bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sexual health among Kenyan male sex workers in a time of COVID-19
Authors: Macharia Pascal , Moore Samantha , Mathenge John , Ndunda Erastus , Lazarus Lisa , McKinnon Lyle R , Lorway Robert 
Published: August 2020

Objective: This report identifies the profound effects that the COVID-19 pandemic and the resultant government lockdown have had on sexual health services delivery to a community of marginalised male sex workers in Nairobi, Kenya. Methods: Based on the experiences shared during ongoing virtual conversations with peer health workers, a case study was developed to identify the challenges encountered by peer health workers. Findings: Peer health workers confronted the new health crisis surrounding COVID-19 while also persisting in their efforts to deliver HIV services to male sex workers. Unable to receive status as ‘essential workers’, their actions often fell short in efforts to maintain male sex workers’ access to vital HIV prevention, treatment and care resources. Conclusion: The struggles encountered, amid dwindling resources, underscore the vital work needed to meet the health needs of a marginalised group that remains largely excluded from the government health system.
Toxicity of Fenclor 42 on Immunocompetent Cells
Authors: Franco Paola , Marelli Ornella , Canti Gianfranco , Ricci Laura , Prandoni Nancy 
Published: August 2020

Polychlorinated biphenyls (PCBs) are environmental contaminants, whose toxicity is related to the degree and the position of chlorine substitutes. Fenclor 42 is a mixture of trichlorobiphenyls employed for industrial use in Italy. In order to evaluate its effects on the immune system, CD2F1 mice were treated with Fenclor 42 at different doses and schedules. Spleen weights, total number of splenocytes and relative spleen weight decreased significatively following a single or a prolonged exposure to different doses of Fenclor 42. An analysis of the functional activity of splenocytes showed that the proliferative response to Con A and PWM mitogens was also inhibited by Fenclor 42. Splenic parameters returned to normal values within 5 days after a single injection and between 8–15 days after a subchronic administration of the compound. The capability of splenocytes to proliferate, following mitogen stimulation, was restored between day 5 and day 8 according to the different schedules of treatment. By comparison, Fenclor 42 never affected NK activity. These data clearly indicate damage at the splenic level by Fenclor 42. Studies are in progress to elucidate the mechanisms involved in the immunotoxic response.
In Vitro Cytotoxicity of 150 Chemicals to 3T3-L1 Cells, Assessed by the FRAME Kenacid Blue Method
Authors: Clothier Richard H. , Hulme Lesley , Ahmed Aamer B. , Reeves Helen L. , Smith Moira , Balls Michael 
Published: August 2020

The cytotoxicities to 3T3-L1 cells of 150 coded chemicals, estimated by the FRAME kenacid blue method, are given as a basis for further studies on the relative in vitro toxicities of related and distinct sets of test chemicals, and as a basis for future attempts at the comparison and correlation of estimates of toxicity obtained in vitro and in vivo. The expression of the results of in vitro cytotoxicity tests is discussed, as are various ways of comparing values obtained for different chemicals. It is suggested that there should be agreement on the inclusion of a standard set of reference chemicals in all cytotoxicity test validation trials.
Induction of Porphyrin Biosynthesis in the Non-Animal Experimental Model of Tissue Explant Cultures: Prevention and Reversal by the Antimitotic Colchicine
Authors: Buzaleh Ana Maria , Afonso Susana G. , Polo Cesar F. , Navone Nora M. , Bianchi Alberto , Schoua Ernesto , Del C. Batlle Alcira M. , Vazquez Elba S. 
Published: August 2020

The addition of different concentrations (5–20mg/dish) of allyl isopropylacetamide (AIA) and veronal (VER) to mouse liver, skin and heart tissue explant cultures increased the biosynthesis of porphyrin from endogenous precursors several-fold as compared to controls. Maximal effects were observed after a 12-hour incubation in liver culture for both AIA and VER (at 5mg drug/dish); after 2 and 6 hours in skin for AIA (10mg/dish) and VER (5mg/dish). In heart, with AIA (5mg/dish) and VER (20mg/dish), a peak was found after 2 hours, but a second increase was observed later after AIA induction. Colchicine (O.1mg/dish) did not by itself alter porphyrin biosynthesis by any tissue However, when added before or after porphyrin induction by AIA, it was able to both prevent and reverse the effect of the inducer in liver explants only, having no action whatever on other tissues or when VER was used. The usefulness of the non-animal experimental model of tissue explant cultures for investigating the porphyrinogenic properties and/or toxicity of drugs and their mechanism of action is emphasised.
Toxicological Responses to Zinc, Copper and Cadmium in a Rat Intestinal Cell Line
Authors: Bises Giovanna , Ranaldi Giulia , Scarino Maria Laura , Zucco Flavia 
Published: August 2020

