110 results on '"Griffiths JC"'
Search Results
2. Adulteration of Drugs and Foods: Compendial Approaches to Lowering Risk
- Author
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Abernethy, DR, primary, Sheehan, C, additional, Griffiths, JC, additional, and Williams, RL, additional
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- 2008
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3. Hereditary Onycho-Osteodysplasia Associated with Club Foot
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Macpherson Da and Griffiths Jc
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medicine.medical_specialty ,Clubfoot ,business.industry ,Genetics, Medical ,General Medicine ,Hereditary Onycho-Osteodysplasia ,030204 cardiovascular system & hematology ,medicine.disease ,Dermatology ,Radiography ,03 medical and health sciences ,0302 clinical medicine ,Nail-Patella Syndrome ,Humans ,Medicine ,030212 general & internal medicine ,Club ,Child ,business ,Foot (unit) ,Nail patella syndrome - Published
- 1964
4. Problem of Renal Hypertension
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Griffiths Jc and Toomey Wf
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medicine.medical_specialty ,Hypertension, Renal ,Leading Articles ,business.industry ,General Engineering ,Urography ,General Medicine ,Surgery ,Diagnosis, Differential ,medicine ,Humans ,General Earth and Planetary Sciences ,Radiology ,Differential diagnosis ,business ,General Environmental Science ,Pyelogram - Published
- 1965
5. Improved liquid chromatographic assay for serum fluorouracil concentrations in the presence of ftorafur
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Griffiths Jc, Floyd Ra, Byfield Je, and Cecil L. Hornbeck
- Subjects
Chromatography ,Chemistry ,Stability study ,Drug Storage ,Ethyl acetate ,Pharmaceutical Science ,chemistry.chemical_compound ,Drug Stability ,Solubilization ,Fluorouracil ,medicine ,Humans ,Ammonium acetate ,medicine.drug ,Chromatography, Liquid ,Gastrointestinal Neoplasms ,Tegafur - Abstract
An improved liquid chromatographic assay for serum ftorafur and fluorouracil is shown to be routine, sensitive, and reproducible using 200 micro l of serum. Dilute ammonium acetate buffer at pH 10.2 is used for solubilization of the evaporated ethyl acetate extract for injection into the liquid chromatograph. A stability study indicated little or no in vitro formation of fluorouracil from ftorafur under the conditions described. Low serum fluorouracil levels were found after administration of therapeutic doses of ftorafur.
- Published
- 1981
6. The presence of serum creatine kinase 2 (MB) in acromegalic myopathy
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Wolf Pl, Erickson R, and Griffiths Jc
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Male ,medicine.medical_specialty ,Biochemistry ,Isozyme ,Muscle hypertrophy ,Muscular Diseases ,Internal medicine ,Acromegaly ,Medicine ,Humans ,Myopathy ,Creatine Kinase ,biology ,business.industry ,Kinase ,Skeletal muscle ,Middle Aged ,medicine.disease ,Isoenzymes ,Endocrinology ,medicine.anatomical_structure ,biology.protein ,Serum creatine kinase ,Creatine kinase ,medicine.symptom ,business ,Cardiomyopathies - Abstract
Increase in size of bone is characteristic of acromegaly. In addition, hypertrophy of other tissues including skeletal muscle and associated myopathy may occur. We recently found 10 U/1 of isoenzyme creatine kinase 2 (MB) or 10.9% of total creatine kinase in a patient with acromegaly who did not show clinical or laboratory evidence of acute myocardial necrosis. The myopathy associated with acromegaly is thus another cause for the presence of serum CK 2 (MB), and CK 2 (MB) is not a specific isoenzyme for myocardial damage since it may be identified in the serum of patients with skeletal muscle conditions.
- Published
- 1978
7. Reversal of ventricular fibrillation without an electrical defibrillator
- Author
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Griffiths Jc
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medicine.medical_specialty ,Epinephrine ,business.industry ,Electric Countershock ,General Medicine ,030204 cardiovascular system & hematology ,medicine.disease ,Heart Arrest ,03 medical and health sciences ,Procaine ,0302 clinical medicine ,Chlorides ,Internal medicine ,Ventricular fibrillation ,Ventricular Fibrillation ,medicine ,Cardiology ,Humans ,030212 general & internal medicine ,business ,medicine.drug ,Defibrillators - Published
- 1962
8. gamma-Glutamyltransferase values in nonalcoholic drinking men
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Griffiths Jc and Marc A. Schuckit
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Adult ,Male ,medicine.medical_specialty ,Alcohol Drinking ,biology ,business.industry ,gamma-Glutamyltransferase ,Gastroenterology ,Alcoholism ,Kinetics ,Psychiatry and Mental health ,Internal medicine ,medicine ,biology.protein ,Humans ,Gamma-glutamyltransferase ,business ,Alcoholic Intoxication - Published
- 1982
9. Ankle-jerk as a Measure of Thyroid Function
- Author
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Griffiths Jc and Toomey Wf
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Reflex, Stretch ,medicine.medical_specialty ,Leading Articles ,business.industry ,Thyroid ,Thyroid Gland ,General Engineering ,Measure (physics) ,General Medicine ,Bioinformatics ,Ankle jerk reflex ,Physical medicine and rehabilitation ,medicine.anatomical_structure ,medicine ,Humans ,General Earth and Planetary Sciences ,Ankle ,Thyroid function ,business ,General Environmental Science - Published
- 1965
10. Television for the Doctor
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Griffiths Jc and Toomey Wf
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World Wide Web ,Computer science ,General Engineering ,General Earth and Planetary Sciences ,General Medicine ,Data science ,General Environmental Science - Published
- 1965
11. Advancing nutrition science to meet evolving global health needs.
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Neufeld LM, Ho E, Obeid R, Tzoulis C, Green M, Huber LG, Stout M, and Griffiths JC
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- Infant, Child, Humans, Global Health, NAD, Choline, Dietary Supplements, Chronic Disease, Xanthophylls, Neurodegenerative Diseases, Nutritional Sciences
- Abstract
Populations in crisis!A global overview of health challenges and policy efforts within the scope of current nutrition issues, from persistent forms of undernutrition, including micronutrient deficiency, to diet-related chronic diseases. Nutrition science has evolved from a therapeutic and prevention emphasis to include a focus on diets and food systems. Working and consensus definitions are needed, as well as guidance related to healthy diets and the emerging issues that require further research and consensus building. Between nutrient deficiency and chronic disease, nutrition has evolved from focusing exclusively on the extremes of overt nutrient deficiency and chronic disease prevention, to equipping bodies with the ability to cope with physiologic, metabolic, and psychological stress. Just what is 'optimal nutrition', is that a valid public health goal, and what terminology is being provided by the nutrition science community? Nutrition research on 'healthspan', resilience, and intrinsic capacity may provide evidence to support optimal nutrition. Finally, experts provide views on ongoing challenges of achieving consensus or acceptance of the various definitions and interventions for health promotion, and how these can inform government health policies.Nutrition topics that receive particular focus in these proceedings include choline, NAD-replenishment in neurodegenerative diseases, and xanthophyll carotenoids. Choline is a crucial nutrient essential for cellular metabolism, requiring consumption from foods or supplements due to inadequate endogenous synthesis. Maternal choline intake is vital for fetal and infant development to prevent neural tube defects. Neurodegenerative diseases pose a growing health challenge, lacking effective therapies. Nutrition, including NAD-replenishing nutrients, might aid prevention. Emerging research indicates xanthophyll carotenoids enhance vision and cognition, potentially impacting age-related diseases., (© 2023. The Author(s).)
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- 2023
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12. Manipulating mitochondrial dynamics in the NTS prevents diet-induced deficits in brown fat morphology and glucose uptake.
- Author
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Fozzato A, New LE, Griffiths JC, Patel B, Deuchars SA, and Filippi BM
- Subjects
- Rats, Animals, Mitochondrial Dynamics, Positron Emission Tomography Computed Tomography, Obesity, Glucose, Diet, High-Fat adverse effects, Adipose Tissue, Brown, Solitary Nucleus
- Abstract
Aims: Brown adipose tissue (BAT) can produce heat by metabolizing glucose and fatty acids. Activation of BAT is controlled by the central nervous system (CNS) through sympathetic innervation. Dysregulation of signalling molecules in selective CNS areas such as the nucleus of tractus solitarius (NTS) are linked with altered BAT activity, obesity and diabetes. High-fat diet (HFD)-feeding increases mitochondrial fragmentation in the NTS, triggering insulin resistance, hyperphagia and weight gain. Here we sought to determine whether changes in mitochondrial dynamics in the NTS can affect BAT glucose uptake., Main Methods: Rats received DVC stereotactic surgery for local brain administration of viruses that express mutated Drp1 genes. BAT glucose uptake was measured with PET/CT scans. Biochemical assays and immunohistochemistry determined altered levels of key signalling molecules and neural innervation of BAT., Key Findings: We show that short-term HFD-feeding decreases BAT glucose uptake. However, inhibiting mitochondrial fragmentation in NTS-astrocytes of HFD-fed rats partially restores BAT glucose uptake accompanied by lower blood glucose and insulin levels. Tyrosine Hydroxylase (TH) revealed that rats with inhibited mitochondrial fragmentation in NTS astrocytes had higher levels of catecholaminergic innervation in BAT compared to HFD-fed rats, and did not exhibit HFD-dependent infiltration of enlarged white fat droplets in the BAT. In regular chow-fed rats, increasing mitochondrial fragmentation in the NTS-astrocytes reduced BAT glucose uptake, TH immune-positive boutons and β3-adrenergic receptor levels., Significance: Our data suggest that targeting mitochondrial dynamics in the NTS-astrocytes could be a beneficial strategy to increase glucose utilization and protect from developing obesity and diabetes., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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13. Women's health: optimal nutrition throughout the lifecycle.
