bluuebunny/crossref_metadata_2025 huggingface dataset:
Chimpanzee Medical Experiments: Moral, Legal and Scientific Concerns
Authors: Balls Michael
Published: August 2020

FRAME'S role in drawing attention to the special scientific and ethical concerns raised by the use of non-human primates as laboratory animals is reviewed, with special emphasis on the FRAME/CRAE proposals to the British Government (1987) and the RSPCA/FRAME survey of research on non-human primates conducted in Great Britain between 1984 and 1988. Attention is then focused on the moral case and the scientific case against using chimpanzees as laboratory animals, with particular emphasis on research on AIDS. Finally, a call is made for universal agreement that no more laboratory experiments should ever be performed on chimpanzees.
The Great Ape Project: Premises and Implications
Authors: Cavalieri Paola , Singer Peter
Published: August 2020

Is it consistent to accept ethical constraints on scientific research when humans are involved, and to reject them when it comes to non-humans? Is the current scientific practice of experimenting on sentient animals a “necessary evil” which must simply be tolerated, or is it an indefensible practice stemming from arbitrary discrimination based on species? These are some of the questions we address in this paper, in order to illustrate the implications for scientific experimentation of the first attempt to grant to some non-human beings the basic rights which have so far been limited to members of our own species. Resulting from the recent rethinking on the moral status of animals, this attempt revolves around the collective argument for the enfranchisement of chimpanzees, gorillas and orang-utans that, together with a distinguished group of scientists and philosophers, we have presented in The Great Ape Project. We draw from this volume some of the evidence that ethologists, language researchers, psychologists and anthropologists have gathered in favour of the attribution to the other great apes of many of the characteristics we traditionally consider to be morally significant when we find them in ourselves. After stressing the relevance of a species-neutral notion of person in the actual philosophical debate, we highlight the overwhelming case for its application, in both the moral and the legal senses, to the other great apes. While, on a general level, this would lead to the inclusion of our closest living relatives in the sphere of equality, as far as the practice of experimentation is concerned, it would result in extending to them those very restrictions which at present apply to scientific research on humans.
Animals, Apes, Men: Equally Victims of Vivisection
Authors: Croce Pietro
Published: August 2020

Interspecies experimentation is always deceptive, whilst intraspecies experimentation is correct and reliable, though under due limits. Healthy volunteers should not be used in medical research, on either ethical or scientific grounds and, in this paper, very strict rules are outlined for regulating medical testing in humans. Testing anti-AIDS drugs on apes or any other animal species is misleading, due to the enormous differences which exist between the reactions of different animal species to drugs in general.
On Keeping your Eyes on the Prize: Dorothy Hegarty and Acceptance of the Concept of Replacement of Laboratory Animal Procedures in Research, Education and Testing
Authors: Balls Michael
Published: August 2020

Dorothy Hegarty, Founder of FRAME, died in August 1995 at the age of 84. The crucial role she played in defining the concept of replacement alternatives to laboratory animal procedures, and in securing its acceptance by the scientific and animal welfare communities and into national and international legislation, is examined through the recollections and assessments of some of those who knew her and worked with or for her.
The Progress of Humane Experimental Technique since 1959: A Personal View
Authors: Burch Rex L.
Published: August 2020

This is very much a personal interpretation of the Three Rs and the efforts by scientists connected with the more humane use of animals. It is intended to illustrate that scientists are given a job to do and, if it involves animals, they have little choice but to use them. It is also intended to illustrate that so many of those so involved are the very people who have made gigantic efforts in finding ways of replacing, reducing and/or refining techniques which require animals.
Cytotoxicity of Biomaterials — Basic Mechanisms and In Vitro Test Methods: A Review
Authors: Groth Thomas , Falck Peter , Miethke Rainer-Reginald
Published: August 2020

Biocompatibility is one of the main prerequisites for the clinical use of biomaterials. Central to the testing of biocompatibility is the estimation of cytotoxicity, which can be assessed in vitro by using a variety of different target primary cells or cell lines. The influence of toxic agents derived from biomaterials on cellular functions and cell viability can be characterised by reductions in cell adhesion, alterations in cellular morphology, reduced cellular proliferation, and cell death, demonstrated by an absence of metabolic activity, structural disintegration and cell lysis. A brief review of the basic mechanisms of cytotoxicity and the use of different in vitro methods for testing the cytotoxicity of biomaterials is presented.
Determination of Critical Cellular Neurotoxic Concentrations in Human Neuroblastoma (SH-SY5Y) Cell Cultures
Authors: Forsby Anna , Pilli Francesco , Bianchi Vera , Walum Erik
Published: August 2020

