bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Dissatisfaction With Care and Diabetes Self-Care Behaviors, Glycemic Management, and Quality of Life of Adults With Type 2 Diabetes Mellitus
Authors: Dalal Jugal , Williams Joni S. , Walker Rebekah J. , Campbell Jennifer A. , Davis Kimberly S. , Egede Leonard E.
Published: August 2020

Purpose

The purpose of the study was to examine the associations between patient dissatisfaction and diabetes outcomes among patients with type 2 diabetes.

Methods

Primary data from 615 adults with type 2 diabetes from 2 adult primary care clinics completed validated questionnaires. Patient dissatisfaction was measured by asking participants to what degree over the past 12 months were they very dissatisfied with the care they received from their primary care provider. Diabetes outcomes included self-care behaviors, quality of life, and A1C. A1C was abstracted from the medical record. Multiple linear regression models were used to assess associations between patient dissatisfaction, self-care, blood glucose, and quality of life.

Results

After adjusting for covariates, this study demonstrated that higher patient dissatisfaction was significantly associated with poor general diet, worse blood glucose levels, and lower mental component score for quality of life.

Conclusions

In patients with type 2 diabetes, patient dissatisfaction had a significant association with higher blood glucose levels, poor general diet, and low quality of life. Demographic factors driving patient dissatisfaction included young age, low income, and low health literacy. Future studies should investigate how to address patient satisfaction in an effort to improve health outcomes.
The Reference Guide to Integrate Smart Insulin Pens Into Data-Driven Diabetes Care and Education Services
Authors: Warshaw Hope , Isaacs Diana , MacLeod Janice
Published: August 2020

Purpose

More than 7 million Americans who have diabetes use insulin therapy. The majority continue to use syringes and vials or traditional insulin pens to deliver their insulin doses. Using these tools to deliver insulin presents numerous challenges for both the person with diabetes and their clinicians. This article provides an in-depth introduction to a new category of insulin delivery devices and integrated management systems, referred to as smart insulin pens. The article includes information about how these integrated insulin delivery systems can reduce many of the challenges of rapid-acting insulin dosing via injection by enabling easier and more accurate dose recording, dose calculations, and sharing of diabetes management data with clinicians. This article also discusses new roles for diabetes care and education specialists in diabetes data-driven care and practice and addresses how smart insulin pens represent one of many newer digital diabetes management tools that can assist people with diabetes and their clinicians to optimally achieve and deliver quality, data-driven diabetes care.

Conclusions

Newer and simplified insulin delivery devices with their integrated management systems, such as smart insulin pens, have the potential to minimize the challenges and complexities associated with insulin injection therapy while also providing people with diabetes and their clinicians more complete and integrated data in easily transmitted reports that support more efficient data analysis.
A Framework for Optimizing Technology-Enabled Diabetes and Cardiometabolic Care and Education: The Role of the Diabetes Care and Education Specialist
Authors: Greenwood Deborah A. , Howell Fran , Scher LaurieAnn , Yousef Gretchen , Rinker Joanne , Yehl Kirsten , Isaacs Diana , Peeples Malinda M.
Published: August 2020

Purpose

The purpose of this article is to present a framework for optimizing technology-enabled diabetes and cardiometabolic care and education using a standardized approach. This approach leverages the expertise of the diabetes care and education specialist, the multiplicity of technologies, and integration with the care team. Technology can offer increased opportunity to improve health outcomes while also offering conveniences for people with diabetes and cardiometabolic conditions. The adoption and acceptance of technology is crucial to recognize the full potential for improving care. Understanding and incorporating the perceptions and behaviors associated with technology use can prevent a fragmented health care experience.

Conclusion

Diabetes care and education specialists (DCES) have a history of utilizing technology and data to deliver care and education when managing chronic conditions. With this unique skill set, DCES are strategically positioned to provide leadership to develop and deliver technology-enabled diabetes and cardiometabolic health services in the rapidly changing healthcare environment.
Political Capital and MNE Responses to Institutional Voids: The case of Chinese state-owned enterprises in Africa
Authors: Wang Dan , Cui Lin , Vu Thin , Feng Taiwen
Published: August 2020

This study explores how multinational enterprises (MNEs) take advantage of their ownership-based political capital – political ties and political identity – in responding to institutional voids in host country contexts. Investigating multiple cases of central and local Chinese state-owned enterprises in Africa, we identify unique responding strategies comprising allied fleet and co-dependent alliance formations to overcome human capital voids, and dual management and closed-door management strategies to address industry standard voids. We propose a typology which extends the theory of MNE responses to institutional voids not only by adding the political dimension to strategy formation in responding to institutional voids, but also by providing greater insights into MNE strategies to convert home-based political capital for better response to host country institutional voids.
Mitigation of Aerosols Generated During Rhinologic Surgery: A Pandemic‐Era Cadaveric Simulation
Authors: Sharma Dhruv , Ye Michael J. , Campiti Vincent J. , Rubel Kolin E. , Higgins Thomas S. , Wu Arthur W. , Shipchandler Taha Z. , Sim Michael W. , Burgin Sarah J. , Illing Elisa A. , Park Jae Hong , Ting Jonathan Y.
Published: August 2020

Objective

After significant restrictions initially due to the COVID‐19 pandemic, otolaryngologists have begun resuming normal clinical practice. However, the risk of SARS‐CoV‐2 transmission to health care workers through aerosolization and airborne transmission during rhinologic surgery remains incompletely characterized. The objective of this study was to quantify the number concentrations of aerosols generated during rhinologic surgery with and without interventions involving 3 passive suction devices.