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Feskens EJM, Bailey R, Bhutta Z, Biesalski HK, Eicher-Miller H, Krämer K, Pan WH, and Griffiths JC
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- Female, Humans, Male, Nutrition Policy, Nutritional Status, Women's Health, Health Promotion, Malnutrition
- Abstract
Sex differences are an important consideration when researching and establishing policies for nutrition and optimal health. For women's health, there are important physiologic, neurologic, and hormonal distinctions throughout the lifecycle that impact nutritional needs. Distinct from those for men, these nutritional needs must be translated into appropriate nutrition policy that aims to not only avoid overt nutritional deficiency, but also to promote health and minimize risk for chronic disease. Through a series of webinars, scientific experts discussed the advances in the understanding of the unique nutritional needs, challenges and opportunities of the various life stages for women across the life course and identified emerging nutritional interventions that may be beneficial for women. Nevertheless, there is concern that existing nutrition policy intended for women's health is falling short with examples of programs that are focused more on delivering calories than achieving optimal nutrition. To be locally effective, targeted nutrition needs to offer different proposals for different cultural, socio-economic, and geographic communities, and needs to be applicable at all stages of growth and development. There must be adequate access to nutritious foods, and the information to understand and implement proven nutritional opportunities. Experts provided recommendations for improvement of current entitlement programs that will address accessibility and other social and environmental issues to support women properly throughout the lifecycle., (© 2022. The Author(s).)
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- 2022
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14. The Botanical Safety Consortium: A public-private partnership to enhance the botanical safety toolkit.
- Author
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Mitchell CA, Dever JT, Gafner S, Griffiths JC, Marsman DS, Rider C, Welch C, and Embry MR
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- Dietary Supplements toxicity, Plant Preparations toxicity, Plants, Medicinal toxicity, Risk Assessment, Biological Products standards, Consumer Product Safety standards, Dietary Supplements standards, Plant Preparations standards, Public-Private Sector Partnerships organization & administration
- Abstract
Botanical dietary supplement use is widespread and growing, therefore, ensuring the safety of botanical products is a public health priority. This commentary describes the mission and objectives of the Botanical Safety Consortium (BSC) - a public-private partnership aimed at enhancing the toolkit for conducting the safety evaluation of botanicals. This partnership is the result of a Memorandum of Understanding between the US FDA, the National Institute of Environmental Health Sciences, and the Health and Environmental Sciences Institute. The BSC serves as a global forum for scientists from government, academia, consumer health groups, industry, and non-profit organizations to work collaboratively on adapting and integrating new approach methodologies (NAMs) into routine botanical safety assessments. The objectives of the BSC are to: 1) engage with a group of global stakeholders to leverage scientific safety approaches; 2) establish appropriate levels of chemical characterization for botanicals as complex mixtures; 3) identify pragmatic, fit-for-purpose NAMs to evaluate botanical safety; 4) evaluate the application of these tools via comparison to the currently available safety information on selected botanicals; 5) and integrate these tools into a framework that can facilitate the evaluation of botanicals. Initially, the BSC is focused on oral exposure from dietary supplements, but this scope could be expanded in future phases of work. This commentary provides an overview of the structure, goals, and strategies of this initiative and insights regarding our first objectives, namely the selection and prioritization of botanicals based on putative toxicological properties., (Copyright © 2021 Elsevier Inc. All rights reserved.)
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- 2022
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15. Science-based policy: targeted nutrition for all ages and the role of bioactives.
- Author
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Kalache A, Bazinet RP, Carlson S, Evans WJ, Kim CH, Lanham-New S, Visioli F, and Griffiths JC
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- Diet, Humans, Longevity, Policy, Life Expectancy, Nutritional Status
- Abstract
Globally, there has been a marked increase in longevity, but it is also apparent that significant inequalities remain, especially the inequality related to insufficient 'health' to enjoy or at least survive those later years. The major causes include lack of access to proper nutrition and healthcare services, and often the basic information to make the personal decisions related to diet and healthcare options and opportunities. Proper nutrition can be the best predictor of a long healthy life expectancy and, conversely, when inadequate and/or improper a prognosticator of a sharply curtailed expectancy. There is a dichotomy in both developed and developing countries as their populations are experiencing the phenomenon of being 'over fed and under nourished', i.e., caloric/energy excess and lack of essential nutrients, leading to health deficiencies, skyrocketing global obesity rates, excess chronic diseases, and premature mortality. There is need for new and/or innovative approaches to promoting health as individuals' age, and for public health programs to be a proactive blessing and not an archaic status quo 'eat your vegetables' mandate. A framework for progress has been proposed and published by the World Health Organization in their Global Strategy and Action Plan on Ageing and Health (WHO (2017) Advancing the right to health: the vital role of law. https://apps.who.int/iris/bitstream/handle/10665/252815/9789241511384-eng.pdf?sequence=1&isAllowed=y . Accessed 07 Jun 2021; WHO (2020a) What is Health Promotion. www.who.int/healthpromotion/fact-sheet/en/ . Accessed 07 Jun 2021; WHO (2020b) NCD mortality and morbidity. www.who.int/gho/ncd/mortality_morbidity/en/ . Accessed 07 Jun 2021). Couple this WHO mandate with current academic research into the processes of ageing, and the ingredients or regimens that have shown benefit and/or promise of such benefits. Now is the time for public health policy to 'not let the perfect be the enemy of the good,' but to progressively make health-promoting nutrition recommendations., (© 2021. The Author(s).)
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- 2021
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16. Inhibition of mitochondrial fission and iNOS in the dorsal vagal complex protects from overeating and weight gain.
- Author
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Patel B, New LE, Griffiths JC, Deuchars J, and Filippi BM
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- Animals, Body Weight physiology, Diet, High-Fat, Dynamins physiology, Feeding Behavior physiology, Glucose metabolism, Hyperphagia metabolism, Hyperphagia prevention & control, Insulin metabolism, Insulin Resistance physiology, Male, Nitric Oxide Synthase Type II metabolism, Obesity metabolism, Obesity prevention & control, Rats, Rats, Sprague-Dawley, Vagus Nerve drug effects, Weight Gain, Dynamins metabolism, Mitochondrial Dynamics physiology, Nitric Oxide Synthase Type II physiology
- Abstract
Objectives: The dorsal vagal complex (DVC) senses insulin and controls glucose homeostasis, feeding behaviour and body weight. Three-days of high-fat diet (HFD) in rats are sufficient to induce insulin resistance in the DVC and impair its ability to regulate feeding behaviour. HFD-feeding is associated with increased dynamin-related protein 1 (Drp1)-dependent mitochondrial fission in the DVC. We investigated the effects that altered Drp1 activity in the DVC has on feeding behaviour. Additionally, we aimed to uncover the molecular events and the neuronal cell populations associated with DVC insulin sensing and resistance., Methods: Eight-week-old male Sprague Dawley rats received DVC stereotactic surgery for brain infusion to facilitate the localised administration of insulin or viruses to express mutated forms of Drp1 or to knockdown inducible nitric oxide synthase (iNOS) in the NTS of the DVC. High-Fat diet feeding was used to cause insulin resistance and obesity., Results: We showed that Drp1 activation in the DVC increases weight gain in rats and Drp1 inhibition in HFD-fed rats reduced food intake, weight gain and adipose tissue. Rats expressing active Drp1 in the DVC had higher levels of iNOS and knockdown of DVC iNOS in HFD-fed rats led to a reduction of food intake, weight gain and adipose tissue. Finally, inhibiting mitochondrial fission in DVC astrocytes was sufficient to protect rats from HFD-dependent insulin resistance, hyperphagia, weight gain and fat deposition., Conclusion: We uncovered new molecular and cellular targets for brain regulation of whole-body metabolism, which could inform new strategies to combat obesity and diabetes., (Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.)
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- 2021
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17. Measuring health promotion: translating science into policy.
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Griffiths JC, De Vries J, McBurney MI, Wopereis S, Serttas S, and Marsman DS
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- Humans, Life Style, Longevity, Policy, Health Promotion, Quality of Life
- Abstract
Commonly, it is the end of life when our health is deteriorating, that many will make drastic lifestyle changes to improve their quality of life. However, it is increasingly recognized that bringing good health-promoting behaviors into practice as early in life as possible has the most significant impact across the maximal healthspan. The WHO has brought clarity to health promotion over the last fifteen years, always centering on language relating to a process of enabling people to increase control over, and to improve, their physical, mental and social health. A good healthspan is not just freedom from morbidity and mortality, it is that joie de vivre ("joy of living") that should accompany every day of our lifespan. Therefore, health promotion includes not only the health sector, but also needs individual commitment to achieve that target of a healthspan aligned with the lifespan. This paper explores health promotion and health literacy, and how to design appropriate nutritional studies to characterize contributors to a positive health outcome, the role the human microbiome plays in promoting health and addressing and alleviating morbidity and diseases, and finally how to characterize phenotypic flexibility and a physiologic resilience that we must maintain as our structural and functional systems are bombarded with the insults and perturbations of life.