The effects of the neurotoxic compounds acrylamide, triethyltin chloride (TET), methyl mercury (II) chloride (MeHg) and lindane on selected neurospecific and general cell functions in differentiated human neuroblastoma SH-SY5Y cells were investigated in an attempt to determine critical cellular neurotoxic concentrations. The cultures were exposed to the neurotoxicants for three days, and then the effects on cell growth, neuronal signal transaction and the induction of axonopathy were measured. For comparison, general cytotoxicity was also determined in human epithelial (HeLa) cells. The cytotoxic activities (IC20 values) in the SH-SY5Y cells were 0.18 ± 0.03μM for TET, 0.20 ± 0.03μM for MeHg, 32 ± 10μM for lindane and 810 ± 170μM for acrylamide. Inhibition of cell growth was similar in HeLa cells. Significantly lower concentrations of MeHg, acrylamide and TET than the IC20 values were sufficient to induce axonopathy. In addition, MeHg and acrylamide increased the basal intracellular free calcium concentration, [Ca2+]i, as well as the carbachol-induced Ca2+ fluxes and the depolarisation-stimulated increase of [Ca2+]i compared to control cells. The elevated [Ca2+]i may be a primary cause of the acrylamide-induced and MeHg-induced neuropathy. Treatment with lindane (1μM) slightly decreased the depolarisation-evoked Ca2+ influx in the neuroblastoma cells. A parallel to the documented neurotoxic mechanism of lindane (i.e. inhibition of the γ-aminobutyric acid-activated Cl- channels) is possible.
Advances in Refinement in Animal Experimentation over the past 25 Years
Authors: Morton David B.
Published: August 2020

This article describes, from a personal viewpoint, some of the major advances in refinement in animal experimentation over the past 25–35 years. It is written mainly from a UK perspective. Aspects of public perception and policy, education and training, and the competence of those involved in animal research, are commented upon. Recognition of adverse effects on animals is seen as the key to the refinement of animal experimentation. Elaboration on, and examples of, this theme are given by referring to refinements in animal husbandry and experimental technique. A brief look forward to the changes that may occur in the next 25 years is also included.
A Comparison of Hepatic Enzyme Activities and their Modulation by Dexamethazone in Freshly Isolated and Cultured Hepatocytes and in the Differentiated Hepatoma Cell Line, 2sFou
Authors: Garle Michael J. , Fry Jeffrey R.
Published: August 2020

Rodent hepatocytes are mitotically inhibited and lose hepatospecific functions over time in culture. In contrast, some differentiated hepatoma cell lines express stable hepatospecific functions in culture, but at much lower levels than those initially found in primary hepatocytes. A number of hepatospecific functions were measured in freshly isolated and cultured rat hepatocytes; these were compared to activities found in the differentiated Reuber hepatoma cell line, 2sFou. The effects of dexamethazone on these activities were also investigated, since dexamethazone is reported to enhance the expression of organotypic functions. The P450-related activities (ethoxyresorufin-O-deethylase activity and pentoxyresorufin-O-depenty-lase activity) and glucose-6-phosphatase activity declined in hepatocytes with increasing time in culture. The same activities in 2sFou cells were similar to those in hepatocytes which had been cultured for 72 hours. Tyrosine amino transferase (TAT) activity declined in hepatocyte cultures with time, but dexamethazone (1μM) restored activity up to freshly isolated cell values. TAT activity in hepatoma cells exceeded that in hepatocytes and was highly inducible by dexamethazone. γ-Glutamyl transpeptidase activity increased with culture time in hepatocytes and was also highly expressed in 2sFou cells. In hepatocytes, the activity of a high affinity alcohol dehydrogenase (ADH) declined with time in culture. In 2sFou cells, there was evidence of a low affinity (extra-hepatic or fetal) form of ADH, which was not evident in cultured hepatocytes.
Application of Statistical Classification Methods to the Evaluation of In Vitro Tests
Authors: Glaser Sabine
Published: August 2020

The first Amden Report defines validation as “The process by which the reliability and relevance of a test are established”. The recommendations of the Amden conference mention the need for biometric methods, but, unfortunately, most publications on alternatives to animal testing procedures do not pay much attention to statistical problems in the validation process. The biometric repertoire consists mainly of scatterplots, correlation coefficients and linear regression.

In the evaluation of an interlaboratory study, we applied multivariate statistical methods to analyse the ability of two in vitro tests to identify severely irritating substances. In this study, conducted by the German Bundesgesundheitsamt, two alternatives to the well-known Draize eye irritancy test — the neutral red uptake test and the HET-CAM test — were investigated. The statistical methods applied were discriminant analysis and the Classification and Regression Trees (CART) method.

The results presented here show that the combination of the endpoints of the in vitro tests, analysed by using the CART method, can give a sensitivity of about 67% with 76% specificity. Discriminant analysis models only achieve a sensitivity of 55%. The results obtained with the data presented here show that these statistical methods are very suitable and useful for this type of problem. This was confirmed by further analyses with discriminant analysis models, which gave a sensitivity of about 80%.
The Use of Porcine Proximal Tubular Cells for Studying Nephrotoxicity In Vitro: The Role of Oxidative Stress in Cisplatin-induced Cell Death
Authors: Kruidering Marieke , van de Water Bob , de Heer Emile , Mulder Gerard J. , Nagelkerke J. Fred
Published: August 2020