An intestinal epithelial cell line from neonatal rat duodenum (IEC-17) was used as a model for investigating metal toxicity. In this paper, we have further characterised toxic effects on IEC-17 cells following exposure to two physiological metals, zinc (Zn2+) and copper (Cu2+) and one non-physiological metal, cadmium (Cd2+). Time-effect experiments showed that the duration of the exposure affected the extent of cell damage only when Cu2+ and Cd2+ were used. During the first 48 hours of Zn2+ exposure, the cells were seriously affected, but subsequently were able to recover. On the other hand, a colony forming ability test and morphological observations showed a special sensitivity of this cell line to Cu2+. A possible explanation is suggested in relation to extracellular matrix formation.
Reduction of Animal Experiments in Education in the Netherlands
Authors: Nab Jan 
Published: August 2020

From an academic point of view the use of animals in education is primarily as tools to achieve learning objectives. The introduction of alternatives in education requires an appreciation of both the learning objectives of these animal experiments and the possibilities and limitations of alternatives. In the Netherlands, a government-funded project is in progress, with the aim of developing the use of alternatives to animal experiments in education The numbers of animals used for educational purposes was reduced by 40% in the period 1978–1988 This paper presents an overview of the objectives of the use of animals for experiments in education and of the alternatives currently available to academia.
Studies of Metabolism Mediated Mutagenicity In Vitro
Authors: Jenssen Dag , Romert Lennart 
Published: August 2020

To understand the cause of the biological effects of xenobiotic metabolism in mammals, investigators have traditionally performed animal experiments by comparing the results of biochemical methods, such as measurement of enzyme activity analysis of the metabolites produced, with the observed toxicological effect. This article deals with in vitro methods for genotoxicity combined with drug metabolising preparations at the organelle, cell or organ levels, as exemplified by microsome preparations, isolated cells/cell lines and organ perfusion systems, respectively. The advantage of some of these methods for studying metabolism-mediated mutagenicity is that the measured endpoint reflects not only the bioactivating phase I reactions, but also the detoxifying phase II reactions, and the transfer of the non-conjugated reactive metabolites to other cells and their ability to cause mutations in these cells. In vivo, all these events are important factors in the initiation of cancer. A mechanistic advantage of the methods for metabolism-mediated mutagenicity in vitro is that the relevance of the different steps in metabolism for the mutational events can seldom be investigated in an in vivo assay. Furthermore, human studies can easily be performed using the co-culture technique with isolated human cells or cell lines.
In Vitro Models to Study Mechanisms of Lung Toxicity
Authors: Ryrfeldt Åke , Cotgreave Ian A. , Moldéus Peter 
Published: August 2020

Several functioning in vitro systems of varying complexity are currently in use for the study of mechanisms of lung toxicity. The isolated perfused lung is the model closest to the in vivo situation. It is a suitable model for combining metabolic and functional studies. It is, for instance, possible to relate changes in lung mechanics and lung perfusion flow to the release of various mediators during exposure of the lung to various agents. A simpler model may be constructed from lung slices which are less viable but suitable for uptake as well as metabolism studies. Specific lung cells such as Clara cells and type II pneumocytes have been isolated and cultured and are valuable tools for studies of the molecular mechanisms of lung toxicity, particularly in cases of cell-specific toxicity. There is, however, a great need to develop techniques for the isolation and culture of other types of lung cells and also to improve the culturing techniques for those already isolated.
Toxicity of Ethylene-bis-dithiocarbamates (EBDCs) in a Human Neuroblastoma Cell Line
Authors: Cova Dario , Fumagalli Pietro , Santagostino Angela 
Published: August 2020