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- 2020
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18. From lifespan to healthspan: the role of nutrition in healthy ageing.
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Wickramasinghe K, Mathers JC, Wopereis S, Marsman DS, and Griffiths JC
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- Humans, Nutritional Requirements, Healthy Aging physiology, Longevity, Nutritional Status
- Abstract
Across the globe, there has been a marked increase in longevity, but significant inequalities remain. These are exacerbated by inadequate access to proper nutrition and health care services and to reliable information to make the decisions related to nutrition and health care. Many in economically developing as well as developed societies are plagued with the double-burden of energy excess and undernutrition. This has resulted in mental and physical deterioration, increased non-communicable disease rates, lost productivity, increased medical costs and reduced quality of life. While adequate nutrition is fundamental to good health at all stages of the life course, the impact of diet on prolonging good quality of life during ageing remains unclear. For progress to continue, there is need for new and/or innovative approaches to promoting health as individuals age, as well as qualitative and quantitative biomarkers and other accepted tools that can measure improvements in physiological integrity throughout life. A framework for progress has been proposed by the World Health Organization in their Global Strategy and Action Plan on Ageing and Health. Here, we focused on the impact of nutrition within this framework, which takes a broad, person-centred emphasis on healthy ageing, stressing the need to better understand each individual's intrinsic capacity, their functional abilities at various life stages, and the impact of their mental, and physical health, as well as the environments they inhabit., (© The Author(s) 2020.)
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- 2020
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19. The History of Laboratory Medicine Part 3: 1986-2004; Two Turbulent Decades.
- Author
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Burlington DB, Guazzo E, and Griffiths JC
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- History, 20th Century, History, 21st Century, Medical Laboratory Science history, Periodicals as Topic history
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- 2020
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20. Development of a consensus approach for botanical safety evaluation - A roundtable report.
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Galli CL, Walker NJ, Oberlies NH, Roe AL, Edwards J, Fitzpatrick S, Griffiths JC, Hayes AW, Mahony C, Marsman DS, and O'Keeffe L
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- Animals, Consensus, Consumer Product Safety, Dose-Response Relationship, Drug, Humans, Models, Biological, Patient Safety, Plant Preparations pharmacokinetics, Risk Assessment, Risk Factors, Toxicokinetics, Toxicology standards, Decision Trees, Dietary Supplements adverse effects, Plant Preparations adverse effects, Toxicology methods
- Abstract
Botanical safety science continues to evolve as new tools for risk assessment become available alongside continual desire by consumers for "natural" botanical ingredients in consumer products. Focusing on botanical food/dietary supplements a recent international roundtable meeting brought together scientists to discuss the needs, available tools, and ongoing data gaps in the botanical safety risk assessment process. Participants discussed the key elements of botanical safety evaluations. They provided perspective on the use of a decision tree methodology to conduct a robust risk assessment and concluded with alignment on a series of consensus statements. This discussion highlighted the strengths and vulnerabilities in common assumptions, and the participants shared additional perspective to ensure that this end-to-end safety approach is sufficient, actionable and timely. Critical areas and data gaps were identified as opportunities for future focus. These include, better context on history of use, systematic assessment of weight of evidence, use of in silico approaches, inclusion of threshold of toxicological concern considerations, individual substances/matrix interactions of plant constituents, assessing botanical-drug interactions and adaptations needed to apply to in vitro and in vivo pharmacokinetic modelling of botanical constituents., (Copyright © 2019. Published by Elsevier B.V.)
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- 2019
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21. Nutrition interventions for healthy ageing across the lifespan: a conference report.
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Kalache A, de Hoogh AI, Howlett SE, Kennedy B, Eggersdorfer M, Marsman DS, Shao A, and Griffiths JC
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- Aged, Aged, 80 and over, Aging physiology, Animals, Biomarkers, Energy Intake, Female, Frailty, Health Education, Health Promotion, Humans, Male, Mice, Middle Aged, Nutritional Physiological Phenomena, Nutritional Status, Quality of Life, Socioeconomic Factors, World Health Organization, Healthy Aging physiology, Longevity physiology, Nutrition Therapy
- Abstract
Thanks to advances in modern medicine over the past century, the world's population has experienced a marked increase in longevity. However, disparities exist that lead to groups with both shorter lifespan and significantly diminished health, especially in the aged. Unequal access to proper nutrition, healthcare services, and information to make informed health and nutrition decisions all contribute to these concerns. This in turn has hastened the ageing process in some and adversely affected others' ability to age healthfully. Many in developing as well as developed societies are plagued with the dichotomy of simultaneous calorie excess and nutrient inadequacy. This has resulted in mental and physical deterioration, increased non-communicable disease rates, lost productivity and quality of life, and increased medical costs. While adequate nutrition is fundamental to good health, it remains unclear what impact various dietary interventions may have on improving healthspan and quality of life with age. With a rapidly ageing global population, there is an urgent need for innovative approaches to health promotion as individual's age. Successful research, education, and interventions should include the development of both qualitative and quantitative biomarkers and other tools which can measure improvements in physiological integrity throughout life. Data-driven health policy shifts should be aimed at reducing the socio-economic inequalities that lead to premature ageing. A framework for progress has been proposed and published by the World Health Organization in its Global Strategy and Action Plan on Ageing and Health. This symposium focused on the impact of nutrition on this framework, stressing the need to better understand an individual's balance of intrinsic capacity and functional abilities at various life stages, and the impact this balance has on their mental and physical health in the environments they inhabit.
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- 2019
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22. Industry Actions to Address Quality Issues for Dietary Supplements, Botanicals, and Other Natural Products.
- Author
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Shenkar J and Griffiths JC
- Subjects
- Consumer Product Safety standards, Dietary Supplements adverse effects, Drug Industry legislation & jurisprudence, Government Regulation, Humans, Patient Safety standards, Phytotherapy adverse effects, Plant Preparations adverse effects, Policy Making, Quality Control, Quality Indicators, Health Care legislation & jurisprudence, Risk Assessment, Dietary Supplements standards, Drug Industry standards, Legislation, Drug standards, Phytotherapy standards, Plant Preparations standards, Quality Indicators, Health Care standards
- Abstract
The concept of "dietary supplements" is either a blessing for those focused on healthy lifestyles and personal management thereof or a crisis fraught with snake oil and drug analogs that are insidiously poisoning the gullible. Lost in this chatter is the role the ethical, and customer-focused industry takes to drive self-directing/self-governing initiatives to demonstrate unequivocally their position as responsible corporate citizens, meeting the needs of the ever-growing body of wellness-seekers., (© 2018 American Society for Clinical Pharmacology and Therapeutics.)
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- 2018
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23. Healthy ageing: the natural consequences of good nutrition-a conference report.
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Marsman D, Belsky DW, Gregori D, Johnson MA, Low Dog T, Meydani S, Pigat S, Sadana R, Shao A, and Griffiths JC
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- Aged, Aged, 80 and over, Aging physiology, Biomarkers, Culture, Diet, Healthy, Georgia, Humans, Immunity, Japan, Longevity physiology, Micronutrients deficiency, Micronutrients physiology, Middle Aged, Nutritional Physiological Phenomena, Public Health, Quality of Life, Vitamin B 12 Deficiency, Vitamin D Deficiency, World Health Organization, Healthy Aging physiology, Nutritional Status physiology
- Abstract
Many countries are witnessing a marked increase in longevity and with this increased lifespan and the desire for healthy ageing, many, however, suffer from the opposite including mental and physical deterioration, lost productivity and quality of life, and increased medical costs. While adequate nutrition is fundamental for good health, it remains unclear what impact various dietary interventions may have on prolonging good quality of life. Studies which span age, geography and income all suggest that access to quality foods, host immunity and response to inflammation/infections, impaired senses (i.e., sight, taste, smell) or mobility are all factors which can limit intake or increase the body's need for specific micronutrients. New clinical studies of healthy ageing are needed and quantitative biomarkers are an essential component, particularly tools which can measure improvements in physiological integrity throughout life, thought to be a primary contributor to a long and productive life (a healthy "lifespan"). A framework for progress has recently been proposed in a WHO report which takes a broad, person-centered focus on healthy ageing, emphasizing the need to better understand an individual's intrinsic capacity, their functional abilities at various life stages, and the impact by mental, and physical health, and the environments they inhabit.
- Published
- 2018
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24. Dietary guidance for lutein: consideration for intake recommendations is scientifically supported.
