Treatment, and Care, 91–116. IGI Global, 2021. http://dx.doi.org/10.4018/978-1-7998-0307-2.ch005.

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Tuberculosis is considered a fatal respiratory disease commonly seen in developing countries. This chapter includes the global scenario of TB patients and brief description of TB history, its pathogenesis, types, diagnosis tests, emergence of MDR (multi drug resistance) and XDR (extensively drug resistance). The traditional chemotherapy of TB includes first and second line drug therapy. These lines of therapies face many difficulties such as low solubility, low bioavailability, and stability issues. Therefore, some new drugs were introduced in the market that showed effective results to the patients. Nanoparticulate drug delivery gained much focus in recent years due to its advantages and ideal characteristics. Numerous nanoparticles, liposomal formulations, and polymeric micelles were reported by the researchers with significant and considerable results. Inhalable formulations were also prepared by scientists that showed effective and remarkable anti-tuberculosis action on TB patients. Many efforts are awaited to completely eradicate TB from the planet.
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Тези доповідей конференцій з теми "BIOAVAILABILITY TEST"

1

Spyropulos, B., J. Fareed, R. M. Emanuel, and D. Hoppensteadt. "COMPARATIVE PHARMACODYNAMICS OF SUBCUTANEOUSLY ADMINISTERED HEPARIN (HEP) AND A LOW MOLECULAR WEIGHT HEPARIN (LMWH) AS STUDIED BY AN EX VIVO FIBRINOPEPTIDE A (FPA) GENERATION TEST." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644173.

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Subcutaneously administered heparins do not produce any sizeable effects on the global tests and their activities are currently measured using amidolytic anti Xa and anti Ila assays. These methods are sensitive only to the individual enzyme and do not reflect other biologic actions. We have used a thromboplastin C activated FPA generation test to measure the pharmacodynamic effects of subcutaneously administered HEP and a LMWH in primates. 400μl of citrated plasma was equilibrated at 37°C for 2 minutes and was activated with 100 μl thromboplastin diluted in .020M CaCl2. FPA was generated for 2 min, inhibited with 50 μl of an inhibitor cocktail and measured using an RIA kit (Mallinckrodt, St, Louis, M0). Marked dose dependent suppression of the FPA generation was noted for varying periods of time by both HEP and LMWH. Stronger effects were observed with LMWH, suggesting better subcutaneous bioavailability and functional effects. Significant FPA generation inhibition was observed even when there was no circulating antiprotease activity present in the plasma. These results suggest that FPA generation test is a sensitive test to measure the pharmacologic effect of heparins. Furthermore the FPA generation tests can be modified to activate the coagulation system at certain sites to study the effect of heparins.
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2

Guo, Xin, and Ming Chang. "Effect of Oil Carbon Chain Length on the Physical Stability and Bioactivity of Nanoemulsion Delivery Systems Incorporating Lipophilic Ingredients." In 2022 AOCS Annual Meeting & Expo. American Oil Chemists' Society (AOCS), 2022. http://dx.doi.org/10.21748/dyso6286.

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In the nanoemulsion-related research, enough studies have concentrated on the effect of oil types, especially oil carbon chain length, on the bioavailability of the phytochemicals. However, there is still a lack of systematical research on the effect of oil carbon chain length influencing whole delivery system, especially for bioactivity evaluation. Herein, the overall aim of this study was to test the effect of oil carbon chain length on the physical stability and bioactivity of the designed nanoemulision system. The emulsion had good physical stability during the incubation time, but no significant differences were detected in the physical stability among different treated groups. The best bioactivity (lipid-lowering effect, in vivo antioxidant activity) of tocopherol and sesamol was in the palm oil (long carbon chain length) group.Overall, this data is meaningful for underlying applications of designed system in lipophilic ingredients delivery.*Xin Guo, Biotechnology Division Student Award Winner*
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3

Gulati, Shelly, Janpierre A. Bonoan, Kylee V. Schesser, Joshua F. Arucan, and Xiaoling Li. "Microfluidic Measurements of Drug Dissolution Using a Quartz Crystal Microbalance." In ASME 2016 14th International Conference on Nanochannels, Microchannels, and Minichannels collocated with the ASME 2016 Heat Transfer Summer Conference and the ASME 2016 Fluids Engineering Division Summer Meeting. American Society of Mechanical Engineers, 2016. http://dx.doi.org/10.1115/icnmm2016-7930.

