Physical activity and bone development during childhood: insights from animal models

2008 ◽  
Vol 105 (1) ◽  
pp. 334-341 ◽  
Author(s):  
Mark R. Forwood
Keyword(s):  
Animal Studies ◽  
Bone Development ◽  
Animal Experiments ◽  
Cell Activity ◽  
Human Growth ◽  
Adaptive Responses ◽  
Static Loads ◽  
Long Duration ◽  
Effective Training ◽  
Hypothalamic Pituitary Axis

Animal studies illustrate greater structural and material adaptations of growing bone to exercise than in adult bones but do not define effective training regimes to optimize bone strength in children. Controlled loading studies in turkey, rat, or mouse bones have revealed mechanisms of mechanotransduction and loading characteristics that optimize the modeling response to applied strains. Insights from these models reveal that static loads do not play a role in mechanotransduction and that bone formation is threshold driven and dependent on strain rate, amplitude, and partitioning of the load. That is, only a few cycles of loading are required at any time to elicit an adaptive response, and distributed bouts of loading, incorporating rest periods, are more osteogenic than single sessions of long duration. These parameters of loading have been translated into feasible public health interventions that exploit the insights gained from animal experiments to achieve adaptive responses in children and adolescents. Studies manipulating estrogen receptors (ER) in mice also demonstrate that skeletal sensitivity to loading during the peripubertal period is due to a direct regulation of mechanotransduction pathways by ER, and not just a simple enhancement of cell activity already marshaled by the hypothalamic-pituitary axis. Unfortunately, because the rate and timing of growth in small animals are completely different from those in humans, these models can be poor tools to elucidate periods during growth in youths, during which the skeleton is more sensitive to loading. However, there are insights from studies of human growth that can improve the interpretation of data from such studies of growth and development in animals.

What Does the Animal Model Teach Us about the Effects of Physical Activity on Growing Bone?

2006 ◽  
Vol 18 (3) ◽  
pp. 282-289 ◽  
Author(s):  
Mark R. Forwood
Keyword(s):  
Physical Activity ◽  
Animal Model ◽  
Growth And Development ◽  
Animal Studies ◽  
Human Growth ◽  
Skeletal Maturation ◽  
Osteogenic Potential ◽  
Static Loads ◽  
Long Duration ◽  
Human Growth And Development

Experiments to design physical activity programs that optimize their osteogenic potential are difficult to accomplish in humans. The aim of this article is to review the contributions that animal studies have made to knowledge of the loading conditions that are osteogenic to the skeleton during growth, as well as to consider to what extent animal studies fail to provide valid models of physical activity and skeletal maturation. Controlled loading studies demonstrate that static loads are ineffective, and that bone formation is threshold driven and dependent on strain rate, amplitude, and duration of loading. Only a few loading cycles per session are required, and distributed bouts are more osteogenic than sessions of long duration. Finally, animal models fail to inform us of the most appropriate ways to account for the variations in biological maturation that occur in our studies of children and adolescents, requiring the use of techniques for studying human growth and development.

scholarly journals Vasopressin at Central Levels and Consequences of Dehydration

2016 ◽  
Vol 68 (Suppl. 2) ◽  
pp. 19-23 ◽  
Author(s):  
Daniel G. Bichet
Keyword(s):  
Animal Studies ◽  
Transient Receptor Potential ◽  
Animal Experiments ◽  
Extracellular Fluid ◽  
Receptor Potential ◽  
Circumventricular Organ ◽  
Thermal Perception ◽  
Trpv1 Channel ◽  
Vasopressin Release ◽  
Transient Receptor

Disorders of water balance are a common feature of clinical practice. An understanding of the physiology and pathophysiology of central vasopressin release and perception of thirst is the key to diagnosis and management of these disorders. Mammals are osmoregulators; they have evolved mechanisms that maintain extracellular fluid osmolality near a stable value, and, in animal studies, osmoregulatory neurons express a truncated delta-N variant of the transient receptor potential vannilloid (TRPV1) channel involved in hypertonicity and thermal perception while systemic hypotonicity might be perceived by TRPV4 channels. Recent cellular and optogenetic animal experiments demonstrate that, in addition to the multifactorial process of excretion, circumventricular organ sensors reacting to osmotic pressure and angiotensin II, subserve genesis of thirst, volume regulation and behavioral effects of thirst avoidance.