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Ranard KM, Jeon S, Mohn ES, Griffiths JC, Johnson EJ, and Erdman JW Jr
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- Clinical Trials as Topic, Diet, Dietary Supplements, Fruit, Humans, Lutein blood, Macular Degeneration blood, Macular Degeneration prevention & control, Vegetables, Lutein administration & dosage, Recommended Dietary Allowances
- Abstract
Lutein, a yellow xanthophyll carotenoid found in egg yolks and many colorful fruits and vegetables, has gained public health interest for its putative role in visual performance and reducing the risk of age-related macular degeneration. The National Academies of Sciences, Engineering and Medicine's recommended Dietary Reference Intakes (DRIs) focus on preventing deficiency and toxicity, but there is a budding interest in establishing DRI-like guidelines for non-essential bioactives, like lutein, that promote optimal health and/or prevent chronic diseases. Lupton et al. developed a set of nine criteria to determine whether a bioactive is ready to be considered for DRI-like recommendations. These criteria include: (1) an accepted definition; (2) a reliable analysis method; (3) a food database with known amounts of the bioactive; (4) cohort studies; (5) clinical trials on metabolic processes; (6) clinical trials for dose-response and efficacy; (7) safety data; (8) systematic reviews and/or meta-analyses; (9) a plausible biological rationale. Based on a review of the literature supporting these criteria, lutein is ready to be considered for intake recommendations. Establishing dietary guidance for lutein would encourage the consumption of lutein-containing foods and raise public awareness about its potential health benefits.
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- 2017
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25. Optimal nutrition and the ever-changing dietary landscape: a conference report.
- Author
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Shao A, Drewnowski A, Willcox DC, Krämer L, Lausted C, Eggersdorfer M, Mathers J, Bell JD, Randolph RK, Witkamp R, and Griffiths JC
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- Biomarkers metabolism, Congresses as Topic, Dietary Supplements, Health Behavior, Healthy Aging, Humans, Hyperphagia prevention & control, Longevity, Malnutrition diagnosis, Malnutrition prevention & control, Micronutrients administration & dosage, Obesity prevention & control, Phytochemicals administration & dosage, Sarcopenia prevention & control, Socioeconomic Factors, Diet, Healthy, Health Promotion, Nutrition Policy
- Abstract
The field of nutrition has evolved rapidly over the past century. Nutrition scientists and policy makers in the developed world have shifted the focus of their efforts from dealing with diseases of overt nutrient deficiency to a new paradigm aimed at coping with conditions of excess-calories, sedentary lifestyles and stress. Advances in nutrition science, technology and manufacturing have largely eradicated nutrient deficiency diseases, while simultaneously facing the growing challenges of obesity, non-communicable diseases and aging. Nutrition research has gone through a necessary evolution, starting with a reductionist approach, driven by an ambition to understand the mechanisms responsible for the effects of individual nutrients at the cellular and molecular levels. This approach has appropriately expanded in recent years to become more holistic with the aim of understanding the role of nutrition in the broader context of dietary patterns. Ultimately, this approach will culminate in a full understanding of the dietary landscape-a web of interactions between nutritional, dietary, social, behavioral and environmental factors-and how it impacts health maintenance and promotion.
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- 2017
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26. Bioactive nutrients - Time for tolerable upper intake levels to address safety.
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Yates AA, Erdman JW Jr, Shao A, Dolan LC, and Griffiths JC
- Subjects
- Animals, Catechin administration & dosage, Catechin adverse effects, Decision Support Techniques, Dose-Response Relationship, Drug, Guidelines as Topic, Humans, Lutein administration & dosage, No-Observed-Adverse-Effect Level, Plant Preparations administration & dosage, Recommended Dietary Allowances, Risk Assessment, Toxicity Tests standards, Toxicology standards, Catechin analogs & derivatives, Consumer Product Safety standards, Dietary Supplements adverse effects, Food Safety, Lutein adverse effects, Plant Preparations adverse effects, Toxicity Tests methods, Toxicology methods
- Abstract
There is increasing interest by consumers, researchers, and regulators into the roles that certain bioactive compounds, derived from plants and other natural sources, can play in health maintenance and promotion, and even prolonging a productive quality of life. Research has rapidly emerged suggesting that a wide range of compounds and mixtures in and from plants (such as fruits and vegetables, tea and cocoa) and animals (such as fish and probiotics) may exert substantial health benefits. There is interest in exploring the possibility of establishing recommended intakes or dietary guidance for certain bioactive substances to help educate consumers. A key aspect of establishing dietary guidance is the assessment of safety/toxicity of these substances. Toxicologists need to be involved in both the development of the safety framework and in the evaluation of the science to establish maximum intake/upper limits., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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27. The Importance of Quality Specifications in Safety Assessments of Amino Acids: The Cases of l-Tryptophan and l-Citrulline.
- Author
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Oketch-Rabah HA, Roe AL, Gurley BJ, Griffiths JC, and Giancaspro GI
- Subjects
- Dietary Supplements, Humans, Quality Control, Toxicity Tests, Citrulline adverse effects, Tryptophan adverse effects
- Abstract
The increasing consumption of amino acids from a wide variety of sources, including dietary supplements, natural health products, medical foods, infant formulas, athletic and work-out products, herbal medicines, and other national and international categories of nutritional and functional food products, increases the exposure to amino acids to amounts far beyond those normally obtained from the diet, thereby necessitating appropriate and robust safety assessments of these ingredients. Safety assessments of amino acids, similar to all food constituents, largely rely on the establishment of an upper limit [Tolerable Upper Intake Level (UL)] considered to be a guide for avoiding high intake, above which adverse or toxic effects might occur. However, reliable ULs have been difficult or impossible to define for amino acids because of inadequate toxicity studies in animals and scarce or missing clinical data, as well as a paucity or absence of adverse event reporting data. This review examines 2 amino acids that have been associated with in-market adverse events to show how quality specifications might have helped prevent the adverse clinical outcomes. We further highlight the importance of various factors that should be incorporated into an overall safety assessment of these and other amino acids. In addition to the traditional reliance on the established UL, well-defined quality specifications, review of synthesis and production strategies, potential interactions with drugs, contraindications with certain disease states, and cautionary use within certain age groups should all be taken into consideration., (© 2016 American Society for Nutrition.)
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- 2016
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28. Assessing Natural Product-Drug Interactions: An End-to-End Safety Framework.
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Roe AL, Paine MF, Gurley BJ, Brouwer KR, Jordan S, and Griffiths JC
- Subjects
- Animals, Biological Assay, Biotransformation, Dietary Supplements standards, Dose-Response Relationship, Drug, Drug-Related Side Effects and Adverse Reactions, Humans, Pharmacovigilance, Plant Preparations administration & dosage, Plant Preparations pharmacokinetics, Plant Preparations standards, Polypharmacy, Quality Control, Risk Assessment, Toxicity Tests standards, Dietary Supplements adverse effects, Herb-Drug Interactions, Plant Preparations adverse effects, Toxicity Tests methods
- Abstract
The use of natural products (NPs), including herbal medicines and other dietary supplements, by North Americans continues to increase across all age groups. This population has access to conventional medications, with significant polypharmacy observed in older adults. Thus, the safety of the interactions between multi-ingredient NPs and drugs is a topic of paramount importance. Considerations such as history of safe use, literature data from animal toxicity and human clinical studies, and NP constituent characterization would provide guidance on whether to assess NP-drug interactions experimentally. The literature is replete with reports of various NP extracts and constituents as potent inhibitors of drug metabolizing enzymes, and transporters. However, without standard methods for NP characterization or in vitro testing, extrapolating these reports to clinically-relevant NP-drug interactions is difficult. This lack of a clear definition of risk precludes clinicians and consumers from making informed decisions about the safety of taking NPs with conventional medications. A framework is needed that describes an integrated robust approach for assessing NP-drug interactions; and, translation of the data into formulation alterations, dose adjustment, labelling, and/or post-marketing surveillance strategies. A session was held at the 41st Annual Summer Meeting of the Toxicology Forum in Colorado Springs, CO, to highlight the challenges and critical components that should be included in a framework approach., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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29. Nutrient reference value: non-communicable disease endpoints--a conference report.