The effects of a widely used antitumour drug, cisplatin, on freshly isolated porcine proximal tubular cells (PPTC) in suspension were investigated. Incubation of the PPTC with 5-500μM cisplatin resulted in a decrease in mitochondrial membrane potential (MMP) and in cell death. In addition, the formation of reactive oxygen species (ROS) was observed within 20 minutes. Prevention of ROS formation with the antioxidants diphenyl- p-phenylene-diamine (DPPD) or desferrioxamine had no effect on the cisplatin-induced effects on MMP and cell death, implying that cisplatin-induced ROS formation is not a cause of cell death. In order to investigate whether the ROS formation was related to mitochondrial damage, we determined the effects of cisplatin on the enzymatic activities of NADP:ubiquinone reductase (Complex I) and succinate:ubiquinone reductase (Complex II) of the respiratory chain. Exposure of the PPTC to cisplatin resulted in a time-dependent and dose-dependent inhibition of the activities of both Complex I and Complex II. The inhibition of these activities and the depletion of ATP could not be prevented by the antioxidants, indicating that these effects are not a consequence of ROS formation. We propose that damage to the mitochondria could be a key event in cisplatin-induced cell death.
Direct Functional Effects of Parathion and Paraoxon on Neuronal Nicotinic and Muscarinic M3 Acetylcholine Receptors
Authors: van den Beukel Ingeborg , van Kleef Regina G.D.M. , Oortgiesen Marga
Published: August 2020

The direct effects of two organophosphates, parathion and paraoxon, on nicotinic and muscarinic acetylcholine receptors in cells from different species were investigated, by using the whole-cell voltage clamp technique. The effects of neuronal type nicotinic receptors in mouse N1E-115, human SH-SY5Y and locust thoracic ganglion cells, and on human muscarinic M3 receptors transfected in Chinese hamster ovary (CHO) cells, were analysed. Parathion and paraoxon inhibit acetylcholine-induced nicotinic inward currents at concentrations in the micromblar range. Surprisingly, parathion is a more potent inhibitor than its active acetyl-cholinesterase-inhibiting metabolite, paraoxon. Moderate differences in sensitivity to the blocking action of the organophosphates appear to exist between cells from different species. Both parathion (100nM) and paraoxon (1μM) induce ion currents in M3-transfected CHO cells. They appear to act as agonists on the human muscarinic M3 receptor, affecting the receptors in a different manner to that of acetylcholine.
In Vitro Toxicology Methods in Risk Assessment
Authors: Purchase Iain F. H.
Published: August 2020

The title of this paper is challenging, because the question of how in vitro methods and results contribute to human health risk assessment is rarely considered. The process of risk assessment usually begins with hazard assessment, which provides a description of the inherent toxicological properties of the chemical. The next step is to assess the relevance of this to humans, i.e. the human hazard assessment. Finally, information on exposure is examined, and risk can then be assessed.

In vitro methods have a limited, but important, role to play in risk assessment. The results can be used for classification and labelling; these are methods of controlling exposure, analogous to risk assessment, but without considering exposure. The Ames Salmonella test is the only in vitro method which is incorporated into regulations and used widely. Data from this test can, at best, lead to classification of a chemical with regard to genotoxicity, but cannot be used for classification and labelling on their own. Several in vitro test systems which assess the topical irritancy and corrosivity of chemicals have been reasonably well validated, and the results from these tests can be used for classification.

The future development of in vitro methods is likely to be slow, as it depends on the development of new concepts and ideas. The in vivo methods which currently have reasonably developed in vitro alternatives will be the easiest to replace. The remaining in vivo methods, which provide toxicological information from repeated chronic dosing, with varied endpoints and by mechanisms which are not understood, will be more difficult to replace.
An In Vitro Model of the Blood-Brain Barrier: The Response of Madin-Darby Canine Kidney Cells to Triethyl Tin
Authors: Veronesi Bellina , Carlsón Kent , Ehrich Marion
Published: August 2020

The development of a cell culture model which simulates the properties of the blood–brain barrier (BBB) is necessary for the detection of neurotoxic chemicals that can disrupt the barrier, and to provide a more “risk relevant” in vitro screening battery. The present study evaluates the Madin-Darby canine kidney (MDCK) epithelial cell line for this purpose. Changes in electrical resistance and enzyme activities were correlated in confluent MDCK cells exposed to the neurotoxic metal, triethyl tin (TET). Concentrations of TET (0.001–10μM) were established that produced depression in electrical resistance of the MDCK cells after exposure for 8 hours or caused fluorescein leakage after exposure for 72 hours. Confluent cultures of MDCK cells were then exposed to these concentrations of TET and assayed after exposure for 24 hours and 72 hours for changes in those enzymes common to both epithelial and cerebral endothelial cells. The results indicated that increased alkaline phosphatase (APP), γ-glutamyl transpeptidase (GGTP) and superoxide dismutase (SOD) characterised the loss of electrical resistance and permeability disruption in TET-exposed MDCK confluent cultures. Relative increases in APP and decreases in GGTP activities preceded cytotoxicity, which was associated with a high SOD activity. Such enzyme changes may be predictive endpoints of barrier cell disruption by neurotoxic metals in this cell line and support the additional evaluation of the MDCK cell line as an in vitro “screen” for chemicals that disrupt the BBB.
Nicotinic Receptors of Different Species Exhibit Differential Sensitivities to Nitromethylene and Organophosphate Insecticides
Authors: Oortgiesen Marga , van Kleef Regina G.D.M. , Zwart Ruud , van den Beukel Ingeborg , Vijverberg Henk P.M.
Published: August 2020

