scholarly journals Predicting and Testing Bioavailability of Magnesium Supplements

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1663 ◽  
Author(s):  
Laura Blancquaert ◽  
Chris Vervaet ◽  
Wim Derave
Keyword(s):  
Serum Magnesium ◽  
Area Under The Curve ◽  
In Vitro Tests ◽  
In Vitro Test ◽  
Beneficial Effects ◽  
Dissolution Tests ◽  
Acute Ingestion ◽  
In Vivo Testing

Despite the presumption of the beneficial effects of magnesium supplementation, little is known about the pharmacokinetics of different magnesium formulations. We aimed to investigate the value of two in vitro approaches to predict bioavailability of magnesium and to validate this in subsequent in vivo testing. In vitro assessment of 15 commercially available magnesium formulations was performed by means of a Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) and by dissolution tests. Two magnesium formulations with contrasting bioavailability prediction from both in vitro tests (best vs. worst) were selected for in vivo testing in 30 subjects. In vivo bioavailability was compared following one acute ingestion by monitoring blood magnesium concentrations up to 6 h following intake. The in vitro tests showed a very wide variation in absorption and dissolution of the 15 magnesium products. In the in vivo testing, a significant different serum magnesium absorption profile was found up to 4 h following supplement ingestion for the two supplements with opposing in vitro test results. Moreover, maximal serum magnesium increase and total area under the curve were significantly different for both supplements (+6.2% vs. +4.6% and 6.87 vs. 0.31 mM.min, respectively). Collectively, poor bioaccessibility and bioavailability in the SHIME model clearly translated into poor dissolution and poor bioavailability in vivo. This provides a valid methodology for the prediction of in vivo bioavailability and effectiveness of micronutrients by specific in vitro approaches.

scholarly journals Multiple-endpoint in vitro carcinogenicity test in human cell line TK6 distinguishes carcinogens from non-carcinogens and highlights mechanisms of action

2020 ◽  
Author(s):  
Katherine E. Chapman ◽  
Eleanor C. Wilde ◽  
Fiona M. Chapman ◽  
Jatin R. Verma ◽  
Ume-Kulsoom Shah ◽  
...  
Keyword(s):  
Cell Line ◽  
Human Cell Line ◽  
Test System ◽  
In Vitro Tests ◽  
Correct Identification ◽  
In Vitro Test ◽  
Human Lymphoblastoid Cell ◽  
Carcinogenic Potential

Abstract Current in vitro genotoxicity tests can produce misleading positive results, indicating an inability to effectively predict a compound’s subsequent carcinogenic potential in vivo. Such oversensitivity can incur unnecessary in vivo tests to further investigate positive in vitro results, supporting the need to improve in vitro tests to better inform risk assessment. It is increasingly acknowledged that more informative in vitro tests using multiple endpoints may support the correct identification of carcinogenic potential. The present study, therefore, employed a holistic, multiple-endpoint approach using low doses of selected carcinogens and non-carcinogens (0.001–770 µM) to assess whether these chemicals caused perturbations in molecular and cellular endpoints relating to the Hallmarks of Cancer. Endpoints included micronucleus induction, alterations in gene expression, cell cycle dynamics, cell morphology and bioenergetics in the human lymphoblastoid cell line TK6. Carcinogens ochratoxin A and oestradiol produced greater Integrated Signature of Carcinogenicity scores for the combined endpoints than the “misleading” in vitro positive compounds, quercetin, 2,4-dichlorophenol and quinacrine dihydrochloride and toxic non-carcinogens, caffeine, cycloheximide and phenformin HCl. This study provides compelling evidence that carcinogens can successfully be distinguished from non-carcinogens using a holistic in vitro test system. Avoidance of misleading in vitro outcomes could lead to the reduction and replacement of animals in carcinogenicity testing.

Comparison of methods for measurement of the pressure exerted by knitted fabrics

2016 ◽  
Vol 87 (17) ◽  
pp. 2117-2126 ◽  
Author(s):  
Małgorzata Cieślak ◽  
Agnieszka Karaszewska ◽  
Ewa Gromadzińska ◽  
Izabela Jasińska ◽  
Irena Kamińska
Keyword(s):  
In Vitro Tests ◽  
Knitted Fabric ◽  
In Vitro Test ◽  
Knitted Fabrics ◽  
Weft Knitted Fabric ◽  
In Vivo Tests ◽  
Vitro Test ◽  
Warp Knitted Fabric

The article presents the results of measurements of pressure exerted by two model knitted products – bands with different structure (WI jersey weft-knitted fabric and WII openwork warp-knitted fabric). The tests were carried out with using the I-Scan system (in vivo and in vitro tests) and the STM 579 device (in vitro test). A comparative analysis of the in vivo and in vitro results for the I-Scan method and in vitro results for the I-Scan and STM 579 method was performed. It was found that the pressure values are lower for openwork warp-knitted fabric than for jersey weft-knitted fabric both in the case of the in vitro and in vivo tests, and the values of pressure for the same band are higher in the case of the in vitro tests.

