3,276 research outputs found
Chronic psychosocial stressors in adulthood: Studies in mice, rats and tree shrews
No full textAbstractHuman psychological stress is the major environmental risk factor for major depression and certain of the anxiety disorders. Psychological stressors often occur in the context of the adult social environment, and they or the memory formed of them impact on the individual across an extended period, thereby constituting chronic psychosocial stress (CPS). Psychosocial stressors often involve loss to the individual, such as the ending of a social relationship or the onset of interpersonal conflict leading to loss of social control and predictability. Given the difficulty in studying the etio-pathophysiological processes mediating between CPS and brain and behavior pathologies in human, considerable effort has been undertaken to study manipulations of the social environment that constitute adulthood chronic psychosocial stressors in other mammals. The majority of such research has been conducted in rodents; the focus for a considerable time period was on rats and more recently both rats and mice have been investigated, the latter species in particular providing the opportunity for essential gene x chronic psychosocial stressor interaction studies. Key studies in the tree shrew demonstrate that this approach should not be limited to rodents, however. The animal adult CPS paradigms are based on resident-intruder confrontations. These are typified by the intruder-subject's brief proximate interactions with and attacks by, and otherwise continuous distal exposure to, the resident stressor. In contrast to humans where cognitive capacities are such that the stressor pertains in its physical absence, the periods of continuous distal exposure are apparently essential in these species. Whilst the focus of this review is on the stressor rather than the stress response, we also describe some of the depression- and anxiety disorder-relevant effects on behavior, physiology and brain structure-function of chronic psychosocial stressors, as well as evidence for the predictive validity of such models in terms of chronic antidepressant efficacy. Nonetheless, there are limitations in the methods used to date, most importantly the current emphasis on studying CPS in males, despite the much higher disorder prevalence in women compared to men. Future studies will need to address these limitations
Effects of antenatal dexamethasone treatment on glucocorticoid receptor and calcyon gene expression in the prefrontal cortex of neonatal and adult common marmoset monkeys
No full textBACKGROUND: Synthetic glucocorticoids such as dexamethasone (DEX) are commonly used to promote fetal lung maturation in at-risk preterm births, but there is emerging evidence of subsequent neurobehavioral abnormalities in these children e.g. problems with inattention/hyperactivity. However, molecular pathways mediating effects of glucocorticoid overexposure on motor and cognitive development are poorly understood. METHODS: In this study with common marmoset monkeys, we investigated for neonatal and adulthood effects of antenatal DEX treatment on the expression of the corticosteroid receptors and also calcyon, a risk gene for attention-deficit/hyperactivity disorder, in the prefrontal cortex (PFC). Pregnant marmosets were exposed to DEX (5 mg/kg body weight) or vehicle during early (days 42-48) or late (days 90-96) stages of the 144-day pregnancy. RESULTS: In neonates, relative to controls, glucocorticoid receptor (GR) mRNA levels were significantly reduced after the late DEX treatment in the medial, orbital and dorsal PFC and after the early DEX treatment in the dorsal PFC. The early DEX exposure, specifically, resulted in significant reduction in calcyon mRNA expression in the medial, orbital, dorsal and lateral PFC relative to controls. Mineralocorticoid receptor (MR) mRNA levels were not significantly affected by DEX treatment. In adults, PFC GR, calcyon, and MR mRNA levels were not significantly affected by early or late prenatal DEX treatment. CONCLUSION: These findings indicate that antenatal DEX treatment could lead to short-term alterations in PFC expression of the GR and calcyon genes, with possible neurodevelopmental functional consequences
The resistance of cortical bone tissue to failure under cyclic loading is reduced with alendronate
No full textBisphosphonates are the most prescribed preventative treatment for osteoporosis. However, their long-term use has recently been associated with atypical fractures of cortical bone in patients who present with low-energy induced breaks of unclear pathophysiology. The effects of bisphosphonates on the mechanical properties of cortical bone have been exclusively studied under simple, monotonic, quasi-static loading. This study examined the cyclic fatigue properties of bisphosphonate-treated cortical bone at a level in which tissue damage initiates and is accumulated prior to frank fracture in low-energy situations. Physiologically relevant, dynamic, 4-point bending applied to beams (1.5 mm × 0.5 mm × 10 mm) machined from dog rib (n=12/group) demonstrated mechanical failure and micro-architectural features that were dependent on drug dose (3 groups: 0, 0.2, 1.0mg/kg/day; alendronate [ALN] for 3 years) with cortical bone tissue elastic