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This work describes a microfluidic drug dissolution testing method that was developed using a commercial quartz crystal microbalance (QCM) resonator combined with an axial microfluidic flow cell. Dissolution testing is used to obtain temporal dissolution profiles of drugs, which provide information on the bioavailability or the drug’s ability to be completely dissolved and then absorbed and utilized by the body. Feasibility of the QCM dissolution testing method was demonstrated using a sample drug system of thin films of benzoic acid dissolved in water, capturing the drug dissolution profile under different microflow conditions. Our analysis method uses the responses of resonance frequency and resistance of the quartz crystal during dissolution testing to determine the characteristic profiles of benzoic acid dissolved over a range of microflows (10–1000 μL/min). The initial dissolution rates were obtained from the characteristic profiles and found to increase with higher flow rates. This aligns with the expected trend of increased dissolution with higher hydrodynamic forces. The QCM-based microfluidic drug dissolution testing method has advantages over conventional dissolution test methods, including reduced sample sizes, rapid test durations, low resource requirements, and flow conditions that more closely model in vivo conditions.
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4

Boneu, B., G. Houin, M. Rostin, J. L. Montastructure, P. d’Azemar, and B. Bayrou. "INTER-INDIVIDUAL PHARMACOKINETIC VARIATIONS AFTER INTRAVENOUS (IV) AND SUBCUTANEOUS (SC) INJECTION OF CY 216 IN HEALTHY SUBJECTS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643235.

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We investigated the pharmacokinetic parameters and their inter individual variations of a low molecular weight heparin (LMWH) derivative (CY 216, Fraxiparine R, Choay). In a cross-over study, 100 anti Xa IC u/kg were injected in 12 healthy volunteers, either by IV or SC route, at one week interval. The pharmacological effects were followed on 12 serial citrated samples for 24h: - anti factor Xa (AXa) activity (chromogenic assay calibrated against CY 216); - APTT and thrombin clotting time prolongation. The main pharmacokinetic parameters (elimination half-life (T|); clearance (cl); distribution volume (Vd); bioavailability F (SC/ IV)) were calculated from the anti Xa activity curves using con-, ventional methods. The results (mean, range) indicated below confirm some classical properties of CY 216: poor anticoagulant effect (APTT-TT), even after IV injection, longer half-life than . standard Heparin (SH), distribution volume similar to plasma volume, excellent bioavailability of the drug.We also emphasize important inter-individual variations between volunteers, as known for the pharmacological effects of SH in vitro and ex-vivo. From those results it could be assumed that, as for SH, close monitoring of treatment with LMWH would be suitable with higher dosages, after validation of the correlations between those biological tests and clinical results.* anti Xa IC u : anti factor X activated Institut Choay unit.
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5

Simion, Demetra, Carmen Gaidau, Mariana Daniela Berechet, Maria Stanca, and Rodica Roxana Constantinescu. "Modeling the Encapsulation of Turmeric in Nanoemulsions." In The 9th International Conference on Advanced Materials and Systems. INCDTP - Leather and Footwear Research Institute (ICPI), Bucharest, Romania, 2022. http://dx.doi.org/10.24264/icams-2022.i.9.

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The interaction of turmeric powder with five surfactants (isopropyl oleate, diester of sucrose, polymethylene-α, ω-bis (N, N-dialkyl-N-deoxy-d-glucitolammonium iodides, bis [2-butyl (sodium bis-thioacetate) sodium dicarboxylate 1,10 decanediyl] ester, demecarium bromide) and obtaining nanoemulsions, has been investigated by spectroscopy, dynamic light scattering, optical microscopy and microbiological tests. The modeling encapsulation of turmeric powder in nanoemulsions was carried out taking into account the following parameters: the concentration and type of surfactants, the ratio between turmeric and surfactant, micellar critical concentration, speed and time of stirring, temperature, pH, average diameter of particles, zeta potential, conductivity. The known antibacterial and anti-inflammatory properties of turmeric can be improved by dispersing it in nanoemulsions resulting in better functional efficacy. The specific factors in designing nanoemulsion systems that affect the chemical stability of the encapsulated turmeric are discussed. In order to enhance turmeric effectiveness and improve bioavailability, surfactant assemblies as the colloidal carriers with desired properties have been largely used. The interaction takes place above the critical concentrations of the surfactants, when the encapsulation/ solubilization of turmeric in the micelles occurs. In our research we have elaborated a method for including turmeric in surfactants, following the preparation parameters modeling with the final aim of developing enhanced antibacterial properties.
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Звіти організацій з теми "BIOAVAILABILITY TEST"

1

Griffin, Susan, and Yvette Lowney. Validation of an In Vitro Bioaccessibility Test Method for Estimation of Bioavailability of Arsenic from Soil and Sediment. Fort Belvoir, VA: Defense Technical Information Center, December 2012. http://dx.doi.org/10.21236/ada579125.