scholarly journals Comparative Studies on the Anticoagulant Profile of Branded Enoxaparin and a New Biosimilar Version

2020 ◽  
Vol 26 ◽  
pp. 107602962096082
Author(s):  
Dalia Qneibi ◽  
Eduardo Ramacciotti ◽  
Ariane Scarlatelli Macedo ◽  
Roberto Augusto Caffaro ◽  
Leandro Barile Agati ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Performance ◽  
Thrombin Generation ◽  
Area Under The Curve ◽  
Factor Xa ◽  
In Vivo Studies ◽  
In Vitro Tests ◽  
Thrombin Time

Low molecular weight heparins (LMWH) represent depolymerized heparin prepared by various methods that exhibit differential, biochemical and pharmacological profiles. Enoxaparin is prepared by benzylation followed by alkaline depolymerization of porcine heparin. Upon the expiration of its patent, several biosimilar versions of enoxaparin have become available. Heparinox (Sodic enoxaparine; Cristália Produtos Químicos Farmacêuticos LTDA, Sao Paulo, Brazil) is a new biosimilar form of enoxaparin. We assessed the molecular weight and the biochemical profile of Heparinox and compared its properties to the original branded enoxaparin (Lovenox; Sanofi, Paris, France). Clotting profiles compared included activated clotting time, activated partial thromboplastin time (aPTT), and thrombin time (TT). Anti-protease assays included anti-factor Xa and anti-factor IIa activities. Thrombin generation was measured using a calibrated automated thrombogram and thrombokinetic profile included peak thrombin, lag time and area under the curve. USP potency was determined using commercially available assay kits. Molecular weight profiling was determined using high performance liquid chromatography. We determined that Heparinox and Lovenox were comparable in their molecular weight profile. Th anticoagulant profile of the branded and biosimilar version were also similar in the clot based aPTT and TT. Similarly, the anti-Xa and anti-IIa activities were comparable in the products. No differences were noted in the thrombin generation inhibitory profile of the branded and biosimilar versions of enoxaparin. Our studies suggest that Heparinox is bioequivalent to the original branded enoxaparin based upon in vitro tests however will require further in vivo studies in animal models and humans to determine their clinical bioequivalence.

Effect of lactoferrin onHelicobacter felisinduced gastritis

2002 ◽  
Vol 80 (1) ◽  
pp. 113-117 ◽  
Author(s):  
Elizabeth J Dial ◽  
Lenard M Lichtenberger
Keyword(s):  
Surface Hydrophobicity ◽  
Human Lactoferrin ◽  
Bovine Lactoferrin ◽  
Recombinant Human Lactoferrin ◽  
Beneficial Effects ◽  
In Vivo Testing ◽  
H Pylori ◽  
Orally Active

Lactoferrin possesses antibiotic, antiinflammatory, and immune-modulating properties that may be active against the gastritis-, ulcer- and cancer-inducing bacterium Helicobacter pylori. In vitro testing of bovine and human lactoferrin by several laboratories has shown significant bacteriostatic and bactericidal activity. Subsequent in vivo testing of bovine lactoferrin in animal models of H. pylori infection has shown beneficial effects of this agent. Our laboratory has utilized a mouse model that is infected with the feline strain of this bacterium, H. felis. The resulting gastritis that develops in this model and the effects of bovine lactoferrin and recombinant human lactoferrin (from Aspergillus niger var. awamori, Agennix Inc., Houston, Tex.) treatment were assessed by various measures. Infected animals treated with orally administered lactoferrin showed reversals in all parameters. In addition, when recombinant human lactoferrin was used in combination with low doses of amoxicillin or tetracycline, there was an enhancement in gastritis-reducing activity. Possible mechanisms for these effects of lactoferrin are discussed. Lactoferrin has significant, orally active in vivo actions and should be further investigated for clinical situations involving Helicobacter infections where it may have utility when administered alone and also when given in combination with established antibiotic agents.Key words: lactoferrin, Helicobacter, gastritis, surface hydrophobicity.