The aim of our research was the in vitro evaluation of the neurotoxic effects of three EBDCs (Nabam, Zineb and Maneb) and ETU on SK-N-BE human neuroblastoma cells as a model for neurotoxicity in humans. The EC50 value was used as an index of the toxicities of these compounds. Since Zineb and Maneb contain zinc and manganese as cations, respectively, in order to determine the contributions of these metals, the EC50s of zinc chloride and manganese chloride were also evaluated. Nabam, Zineb and Maneb had EC50 values ranging from 1μM to 30μM; the EC50s of manganese and zinc in this human cell line were found to be of the same order of magnitude as those of the EBDC fungicides. These in vitro effects are discussed in relation to the possible use of neuronal cell lines for detecting the neurotoxicities of these compounds.
Effects of Neutral Shampoos on Cultures of Human Fibroblasts
Authors: Cavalletti Teresa , Reali Eva , Marangoni Claudia , Bader Stefano , Traniello Serena 
Published: August 2020

Criteria used to predict the effect of neutral shampoos on fibroblast cultures were based on assays which were easy to perform, reproducible and adaptable to a large number of substances. The tests were based on the determination of the integrity of the plasma membrane, the rate of protein synthesis, and cell viability. Six different shampoos were tested: four were of the best quality commercially available, while the other two were new compounds. The substances were tested over a wide concentration range and were applied to human fibroblast cultures for various exposure times. Lactate dehydrogenase release into the medium was used as a marker of plasma membrane integrity, the amount of [3H]-labelled protein in the fibroblasts was measured to assess the function of the cell biosynthetic machinery, and the number of damaged cells which did not take up the neutral red dye showed the percentage of cytolysis. The results indicated significant differences between the six shampoos, and a relationship between the biochemical parameters was found. This suggests that these tests on cell functionality may represent reliable markers for monitoring the cellular target damaged by xenobiotic compounds.
Polyclonal IgY Antibodies from Chicken Egg Yolk — an Alternative to the Production of Mammalian IgG Type Antibodies in Rabbits
Authors: Schade Rüdiger , Pfister Claus , Halatsch Rainer , Henklein Peter 
Published: August 2020

Based on a physiological process, antibodies are concentrated in the yolk of chicken eggs, and can be used as a convenient source of polyclonal antibodies. Hens were immunised with a BSA-cholecystokinin octapeptide conjugate (CCK-8) to obtain antibodies against CCK-8. A simple method is described for extracting the antibodies from egg yolk, which can then successfully be used in immunocytochemical studies. Using these antibodies, CCK-like immunoreactivity was found in brain sections of rats, both by fluorescein isothiocyanate and peroxidase staining. The specificities of these antibodies were different from those of rabbit antibodies against the C-terminal part of CCK-8. The applicability of egg yolk antibodies in immunological investigations is reviewed and discussed in detail. The properties of avian egg yolk antibodies are compared with those of polyclonal antibodies obtained from mammals (e.g. the rabbit). The more general use of avian antibodies is emphasised as a real alternative, taking into consideration the reduction in animal suffering involved in comparison with the classical immunisation techniques used on rabbits.
Hepatocytes in Primary Culture: An Alternative to LD50 Testing? Validation of a Predictive Model by Multivariate Analysis
Authors: Peloux Anne-Françoise , Fédérici Christian , Bichet Nicole , Gouy Daniel , Cano Jean-Paul 
Published: August 2020

The cytotoxicity of 30 chemicals was assessed in rat hepatocyte primary cultures using four methods: lactate dehydrogenase release, neutral red uptake, the MTT assay, and measurement of total protein content. Comparison of the data obtained in vitro (IC50 values) and in vivo (LD50 values) resulted in a significant correlation (p<0.001) between IC50 values and intravenous LD50 values. The validity, as well as the predictability of the model, were determined by multivariate analysis (principal component analysis and correspondence analysis). The predictability area, expressed in IC50 values, was in the range of 0–l,500μg/ml and reached 95%, with a 75–100% confidence interval (p = 0.05). Assessment of the cytotoxicity of 54 additional chemicals would provide a more accurate predictability limit around l,500μg/ml and the estimated predictability confidence interval could be reduced to 90–100%.
Evaluation of Toxicity Testing of 20 MEIC Chemicals on Hep-2 Cells Using Two Viability Endpoints
Authors: Zanetti Cristiana , De Angelis Isabella , Stammati Anna-Laura , Zucco Flavia 
Published: August 2020