The effects of nitromethylene heterocycle (NMH) and organophosphate (OP) insecticides were studied on nicotinic acetylcholine receptors (nAChR) in cultured cells of different species origin, in order to examine the selectivity of these compounds at the level of the target sites. In mouse muscle BC3H1, mouse NIE-115 and human SH-SY5Y neuroblastoma, and locust thoracic ganglion cells, the neurotransmitter, acetylcholine (ACh), induces a similar transient inward current. Dependent on the cell type, the six NMHs acted as agonists and/or antagonists on nAChR. Distinct agonistic effects of NMHs on nAChR are observed on insect neurons only. Further, NMHs potently block nicotinic responses in insects, while mammalian cells are only moderately affected. In all cases, the neuronal type nAChR was more sensitive to blocking than the endplate type nAChR in mammalian cells.

Parathion and paraoxon at micromolar concentrations inhibit ACh-induced nicotinic inward currents. The insecticide, parathion, is a 50-fold more potent inhibitor than its acetyl-cholinesterase-inhibiting metabolite, paraoxon. Moderate differences in sensitivity to the blocking action of the OPs appear to exist among cells of different species. The results demonstrate that the experimental approach of fundamental electrophysiology and the use of cell lines are relevant tools for investigating the species specificity of neurotoxic compounds.
Exposure of Cultured Microglial Cells to Interferon-gamma
Authors: Grundt Inger K. , Nyland Harald
Published: August 2020

The reactions of a microglial cell population to exposure to interferon-gamma (IFN-γ) were studied in primary cultures of mixed glial cells from the brains of newborn rats. One week after seeding, the cells were exposed to 200U/ml of IFN-γ for 24 and 48 hours. After exposure to IFN-γ for 48 hours, a third of the cultures were exposed to phorbol myristate acetate (PMA) for 90 minutes. Transformation of the microglial cells in response to this treatment was observed by using a light microscope. On time-lapse film, an increase in the mobility of the cells and an increase in the number of amoeba-like microglia were among the most evident changes induced by IFN-γ. These changes became more pronounced when the exposure time was increased. The addition of PMA significantly enhanced this process. After exposure to IFN-γ for 48 hours, expression of the MHC class II antigen was observed. The interleukin-1β content of the cells was increased in the cultures after 24 hours, but declined after further exposure.
In Vitro Cytotoxicity Testing of Potentially Active Anti-HIV Drugs with Cultured Cells
Authors: Hopkinson Desirée , Scheiner Peter , Barile Frank A.
Published: August 2020

This study compared the ability of two continuous cell lines to predict the cytotoxicity of potentially active anti-HIV drugs. Human fetal lung fibroblasts (HFL1) and CD4+ T-lymphocytes (CEM-IW) were incubated in the absence or presence of increasing concentrations of 12 antiviral compounds. These six-membered unsaturated nucleoside analogues were stereospecifically synthesised in our laboratories, and were evaluated for cytotoxicity as well as for antiviral activity. Cells were incubated for six days and mitochondrial activity (XTT and MTT assays) was used to assess cytotoxicity. IC50 values were derived from concentration–effect curves after linear regression analysis. Comparison of the two sets of cytotoxicity data suggests that the experimental IC50 values from HFL1 cells correlate well with the values obtained in lymphocyte studies performed at the National Cancer Institute laboratories (r value = 0.93). For the 12 antiviral chemicals, and those we have tested previously, these methods probably detect basal cytotoxicity, i.e. the toxicity of a chemical to basic cellular functions and structures common to all mammalian specialised cells. However, as with any testing procedure, some chemicals may elude the cytotoxicity screen, as a result of false negatives due to solubility, miscibility and organ-specific effects, and could be mislabelled as having low toxic potential. It is therefore conceivable that tests involving continuous differentiated cell lines of various origins could be developed to cover a large percentage of toxic effects, thereby reducing the need to introduce many laborious assay systems with freshly-isolated primary cultures.
FRAME Recommendations for the Application of the Three Rs to the Regulatory Toxicity Testing of Food Additives
Authors: Broadhead Caren L. , Combes Robert D.
Published: August 2020

Direct food additives are tested for genotoxicity, acute and subchronic toxicity, carcinogenicity and teratogenicity. International guidelines differ in the types of tests required, the duration of the tests, the species of animals to be used, the number of animals recommended and the method of housing experimental animals. This lack of harmonisation is wasteful in terms of animal use and creates additional and, perhaps, unnecessary work for the food industry. In addition, unlike other chemicals, food additives pose a special problem for toxicity testing due to repeated low-dose, life-time human exposure, which is difficult to model in animal studies. In an assessment of the extent to which the Three Rs (reduction, refinement and replacement) can be applied to food additive toxicity testing, it was concluded that differences in regulatory requirements and testing protocols can be improved in both the short term and longer term. Suggestions for improvements to existing alternative approaches for food toxicity testing are made.
The Human Leukemic HL-60 Cell Line: An in Vitro Model for Cell Death Endpoint Identification
Authors: Zanetti Cristiana , Stammati Arrnalaura , Sapora Orazio , Zucco Flavia
Published: August 2020