Study Design

Cadaver simulation.

Setting

Dedicated surgical laboratory.

Subjects and Methods

In a simulation of rhinologic procedures with and without different passive suction interventions, the concentrations of generated aerosols in the particle size range of 0.30 to 10.0 µm were quantified with an optical particle sizer.

Results

Functional endoscopic sinus surgery with and without microdebrider, high‐speed powered drilling, use of an ultrasonic aspirator, and electrocautery all produced statistically significant increases in concentrations of aerosols of various sizes (P <. 05). Powered drilling, ultrasonic aspirator, and electrocautery generated the highest concentration of aerosols, predominantly submicroparticles <1 µm. All interventions with a suction device were effective in reducing aerosols, though the surgical smoke evacuation system was the most effective passive suction method in 2 of the 5 surgical conditions with statistical significance (P <. 05).

Conclusion

Significant aerosol concentrations were produced in the range of 0.30 to 10.0 µm during all rhinologic procedures in this cadaver simulation. Rhinologic surgery with a passive suction device results in significant mitigation of generated aerosols.
The Face of COVID‐19: Facial Pressure Wounds Related to Prone Positioning in Patients Undergoing Ventilation in the Intensive Care Unit
Authors: Jiang Sydney T. , Fang Christina H. , Chen Jen‐Ting , Smith Richard V.
Published: August 2020

In the setting of COVID‐19 (coronavirus disease 2019)–associated moderate and severe acute respiratory distress, persistently hypoxemic patients often require prone positioning for >16 hours. We report facial pressure wounds and ear necrosis as a consequence of prone positioning in patients undergoing ventilation in the intensive care unit in a tertiary medical center in New York City.
A Mixed-Methods Approach for Embedding Cost Analysis Within Fidelity Assessment in School-Based Programs
Authors: Bradshaw Catherine P. , Debnam Katrina J. , Player Daniel , Bowden Brooks , Lindstrom Johnson Sarah
Published: August 2020

This mixed-methods study describes a framework for conducting cost analyses of school-based programs leveraging fidelity data and applying the ingredients method. We illustrate this approach by applying it to Positive Behavioral Interventions and Supports (PBIS), drawing on multiple sources of data from a sample of U.S. 77 schools that were trained in PBIS. We concluded that the average per school cost of PBIS was US$53,216.00 (median = US$36,698), with an average per-pupil cost of US$90.00 (median = US$58.00), which is considerably less than other school-based prevention models. The cost did, however, differ by implementation level, such that high-fidelity implementation tended to cost more than low-fidelity implementation. We provide a case illustration to elucidate some of the cost drivers of PBIS implementation. Specifically, these data highlight the variability in the amount of training and coaching by the specific evidence-based program implemented within the tiered PBIS framework. Through this case illustration, we demonstrate the utility of tracking costs of school-based program within the context of fidelity data collection. The findings also suggest the potential cost savings of PBIS, both when compared with other evidence-based interventions as well as the known costs of negative school outcomes like dropout.
Gastrointestinal complications following cardiac surgery
Authors: Chor Cheryl Yan Ting , Mahmood Saira , Khan Inayat Hussain , Shirke Manasi , Harky Amer
Published: August 2020

Gastrointestinal complications after cardiac surgery may be uncommon but they carry high mortality rates. Incidences range from 0.5% to 5.5%, while mortality rates of such complications vary from 0.3% to 87%. They range from small gastrointestinal bleeds, ileus, and pancreatitis to life-threatening complications such as liver failure and ischemic bowel. Due to the vague and often absence of specific signs and symptoms, diagnosis of a gastrointestinal complication is often late. This article aims to review and summarize the literature concerning gastrointestinal complications after cardiac surgery. We discuss the causes, risk factors, diagnosis, preventative measures, and management of these complications. In general, risk factor identification, preventive measures, early diagnosis, and swift management are the keys to reducing the occurrence of gastrointestinal complications and their associated morbidity and mortality.
Personality Pathology among Adults with History of Childhood Sexual Abuse: Study of the Relevance of DSM-5 Proposed Traits and Psychobiological Features of Temperament and Character
Authors: Hemmati Azad , Newton-Howes Giles , Falahi Shafea , Mostafavi Sattar , Colarusso Calvin A. , Komasi Saeid
Published: August 2020

Background:

The main aim of this study was to determine whether childhood sexual abuse (CSA) is reflected in the pathological traits of the alternative model of personality disorders (AMPD) in section-III of DSM-5 and Cloninger’s temperament and character profiles.