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Lupton JR, Blumberg JB, L'Abbe M, LeDoux M, Rice HB, von Schacky C, Yaktine A, and Griffiths JC
- Subjects
- Evidence-Based Medicine, Humans, Reference Values, Cardiovascular Diseases prevention & control, Diet standards, Fatty Acids, Omega-3 administration & dosage, Recommended Dietary Allowances
- Abstract
Nutrition is complex-and seemingly getting more complicated. Most consumers are familiar with "essential nutrients," e.g., vitamins and minerals, and more recently protein and important amino acids. These essential nutrients have nutrient reference values, referred to as dietary reference intakes (DRIs) developed by consensus committees of scientific experts convened by the Institute of Medicine of the National Academy of Sciences, Engineering, and Medicine and carried out by the Food and Nutrition Board. The DRIs comprise a set of four nutrient-based reverence values, the estimated average requirements, the recommended dietary allowances (RDAs), the adequate intakes and the tolerable upper intake levels for micronutrient intakes and an acceptable macronutrient distribution range for macronutrient intakes. From the RDA, the US Food and Drug Administration (FDA) derives a labeling value called the daily value (DV), which appears on the nutrition label of all foods for sale in the US. The DRI reports do not make recommendations about whether the DV labeling values can be set only for what have been defined to date as "essential nutrients." For example, the FDA set a labeling value for "dietary fiber" without having the DV. Nutrient reference values-requirements are set by Codex Alimentarius for essential nutrients, and regulatory bodies in many countries use these Codex values in setting national policy for recommended dietary intakes. However, the focus of this conference is not on essential nutrients, but on the "nonessential nutrients," also termed dietary bioactive components. They can be defined as "Constituents in foods or dietary supplements, other than those needed to meet basic human nutritional needs, which are responsible for changes in health status (Office of Disease Prevention and Health Promotion, Office of Public Health and Science, Department of Health and Human Services in Fed Regist 69:55821-55822, 2004)." Substantial and often persuasive scientific evidence does exist to confirm a relationship between the intake of a specific bioactive constituent and enhanced health conditions or reduced risk of a chronic disease. Further, research on the putative mechanisms of action of various classes of bioactives is supported by national and pan-national government agencies, and academic institutions, as well as functional food and dietary supplement manufacturers. Consumers are becoming educated and are seeking to purchase products containing bioactives, yet there is no evaluative process in place to let the public know how strong the science is behind the benefits or the quantitative amounts needed to achieve these beneficial health effects or to avoid exceeding the upper level (UL). When one lacks an essential nutrient, overt deficiency with concomitant physiological determents and eventually death are expected. The absence of bioactive substances from the diet results in suboptimal health, e.g., poor cellular and/or physiological function, which is relative and not absolute. Regrettably at this time, there is no DRI process to evaluate bioactives, although a recent workshop convened by the National Institutes of Health (Options for Consideration of Chronic Disease Endpoints for Dietary Reference Intakes (DRIs); March 10-11, 2015; http://health.gov/dietaryguidelines/dri/ ) did explore the process to develop DVs for nutrients, the lack of which result in increased risk of chronic disease (non-communicable disease) endpoints. A final report is expected soon. This conference (CRN-International Scientific Symposium; "Nutrient Reference Value-Non-Communicable Disease (NRV-NCD) Endpoints," 20 November in Kronberg, Germany; http://www.crn-i.ch/2015symposium/ ) explores concepts related to the Codex NRV process, the public health opportunities in setting NRVs for bioactive constituents, and further research and details on the specific class of bioactives, n-3 long-chain polyunsaturated fatty acids (also termed omega-3 fatty acids) and their constituents, specifically docosahexaenoic acid and eicosapentaenoic acid.
- Published
- 2016
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30. A quality dietary supplement: before you start and after it's marketed--a conference report.
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LeDoux MA, Appelhans KR, Braun LA, Dziedziczak D, Jennings S, Liu L, Osiecki H, Wyszumiala E, and Griffiths JC
- Subjects
- Congresses as Topic, Consumer Product Safety, Food Handling, Food Storage, Humans, Life Style, Nutrition Policy, Patient Compliance, Quality of Life, United States, United States Food and Drug Administration, Dietary Supplements
- Abstract
Consumers worldwide are turning to dietary supplements as one part of their personal goal to lead healthier and more active lives. In truth, the quality of life now supersedes the length of life as no one would trade living to one hundred (the last forty with compromised physical abilities and decreased mental acuity) for 80 years of travel, time with family, and intellectual pursuits. If there is the possibility of preventing a disease or debilitating condition through efficient lifestyle changes (additions, subtractions, modifications) and to also avoid the costly and escalating medical and pharmaceutical treatments that accompany having the disease/condition, then a sensible individual would focus on their overall health and wellness…proactively, instead of reactively. However, an important caveat is that over-regulation or inappropriate application of current regulations can increase the price of dietary supplements and nutritional products and thus cause underutilization of the potentially beneficial physiological attributes of these products. Conversely, strict adherence to regulatory guidelines could result in safer dietary supplements and fewer adverse reactions requiring medical attention. If new regulations or stricter interpretation/application of existing regulations result in certain dietary supplements being taken off the market, will continued demand create a completely unregulated, underground economy that will create unforeseen problems? More research should be supported by government agencies to determine the effectiveness of dietary supplements, nutritional products and complementary medicine in reducing personal and societal medical costs and further contribution to the overall health of the population.
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- 2015
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31. Exploring the benefits and challenges of establishing a DRI-like process for bioactives.
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Lupton JR, Atkinson SA, Chang N, Fraga CG, Levy J, Messina M, Richardson DP, van Ommen B, Yang Y, Griffiths JC, and Hathcock J
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- Dietary Proteins administration & dosage, Dietary Supplements, Fatty Acids, Essential administration & dosage, Health Promotion, Humans, Trace Elements administration & dosage, Vitamins administration & dosage, Diet standards, Dietary Fiber administration & dosage, Flavonoids administration & dosage, Recommended Dietary Allowances
- Abstract
Bioactives can be defined as: "Constituents in foods or dietary supplements, other than those needed to meet basic human nutritional needs, which are responsible for changes in health status" (Office of Disease Prevention and Health Promotion, Office of Public Health and Science, Department of Health and Human Services in Fed Reg 69:55821-55822, 2004). Although traditional nutrients, such as vitamins, minerals, protein, essential fatty acids and essential amino acids, have dietary reference intake (DRI) values, there is no such evaluative process for bioactives. For certain classes of bioactives, substantial scientific evidence exists to validate a relationship between their intake and enhanced health conditions or reduced risk of disease. In addition, the study of bioactives and their relationship to disease risk is a growing area of research supported by government, academic institutions, and food and supplement manufacturers. Importantly, consumers are purchasing foods containing bioactives, yet there is no evaluative process in place to let the public know how strong the science is behind the benefits or the quantitative amounts needed to achieve these beneficial health effects. This conference, Bioactives: Qualitative Nutrient Reference Values for Life-stage Groups?, explored why it is important to have a DRI-like process for bioactives and challenges for establishing such a process.
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- 2014
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32. Nutrient reference values for bioactives: new approaches needed? A conference report.
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Biesalski HK, Erdman JW Jr, Hathcock J, Ellwood K, Beatty S, Johnson E, Marchioli R, Lauritzen L, Rice HB, Shao A, and Griffiths JC
- Subjects
- Brain physiology, Carotenoids, Child, Food, Food Labeling, Health Promotion, Humans, Macular Degeneration prevention & control, Nutritional Requirements, Reference Values, United States, Vision, Ocular, Zeaxanthins, Diet, Fatty Acids, Omega-3, Lutein, Nutrition Policy, Xanthophylls
- Abstract
Nutrients can be classified as either "essential" or "non-essential," the latter are also termed bioactive substances. Whereas the absence of essential nutrients from the diet results in overt deficiency often times with moderate to severe physiological decrements, the absence of bioactive substances from the diet results in suboptimal health. Nutrient reference values are set by Codex Alimentarius and regulatory bodies in many countries, mostly for essential nutrients with recommended daily intakes. The IOM in the United States has defined a set of four DRIs that, when data are appropriate, include an EAR, a RDA that is derived from the EAR, an AI for nutrients without appropriate data to identify an EAR, and an UL. From the RDA, the United States derives a labeling value called the DV, which applies to older children and most adults. In Codex, the equivalents of the DVs are the NRVs to be used in calculating percentage values on food labels. Nothing in the IOM documents specifies that labeling values can be set only for what have been defined to date as essential nutrients. Indeed, the US Food and Drug Administration sets a labeling value for dietary fiber based on the IOM AI for this ingredient. This conference explores the definitions, concepts, and data on two of the best examples of bioactive substances that, perhaps, should have NRVs: lutein and zeaxanthin, and n-3 long-chain polyunsaturated fatty acids.
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- 2013
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33. Total Protein Methods and Their Potential Utility to Reduce the Risk of Food Protein Adulteration.
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Moore JC, DeVries JW, Lipp M, Griffiths JC, and Abernethy DR
- Abstract
Kjeldahl and combustion (Dumas) methods are widely accepted for total protein determination but lack analytical selectivity for protein because they measure protein on the basis of sample nitrogen content. Adulteration incidents exploiting this analytical vulnerability (for example, melamine) demonstrate that these methods are no longer sufficient to protect the public health. This article explores the challenges and opportunities to move beyond total nitrogen based methods for total protein measurement. First, it explores the early history of protein measurement science, complexities of current global protein measurement activities, and ideal analytical performance characteristics for new methods. Second, it comprehensively reviews the pros and cons of current and emerging approaches for protein measurement, including their selectivity for protein, ability to detect adulteration, and practicality for routine use throughout the supply chain. It concludes that some existing highly selective methods for food protein measurement have potential for routine quality control. It also concludes that their successful implementation will require matrix-specific validation and the use of supporting reference materials. These methods may be suitable only for food ingredients that have a low degree of compositional variability and are not complex finished food products., (© 2010 Institute of Food Technologists®.)
- Published
- 2010
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34. Adulteration of drugs and foods: compendial approaches to lowering risk.
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Abernethy DR, Sheehan C, Griffiths JC, and Williams RL
- Subjects
- Animals, Drug Contamination legislation & jurisprudence, Drug-Related Side Effects and Adverse Reactions, Food adverse effects, Food Contamination analysis, Food Contamination legislation & jurisprudence, Humans, Pharmaceutical Preparations analysis, Risk Factors, United States, United States Food and Drug Administration legislation & jurisprudence, United States Food and Drug Administration standards, Drug Contamination prevention & control, Food standards, Food Contamination prevention & control, Pharmaceutical Preparations standards
- Published
- 2009
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35. Lack of oral embryotoxicity/teratogenicity with D-ribose in Wistar rats.