The aim of this study was to investigate the endpoints related to cell death, either necrosis or apoptosis, induced by four chemicals in the promyelocytic leukemia cell line, HL-60. Cell morphology, DNA fragmentation, cytofluorimetric analysis and oxygen consumption were used to classify the type of cell death observed. In our analysis, we found that not all the selected parameters reproduced the differences observed in the cell death caused by the four chemicals tested. As cell death is a very complex phenomenon, several factors should be taken into account (cell type, exposure time and chemical concentration), if chemicals are to be classified according to differences in the mechanisms more directly involved in cell death.
Effects of Benomyl on Cytochrome P450 Monooxygenase Systems in the Hep G2 Cell Line
Authors: Radice Sonia , Marabini Laura , Cipelletti Barbara , Chiesara Enzo
Published: August 2020

Changes in the cytochrome P450 monooxygenase system were investigated in Hep G2 cells treated for 24 hours with various concentrations of benomyl. Decreases in both benzo[a]pyrene hydroxylase (AHH) and ethoxyresorufin deethylase (EROD), markers of the P4501A1 isoenzyme, were noted. Ethoxycoumarin deethylase (ECOD), a marker of the P4502B1 isoenzyme, showed a dose-dependent increase. Characterisation by SDS-polyacryl-amide gel electrophoresis of Hep G2 cell microsomal proteins revealed a decrease in the polypeptide bands at 55.5kD (P4501A1) and 48kD (P4501A1 and P4502B1) and an increase in the polypeptide band at 52kD (P4502B1). Benomyl induced a decrease in cytochrome P4501A1 and an increase in cytochrome P4502B1 in Hep G2 cells, as indicated by variations in AHH, EROD and ECOD activity, and by characterisation of microsomal proteins by SDS-polyacryl-amide gel electrophoresis.
A Cytogenetic Approach to the Study of Genotoxic Effects of Fungicides: An in Vitro Study in Lymphocyte Cultures with Thiophanate-methyl
Authors: Hrelia Patrizia , Fimognari Carmela , Vigagni Fernanda , Maffei Francesca , Cantelli-Forti Giorgio
Published: August 2020

This study was designed to evaluate the mechanisms of genetic damage by fungicides in cultured human peripheral blood lymphocytes by means of a molecular cytogenetic approach. For example, thiophanate-methyl (30μg/ml-300μg/ml) was shown to significantly induce chromosome aberrations and micronuclei in human lymphocytes cultured in vitro. Fluorescence in situ hybridisation with centromeric DNA probes demonstrated that most micronuclei induced by thiophanate-methyl did not show any centromeric signals, indicating a relatively stronger clastogenic activity. Results obtained with thiophanate-methyl showed that a comprehensive examination of the mechanisms of toxicity at the genetic level provides valuable information, which is of importance in the safety assessment of the fungicide.
Cytotoxic Effects of Paracetamol in Vitro: The Effects of an S9 Fraction
Authors: Ruppová Katarina , Slameñová Darina , Wsølová Ladislave , Gábelová Alena , Vargová Maria
Published: August 2020

The cytotoxic effects of short-term and long-term exposure of HeLa cells to paracetamol (acetaminophen) were assayed by total protein content reduction (microprotein assay) and by [14C]-L-leucine incorporation into macromolecular acid-insoluble cell fraction. The level of total protein content was followed over 72 hours and the level of [14C]-L-leucine incorporation over 24 hours, after paracetamol treatment. Statistical evaluation did not show a significant difference between results obtained by these two methods. In addition, the influence of S9 fraction on [14C]-L-leucine incorporation and the growth activity of paracetamol-treated HeLa cells were assayed. In these experiments, short-term paracetamol treatments (2 hours in phosphate buffered saline), were used. Statistical analysis of the data did not show an increase in paracetamol-induced cytotoxicity in the presence of the S9 fraction; on the contrary, a protective effect of S9 fraction on paracetamol-treated cells was found.
Effects of Surfactant Retreatment in Vitro: A Method to Evaluate Changes in Cell Junctions and in Cell Viability
Authors: Clothier Richard , Sansom Rebekah
Published: August 2020

Madin-Darby canine kidney (MDCK) cells form cell junctions in vitro, which can be damaged and restored following exposure to a mild cytotoxicant. Both tight junctional integrity and cell viability can be measured by using the fluorescein leakage assay and the Alamar Blue™ assay, respectively, without terminating the cell cultures. By combining these two assay endpoints, it is possible to examine the effects of a repeated cocamidopropylbetaine treatment on a confluent layer of MDCK cells. While the tight junctions could be restored after a single treatment with 2.5mg/ml or 10mg/ml cocamidopropylbetaine, after a second insult, recovery was noted for those treated with 2.5mg/ml, but not for those exposed to 10mg/ml. Following the second insult, the cells did not regain the control level of viability.
NHIK 3025 Cell Culture: A New in Vitro Test for Phototoxicity Screening
Authors: Selvaag Edgar , Anholt Helle , Moan Johan , Thune Per
Published: August 2020