Methods:

The Persian versions of Personality Inventory for DSM-5 (PID-5), Temperament and Character Inventory (TCI-125), and Structured Clinical Inventory for DSM-IV-TR-Axis II-Screening Questionnaire (SCID-II-SQ) were administered to 43 Iranian college students who reported a history of CSA and 390 participants who did not. Bivariate Pearson correlations and general linear model repeated measures (GLMRM) were used to compare results.

Results:

Bivariate correlations indicated that both the PID-5 and TCI-125 were significantly associated with their relevant personality disorders. Profile analysis showed that the pathological trait domains of the PID-5, except for negative affectivity, were significantly greater in those with an experience of CSA. Of the seven dimensions of TCI-125, novelty seeking and persistence were higher in those with an experience of CSA, but reward dependence, self-directedness, and cooperativeness were lower.

Conclusions:

These results confirmed a correlation between CSA and personality dysfunction. The pattern of dysfunction was complex and somewhat different from the two facet measures used.
Reasonable Accommodation at the Workplace for Professionals with Severe Mental Illness: A Qualitative Study of Needs
Authors: Rangarajan Subhashini K , Muliyala Krishna Prasad , Jadhav Prabhu , Philip Sharad , Angothu Hareesh , Thirthalli Jagadisha
Published: August 2020

Background:

Professionals with Severe Mental Illness (PwSMI) often face challenges in obtaining and retaining employment. For equal and effective participation, they may require reasonable workplace adjustments. The recently legislated Rights of Persons With Disabilities Act 2016 in India defines such adjustments as reasonable accommodations.

Methods:

In-depth qualitative interviews were conducted with 15 consenting PwSMI availing psychiatric rehabilitation services at a tertiary mental health institute in India, five mental health professionals, and five employers. The audio-recorded interviews were transcribed and coded manually by two independent investigators. Inductive content analysis approach was used for qualitative analysis.

Results:

The detected themes included modifications in work schedule, supports to improve work efficiency, modifications in the work environment, modifications in the work-related appraisal, supportive employer policy, and integration of services. The participants described the term “undue burden” to be ambiguous.

Conclusions:

The reported reasonable accommodations are non-structural and mainly dependent on human assistance. Vocational rehabilitation and job reintegration efforts can focus on guided negotiations between employers and PwSMI. This is dependent on at least some degree of disclosure. Awareness regarding reasonable accommodation and stigma reduction is necessary for successful implementation.
Employee Competencies as Predictors of Organizational Performance: A Study of Public and Private Sector Banks
Authors: Salman Mohammad , Ganie Showkat Ahmad , Saleem Imran
Published: August 2020

Drawing on the resource-based view, this paper seeks to examine the influence of employee competencies on organizational performance using a sample of 325 managerial and non-managerial employees working in Indian public and private sector banks. The study employed a cross-sectional research design, and the data were collected through a structured questionnaire using convenience sampling. Confirmatory factor analysis was used to check the reliability and validity of the dimensions, and the proposed hypotheses were tested by using structural equation modelling. The results indicated a positive and significant impact of selected employee competencies on organizational performance except for self-competence, which showed an insignificant and negative effect. The study is of immense potential to help policy and decision-makers of the Indian banking industry to develop and implement strategies for improving employee competencies, which, in turn, are instrumental in enhancing organizational performance. This study is a unique attempt to examine the impact of various employee competence dimensions on organizational performance, particularly in the Indian banking industry.
Development and Validation of an Empirical Model-based Instrument to Measure Empathy-driven Organizational Cultures in Indian Schools
Authors: Roy Debarshi
Published: August 2020

It has been widely acknowledged that empathy plays an important role in school education, but empathy as a part of school organizational culture has not been extensively studied in the Indian context. This study explores empathy as the driver for school organizational culture and strives to create a platform for school organizational designs with empathy as the core construct. The study was conducted with two main objectives: (a) to establish and validate a model of empathy-driven school organizational culture and (b) to develop a valid and reliable instrument to measure organizational empathy in Indian schools. A random sample of 441 students participated in the study. The empathy-driven model was validated through exploratory and confirmatory factor analysis. A part of the questionnaire used for the first part of the study was used for the second part as an independent instrument and validated through confirmatory factor analysis. The instrument was further validated for convergent, discriminant and concurrent validity. Thus, a model for empathy-driven school organizations was validated and a reliable and valid instrument for measuring empathy-driven cultures in schools was developed.
Eating behavior: The influence of age, nutrition knowledge, and Mediterranean diet
Authors: Ferreira-Pêgo Cíntia , Rodrigues Joana , Costa Adriana , Sousa Bruno
Published: August 2020

Background:

Student life during the university period is characterized by many changes in eating behaviors and dietary patterns due to adaptation to a new environment, study stress, lack of proper time management, and busy class schedules. These unhealthy actions may be detrimental to cognitive processing and influence academic performance, which is related to professional success.

Aim:

To assess different eating patterns in Portuguese university students and relate them to several sociodemographic variables.

Methods:

Cross-sectional information about eating behavior was assessed using the Dutch Eating Behavior Questionnaire in 169 students between 18 and 50 years of age, from the Universidade Lusófona de Humanidades e Tecnologias and from different academic courses, some related to health sciences. Mediterranean diet adherence was also assessed using a validated 14-item questionnaire.