Oxidants and antioxidants in exercise

1995 ◽  
Vol 79 (3) ◽  
pp. 675-686 ◽  
Author(s):  
C. K. Sen
Keyword(s):  
Oxidative Stress ◽  
Physical Activity ◽  
Exercise Training ◽  
Animal Studies ◽  
Dietary Habits ◽  
Antioxidant Defenses ◽  
Current State ◽  
Strenuous Physical Exercise ◽  
Long Duration ◽  
Exercise Induced

There is consistent evidence from human and animal studies that strenuous physical exercise may induce a state wherein the antioxidant defenses of several tissues are overwhelmed by excess reactive oxygen. A wide variety of physiological and dietary antioxidants act in concert to evade such a stress. Submaximal long-duration exercise training may augment the physiological antioxidant defenses in several tissues; however, this enhanced protection may not be sufficient to completely protect highly fit individuals from exhaustive exercise-induced oxidative stress. Regular physical activity in association with dietary habits that ensure adequate supply of a combination of appropriate antioxidants may be expected to yield desirable results. The significance of this area of research, current state of information, and possibilities of further investigation are briefly reviewed.

The Implications of Microarray Technology for Animal Use in Scientific Research

2002 ◽  
Vol 30 (4) ◽  
pp. 459-465 ◽  
Author(s):  
Elizabeth S. Jenkins ◽  
Caren Broadhead ◽  
Robert D. Combes
Keyword(s):  
Animal Studies ◽  
Animal Experiments ◽  
Scientific Research ◽  
Toxicity Testing ◽  
Laboratory Animals ◽  
Biological Research ◽  
Microarray Technology ◽  
Single Experiment ◽  
Technical Problems ◽  
Animal Use

Microarray technology has the potential to affect the number of laboratory animals used, the severity of animal experiments, and the development of non-animal alternatives in several areas of scientific research. Microarrays can contain hundreds or thousands of microscopic spots of DNA, immobilised on a solid support, and their use enables global patterns of gene expression to be determined in a single experiment. This technology is being used to improve our understanding of the operation of biological systems during health and disease, and their responses to chemical insults. Although it is impossible to predict with certainty any future trends regarding animal use, microarray technology might not initially reduce animal use, as is often claimed to be the case. The accelerated pace of research as a result of the use of microarrays could increase overall animal use in basic and applied biological research, by increasing the numbers of interesting genes identified for further analysis, and the number of potential targets for drug development. Each new lead will require further evaluation in studies that could involve animals. In toxicity testing, microarray studies could lead to increases in animal studies, if further confirmatory and other studies are performed. However, before such technology can be used more extensively, several technical problems need to be overcome, and the relevance of the data to biological processes needs to be assessed. Were microarray technology to be used in the manner envisaged by its protagonists, there need to be efforts to increase the likelihood that its application will create new opportunities for reducing, refining and replacing animal use. This comment is a critical assessment of the possible implications of the application of microarray technology on animal experimentation in various research areas, and makes some recommendations for maximising the application of the Three Rs.

scholarly journals Pathology Study Design, Conduct, and Reporting to Achieve Rigor and Reproducibility in Translational Research Using Animal Models

ILAR Journal ◽  
2018 ◽  
Vol 59 (1) ◽  
pp. 4-12 ◽  
Author(s):  
Jeffrey I Everitt ◽  
Piper M Treuting ◽  
Cheryl Scudamore ◽  
Rani Sellers ◽  
Patricia V Turner ◽  
...  
Keyword(s):  
Animal Models ◽  
Best Practices ◽  
Translational Research ◽  
Safety Assessment ◽  
Animal Studies ◽  
Animal Experiments ◽  
Study Data ◽  
Track Record ◽  
Preclinical Animal Models

AbstractIn translational research, animal models are an important tool to aid in decision-making when taking potential therapies into human clinical trials. Recently, there have been a number of papers that have suggested limited concordance of preclinical animal experiments with subsequent human clinical experience. Assessments of preclinical animal studies have led to concerns about the reproducibility of data and have highlighted the need for an emphasis on rigor and quality in the planning, conduct, analysis, and reporting of such studies. The incorporation of a wider role for the comparative pathologist using pathology best practices in the planning and conduct of animal model-based research is one way to increase the quality and reproducibility of data. The use of optimal design and planning of tissue collection, incorporation of pathology methods into written protocols, conduct of pathology procedures using accepted best practices, and the use of optimal pathology analysis and reporting methods enhance the quality of the data acquired from many types of preclinical animal models and studies. Many of these pathology practices are well established in the discipline of toxicologic pathology and have a proven and useful track record in enhancing the data from animal-based studies used in safety assessment of human therapeutics. Some of this experience can be adopted by the wider community of preclinical investigators to increase the reproducibility of animal study data.