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2

Mochan, Daria. Evaluation of a Rapid-screening Toxicity Test Using the Ciliate, Colpoda inflata (Stokes): Sensitivity and Bioavailability to Model Compounds. Portland State University Library, January 2000. http://dx.doi.org/10.15760/etd.7041.

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3

Belkin, Shimshon, Sylvia Daunert, and Mona Wells. Whole-Cell Biosensor Panel for Agricultural Endocrine Disruptors. United States Department of Agriculture, December 2010. http://dx.doi.org/10.32747/2010.7696542.bard.

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Objectives: The overall objective as defined in the approved proposal was the development of a whole-cell sensor panel for the detection of endocrine disruption activities of agriculturally relevant chemicals. To achieve this goal several specific objectives were outlined: (a) The development of new genetically engineered wholecell sensor strains; (b) the combination of multiple strains into a single sensor panel to effect multiple response modes; (c) development of a computerized algorithm to analyze the panel responses; (d) laboratory testing and calibration; (e) field testing. In the course of the project, mostly due to the change in the US partner, three modifications were introduced to the original objectives: (a) the scope of the project was expanded to include pharmaceuticals (with a focus on antibiotics) in addition to endocrine disrupting chemicals, (b) the computerized algorithm was not fully developed and (c) the field test was not carried out. Background: Chemical agents, such as pesticides applied at inappropriate levels, may compromise water quality or contaminate soils and hence threaten human populations. In recent years, two classes of compounds have been increasingly implicated as emerging risks in agriculturally-related pollution: endocrine disrupting compounds (EDCs) and pharmaceuticals. The latter group may reach the environment by the use of wastewater effluents, whereas many pesticides have been implicated as EDCs. Both groups pose a threat in proportion to their bioavailability, since that which is biounavailable or can be rendered so is a priori not a threat; bioavailability, in turn, is mediated by complex matrices such as soils. Genetically engineered biosensor bacteria hold great promise for sensing bioavailability because the sensor is a live soil- and water-compatible organism with biological response dynamics, and because its response can be genetically “tailored” to report on general toxicity, on bioavailability, and on the presence of specific classes of toxicants. In the present project we have developed a bacterial-based sensor panel incorporating multiple strains of genetically engineered biosensors for the purpose of detecting different types of biological effects. The overall objective as defined in the approved proposal was the development of a whole-cell sensor panel for the detection of endocrine disruption activities of agriculturally relevant chemicals. To achieve this goal several specific objectives were outlined: (a) The development of new genetically engineered wholecell sensor strains; (b) the combination of multiple strains into a single sensor panel to effect multiple response modes; (c) development of a computerized algorithm to analyze the panel responses; (d) laboratory testing and calibration; (e) field testing. In the course of the project, mostly due to the change in the US partner, three modifications were introduced to the original objectives: (a) the scope of the project was expanded to include pharmaceuticals (with a focus on antibiotics) in addition to endocrine disrupting chemicals, (b) the computerized algorithm was not fully developed and (c) the field test was not carried out. Major achievements: (a) construction of innovative bacterial sensor strains for accurate and sensitive detection of agriculturally-relevant pollutants, with a focus on endocrine disrupting compounds (UK and HUJ) and antibiotics (HUJ); (b) optimization of methods for long-term preservation of the reporter bacteria, either by direct deposition on solid surfaces (HUJ) or by the construction of spore-forming Bacillus-based sensors (UK); (c) partial development of a computerized algorithm for the analysis of sensor panel responses. Implications: The sensor panel developed in the course of the project was shown to be applicable for the detection of a broad range of antibiotics and EDCs. Following a suitable development phase, the panel will be ready for testing in an agricultural environment, as an innovative tool for assessing the environmental impacts of EDCs and pharmaceuticals. Furthermore, while the current study relates directly to issues of water quality and soil health, its implications are much broader, with potential uses is risk-based assessment related to the clinical, pharmaceutical, and chemical industries as well as to homeland security.
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Altstein, Miriam, and Ronald Nachman. Rationally designed insect neuropeptide agonists and antagonists: application for the characterization of the pyrokinin/Pban mechanisms of action in insects. United States Department of Agriculture, October 2006. http://dx.doi.org/10.32747/2006.7587235.bard.