Results:

According to the analyses of the 169 participants included in the sample, 33 presented restrained eating behavior, with 73 presenting external and 63 emotional. In the same line of thought, 62.10% of nutrition sciences students presented emotional eating behavior and overall it was observed that these students were more likely to have emotional eating behavior. Otherwise, presenting restrained eating behavior was statistically associated with being older and having higher Mediterranean diet adherence.

Conclusions:

Studying nutrition sciences was associated with having emotional eating behavior. Older students and those who adhere more closely to the Mediterranean diet were associated with having restrained eating behavior.
Some Reasons Why Preclinical Studies of Psychiatric Disorders Fail to Translate: What Can Be Rescued from the Misunderstanding and Misuse of Animal ‘Models’?
Authors: Stanford S. Clare
Published: August 2020

The repeated failure of animal models to yield findings that translate into humans is a serious threat to the credibility of preclinical biomedical research. The use of animals in research that lacks translational validity is unacceptable in any ethical environment, and so this problem needs urgent attention. To reproduce any human illness in animals is a serious challenge, but this is especially the case for psychiatric disorders. Yet, many authors do not hesitate to describe their findings as a ‘model’ of such a disorder. More cautious scientists describe the behavioural phenotype as ‘disorder-like’, without specifying the way(s) in which the abnormal behaviour could be regarded as being analogous to any of the diagnostic features of the disorder in question. By way of discussing these problems, this article focuses on common, but flawed, assumptions that pervade preclinical research of depression and antidepressants. Particular attention is given to the difference between putative ‘models’ of this illness and predictive screens for candidate drug treatments, which is evidently widely misunderstood. However, the problems highlighted in this article are generic and afflict research of all psychiatric disorders. This dire situation will be resolved only when funders and journal editors take action to ensure that researchers interpret their findings in a less ambitious, but more realistic, evidence-based way that would parallel changes in research of the cause(s), diagnosis and treatment of psychiatric problems in humans.
Repeated Exposure of Glial Cells in Primary Cultures to Amitriptyline and Diazepam
Authors: Grundt Inger K. , Rise Marvelyn
Published: August 2020

Mixed glial cells in primary cultures were exposed to amitriptyline (AT) and diazepam (Dia). Morphological observations during 17–18 days of exposure, revealed that 10μM and 100μM were critical concentrations for AT and Dia, respectively. Exposure to concentrations above the critical concentrations led to culture death. Concentrations below 10μM AT and 100μM Dia stimulated the proliferation of glial cells. The microglia cells were stimulated to proliferate and individual cells to hypertrophy. On the other hand, in Dia-treated cultures, the development of microglia cells did not differ from that in control cultures. Both drugs stimulated the development of oligodendroglia cells (OG). With decreasing concentrations of the drugs, the number of OG increased and the enzymes 2'3’-cyclic nucleotide 3’-phosphodiesterase (CNP) and acid phosphatase (AcP), were elevated in inverse proportion to the concentration of drugs.
Anomalous dose-response relationship due to association colloidal behaviour of soluble amphiphilic compounds
Authors: Isomaa Boris , Hägerstrand Henry , Toivola Diana
Published: August 2020

Water-soluble amphiphiles may, above a certain concentration, form colloidal aggregates (micelles or liquid crystals). If such aggregates are formed, there may be a competition between the micelles or the liquid crystals and the biological target for the monomelic form of the amphiphile. This may reduce the number of monomers available for the biological target, which in turn may be reflected in concentration-dependent processes. Therefore, caution should be taken when examining dose-response with soluble amphiphiles forming micelles at low concentrations.
The Use of Primary Cultured Rat Hepatocytes for the Assessment of Xenobiotic Effects on Biotransformation
Authors: Schepers Gabi , Aschmann Christiane , Mörchel Sabine
Published: August 2020

An in vitro test protocol is reported, which, using primary cultured rat hepatocytes, allows for the screening of xenobiotic effects on biotransformation as well as on basal cellular functions. O-Deethylation of 7-ethoxycoumarin (7-EC) and subsequent conjugation of the metabolite 7-hydroxycoumarin (7-HC) with sulphate or glucuronic acid are determined, as representative parameters for the hepatic biotransformation. Cell viability is examined by measuring cellular ATP content and leakage of lactate dehydrogenase. With respect to immediate and delayed effects on biotransformation reactions, the standard test protocol includes exposure to xenobiotics for 1, 24 and 48 hours. Different response patterns could be demonstrated for the solvents dimethylformamide (DMF) and dimethylsulphoxide (DMSO), and the chlorinated phenols, pentachlorophenol (PCP) and hexachlorophene (HCP), which are known to uncouple mitochondrial respiration. Short-term incubation with the solvents resulted in decreased 7-EC- O-deethylation without signs of cytotoxicity. PCP and HCP inhibited 7-EC- O-deethylation and 7-HC-conjugation, affecting sulphate and glucuronide formation differently. 24-hour exposures to PCP and HCP resulted in decreased 7-ethoxycoumarin- O-deethylase activity, which correlated with diminished cell viability, while DMSO and DMF enhanced 7-EC- O-deethylation at sub-cytotoxic concentrations. After exposure for 48 hours to the solvents, enzyme induction was even more pronounced.
Testing of Polymer Materials: What Methods Should be Used?
Authors: Kjellstrand Per , Boberg Ulf
Published: August 2020