The aim of the MEIC programme is to validate different in vitro testing protocols at an international level, comparing the results obtained for a series of compounds with the respective human in vivo data. The first 20 chemicals of the MEIC programme have been tested on a human epithelial cell line, Hep-2. Dose-response curves were determined by two viability endpoints, total protein content and percentage of LDH released, after exposure of confluent cultures for 24 hours. A good agreement was found in the LC50 ranking of the compounds obtained by the two parameters. Moreover, the effects of these compounds on the energetic pathway have been studied using a Clark electrode, at doses corresponding to the LC50 and just after the addition of the compound to the cells. A remarkable difference in the overall picture of toxicity is detected by assessing this specific target. The data obtained in this study are in good agreement with other, already published, MEIC project results.
Changes in Astroglial Cell Volume after Exposure to HgCl2 or CH3HgCl
Authors: Rönnbäck Lars , Hansson Elisabeth 
Published: August 2020

Cell volume was determined by measuring [14C]-3- O-methyl glucose uptake in astroglial-enriched primary cultures. Control cell volume was 3.20μl/mg protein. After incubation in 10 5M HgCl2 for 60 minutes, there was a 71% increase in cell volume. This increase was partially inhibited in the presence of the α1 receptor agonist, phenylephrine, or by the α2 receptor agonist clonidine, and was completely reversible by their respective antagonists, prazosine and yohimbine. The β receptor agonist, isoproterenol, which in itself increased cell volume, and 5-hydroxytryptamine (5HT) did not affect the HgCl2-induced changes in cell volume. 10 5M CH3HgCl increased cell volume by 26% after 30 minutes of incubation. This increase was not significantly influenced by adrenoceptor agonists or 5HT. It therefore seems that mercurial-induced changes in cell volume can be regulated by astroglial receptor stimulation.
The HET-CAM Test: A Study of the Irritation Potential of Chemicals and Formulations
Authors: de Silva Odile , Rougier André , Dossou Koovi G. 
Published: August 2020

The HET-CAM (hen's egg test-chorio-allantoic membrane), described by Luepke in 1985, permits the study of immediate effects following the administration of test substances to the chorioallantoic membrane of 10-day-incubated White Leghorn chicken eggs. The results of a study of 60 chemicals and 41 cosmetic formulations are presented here. Intralaboratory reproducibility was established with a double-blind study of 20 surfactants at two concentrations. The results show a high rank correlation between the scores given by both experimenters: the Spearman's rho is greater than 0.9 (p < 10-8). The 60 chemicals were studied at a concentration equivalent to 10% of the concentration tested in vivo. They were classified according to the three EEC categories of ocular irritancy, and when a correlation between the HET-CAM scores and historical Draize in vivo data was determined, the corresponding Spearman's rho value was 0.72 (p < 10-4). The 41 formulations (make-up removers, shower gels, shampoos, creams and body milks) were tested by two protocols: rinsed and non-rinsed. The correlation between the HET-CAM scores and the historical Draize in vivo maximum average scores was studied, and the rhos obtained were 0.77 and 0.76 (p < 10 -8), respectively. The advantages of the HET-CAM method lie in its sensitivity, rapidity and moderate cost. Both chemicals and cosmetics formulations can be tested, and specific families can be assessed using modified and more-appropriate protocols. However, to ensure that a good reproducibility and sensitivity is provided, the use of reference materials is strongly recommended. The satisfactory performances of the HET-CAM test in many previous evaluation studies (e.g. those of the BGA, CTFA, EEC and OPAL) show that it can be a useful assay as part of a battery of in vitro tests for the screening of new ingredients and formulations.
The Agarose Overlay Method as a Screening Approach for Ocular Irritancy: Application to Cosmetic Products
Authors: Combrier Emmanuel , Castelli Dominique 
Published: August 2020