In Vitro Toxicology and the Test Guidelines

1996 ◽  
Vol 24 (3) ◽  
pp. 435-438
Author(s):  
Kimmo Louekari
Keyword(s):  
Cost Effective ◽  
Test Methods ◽  
In Vitro Tests ◽  
In Vitro Test ◽  
In Vitro Methods ◽  
Effective Manner ◽  
Genotoxic Carcinogens ◽  
Vitro Test

Ethical, economical and scientific considerations should encourage the development of alternative and in vitro test methods. Before their adoption, in vitro methods need to be validated and scientifically justified. Demand for rigorous validation schemes for in vitro tests must be emphasised, even more than in the case of in vivo tests. The OECD has adopted in vitro guidelines for testing genotoxicity; several endpoints and mechanisms can be studied in a cost-effective manner in vitro. Similar advantages could be afforded if acute irritation and corrosion, as well as the non-genotoxic carcinogenic effects of chemicals, could be studied in vitro. Evaluation of the validation status of various methods used to study non-genotoxic carcinogens was begun by the Nordic Working Group on In Vitro Methods for Non-genotoxic Mechanisms in 1996. In some established OECD test guidelines (for example, the dermal irritation/corrosion test), there is already room for the application of in vitro methods which have not been formally validated. In January 1996, the OECD Workshop on Harmonisation of Validation and Acceptance Criteria for Alternative Toxicological Test Methods set the basis for internationally acceptable principles to be followed in the validation of in vitro test methods.

An Investigation of the Assay of Heparin Based on Its Activity in Vivo

1967 ◽  
Vol 18 (01/02) ◽  
pp. 150-160 ◽  
Author(s):  
W. E Rezansoff ◽  
L. B Jaques
Keyword(s):  
Lipolytic Activity ◽  
Area Under The Curve ◽  
Test System ◽  
Assay Method ◽  
In Vitro Tests ◽  
Clotting Time ◽  
Oil Emulsion ◽  
Effective Doses

SummaryThe potency of different heparin preparations was investigated in vivo, by measuring the Lee and White clotting time, lipolytic activity and partial thromboplastin time of blood samples drawn at intervals after the intravenous injection of heparin into the anesthetized dog. The blood clotting time in log minutes, the thromboplastin time in log seconds, and the plasma lipolytic activity measured as the decrease in optical density of a synthetic cocuont oil emulsion per unit of time after incubation with postheparin plasma, were plotted against time after injection. A linear relation was obtained between the dose of heparin and the response measured as the area under the curve.The in vivo responses for 6 heparin preparations at 3 dose levels were compared with those for a reference heparin. The potency of each relative to the reference was estimated as the ratio of equally effective doses. The results obtained were compared with assay values reported for in vitro tests - U.S.P. , Howell, colorimetric (Lovibond, Beckman DK-2 spectrophotometer and microelectrophoresis on agarose) . There was no consistent case of one assay methodgiving results greatly different from the others and no assay method consistently described the activity of the heparin preparation in another test system, in vitro or in vivo.

scholarly journals In vivo toxicity of a new antifungal agent 2,4-dithiophenoxy-1-iodo-4-bromo benzene: a follow up on our in vitro study / In vivo toksičnost novoga antimikotika 2,4-ditiofenoksi-1-jodo-4-bromobenzena: proširenje in vitro istraživanja

2015 ◽  
Vol 66 (1) ◽  
pp. 63-72 ◽  
Author(s):  
Aysun Kılıç Süloğlu ◽  
Evrim Koçkaya ◽  
Elif Karacaoğlu ◽  
Güldeniz Selmanoğlu ◽  
Elif Loğoğlu
Keyword(s):  
Antifungal Agent ◽  
Fungal Infections ◽  
In Vitro Study ◽  
Female Rats ◽  
In Vitro Tests ◽  
In Vitro Test ◽  
Benzene Derivative ◽  
New Drug

Abstract Triazole fungicide fluconazole has become the most widely used antifungal agent in the world, mainly because of its ability to penetrate well into body fluids and tissues. However, it has been reported to interact with many drugs and because of its common use, the risk of resistance to fluconazole increases. This calls for new anti-fungal drugs that would be able to replace it. In 2006, a new thialo benzene derivative - 2,4-dithiophenoxy-1-iodo-4-bromo benzene (C18H12S2IBr) - was synthesised with a carbon backbone similar to fluconazole, and, according to the early in vitro tests, much greater efficiency. Followed an in vitro test of its cytotoxicity, in which the new drug showed promising results as an alternative to fluconazole. The aim of this study was take the next step and test C18H12S2IBr toxicity in vivo. We opted for a four-week test on Wistar rats, in which the new antifungal agent was orally applied at doses two and a half and five times lower than those of fluconazole. There were no changes in daily food and water consumption, but weight gain in female rats and relative organ weights changed in the treated groups, pointing to sex-related differences in drug metabolism and effects. Fluconazole significantly increased leukocytes and lowered neutrophils whereas C18H12S2IBr did not, while other haematological changes in respect to the vehicle control were similar between the treated groups. Differences in cytochrome c in the liver and kidney suggested greater apoptotic effect of the new drug, but interpretation remains inconclusive, considering that other key indicators (biochemistry and histopathology) do not support greater toxicity. Considering that C18H12S2IBr is more active at lower concentrations and has comparable toxic effects to fluconazole in rats, this new compound shows some promise in the treatment of fungal infections. Future, more detailed animal studies are needed, that will include drug interactions and molecular toxicity pathways. If the results are promising, clinical studies should follow.