Tests, performed over a ten-year period, on 653 polymers intended for use in extracorporeal renal replacement therapy, were evaluated. The test battery used included animal tests, in vitro tests and chemical tests. Some tests were found to have a very low sensitivity. Thus, acute systemic toxicity testing in mice with sodium chloride, ethanol or paraffin oil as extractants was performed on a total of 806 occasions. Only two of these resulted in a “fail” decision. The final outcome of the tests for the majority of materials could be predicted by the results of the UV absorption, chloride, inhibition of cell growth, and tin tests. Of the materials that passed these four tests, less than 2% were not approved on the basis of the whole test battery. The experiments show that only a limited number of tests have to be performed when testing polymers intended for use in extracorporeal renal replacement therapy.
On Establishing the Safety of Cosmetic Ingredients and Products Produced and/or Marketed within the European Economic Community
Authors: Balls Michael
Published: August 2020

In order to provide for greater assurance of the safety of cosmetic ingredients and products manufactured and/or marketed within the European Economic Community (EEC), without a significant increase in the need for animal testing, it is proposed that a Cosmetic Safety Review Committee (CSRC) be appointed to replace the Scientific Committee on Cosmetology (SCO, which currently advises the Commission of the European Communities (CEC). It is further proposed that a list of ingredients already in use be established, and that these ingredients then be ranked in order of need for safety review, on the basis of scale of use (tonnage), frequency of use (formulations), biological activity, etc. Proposals are also made for product safety assessment, and for the presentation of ingredient and product safety reviews to the CEC and the Member States of the EEC, via the CSRC.
Effects of High Pressure and Metal Salts on Cell Growth
Authors: Jenssen Jon , Syversen Tore
Published: August 2020

The effects of chromate, vanadate, nickel, manganese, copper and barium, both separately and in combination with high pressure helium gas, have been studied in an epithelial-like cell line — Chinese hamster ovary (CHO) cells, using inhibition of cell growth as the cytotoxic endpoint.

High pressure (175 bar) by itself reduced the net growth of CHO cells to 71.7 ± 5.5% (mean ± SD) of normobaric control growth. The combined effects of high pressure and metal salts were additive for the lowest concentrations of chromate, copper, manganese and barium, more than additive for the lowest concentration of nickel, and less than additive for vanadate and the highest concentrations of chromate, copper, manganese and barium.

A ranking of the normobaric growth inhibition of the metal salts, estimated as the concentration giving 50% inhibition, was Cr>V>Mn>Ni>Cu>Ba. The growth inhibition of barium was less than 50% at a concentration of ImM BaCl2. The combined exposure to high pressure and the metal salt did not change the toxicity ranking.
Metabolic Studies in Human Subjects
Authors: Frayn Keith N.
Published: August 2020

Details of the major pathways of metabolism have been elucidated, in large measure through work on experimental animals. It is unlikely that they differ qualitatively between mammalian species. The more important challenge facing researchers today is that of metabolic regulation, and of the integrated control of metabolic pathways in the whole organism. These aspects may well differ quantitatively or even qualitatively between species. In this review, methods for studying metabolism and metabolic regulation in humans are described. There are both scientific and practical advantages to performing studies of metabolic regulation in humans. The scientific advantages are clear from some fundamental differences in metabolic regulation between rats and humans, such as the importance of de novo lipogenesis to the deposition of body fat, and the metabolism of atherogenic triacylglycerol-rich lipoproteins. The practical advantages result mainly from the size of a human compared with that of most laboratory animals, enabling large blood samples to be obtained, and several measurement techniques to be applied at one time. Reasons for the persistence of animal experimentation as the norm, rather than the exception, among life science researchers are discussed.
The Use of an Opacitometer to Compare the In Vitro Cornea Opacifying Effects of Timolol With and Without Benzalkonium Chloride
Authors: Igarashi Haruyoshi , Katsuta Yasunaga , Nakazato Yoshiharu , Kawasaki Tohru
Published: August 2020

We have evaluated a new in vitro opacitometer method as an alternative to the in vivo Draize test for ocular irritancy. Several concentrations of timolol maleate (timolol) with or without 0.005% benzalkonium chloride were applied to porcine isolated corneas which were either intact or with the epithelium, endothelium, or both epithelium and endothelium removed. Corneal opacities were measured using an opacitometer. In general, timolol with benzalkonium chloride caused a greater degree of opacity to develop in the cornea than did timolol alone. At the lower concentrations of timolol, the increased opacity probably represented additive effects of the two compounds. However, at the highest concentration of timolol (5 x 10 2M), there was an enhanced opacification in the presence of benzalkonium chloride, which may have been due to an increase in penetration, particularly through the epithelium. Timolol caused a greater degree of opacity to develop in the isolated intact porcine corneas when the drug was applied to the endothelial surface, than when applied to the epithelial surface or to both the epithelial and endothelial surfaces. However, timolol with benzalkonium chloride caused a greater degree of opacity in the intact cornea, when the drug was applied to both surfaces than when it was applied only to the epithelial or the endothelial surface.
Preselection of Potential Cancerostatics by Automatic Analysis of Suspended and Adherent Cells Incubated in Microplates
Authors: Gutsche Walter , Stelzner Axel
Published: August 2020