- Author
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Griffiths JC, Borzelleca JF, and St Cyr J
- Subjects
- Animals, Cecum drug effects, Cecum pathology, Consumer Product Safety, Female, Intubation, Gastrointestinal, Liver drug effects, Liver pathology, Male, Maternal Exposure, Pregnancy, Rats, Rats, Wistar, Ribose administration & dosage, Toxicity Tests, Dietary Supplements toxicity, Fetus drug effects, Ribose toxicity
- Abstract
The present oral embryotoxicity/teratogenicity study of d-Ribose (DR) was conducted in female rats; 28 rats/group were exposed via the diet to 0, 5, 10, or 20% DR (0.0, 4.25, 7.94, 9.91g/kg body weight/day), from day 0 of gestation until Caesarian section and maternal sacrifice on day 21. All animals survived to the end of the study. Fecundity index, gestation index, pre-implantation loss, post-implantation loss, and sex ratio were all unaffected by treatment with DR. External observations of fetuses and placentas were unremarkable across the study groups. Mean fetal and placental weights, across all viable fetuses, did not differ significantly between treated and control groups. Observations of visceral malformations, anomalies, and variations were unremarkable and did not differ between treated and control groups. In summary, administration of DR to pregnant rats at concentrations up to 20% of the diet resulted in no significant adverse effects on the developing embryo/fetus at doses that were not otherwise a severe metabolic stress on the dam. A No Observed Adverse Effect Level (NOAEL) for teratogenicity could be seen at a concentration of 5% DR in the diet, corresponding to an average daily intake of DR of between 3.64 and 4.61g/kg body weight/day.
- Published
- 2007
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36. Sub-chronic (13-week) oral toxicity study with D-ribose in Wistar rats.
- Author
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Griffiths JC, Borzelleca JF, and St Cyr J
- Subjects
- Administration, Oral, Animals, Body Weight drug effects, Cecum drug effects, Cecum pathology, Diet, Dose-Response Relationship, Drug, Drinking drug effects, Eating drug effects, Female, Longevity drug effects, Male, No-Observed-Adverse-Effect Level, Organ Size drug effects, Rats, Rats, Wistar, Dietary Supplements toxicity, Ribose toxicity
- Abstract
The present study evaluated the toxicity from sub-chronic administration of D-ribose (DR) to male and female albino Wistar rats. Groups of 20 male and 20 female rats were exposed via the diet to 0%, 5%, 10%, or 20% DR, seven days per week (mean daily intake of 0.0, 3.6, 7.6, and 15.0 g/kg body weight/day in males and 0.0, 4.4, 8.5, and 15.7 g/kg body weight/day in females), for 13 consecutive weeks. Mean feed consumption and feed conversion efficiency values were comparable across all study groups; however, and mean body weights of all treated animals were decreased relative to those of controls. Absolute cecal weights were increased in the mid- and high-dose animals, and the relative weights were increased in all treated animals. Analysis of microscopic histopathology revealed no evidence of changes that could be attributed to the DR treatment. It is scientifically reasonable to conclude that the present study supports a concentration of 5% DR in the diet, corresponding to an average daily intake of DR of 3.6 and 4.4 g/kg body weight/day in male and female rats, respectively, as being the absolute no observed adverse effect level (NOAEL) for this substance.
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- 2007
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37. Acute and subchronic toxicity studies on Sel-Plex, a standardized, registered high-selenium yeast.
- Author
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Griffiths JC, Matulka RA, and Power R
- Subjects
- Animals, Cholesterol blood, Dogs, Female, Lethal Dose 50, Liver drug effects, Liver pathology, Male, Mice, No-Observed-Adverse-Effect Level, Rats, Rats, Sprague-Dawley, Weight Gain drug effects, Dietary Supplements toxicity, Saccharomyces cerevisiae, Selenium administration & dosage, Selenium toxicity, Sodium Selenite toxicity
- Abstract
Selenium has been recognized as an essential nutrient for human health; however, its bioavailability is primarily dependent upon the type of selenium, elemental versus organic. In geographic areas low in selenium, there is the potential for animals (including humans) to become selenium deficient and this potential deficiency can be remedied by consumption of exogenous selenium, including selenium-enriched yeast (Saccharomyces cerevisiae) that contains high levels of organic selenium (e.g., selenized yeast). The present studies were conducted to investigate potential oral toxicity of a unique selenized yeast preparation (Sel-Plex) when administered to (1) adult female CHS Swiss mice ICo:OFI (IOPS Caw); (2) adult female CHS Sprague-Dawley rats; and (3) adult male and female Sprague-Dawley CD rats. For the 28- and 90-day toxicity studies, (1) adult male and female Sprague-Dawley CRL:CD(R)(SD) IGS BR strain rats and (2) adult male and female 6- to 7-month-old Beagle dogs were used. The LD50 for mice was >or=2000 mg Sel-Plex/kg (>or=4.06 mg Se/kg) and for rats, was greater than >or=2000 mg Sel-Plex/kg (>or=4.06 mg Se/kg). In the two 28-day studies, for rats, the no observed adverse effects level (NOAEL) was 50 mg Sel-Plex/kg/day (0.1 mg Se/kg/day), and for the dogs, the NOAEL was 22.5 mg Sel-Plex/kg/day (0.045 mg Se/kg/day). For the two 90-day studies, for rats the NOAEL for Sel-Plex was 114 mg/kg/day (0.23 mg Se/kg/day), and for dogs, the NOAEL was 30 mg Sel-Plex/kg/day (0.06 mg Se/kg/day): the latter being the NOAEL in the most sensitive species.
- Published
- 2006
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38. Genotoxicity studies on Sel-Plex, a standardized, registered high-selenium yeast.
- Author
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Griffiths JC, Matulka RA, and Power R
- Subjects
- Animals, Bone Marrow Cells drug effects, Cells, Cultured, Chromosome Aberrations, Female, Humans, Lymphocytes drug effects, Male, Mice, Micronucleus Tests, Salmonella typhimurium drug effects, Salmonella typhimurium genetics, Salmonella typhimurium metabolism, Dietary Supplements toxicity, Saccharomyces cerevisiae, Selenium administration & dosage, Selenium toxicity
- Abstract
Selenium, recognized as an essential nutrient for human health, is a component of proteins and enzymes required for various biological functions and is currently being used as a feed supplement for livestock in geographical areas that are naturally low in selenium. Selenium is structurally similar to sulfur, replacing the sulfur atom in stoichiometric amounts and thus functions through an association with proteins, termed selenoproteins. In geographic areas low in selenium, there is the potential for animals (including humans) to become selenium deficient and this potential deficiency can be remedied by consumption of exogenous selenium, including selenium-enriched yeast (Saccharomyces cerevisiae) that contains high levels of organic selenium (e.g., selenized yeast). A unique, standardized, registered high selenium food-grade baker's yeast (S. cerevisiae; Sel-Plex), was tested in the following battery of Genotoxicity assays; (1) a bacterial reverse mutation test (Ames test); (2) an in vitro mammalian chromosome aberration test; and (3) a mouse micronucleus test. Under the conditions of this assay, Sel-Plex showed no evidence of mutagenic activity in Salmonella typhimurium, in the bacterial reverse mutation test. Sel-Plex did not induce significant chromosomal aberrations in cultured human lymphocytes in the in vitro mammalian chromosome aberration test. Sel-Plex did not statistically increase the frequency or proportion of micronucleated immature erythrocytes in the mouse micronucleus test. Thus, from the studies presented here, the authors conclude that Sel-Plex is nongenotoxic.
- Published
- 2006
- Full Text
- View/download PDF
39. Toxicology and pharmacology of sodium ricinoleate.
- Author
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Burdock GA, Carabin IG, and Griffiths JC
- Subjects
- Animals, Castor Oil pharmacokinetics, Castor Oil pharmacology, Castor Oil toxicity, Humans, Ricinoleic Acids pharmacokinetics, Ricinoleic Acids toxicity, Ricinoleic Acids pharmacology
- Abstract
Ricinoleic acid constitutes approximately 90% of the fatty acid content of castor oil. Castor oil is known for its purgative effects and can be used to induce labor. Both castor oil and ricinoleic acid are approved for use in food. The mechanistic basis for purgative actions likely includes the membrane-disruptive effects of detergent-like molecules, such as sodium ricinoleate (a 'soap'). These effects have been shown to be dose-related and to exhibit a threshold below which no laxative response was evident, in both animals and in humans. Castor oil was not toxic in subchronic feeding studies in rodents at doses ranging up to 10-20% of the diet. Sodium ricinoleate, as a surfactant, demonstrates predictable skin and mucus membrane irritant effects, and may induce a Type IV dermal sensitization response in those previously sensitized to it. However, food-grade castor oil and sodium ricinoleate are prepared in such a manner as to be free of the castor bean constituents that have been proven to be the source of reported Type I immediate hypersensitivity responses. Feeding studies with castor oil in rodents provide a basis for a no observable adverse effect level (NOAEL) estimate of 7,500 mg/kg/day and 5,000 mg/kg/day in mice and rats, respectively (). Applying an uncertainty factor of 100 to the lesser of these NOAELs, one can thus estimate an acceptable daily intake (ADI) in man to be 50 mg/kg, or 3,000 mg of castor oil per day in an average 60 kg person. As ricinoleic acid constitutes approximately 90% of castor oil, applying this calculation to the 3,000 mg/day estimated ADI in humans for castor oil (given the rapid hydrolysis of castor oil glyceride in the gastrointestinal tract), the acceptable daily intake of ricinoleic acid may be as high as 2,400 mg/person.