In Vitro Toxicity Testing: Purpose, Validation and Strategy

1990 ◽  
Vol 18 (1_part_1) ◽  
pp. 11-18 ◽  
Author(s):  
Oliver P. Flint
Keyword(s):  
Cell Function ◽  
Toxicity Testing ◽  
In Vitro Toxicity ◽  
In Vitro Tests ◽  
In Vitro Test ◽  
Vitro Test ◽  
Basal Cytotoxicity ◽  
Biological Endpoint

The fullest potential for in vitro evaluation of toxicity will be realised in the context of the process of assessing the risk of human toxicity. This article is an attempt to clarify what contributions can be made by in vitro tests and what types of in vitro test can best be used. In vitro tests are clarified according to the type of biological endpoint evaluated, first into tests for general (‘basal’) cytotoxicity and, secondly, into tests for differentiated cell function. The role of each type of test is analysed and it is suggested that tests for general cytotoxicity, as opposed to differentiated function, are difficult to interpret in terms of in vivo toxicity. A general approach to evaluating in vitro tests is described, and a strategy for using these tests is proposed.

The Application of in Vitro Models to Research on Demineralization and Remineralization of the Teeth

1995 ◽  
Vol 9 (3) ◽  
pp. 175-193 ◽  
Author(s):  
D.J. White
Keyword(s):  
Analytical Techniques ◽  
Test Methods ◽  
In Vitro Models ◽  
In Vitro Tests ◽  
In Vitro Testing ◽  
In Vitro Test ◽  
Dental Tissues ◽  
Testing Protocols

Progress in in vivo and in situ experimentation has led many researchers to speculate as to the relevance and importance of in vitro testing protocols in caries research. A Medline/Biosis search for the present review revealed well over 300 citations (since 1989) documenting in vitro tests associated with caries research on mineralization and fluoride reactivity. The present survey documents these recent applications of in vitro test methods in both mechanistic and 'profile'* caries research. In mechanistic studies, in vitro protocols over the past five years have made possible detailed studies of dynamics occurring in mineral loss and gain from dental tissues and the reaction dynamics associated with fluoride anticaries activity. Similarly, in profile applications, in vitro protocols make possible the inexpensive and rapid-yet sensitive-assessment of F anticaries efficacy within fluoride-active systems, and these tests represent a key component of product activity confirmation. The ability to carry out single variable experiments under highly controlled conditions remains a key advantage in in vitro experimentation, and will likely drive even further utilization, as advances continue in physical-chemical and analytical techniques for substrate analysis in these protocols. Despite their advantages, in vitro testing protocols have significant limitations, most particularly related to their inability to simulate the complex biological processes involved in caries.

Quantification of Eye Irritation Based upon In Vitro Changes of Corneal Thickness

1990 ◽  
Vol 17 (3) ◽  
pp. 255-262
Author(s):  
Guido A. Jacobs ◽  
Mark A. Martens
Keyword(s):  
Linear Correlation ◽  
Objective Assessment ◽  
Corneal Thickness ◽  
In Vitro Tests ◽  
In Vitro Test ◽  
Eye Irritation ◽  
The Mean ◽  
Observation Times

Measurement of corneal swelling is an objective assessment of irritation in in vivo tests. The same measurement may be made in in vitro tests using the isolated eye test (IET), which has been recommended by the European Community as an alternative for in vivo eye irritation tests. In order to compare the corneal swelling in vivo and in vitro, tests were performed with 34 substances. The in vitro test results were assessed for their ability to predict eye-irritant potential. The corneal swelling data in vivo after 4, 24, 48 and 72 hours were compared with the in vitro data obtained after 2 and 4 hours. Slight linear correlation was found between the corneal swelling in vivo after 4 hours and the corneal swelling in vitro after 4 hours (r=0.77). The substances tested can be divided into two groups, according to their ability to create opacity in either the epithelial layer or in the stroma. When the substances causing epithelial opacity were omitted from the comparison, a much better linear correlation was obtained between the mean corneal swelling 121 vitro over 2 and 4 hours and the mean corneal swelling calculated in vivo for all animals and over three observation times (24, 48 and 72 hours; r=0.91), the latter being the observation times prescribed by EC legislation (1). A comparison of the mean corneal opacity scores observed in vivo and the mean percentage corneal swelling in vitro gave a satisfactory linear correlation (r=0.89). From this study it can be deduced that a mean corneal swelling of 55%, obtained in isolated eyes over 2 and 4 hours, corresponds with the limit for classification as irritant, to the eye. When this criterion was applied to all substances causing no epithelial opacity (n=28), only one false positive and no false negatives were found.

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