Alternative toxicological screening programmes, without the use of animal experiments, are intended to eliminate dangerous substances and to find new pharmacologically active agents in cell cultures. They can also provide information on the cytostatic activities of the agents. Intercalating cytostatics which bind DNA were selected by measuring the statistical distributions of the cell diameters of K-562 and L-929 cells by using an electronic cell analyser (CASY1). These compounds were identified by cell enlargement or from flat concentration-activity curves created with the cell analyser system. Incubation for 72 hours with DNA-binding agents, such as doxorubicin, daunorubicin and Mitoxantron®, resulted in enlargement of cell diameter and cell volume. The antineoplastic agents actinomycin D and ambazone had no comparable effect. Comparisons of the different parameters obtained with CASY1 measurement were performed with Microsoft EXCEL.
Toxicity of 20 Chemicals from the MEIC Programme Determined by Growth Inhibition of L-929 Fibroblast-like Cells
Authors: Järkelid Lena , Kjellstrand Per , Martinson Evi , Wieslander Anders
Published: August 2020

The Multicentre Evaluation of In vitro Cytotoxicity (MEIC) programme is an international project aimed at evaluating the relevance of in vitro tests in predicting human toxicity. We have screened 20 chemicals (MEIC codes 31-50) from the programme, by using a cytotoxicity test based on growth inhibition of the mouse fibroblast-like L-929 cell line. Inhibition of cell growth was determined by the neutral red uptake method, which is well established and is used for screening the cytotoxicity of chemicals and plastics for pharmaceuticals and medical devices. The concentrations causing 50% inhibition of cell growth after a 72-hour exposure period varied from 3.1μM for hexachlorophene, to 1.4mM for caffeine. This is within the same range as results recently obtained with five other cell models. However, with some chemicals (chloroform, carbon tetrachloride and dichloromethane), no reliable results were obtained. These substances could not be dissolved in a reproducible way in any of the solvents used and, furthermore, they were highly volatile, which led to difficulties in maintaining the concentrations.
Clive Hollands OBE (1929–1996): The Compassionate Bugler
Authors: Ward Les
Published: August 2020

Clive Hollands, former Director of the Scottish Society for the Prevention of Vivisection, Secretary of the Committee for the Reform of Animal Experimentation, former member of the Animal Procedures Committee, and member of the Farm Animal Welfare Council, died in November 1996 at the age of 67. His many contributions to human and animal welfare are reviewed by some of his many friends and colleagues.
Detoxification Strategies of Two Types of Spiders Revealed by Cypermethrin Application
Authors: Nielsen Søren Achim , Clausen Jørgen , Toft Søren
Published: August 2020

In order to compare the detoxification capacities of two species of spiders, Linyphia triangularis and Pardosa prativaga were exposed to a commonly used pesticide, cypermethrin (a chlorinated pyrethroid). Two detoxification enzyme systems — glutathione S-transferase (GST) and glutathione peroxidase (GSH-Px) — were assayed as biomarkers. The two species of spiders have different life-styles and eat different food, and in our experiment were at different stages of their life-cycle. Therefore, differences in detoxification strategies could be expected. From our results, we suggest two different strategies. L. triangularis had a generally high basal level of GST, which could be further induced by exposure to cypermethrin. The basal activity of GSH-Px was relatively low, and no response to toxic exposure could be traced. Thus, this enzyme plays only a minor role in the detoxification process of cypermethrin in L. triangularis. In P. prativaga, a low basal GST activity was found. However, the basal level of GSH-Px was comparable to that of L. triangularis. A significant rise in GSH-Px activity (with t-butyl-hydroxyperoxide as substrate) was apparent 12 hours after exposure. This may indicate that P450 enzyme systems are involved in the cypermethrin metabolising process in P. prativaga. In addition, GSH-Px activity (with H2O2 as substrate) could be traced in P. prativaga but not in L. triangularis, indicating that a true peroxidase system is active in P. prativaga.
Cytotoxicity of Metal Cations used in Dental Cast Alloys
Authors: Schmalz Gottfried , Arenholt-Bindslev Dorthe , Pfüller Silke , Schweikl Helmut
Published: August 2020