- Published
- 2006
- Full Text
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40. The importance of GRAS to the functional food and nutraceutical industries.
- Author
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Burdock GA, Carabin IG, and Griffiths JC
- Subjects
- Consumer Product Safety, Food Industry, Food Labeling, Humans, United States, United States Food and Drug Administration, Dietary Supplements, Food, Organic, Legislation, Food
- Abstract
At a time when 150 million Americans spend over $20.5 billion on functional foods, nutraceuticals and dietary supplements, the Food and Drug Administration (FDA) is doing little to ensure that all the safe and efficacious products that could come to the market are allowed to do so. FDA has only responded slowly and reluctantly to Congressional action and to mandates from the Courts to implement the law. Additionally, FDA had set the bar too high for Health Claims and was forced by the Courts to implement a more reasonable standard, but the response, Qualified Health Claims, has failed to gain the confidence of the public because of the confusing wording of the claims demanded by FDA. Congressional efforts to assure consumer access to dietary supplements have been met with similar resistance from FDA. The Dietary Supplement Health and Education Act (DSHEA) was the product of a compromise with a lower threshold for demonstration of safety (reasonable expectation of no harm) that would be met by consumer self-policing and assumption of some risk. FDA has thwarted this effort by raising the bar for New Dietary Ingredient Notifications (NDIN) to what appears to be the higher threshold for the safety of food ingredients (reasonable certainty of no harm)--FDA apparently sees these two safety thresholds as a distinction without a difference. As a result, increasing numbers of dietary supplement manufacturers, unwilling to gamble the future of their products to a system that provides little hope for the FDA's response of "no objection", have committed the additional resources necessary to obtain Generally Recognized As Safe (GRAS) status for their supplements. The pressure on FDA and Congress for change is again building with increased dissatisfaction among consumers as the result of confusing labels. A second force for change will be a need to uncouple the FDA mandated substance-disease relationship and return to the substance-claim relationship to allow for progress in nutrigenomics and metabolomics, which will result in an increasing number of substance-biomarker claims.
- Published
- 2006
- Full Text
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41. Safety evaluation of a natural tomato oleoresin extract derived from food-processing tomatoes.
- Author
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Matulka RA, Hood AM, and Griffiths JC
- Subjects
- Administration, Cutaneous, Administration, Oral, Animals, Female, Food-Processing Industry, Guinea Pigs, Lethal Dose 50, Lycopene, Male, Mutagenicity Tests, No-Observed-Adverse-Effect Level, Rabbits, Rats, Rats, Sprague-Dawley, Risk Assessment, Skin Irritancy Tests, Skin Tests, Toxicity Tests, Chronic, Antioxidants toxicity, Carotenoids toxicity, Solanum lycopersicum, Plant Extracts toxicity
- Abstract
Experimental and epidemiological studies indicate that consumption of tomato products containing high amounts of lycopene is associated with lowered cancer risk. The protective effects of lycopene may be related to its antioxidant potential. Lycopene has been demonstrated to inhibit oxidation. A proprietary, natural tomato oleoresin extract (NTOE), is a purified tomato oleoresin containing 6% lycopene produced from tomatoes. NTOE was evaluated for toxicological effects, and found the 50% lethal dose (LD(50)), derived from the acute oral toxicity study, was greater than 5000 mg/kg body weight. The no-observed-adverse-effect level (NOAEL) derived from the 13-week study was 4500 mg/kg/day. Acute dermal toxicity study of NTOE found no toxicity at 2000 mg/kg body weight. NTOE lacked dermal irritation in the rabbit model, but was found to have moderate eye-irritant capabilities. NTOE tested at 5% (w/w) in petroleum jelly was a moderate sensitizer in the guinea pig model. There was no evidence of mutagenic potential up to 5000 microg/plate, as determined by the Ames assay. These results demonstrate the inability of NTOE to produce oral, dermal or mutagenic toxicity in animal models at doses greater than 300 times the normal human consumption of lycopene. Consumption analysis of lycopene-containing foods estimated mean daily intake of lycopene at 8.2mg/day.
- Published
- 2004
- Full Text
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42. Safety of ephedra: lessons learned.
- Author
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Soni MG, Carabin IG, Griffiths JC, and Burdock GA
- Subjects
- Anti-Asthmatic Agents therapeutic use, China, Ephedra toxicity, Ephedrine pharmacokinetics, Ephedrine therapeutic use, History, Ancient, Humans, Phytotherapy history, United States, United States Food and Drug Administration, Ephedra adverse effects
- Abstract
The safe use of ephedra represents the best possible outcome of a convergence of variables, some with troubling potential outcomes. Commercially used ephedra and its products is prepared from Ephedra spp. and as such is subject to a variety of influences (including differences in species and strain; growth, harvest and storage conditions) all of which may influence the content of constituents (which may, in turn, affect the absorption, distribution, and metabolism of active constituents) and taken together, influences the net pharmacological effect. Further, as a natural substance with an easily perceived and desirable (i.e. weight-loss) pharmacological effect, ephedra is also susceptible to a variety of adulterants, both economic and efficacious. All of the foregoing represent potential for misadventure before ephedra even reaches the consumer. The consumer introduces a constellation of variables as well, including, but not limited to, acute and chronic diseases, inborn errors in metabolism, simultaneous use of prescription and over-the-counter drugs, dietary supplements, alcohol, illicit substances and certain foods (e.g. chocolate, caffeinated drinks), all or some of which may exert synergistic, additive or even antagonistic influences on the desired physiologic outcome. The foregoing not withstanding, the majority of the published nonclinical and clinical studies, and history of use, support the safety of ephedra at the proposed use levels. However, the reports of adverse events submitted to FDA raise concern about the risk associated with ephedra without establishing a direct causal relationship. Given the foregoing, how best can a decision on safety be made? Should the question actually be "can ephedra be as toxic as reported?"
- Published
- 2004
- Full Text
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43. Chronic toxicity and oncogenicity of N-methylpyrrolidone (NMP) in rats and mice by dietary administration.
- Author
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Malley LA, Kennedy GL, Elliott GS, Slone TW, Mellert W, Deckardt K, Kuttler K, Hildebrand B, Banton MI, Parod RJ, and Griffiths JC
- Subjects
- Animals, Carcinogenicity Tests, Chronic Disease, Diet, Female, Male, Mice, Mice, Inbred Strains, Pyrrolidinones administration & dosage, Rats, Rats, Inbred Strains, Sex Factors, Species Specificity, Toxicity Tests, Kidney Diseases chemically induced, Liver Neoplasms, Experimental chemically induced, Pyrrolidinones toxicity
- Abstract
A two-year feeding study in rats and an 18-month feeding study in mice were conducted to evaluate the potential chronic toxicity and oncogenicity of NMP in Crl:CD (SD)BR rats and B6C3F1/CrlBR mice. Groups of 62 male and female rats were administered diets containing 0, 1600, 5000, or 15,000 ppm of NMP for approximately 2 years. Groups of 50 male and female mice were administered diets containing 0, 600, 1200, or 7200 ppm NMP for approximately 18 months. In vivo parameters were evaluated weekly during the first 3 months of the study, and every other week or monthly during the remainder of the study. For rats, an ophthalmoscopic examination was conducted prior to study start and near the end of the study. Periodically, blood samples were collected from rats and mice for determination of leukocyte differential counts, and from mice for red blood cell morphology. After approximately 2 years of dietary administration in rats and 18 months in mice, all surviving animals were sacrificed. Selected tissues were processed for morphological evaluation. Over the course of the two-year study in rats, test substance-related decrements in body weight and weight gain occurred in 15,000 ppm males and females, which correlated with decreased food consumption and food efficiency. A toxicologically significant, test substance-related increase in the incidence of severe chronic progressive nephropathy occurred in 15,000 ppm males. Several morphological changes noted grossly and/or microscopically were secondary to the increased severity of chronic progressive nephropathy. NMP was not oncogenic in male or female rats at dietary concentrations of 15,000 ppm and below. A test substance-related decrease in the percentage of 15,000 ppm males surviving to the end of the two-year study compared to the control group resulted from the higher incidence of severe chronic progressive nephropathy. However, a sufficient population of 15,000 ppm rats were at risk for potential oncogenicity, so the lower survival did not impair the ability to detect an oncogenic response in this study. There were no adverse, test substance-related effects on the incidences of clinical observations, ophthalmic observations, or differential leukocyte counts in males or females, or on survival of females at any dietary concentration. Male and female mice administered dietary concentrations of 7200 ppm had significantly increased liver weight, significantly increased incidence of hepatocellular adenoma, and significantly increased foci of cellular alteration in the liver. At 7200 ppm, male mice also had an increased incidence of hepatocellular carcinoma while the increased incidence of hepatocellular carcinoma in female mice fell within the historical control range. In addition, the incidence of hepatocellular hypertrophy was increased in 7200 ppm males. Liver weight and hepatocellular hypertrophy were also increased in 1200 ppm males. There were no adverse, test substance-related effects on the incidences of clinical observations, food consumption, body weight, differential leukocyte counts, red blood cell morphology, or survival in either males or females at any dietary concentration. Under the conditions of the study, the no-observed-effect level for NMP was 5000 ppm for male and female rats, 600 ppm for male mice, and 1200 ppm for female mice.