In this study, we used NHIK (Norsk Hydro's Institutt for Kreftforskning) 3025 cells, derived from a human carcinoma of the cervix, to screen for phototoxicity. Previously, NHIK 3025 cells have been used in porphyrin research. A number of sulphonamide-derived oral anti-diabetics and diuretics were incubated together with the NHIK cells for one hour and irradiated with broad band UV and UVA radiation. Cell death was observed in the presence of two oral anti-diabetic drugs and ten diurectic drugs, and was dependent on UVA exposure and the concentration of the test substance. This model proved valuable for the detection of known phototoxic substances, and, in addition, phototoxic properties were demonstrated for a number of substances not previously shown to exert these effects. Electron microscopy of the cells, in the presence of the diuretic bemetizide, showed that biomembranes are the main target for phototoxicity, although nuclear damage was also demonstrated. The addition of antioxidants reduced the amount of phototoxic cell death, indicating the participation of reactive oxygen species in the process. These procedures show that this model can be useful both in screening procedures and in mechanistic investigations.
IGNITE: Empowering high ability underachieving students to become focused learners in mainstream classes
Authors: Long Lye Chan , Erwin Adrienne
Published: August 2020

IGNITE, a high school-based programme, was developed for high ability underachievers using the Achievement Orientation Model (AOM), Maker Model, and Bibliotherapy in a mainstream setting. This paper reports on the effects discovered while implementing the programme over the course of 2 years. Year 7 (13 year olds) and Year 9 (15 year olds) students were trained to use the two interventions, incorporating one of these interventions to challenge their learning in the classroom. The programme for each cohort lasted approximately 10 weeks. Identification alone appeared to increase academic self-efficacy for many of these underachievers. Students were empowered by the student agency involved which supports many of the AOM’s assertions, in particular, environmental perceptions and goal valuation. The interventions, Maker Model and Bibliotherapy, should be used concurrently to produce self-directed students and reduce underachievement in high ability students as they appear to target different factors in the Achievement Orientation Model.
Association between tissue hypoxia, perfusion restrictions, and microvascular architecture alterations with lesion-induced impairment of neurovascular coupling
Authors: Stadlbauer Andreas , Kinfe Thomas M , Zimmermann Max , Eyüpoglu Ilker , Brandner Nadja , Buchfelder Michael , Zaiss Moritz , Dörfler Arnd , Brandner Sebastian
Published: August 2020

Functional magnetic resonance imaging (fMRI) has been mainly utilized for the preoperative localization of eloquent cortical areas. However, lesion-induced impairment of neurovascular coupling (NVC) in the lesion border zone may lead to false-negative fMRI results. The purpose of this study was to determine physiological factors impacting the NVC. Twenty patients suffering from brain lesions were preoperatively examined using multimodal neuroimaging including fMRI, magnetoencephalography (MEG) during language or sensorimotor tasks (depending on lesion location), and a novel physiologic MRI approach for the combined quantification of oxygen metabolism, perfusion state, and microvascular architecture. Congruence of brain activity patterns between fMRI and MEG were found in 13 patients. In contrast, we observed missing fMRI activity in perilesional cortex that demonstrated MEG activity in seven patients, which was interpreted as lesion-induced impairment of NVC. In these brain regions with impaired NVC, physiologic MRI revealed significant brain tissue hypoxia, as well as significantly decreased macro- and microvascular perfusion and microvascular architecture. We demonstrated that perilesional hypoxia with reduced vascular perfusion and architecture is associated with lesion-induced impairment of NVC. Our physiologic MRI approach is a clinically applicable method for preoperative risk assessment for the presence of false-negative fMRI results and may prevent severe postoperative functional deficits.
Cardiac arrest and resuscitation activates the hypothalamic-pituitary-adrenal axis and results in severe immunosuppression
Authors: Zhao Qiang , Shen Yuntian , Li Ran , Wu Jiangbo , Lyu Jingjun , Jiang Maorong , Lu Liping , Zhu Minghua , Wang Wei , Wang Zhuoran , Liu Qiang , Hoffmann Ulrike , Karhausen Jörn , Sheng Huaxin , Zhang Weiguo , Yang Wei
Published: August 2020

In patients who are successfully resuscitated after initial cardiac arrest (CA), mortality and morbidity rates are high, due to ischemia/reperfusion injury to the whole body including the nervous and immune systems. How the interactions between these two critical systems contribute to post-CA outcome remains largely unknown. Using a mouse model of CA and cardiopulmonary resuscitation (CA/CPR), we demonstrate that CA/CPR induced neuroinflammation in the brain, in particular, a marked increase in pro-inflammatory cytokines, which subsequently activated the hypothalamic-pituitary-adrenal (HPA) axis. Importantly, this activation was associated with a severe immunosuppression phenotype after CA. The phenotype was characterized by a striking reduction in size of lymphoid organs accompanied by a massive loss of immune cells and reduced immune function of splenic lymphocytes. The mechanistic link between post-CA immunosuppression and the HPA axis was substantiated, as we discovered that glucocorticoid treatment, which mimics effects of the activated HPA axis, exacerbated post-CA immunosuppression, while RU486 treatment, which suppresses its effects, significantly mitigated lymphopenia and lymphoid organ atrophy and improved CA outcome. Taken together, targeting the HPA axis could be a viable immunomodulatory therapeutic to preserve immune homeostasis after CA/CPR and thus improve prognosis of post-resuscitation CA patients.
Malay Muslim Religious Ideology: Representations of Gendered Beauty Ideals in Women’s Magazines
Authors: French Juliana , Lee Christina Kwai Choi , Brace-Govan Jan
Published: August 2020