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The general objective of this BARD project focused on rationally designed insect neuropeptide (NP) agonists and antagonists, their application for the characterization of the mechanisms of action of the pyrokinin/PBAN (PK-PBAN) family and the development of biostable, bioavailable versions that can provide the basis for development of novel, environmentally-friendly pest insect control agents. The specific objectives of the study, as originally proposed, were to: (i) Test stimulatory potencies of rationally designed backbone cyclic (BBC) peptides on pheromonotropic, melanotropic, myotropic and pupariation activities; (ii) Test the inhibitory potencies of the BBC compounds on the above activities evoked either by synthetic peptides (PBAN, LPK, myotropin and pheromonotropin) or by the natural endogenous mechanism; (iii) Determine the bioavailability of the most potent BBC compounds that will be found in (ii); (iv) Design, synthesize and examine novel PK/PBAN analogs with enhanced bioavailability and receptor binding; (v) Design and synthesize ‘magic bullet’ analogs and examine their ability to selectively kill cells expressing the PK/PBAN receptor. To achieve these goals the agonistic and antagonistic activities/properties of rationally designed linear and BBC neuropeptide (NP) were thoroughly studied and the information obtained was further used for the design and synthesis of improved compounds toward the design of an insecticide prototype. The study revealed important information on the structure activity relationship (SAR) of agonistic/antagonistic peptides, including definitive identification of the orientation of the Pro residue as trans for agonist activity in 4 PK/PBANbioassays (pheromonotropic, pupariation, melanotropic, & hindgut contractile) and a PK-related CAP₂b bioassay (diuretic); indications that led to the identification of a novel scaffold to develop biostbiostable, bioavailable peptidomimetic PK/PBANagonists/antagonists. The work led to the development of an arsenal of PK/PBAN antagonists with a variety of selectivity profiles; whether between different PKbioassays, or within the same bioassay between different natural elicitors. Examples include selective and non-selective BBC and novel amphiphilic PK pheromonotropic and melanotropic antagonists some of which are capable of penetrating the moth cuticle in efficacious quantities. One of the latter analog group demonstrated unprecedented versatility in its ability to antagonize a broad spectrum of pheromonotropic elicitors. A novel, transPro mimetic motif was proposed & used to develop a strong, selective PK agonist of the melanotropic bioassay in moths. The first antagonist (pure) of PK-related CAP₂b diuresis in flies was developed using a cisPro mimetic motif; an indication that while a transPro orientation is associated with receptor agonism, a cisPro orientation is linked with an antagonist interaction. A novel, biostablePK analog, incorporating β-amino acids at key peptidase-susceptible sites, exhibited in vivo pheromonotropic activity that by far exceeded that of PBAN when applied topically. Direct analysis of neural tissue by state-of-the-art MALDI-TOF/TOF mass spectrometry was used to identify specific PK/PK-related peptides native to eight arthropod pest species [house (M. domestica), stable (S. calcitrans), horn (H. irritans) & flesh (N. bullata) flies; Southern cattle fever tick (B. microplus), European tick (I. ricinus), yellow fever mosquito (A. aegypti), & Southern Green Stink Bug (N. viridula)]; including the unprecedented identification of mass-identical Leu/Ile residues and the first identification of NPs from a tick or the CNS of Hemiptera. Evidence was obtained for the selection of Neb-PK-2 as the primary pupariation factor of the flesh fly (N. bullata) among native PK/PK-related candidates. The peptidomic techniques were also used to map the location of PK/PK-related NP in the nervous system of the model fly D. melanogaster. Knowledge of specific PK sequences can aid in the future design of species specific (or non-specific) NP agonists/antagonists. In addition, the study led to the first cloning of a PK/PBAN receptor from insect larvae (S. littoralis), providing the basis for SAR analysis for the future design of 2ⁿᵈgeneration selective and/or nonselective agonists/antagonists. Development of a microplate ligand binding assay using the PK/PBAN pheromone gland receptor was also carried out. The assay will enable screening, including high throughput, of various libraries (chemical, molecular & natural product) for the discovery of receptor specific agonists/antagonists. In summary, the body of work achieves several key milestones and brings us significantly closer to the development of novel, environmentally friendly pest insect management agents based on insect PK/PBANNPs capable of disrupting critical NP-regulated functions.
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