The in vitro agarose overlay method was investigated as an alternative to the Draize eye irritation test for the evaluation of the ocular irritancy of cosmetic products. Modifications to the original protocol include the definition of an area of lysis (expressed as a weighty)/toxicity relationship for each product by a planimetric method and the creation of an agarose classification. 56 different cosmetic formulations, including emulsions, gels, lotions and tonics, were evaluated using this modified test, and the results were correlated with in vivo Draize data. Four different agarose classes were delimited: non-irritant; minimally irritant; mildly irritant; and irritant; corresponding respectively to the following scoring scales (x 10 4g): 0; 0 <x<200; 200≤ x <450 and ≥ 450. A high correlation between the agarose overlay method and the Draize test was observed when taking into account two classes: non-irritant (non-irritant, minimally irritant) and irritant (mildly irritant, moderately irritant [Draize] or irritant [agarose]) as shown by an 86% concordance value. In this study, the sensitivity was 92% (11–12 irritants were predicted by the agarose diffusion method) and the specificity was 84%. The overestimation error of 16% suggests that the agarose overlay method might be slightly more sensitive than the Draize eye test. When applying the kappa test, the agarose overlay method reached a 64% coefficient, attesting that the good correlation with the Draize test was not due to chance. In relation to the Landis & Koch classification, this percentage places the agarose overlay method in the “good concordance” class. Based on these results, the use of the agarose overlay method for screening the ocular irritation potential for the cosmetics industry can be considered to be a very interesting alternative to be included in a battery of tests.
In Vitro Mechanistic Toxicology Evaluation of the Antibiotic, Paldimycin Sodium, in Chang Liver Cells
Authors: Linseman Daniel A. , Raczniak Timothy J. , Bacon James A. , Linseman Kelly L. , Shilliday F. Barclay , Branstetter Daniel G. 
Published: August 2020

The basal in vitro cytotoxic potential of the antibiotic, paldimycin sodium, was investigated in Chang liver cells. The potential roles of lipid peroxidation, protein binding, and proteolytic enzyme activation in the cytotoxic mechanism of paldimycin were also examined. Cytotoxicity was assessed by measuring decreases in cell proliferation, increases in medium LDH activity due to cytoplasmic leakage, and morphological changes. Lipid peroxidation, protein binding, and proteolytic enzyme activation were investigated by co-treating cells with paldimycin and compounds which act as modifiers of the above pathways, such as antioxidants, sulphydryl compounds, and protease inhibitors, respectively. Paldimycin demonstrated a greater degree of basal cytotoxicity than was previously shown for several aminoglycoside and tetracycline antibiotics in Chang liver cells. Lipid peroxidation and proteolytic enzyme activation had no significant involvement in the observed cytotoxicity, whereas protein binding (more specifically, sulphydryl binding) was a principal mechanism of paldimycin-induced cytotoxicity in Chang liver cells. In addition, this sulphydryl binding was shown to be mediated via an exposed isothiocyanate moiety on the paldimycin molecule. The results of the co-treatment experiments described above are in agreement with data obtained in several other in vitro systems, including cell-free systems, isolated proteins, tissue homogenates, and primary isolates of cardiac myocytes.
The Scientific Basis of the EYTEX™ System
Authors: Gordon Virginia C. 
Published: August 2020

The EYTEX™ system is an in vitro method for predicting in vivo ocular irritation via a target biomacromolecular approach. EYTEX™ uses changes of relevant macromolecules upon exposure to chemicals and formulations to predict in vivo irritancy and toxicity endpoints. The EYTEX™ system is based on alterations in the conformation and hydration of an ordered macromolecular matrix. An oligomeric protein with a molar mass of approximately 300,000g/mol is the major active component of the reagent. This oligomer, characterised by 12 subunits, associates itself into strands which are then incorporated into a gel network. This network also includes smaller proteins, peptides, amino acids, aminoglycans and mucopolysaccharides, which contribute to the overall response of the macromolecular matrix to a diverse array of test compounds, such as acids, bases, salts, solvents, surfactants, lubricants, preservatives, emulsions, dyes, amines, amides and many others. The method has been extensively evaluated using chemicals and formulations from diverse classes and with different ranges of toxicity, representing various mechanisms of ocular toxicity. Results using the in vitro test correlate broadly with the Draize in vivo eye irritancy test results. Quantification of the EYTEX™ method is based on measurement of changes in optical density of the matrix, which are sensitive to the conformation and hydration of protein, as well as the order in the matrix. These changes, which occur when the matrix is exposed to chemicals and formulations, can be used to predict in vivo ocular irritancy. Calibrators and controls provide assay standardisation with a 4–8% coefficient of variation. Multiple dose and time variables relating to irritancy potential can be assessed and compared with Draize in vivo results. The EYTEX™ system provides a comprehensive set of four protocols suitable for analysing chemicals and formulations with varying degrees and mechanisms of ocular irritancy.