- Published
- 2001
- Full Text
- View/download PDF
44. 90-day subchronic toxicity study in rats and mice fed N-methylpyrrolidone (NMP) including neurotoxicity evaluation in rats.
- Author
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Malley LA, Kennedy GL, Elliott GS, Slone TW, Mellert W, Deckardt K, Gembardt C, Hildebrand B, Parod RJ, McCarthy TJ, and Griffiths JC
- Subjects
- Animals, Behavior, Animal drug effects, Body Weight drug effects, Dose-Response Relationship, Drug, Female, Kidney drug effects, Kidney pathology, Liver drug effects, Liver pathology, Male, Mice, No-Observed-Adverse-Effect Level, Organ Size drug effects, Rats, Pyrrolidinones toxicity
- Abstract
In mice, there were no effects on body weight or food consumption. As observed in rats, mice fed 2,500 or 7,500 ppm exhibited a change in urine coloration which was not associated with morphological changes in cholesterol, triglycerides, calcium, and alkaline phosphatase occurred at 28 days but not 90 days. These changes are thus assessed as being of minor toxicological relevance. Liver weights were elevated in males fed 2,500 or 7,500 ppm and centrilobular hypertrophy was seen in both sexes fed 7,500 ppm. These changes may be regarded as an adaptation process but are clearly related to NMP exposure. Other toxicological endpoints examined were unaffected by NMP. The NOAEL was 3,000 ppm for both sexes of rats based on body weight effects and changes in 3 neurobehavioral parameters (males only) at higher feeding levels. In mice, the NOAEL was 1,000 ppm based on liver responses to higher concentrations.
- Published
- 1999
- Full Text
- View/download PDF
45. Assessment of Herpesvirus saimiri as a potential human gene therapy vector.
- Author
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Stevenson AJ, Cooper M, Griffiths JC, Gibson PC, Whitehouse A, Jones EF, Markham AF, Kinsey SE, and Meredith DM
- Subjects
- Blotting, Southern, Cell Line, Transformed, Cells, Cultured, Fluorescent Antibody Technique, Indirect, HT29 Cells, Humans, Jurkat Cells, K562 Cells, Tumor Cells, Cultured, Genetic Therapy methods, Genetic Vectors, Herpesvirus 2, Saimiriine genetics, Herpesvirus 2, Saimiriine growth & development
- Abstract
Herpesvirus saimiri has characteristics that make it amenable to development as a gene therapy vector. The viral genome is thought to be capable of accommodating large quantities of heterologous DNA while the virus itself can infect many different cell types. Virus infection has been shown in many cases to be persistent by virtue of episomal maintenance in the target cell. In this article we examine the ability of nonselectable recombinant viruses expressing the beta-galactosidase gene product to infect a variety of human cells and demonstrate that this virus could be developed as an alternative hematopoietic stem cell gene therapy vector. In contrast to earlier observations, we demonstrate by a number of methods that the virus has the ability to replicate in many human cell types, suggesting the need for the development of a disabled virus for use as a gene therapy vector.
- Published
- 1999
46. The herpesvirus saimiri ORF50 gene, encoding a transcriptional activator homologous to the Epstein-Barr virus R protein, is transcribed from two distinct promoters of different temporal phases.
- Author
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Whitehouse A, Carr IM, Griffiths JC, and Meredith DM
- Subjects
- Animals, Aotidae, Cell Line, Viral Proteins, Genes, Viral, Herpesvirus 2, Saimiriine genetics, Herpesvirus 4, Human genetics, Immediate-Early Proteins genetics, Open Reading Frames, Promoter Regions, Genetic, Trans-Activators genetics, Transcription Factors genetics, Transcription, Genetic
- Abstract
The mRNA species encoding the herpesvirus saimiri (HVS) homolog of the Epstein-Barr virus R transcriptional activator (termed ORF50) have been identified and used to determine transcriptional start sites within the gene. The first transcript is spliced and starts from a promoter within ORF49 containing a single intron; the second is produced from a promoter within the second exon and is in the same reading frame. The spliced transcript is detected at early times during productive virus replication in OMK cells, whereas the nonspliced transcript is detected later. The spliced transcript is fivefold-more potent in activating the delayed-early ORF6 promoter; the function of the nonspliced transcript is unclear. Thus, the role of this protein in activating herpesvirus saimiri from the latent state may differ significantly from that of the Epstein-Barr virus R protein.
- Published
- 1997
- Full Text
- View/download PDF
47. Carcinogenic risks of inorganic arsenic in perspective.
- Author
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Byrd DM, Roegner ML, Griffiths JC, Lamm SH, Grumski KS, Wilson R, and Lai S
- Subjects
- Aged, Dose-Response Relationship, Drug, Female, Humans, Kidney Neoplasms epidemiology, Male, Prevalence, Risk Assessment, Risk Factors, Skin Neoplasms epidemiology, Survival Rate, Urinary Bladder Neoplasms epidemiology, Arsenic adverse effects, Kidney Neoplasms chemically induced, Linear Models, Skin Neoplasms chemically induced, Urinary Bladder Neoplasms chemically induced, Water Pollutants adverse effects
- Abstract
Induction of cancer by inorganic arsenic occurs inconsistently between species and between routes of exposure, and it exhibits different dose-response relationships between different target organs. Inhaled or ingested arsenic causes cancer in humans but not in other species. Inhaled arsenic primarily induces lung cancer, whereas ingested arsenic induces cancer at multiple sites, including the skin and various other organs. Cancer potency appears to vary by route of exposure (ingestion or inhalation) and by organ site, and increases markedly at higher exposures in some instances. To understand what might explain these inconsistencies, we reviewed several hypotheses about the mechanism of cancer induction by arsenic. Arsenic disposition does not provide satisfactory explanations. Induction of cell proliferation by arsenic is a mechanism of carcinogenesis that is biologically plausible and compatible with differential effects for species or differential dose rates for organ sites. The presence of other carcinogens, or risk modifiers, at levels that correlate with arsenic in drinking water supplies, may be a factor in all three inconsistencies: interspecies specificity, organ sensitivity to route of administration, and organ sensitivity to dose rate.
- Published
- 1996
- Full Text
- View/download PDF
48. A transient three-plasmid expression system for the production of high titer retroviral vectors.
- Author
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Soneoka Y, Cannon PM, Ramsdale EE, Griffiths JC, Romano G, Kingsman SM, and Kingsman AJ
- Subjects
- 3T3 Cells, Animals, Antigens, Polyomavirus Transforming physiology, Base Sequence, Butyrates pharmacology, Butyric Acid, Cell Line, Cloning, Molecular methods, Cytomegalovirus genetics, Genes, Reporter, Genes, Viral, Genes, env, Genes, gag, Genes, pol, Helper Viruses physiology, Humans, Mice, Molecular Sequence Data, Promoter Regions, Genetic, Replication Origin, Simian virus 40 genetics, Transfection, Viral Structural Proteins genetics, Gene Expression Regulation, Viral drug effects, Genetic Vectors genetics, Moloney murine leukemia virus genetics, Plasmids genetics
- Abstract
We have constructed a series of MLV-based retroviral vectors and packaging components expressed from the CMV promoter and carried on plasmids containing SV40 origins of replication. These two features greatly enhanced retroviral gene expression when introduced into cell lines carrying the SV40 large T antigen. The two packaging components, gag-pol and env, were placed on separate plasmids to reduce helper virus formation. Using a highly transfectable human cell line and sodium butyrate to further increase expression of each component, we achieved helper-free viral stocks of approximately 10(7) infectious units/ml by 48 h after transient co-transfection with the three plasmid components. This system can be used both for the generation of high titer retroviral stocks for transduction and for the rapid screening of a large number of MLV gag-pol or env mutants.
- Published
- 1995
- Full Text
- View/download PDF
49. Alkaline phosphatase. Pandora's box opens.
- Author
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Griffiths JC
- Subjects
- Adult, Alkaline Phosphatase history, Alkaline Phosphatase metabolism, Cell Death, Child, History, 20th Century, Humans, Infant, Isoelectric Focusing, Isoenzymes metabolism, Alkaline Phosphatase analysis, CD4-Positive T-Lymphocytes enzymology, HIV Infections enzymology, Isoenzymes analysis, Neoplasms enzymology
- Published
- 1994
50. Acquired Brown's syndrome.
- Author
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Barnett AJ, Griffiths JC, and West RH
- Subjects
- Adult, Diplopia etiology, Female, Humans, Publishing, Ophthalmoplegia complications, Scleroderma, Systemic complications
- Published
- 1993
- Full Text
- View/download PDF
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