Galanin gene expression in radiothyroidectomy-induced thyrotroph adenomas

1996 ◽  
Vol 271 (1) ◽  
pp. E24-E30
Author(s):  
J. F. Hyde ◽  
J. P. Moore ◽  
K. W. Drake ◽  
D. G. Morrison
Keyword(s):  
Gene Expression ◽  
Thyroid Hormones ◽  
Anterior Pituitary ◽  
Human Growth ◽  
Mrna Levels ◽  
Male Mice ◽  
Pituitary Glands ◽  
Positive Regulators ◽  
Hypothalamic Pituitary Axis ◽  
Iodine 131

Galanin gene expression is markedly increased in the anterior pituitary glands of estrogen-treated rats (lactotroph hyperplasia) as well as human growth hormone-releasing hormone transgenic mice (somatotroph hyperplasia). The objective of this study was to examine galanin in a mouse model of thyrotroph adenoma formation. Male mice were radiothyroidectomized by use of iodine-131 (131I), and galanin peptide levels were assessed in the hypothalamic-pituitary axis. Immunoreactive galanin concentrations in the anterior pituitaries of 131I-treated mice were decreased 80% at 3, 6, 9, and 12 mo after radiothyroidectomy. Galanin peptide levels in the hypothalamus were decreased 20-25% at these times. Treatment with either estradiol or 3,3',5-triiodo-L-thyronine increased galanin peptide concentrations in the anterior pituitaries of 131I-treated mice, but neither treatment restored galanin concentrations. Galanin mRNA levels were decreased > 80% 1 yr after radiothyroidectomy. We conclude that, unlike animal models of lactotroph and somatotroph hyperplasia, galanin gene expression is suppressed throughout the development of thyrotroph adenomas, suggesting that galanin does not have a stimulatory role in the proliferation of thyrotrophs. Moreover, these data show that thyroid hormones are important positive regulators of galanin gene expression in the mouse and that estrogen may stimulate galanin gene expression in the absence of thyroid hormones.

Hypoxia as a key player in the AKI-to-CKD transition

2014 ◽  
Vol 307 (11) ◽  
pp. F1187-F1195 ◽  
Author(s):  
Shinji Tanaka ◽  
Tetsuhiro Tanaka ◽  
Masaomi Nangaku
Keyword(s):  
Epithelial Cells ◽  
Animal Studies ◽  
Hypoxia Inducible Factor ◽  
Animal Experiments ◽  
Kidney Injury ◽  
Inflammatory Cells ◽  
Complete Recovery ◽  
Tubular Epithelial Cells ◽  
Capillary Rarefaction ◽  
Endothelial Growth Factor

Recent clinical and animal studies have shown that acute kidney injury (AKI), even if followed by complete recovery of renal function, can eventually result in chronic kidney disease (CKD). Renal hypoxia is emerging as a key player in the pathophysiology of the AKI-to-CKD transition. Capillary rarefaction after AKI episodes induces renal hypoxia, which can in turn profoundly affect tubular epithelial cells, (myo)fibroblasts, and inflammatory cells, culminating in tubulointerstitial fibrosis, i.e., progression to CKD. Damaged tubular epithelial cells that fail to redifferentiate might supply a decreased amount of vascular endothelial growth factor and contribute to capillary rarefaction, thus aggravating hypoxia and forming a vicious cycle. Mounting evidence also shows that epigenetic changes are closely related to renal hypoxia in the pathophysiology of CKD progression. Animal experiments suggest that targeting hypoxia is a promising strategy to block the transition from AKI to CKD. However, the precise mechanisms by which hypoxia induces the AKI-to-CKD transition and by which hypoxia-inducible factor activation can exert a protective effect in this context should be clarified in further studies.

scholarly journals The conflicting effects of maternal nutrient restriction and early-life obesity on renal health