The toxicity of dental alloys depends upon the quantity and chemical state of metal elements released from the alloy into the affected tissue. The purpose of the present study was to investigate the effects of various cell lines, various cell numbers, and various serum concentrations on the cytotoxicity of metal cations which are components of dental alloys. Aqueous salt solutions were tested on two continuous cell lines (L-929 mouse fibroblast-like cells and HaK hamster epithelial-like kidney cells) and on primary human gingival fibroblasts. The cell culture medium was routinely supplemented with 5% fetal calf serum. The influence of the serum concentration on the cytotoxic potencies of metal cations was investigated by increasing the concentration to 20% in one series of experiments with L-929 cells. Cell reactions were recorded with the MTT test after exposure for 24 hours. The rank order of the cytotoxicity of cations in L-929 cells (10,000 cells/well, 5% serum) from the most to the least toxic was: Ag+, Zn2+, Cd2+, Hg2+, Au3+, Pt4+, Co2+, Cu2+, Ni2+, Pd2+, Mn2+, Nb5+, Mo5+, Ga3+, Cr3+, In3+, Sn2+. A variation in cell number between 5000 and 10,000 cells/well did not influence the results. Furthermore, no differences were observed in the cytotoxic responses of the two continuous cell lines. Variation in the serum content of L-929 cell culture medium had no significant influence on the cytotoxicity of most metal cations, except for Nb5+, Ni2+, Sn2+. Primary human gingival fibroblasts showed the same rank order of toxicity as the continuous cell lines, but at higher concentrations of the test materials.
Cytotoxic and Genotoxic Effects of Sodium Fluoride on Mammalian Cells at Neutral or Acid pH: A Summary of Published Work
Authors: Slameñová Darina , Gábelová Alena , Ruppová Katarina , Wsólová Ladislave
Published: August 2020

This paper forms a short review of some of our previously published work. We assessed the cytotoxic and genotoxic effects of sodium fluoride (NaF) on the Chinese hamster V79 cell line and the human EUE cell line at neutral and acid pH (as found in the stomach). The effects of NaF on cell proliferation, DNA synthesis, protein synthesis and mutagenesis were assessed. The results found showed no mutagenic effects after exposure to NaF, despite some cytogenic effects, suggesting that NaF probably does not represent any serious mutagenic or carcinogenic threat to humans.
The Prediction of Skin Permeability by Using Physicochemical Data
Authors: Kirchner Lisa A. , Moody Richard P. , Doyle Edward , Bose Ranjan , Jeffery Jamie , Chu Ih
Published: August 2020

A database on physicochemical properties and skin permeation compiled by Health Canada was analysed by using linear regression analysis. The correlation between permeability coefficient (Kp) and the octanol–water partition coefficient (Kow) has been improved by grouping the compounds according to their respective molar volumes. Linear regression analysis of the individual groups has demonstrated a positive correlation for the majority of the groups, with the compounds in the lowest molar volume range (≤ 75Å3) having the best correlation (r2 = 0.86), and the compounds in the highest molar volume range (≥ 30lÅ3) being the least well-correlated (r2 = 0.55). Due to the diversity of the chemicals used in this analysis, and the statistically significant correlations obtained, this model could permit the prediction of skin permeation of a wide variety of chemical compounds. Although of a simplistic nature, and not yet experimentally validated, this quantitative structure-activity relationship may be useful for predicting human skin permeability coefficients for compounds that fall within the constraints of this data set.
A General Measure of In Vitro Phototoxicity Derived from Pairs of Dose-Response Curves and its Use for Predicting the In Vivo Phototoxicity of Chemicals
Authors: Holzhütter Hermann-Georg
Published: August 2020

In pharmacology, it is common to evaluate the influence of external effectors (for example, temperature, pH, and presence of a second drug) on dose-response relations by the potency factor (PF50): [Formula: see text] where ED50 (± effector) denotes the 50% effective dose in the presence and in the absence of the effector, respectively. In this paper, the external effector is ultraviolet (UV) light, and PF50 is referred to as the photoirritancy factor (PIF). There are two parameters which limit the applicability and toxicological reliability of the PIF. Firstly, the physical properties (for example, water solubility) of the chemical tested and the constraints of the biological test system may make it difficult, or even impossible, to achieve sufficiently high doses to observe 50% of the maximal response. In such cases, no numeric value of the potency factor can be computed. Secondly, the potency factor does not take into account the absolute change in response induced by UV light, i.e. depending on the shape of the ±UV dose-response curves, the absolute change in response may be small although the PIF is large, and vice versa. This paper proposes a more general measure of phototoxicity, the mean photo effect (MPE), which can be assessed from pairs of dose-response curves, even if the 50% response level is not reached in one curve or in both. The MPE is a weighted average of PIFd values across different dose levels (d being common to both dose-response curves). The absolute response changes, ΔRd, i.e. the differences between the -UV curve and the +UV curve are used as weighting factors. The numerical computation of the MPE is based on theoretical curves obtained by fitting a mathematical model to the experimental dose-response data. Plotting PIFd and ΔRd versus the corresponding doses permits differences in the shapes of the two curves to be assessed, and possible alterations in the toxic mechanisms induced by UV light to be revealed. The variance of MPE is estimated by a bootstrap procedure. The use of the MPE is illustrated by its application to dose-response data obtained with a human keratinocyte assay of fibroblasts in the EU/COLIPA international validation project on photoirritancy.
Nephrotoxicity Testing In Vitro: The Current Situation
Authors: Morin Jean-Paul , De Broe Marc E. , Pfaller Walter , Schmuck Gabriele
Published: August 2020