Responding to Drenten and McManus (2016) call on the lack of scholarship on the intersections of macromarketing and religion, this article uses magazines to demonstrate how beauty discourses reinforce or contest religious ideology in Malaysia. We draw from institutional logics to show how magazine discourses present macrolevel belief systems that can both shape and constrain the micro level behaviour of women. We identify three dialectical tensions of gendered beauty ideals as firstly both something that is embraced and something that is imposed; secondly it is collectively and individually displayed in fashion and thirdly offers contradictory discourses over blending-in versus standing-out in physical appearance. This study supplements the very limited literature on how the media as an institutional and social structure injects religious ideology to gendered representations of beauty ideals.
Association between the interferon-γ +874T/A polymorphism and susceptibility to hepatitis B virus infection: a meta-analysis
Authors: Li Liang
Published: August 2020

Objective

This study investigated the correlation between the interferon (IFN)-γ +874T/A polymorphism and hepatitis B virus (HBV) susceptibility using meta-analysis.

Methods

PubMed, EMBASE, Web of Science, CNKI, and China Wanfang databases were searched for case–control studies investigating the IFN-γ +874T/A polymorphism and HBV susceptibility from the time of database establishment to April 2020. Stata 15.0 software was used, and the subgroups of ethnicity and Hardy–Weinberg equilibrium were analyzed.

Results

Thirteen articles were included in this study. Significant differences were seen in the allelic model, dominant model, homozygous model, and heterozygous model, but heterogeneity was high. Analysis of the East Asian population revealed combined odds ratios of the allelic model (T vs. A), dominant model (TT + TA vs. AA), homozygous model (TT vs. AA), and heterozygous model (TA vs. AA) of 0.61, 0.56, 0.50, and 0.59, respectively. The difference was significant and the heterogeneity low. The recessive model showed no significance in the overall comparison, or in East Asian and Caucasian populations.

Conclusions

The IFN-γ +874T/A polymorphism is associated with the risk of HBV, especially in the East Asian population. Individuals with the T allele and TT and TA genotypes have a reduced risk of HBV infection.
A Pilot Study of An Intervention to Increase Family Member Involvement in Nursing Home Care Plan Meetings
Authors: Oliver Debra Parker , Rolbiecki Abigail J. , Washington Karla , Kruse Robin L. , Popejoy Lori , Smith Jamie B. , Demiris George
Published: August 2020

Background and Objectives:

Many family members struggle to negotiate their aging relative’s care with nursing home staff, potentially leading to depression and other negative outcomes for residents’ families. This pilot study tested an intervention designed to empower residents’ family members to attend and participate in nursing home care plan meetings.

Research Design and Methods:

We conducted a small, randomized, controlled trial of the Families Involved in Nursing home Decision-making (FIND) intervention, which used web conferencing to facilitate family participation in care plan meetings.

Results:

Overall, FIND was feasible and acceptable. Family members who received the FIND intervention were more likely to experience decreased depressive symptoms than those who did not.

Discussion and Implications:

FIND is a promising approach to reduce depression among family members of nursing home residents. Findings support the need for a follow-up clinical trial.
Development of the School Mental Health Self-Efficacy Teacher Survey Using Rasch Analysis
Authors: Brann Kristy L. , Boone William J. , Splett Joni W. , Clemons Courtney , Bidwell Sarah L.
Published: August 2020

Given the important role that teachers play in supporting student mental health, it is critical teachers feel confident in their ability to fill such roles. To inform strategies intended to improve teacher confidence in supporting student mental health, a psychometrically sound tool assessing teacher school mental health self-efficacy is needed. The current article details the initial development and psychometric functioning of the school mental health self-efficacy teacher survey (SMH-SETS). A component of the development included Rasch analysis of pilot data to provide a psychometric appraisal of the SMH-SETS functioning and initial psychometric evidence. Results suggest the SMH-SETS exhibits strong psychometric properties and can be used to measure school mental health self-efficacy, track self-efficacy over time, and inform training and professional development.
Safe use of chemicals and risk communication among dentists and dental students in Greece
Authors: Koulaouzidou Elisabeth A , Tsitsimpikou Christina , Nikolaidis Alexandros K , Karanasiou Christina , Foufa Eleni , Tsarouhas Konstantinos
Published: August 2020