2011 ◽  
Vol 70 (2) ◽  
pp. 268-275 ◽  
Author(s):  
H. P. Fainberg ◽  
H. Budge ◽  
M. E. Symonds
Keyword(s):  
Early Life ◽  
Animal Studies ◽  
Structural Changes ◽  
Maternal Nutrition ◽  
Renal Diseases ◽  
Low Grade ◽  
Adaptive Responses ◽  
Chronic Inflammatory Response ◽  
Cellular Apoptosis ◽  
Juvenile Obesity

Epidemiological and animal studies have demonstrated that early-life nutrition alters the metabolic responses and generates structural changes in complex tissues, such as the kidneys, which may lead to a reduction in the offspring lifespan. Independently, obesity induces a spontaneous low-grade chronic inflammatory response by modulating several of the major metabolic pathways that ultimately compromise long-term renal health. However, the combined effects of maternal nutrition and early-life obesity in the development of renal diseases are far from conclusive. Previous results, using the ovine model, demonstrated that the combination of a reduction in fetal nutrition and juvenile obesity induced a series of adaptations associated with severe metabolic syndrome in the heart and adipose tissue. Surprisingly, exposure to an obesogenic environment in the kidney of those offspring produced an apparent reduction in glomerulosclerosis in relation to age- and weight-matched controls. However, this reduction in cellular apoptosis was accompanied by a rise in glomerular filtration rate and blood pressure of equal intensity when compared with obese controls. The intention of this review is to explain the adaptive responses observed in this model, based on insights into the mechanism of renal fetal programming, and their potential interactions with some of the metabolic changes produced by obesity.

Varieties of Residual Experience

1980 ◽  
Vol 32 (3) ◽  
pp. 365-386 ◽  
Author(s):  
L. Weiskrantz
Keyword(s):  
Human Subject ◽  
Animal Studies ◽  
Animal Experiments ◽  
Occipital Lobe ◽  
Preliminary Evidence ◽  
Clinical Findings ◽  
Residual Capacity ◽  
Different Dimensions ◽  
Movement Orientation ◽  
Discrimination Methods

The apparent discrepancy between the results of animal studies and clinical findings on the effects of occipital lobe damage became even greater with the results of animal experiments over the past 20 years in which subjects showed significant residual vision. But there is now evidence that the human subject can also show considerable residual capacity. It appears to be extremely helpful to use forced choice discrimination methods and specific training, as with animals, rather than to depend on verbal commentary by the human subject, who may be unaware of his discriminative capacity. Where man and monkey can be compared, it would appear that they are not qualitatively different, and that residual capacity is biased for detection and localisation rather than identification. Preliminary evidence is presented on the incidence of “blind-sight” and related aspects of residual function, including examination of different dimensions such as form, detection, movement, orientation, and spatial localisation within field defects. Some of these dimensions appear to be dissociable, but each also seems capable of disconnexion from the subject's own commentary and acknowledgement.

Assisted reproductive research: Laser assisted hatching and spindle detection (spindle view technique)

2004 ◽  
Vol 52 (1) ◽  
pp. 113-123 ◽  
Author(s):  
Katalin Kanyó ◽  
J. Konc ◽  
L. Solti ◽  
S. Cseh
Keyword(s):  
Animal Studies ◽  
Harmful Effect ◽  
Animal Experiments ◽  
Oocyte Quality ◽  
Assisted Hatching ◽  
Safe Procedure ◽  
Living Mouse ◽  
Reproductive Techniques ◽  
Developmental Capacity

Animal experiments are very important for the development of new assisted reproductive techniques (ART) for use in human and animal reproductive medicine. Most technical aspects of reproductive manipulation of humans and animals are very similar, and many components of successful human ART used nowadays have been derived from animal studies. In this study we examined (1) the use of 'non-contact' laser for assisted hatching, (2) whether spindles in living mouse oocytes could safely be imaged/examined by polarisation microscope (polscope) and (3) the influence of environment (e.g. temperature, in vitro culture, etc.) on spindle detection/visualisation. The data of the study presented here show that (1) laser assisted hatching (AH) is a fast, very accurate and safe procedure without any harmful effect on embryo development and it can support very effectively the implantation of embryos, (2) the use of polscope facilitates the evaluation of oocyte quality and the selection of oocytes with spindle, (3) by monitoring the spindle position during intracytoplasmic sperm injection (ICSI), we can reduce spindle damage and increase the chance of fertilisation. Further studies are underway to test the hypothesised connection between spindle birefringence and developmental capacity of oocytes/embryos.

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