An ECVAM task force on nephrotoxicity has been established to advise, in particular, on the follow-up to recommendations made in the ECVAM workshop report on nephrotoxicity testing in vitro. Since this workshop was held, in 1994, there have been several improvements in the techniques used. For example, the duration of renal slice viability, and the maintenance of functional activities in slices, have been improved by using dynamic incubation systems with higher oxygen tensions and more-appropriate cell culture media. Highly differentiated primary cultures of pig, human and rabbit proximal tubule cells have been established by using specific cell isolation procedures and/or selective culture media. To date, the most comparable phenotypic expression and transepithelial transport capacities to proximal tubules in vivo have been obtained with primary cultures of rabbit proximal tubule cells which are grown on bicompartmental supports; in this system, transepithelial substrate gradients are generated and the transepithelial transport of both organic anions and cations is highly active. This in vitro system has been selected by ECVAM for further evaluation and prevalidation. Industrial needs in the area of nephrotoxicity testing have been identified, and recommendations are made at the end of this report concerning possible future initiatives.
In Vitro Cytotoxicity of Textile Dyes and Extracts of Dyed/Finished Fabrics
Authors: Kopponen Päivi , Asikainen Mirkka , Törrönen Riitta , Klemola Kaisa , Liesivuori Jyrki , Kärenlampi Sirpa
Published: August 2020

The aim of this study was to investigate whether an in vitro test can give an indication of the overall toxicity of fabric extracts, and whether this toxicity correlates with the toxicity of the dyes and finishes used. Thirteen textile dyes and dyed/finished cotton fabrics were tested by using the Hepa-1 cytotoxicity test. Black sulphur and two blue reactive dyes were the most toxic, with IC50 (the concentration at which the total protein content was 50% of the protein content of non-exposed cells) values of 40–65μg/ml. The least toxic dyes, the black and yellow mix reactive dyes, had IC50 values of 825μg/ml and 703μg/ml, respectively. There was no correlation between the toxicities of the dyes and the fabric extracts; the extract from naphtholdyed fabric was the most cytotoxic. These results strongly support the hypothesis that the toxicity of a fabric extract cannot be predicted directly from the toxicity of the dye itself. The results also showed that flame-retardant and water/soil-repellent finishes can alter the cytotoxicity. In vitro tests, as exemplified by the Hepa-1 cytotoxicity test, could provide useful information for developing new ecotextiles.
The Bioavailability of Substances Administered to Chick Embryos: The Maximum Effective Route of Administration
Authors: Veselý Drahomír , Veselá Doubravka , Jelínek Richard
Published: August 2020

Toxicokinetic studies are of key importance in both the design and the interpretation of developmental toxicity studies. The aim of this study was to determine concentrations of test substances within the chick embryo following the administration schedule recommended in the chick embryotoxicity screening test (CHEST). The concentration-time relationships were investigated by using four labelled substances with various physicochemical and embryo-toxic properties ([14C] sodium acetate, [14C] palmitic acid, [3H] Cortisol and [3H] cytosine arabinoside). These labelled chemicals were mixed with cold substances and singly administered at two dose levels to chick embryos on days 2, 3 and 4 of incubation. Extrachorial and subgerminal routes were used on day 2, and extrachorial and intra-amniotic applications were chosen on days 3 and 4. The concentration of labelled chemical present within the embryo was assessed at predetermined intervals by scintillation fluorimetry (from 6 minutes to 96 hours after administration), and used for estimating the concentration curves. Regardless of the substance, dose and application route, the concentration curves exhibited a characteristic pattern, reaching their peaks within the first 6 hours, and dropping down to near zero 48–96 hours after administration. The decrease followed the first order law, demonstrating that, within the CHEST system, the avian embryo does not act as a closed system. With regard to the total amount of substance entering the embryo, extrachorial administration appeared to be superior to subgerminal administration on day 2. Intra-amniotic administration was superior to extrachorial administration on days 3 and 4. These differences were most pronounced after administration of lipid-soluble palmitic acid. The concentrations within embryonic tissues were directly dose-dependent. After consideration of all these findings, we concluded that the CHEST system probably has closer similarity to the toxicokinetics of exposure of mammalian embryos (i.e. reaching a peak and then a gradual decline over time) than any other in vitro test of developmental toxicity, where the chemical is simply added to culture media. Several practical recommendations for improving the CHEST system were derived.
Evaluation of a Commercial Kit for Glutathione Estimation in Cellular Systems
Authors: Atmaca Mukadder , Hammond Alison H. , Fry Jeffrey R.
Published: August 2020

The major aim of this study was to identify an appropriate assay to use routinely for cellular glutathione measurement. The Saville assay has been widely used in cytotoxicity studies, while the GSH-400 assay is a commercial kit which only recently became available. Therefore, in this study, the accuracy and sensitivity of the Saville and GSH-400 assays were compared. Results presented herein indicate that the Saville assay gave a lower blank absorbance and higher sensitivity when compared to the GSH-400 assay.