Use of chemicals, most often classified for intrinsic hazards, is rather common among dentists. To date, no data have been recorded in the European Union (EU) on dentists’ awareness regarding the safe use of chemicals. In the EU regulatory framework, two Regulations with wide applications, namely Regulations (EC) 1907/2006 (REACH) and 1272/2008 (CLP), have been introduced to protect human health and the environment and clearly communicate hazards posed by chemicals to workers and consumers. The aim of this study was to assess the extent of comprehension of hazard communication of chemicals among Greek dentists. For this, a closed-ended, anonymous and validated questionnaire was initially distributed to a total of 300 Greek dentists, both professionals and university students, over a period of 4 months. The collected data from 240 final responders were subjected to statistical analysis (frequencies, percentages, chi-square (χ2) and significance ( p < 0.05)). The vast majority (90%) of the interviewed dentists are not aware of the CLP. Main sources of information regarding chemical hazard and safe use was the supplier through direct communication (90%), while some dentists also consulted the product labels (39%) and the material safety data sheets (54%). Regarding hazard communication, the perceived information from the pictograms is confusing to the vast majority of the dentists (86%), especially for systemic hazards (carcinogenicity and/or reproductive toxicity). In addition, 88% of the professional dentists have not noticed any changes in the labelling of chemical products, which also shows the low input of labels to hazard communication. On the other hand, 90% of the responders always utilize personal protective equipment (PPE), although it is not clear whether this PPE is adequate. In conclusion, rising awareness campaigns are needed, in collaboration with universities and dental care professional associations, to inform dentists about the safe use of chemicals not only to ensure protection of their own health but also to contribute to environmental sustainability.
Association between genotoxic properties of inhalation anesthetics and oxidative stress biomarkers
Authors: Neghab Masoud , Kargar-Shouroki Fatemeh , Mozdarani Hossein , Yousefinejad Saeed , Alipour Hamzeh , Fardid Reza
Published: August 2020

Exposure to inhalation anesthetics (IAs) has been associated with DNA damage as reflected in the increased frequency of micronuclei (MN) and chromosomal aberrations (CAs). The present study was undertaken to ascertain whether there was any correlation between increased MN and CA and the extent of oxidative stress as well as the antioxidant status of a group of operating room personnel exposed to a mixture of IAs, including nitrous oxide, isoflurane, and sevoflurane. In this cross-sectional study, 60 operating room personnel (exposed group) in whom the frequencies of MN and CA had already been shown to be significantly higher than those of a referent group, as well as 60 unexposed nurses, were studied. Venous blood samples were taken from all participants, and malondialdehyde (MDA) levels as an index of oxidative stress (OS) and the activity of superoxide dismutase (SOD) and levels of total antioxidant capacity (TAC) as indices of antioxidant status were measured. The level of TAC (1.76 ± 0.59 mM vs. 2.13 ± 0.64 mM, p = 0.001) and the activity of SOD (11.22 ± 5.11 U/ml vs. 13.36 ± 4.12 U/ml, p = 0.01) were significantly lower, while the mean value of MDA was significantly higher (2.46 ± 0.66 µM vs. 2.19 ± 0.68 µM, p = 0.03) in the exposed group than in the nonexposed group. After adjusting for potential confounders, there were statistically significant associations between exposure to IAs, gender, SOD, and TAC with MN frequency and between exposure to IAs and SOD with numbers of CA. The findings of the present study indicated that exposure to IAs was associated with OS, and this, in turn, may be causally linked with DNA damage.
Surface characteristics of titanium dental implants with improved microdesigns: An in vivo study of their osseointegration performance in goat mandible
Authors: Mistry Surajit , Burman Subhasish , Roy Subhasis , Maitra Nilendu Jyoti , Roy Rajiv , Chanda Abhijit
Published: August 2020

Current trends in endosseous implant research are focused on the modification of microdesign of implants to achieve early and strong osseointegration. This study compares the influence of zinc doped hydroxyapatite (ZnHAp) coated, hydrothermally treated (HT) and machined Ti6Al4V (control) implants on osseointegration. The surface characterisation and microbial affinity test for implants were performed. Twenty seven (27) cylinders (3 types in each animal) were placed in the mandible of 9 black Bengal goats. Bone-implant interface was examined with histological, radiological parameters and scanning electron microscopy at 6, 12, and 24 weeks post-implantation. Surface roughness alterations of bone-separated implants were analysed by non-contact profilometer with time. The ZnHAp coated implants revealed direct and early bone-implant contact but high bacterial adherence and coating cracks. Low bacterial affinity and early strong bony integration was observed with HT implants. Poor bacterial affinity and delayed but strong fixation was evident with control implants. Based on the results of laboratory and animal experiments, we conclude that the hydrothermal modification of titanium implant is the more suitable way to achieve safe and effective osseointegration than the other two implant types for endosseous application.
Dual-mass electromagnetic energy harvesting from galloping oscillations and base excitation
Authors: Karličić Danilo , Cajić Milan , Adhikari Sondipon
Published: August 2020

This paper investigates electromagnetic energy harvesting based on vibration energy extraction from the vibration of a bluff body elastically connected with an additional nonlinear oscillator and subjected to fluid flow and base excitation. The mechanical part is modeled as a system of two coupled oscillators where a combination of harmonic base excitation and fluid forces leads to a steady-state regime. The electromagnetic generator as part of the harvesting device is represented by the equivalent electrical circuit with power dissipated at an electrical load resistance. The mathematical model is based on a set of two coupled nonlinear ordinary differential equations considering the transverse displacement of a bluff body, additional nonlinear oscillator, and currents induced in the electromagnetic generator. By introducing the incremental harmonic balance and continuation methods nonlinear periodic responses are investigated and complex dynamic behavior presented through corresponding response diagrams. The results indicate that for some values of system parameters multiple periodic solutions appear in the form of loops and hysteresis. Finally, the average power of proposed energy harvester is given in time history diagrams for different values of nonlinear stiffness parameter and velocity of fluid flow.