modulus (initial cycles of loading) reduced by 21% (p<0.001) and fatigue life (number of cycles to failure) reduced in a stress-life approach by greater than 3-fold with ALN1.0 (p<0.05). While not affecting the number of osteons, ALN treatment reduced other features associated with bone remodeling, such as the size of osteons (-14%; ALN1.0: 10.5±1.8, VEH: 12.2±1.6, ×10(3) μm2; p<0.01) and the density of osteocyte lacunae (-20%; ALN1.0: 11.4±3.3, VEH: 14.3±3.6, ×10(2) #/mm2; p<0.05). Furthermore, the osteocyte lacunar density was directly proportional to initial elastic modulus when the groups were pooled (R=0.54, p<0.01). These findings suggest that the structural components normally contributing to healthy cortical bone tissue are altered by high-dose ALN treatment and contribute to reduced mechanical properties under cyclic loading conditions.NOTICE: this is the author's version of a work that was accepted for publication in Bone. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Bone, Volume 64 (July 2014) DOI: 10.1016/j.bone.2014.03.045Peer reviewe
The developmental impact of prenatal stress, prenatal dexamethasone and postnatal social stress on physiology, behaviour and neuroanatomy of primate offspring: studies in rhesus macaque and common marmoset
No full textRATIONALE: Exposure of the immature mammalian brain to stress factors, including stress levels of glucocorticoids, either prenatally or postnatally, is regarded as a major regulatory factor in short- and long-term brain function and, in human, as a major aetiological factor in neuropsychiatric disorders. Experimental human studies are not feasible and animal studies are required to demonstrate causality and elucidate mechanisms. A number of studies have been conducted and reviewed in rodents but there are relatively few studies in primates. OBJECTIVES: Here we present an overview of our published studies and some original data on the effects of: (1) prenatal stress on hypothalamic-pituitary-adrenal (HPA) re/activity and hippocampus neuroanatomy in juvenile-adolescent rhesus macaques; (2) prenatal dexamethasone (DEX) on HPA activity, behaviour and prefrontal cortex neuroanatomy in infant-adolescent common marmosets; (3) postnatal daily parental separation stress on HPA re/activity, behaviour, sleep and hippocampus and prefrontal cortex neuroanatomy in infant-adolescent common marmoset. RESULTS: Prenatal stress increased basal cortisol levels and reduced neurogenesis in macaque. Prenatal DEX was without effect on HPA activity and reduced social play and skilled motor behaviour in marmoset. Postnatal social stress increased basal cortisol levels, reduced social play, increased awakening and reduced hippocampal glucocorticoid and mineralocorticoid receptor expression in marmoset. CONCLUSIONS: Perinatal stress-related environmental events exert short- and long-term effects on HPA function, behaviour and brain status in rhesus macaque and common marmoset. The mechanisms mediating the enduring effects remain to be elucidated, with candidates including increased basal HPA function and epigenetic programming
Differential Excretion of Urinary Oestrogen by Breeding Females and Daughters in the Red-Bellied Tamarin (Saguinus labiatus)
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American Society of Biomechanics Journal of Biomechanics Award 2013: Cortical bone tissue mechanical quality and biological mechanisms possibly underlying atypical fractures
No full textThe biomechanics literature contains many well-understood mechanisms behind typical fracture types that have important roles in treatment planning. The recent association of "atypical" fractures with long-term use of drugs designed to prevent osteoporosis has renewed interest in the effects of agents on bone tissue-level quality. While this class of fracture was recognized prior to the introduction of the anti-resorptive bisphosphonate drugs and recently likened to stress fractures, the mechanism(s) that lead to atypical fractures have not been definitively identified. Thus, a causal relationship between these drugs and atypical fracture has not been established. Physicians, bioengineers and others interested in the biomechanics of bone are working to improve fracture-prevention diagnostics, and the design of treatments to avoid this serious side-effect in the future. This review examines the mechanisms behind the bone tissue damage that may produce the atypical fracture pattern observed increasingly with long-term bisphosphonate use. Our recent findings and those of others reviewed support that the mechanisms behind normal, healthy excavation and tunnel filling by bone remodeling units within cortical tissue strengthen mechanical integrity. The ability of cortical bone to resist the damage induced during cyclic loading may be altered by the reduced remodeling and increased tissue age resulting from long-term bisphosphonate treatment. Development of assessments for such potential fractures would restore confidence in pharmaceutical treatments that have the potential to spare millions in our aging population from the morbidity and death that often follow bone fracture.Peer reviewe
Llywelyn ab Iorwerth : the making of a Welsh prince
No full textLlywelyn ab Iorwerth (1173-1140) has long been considered one of the leading heroes of Wales. The life and rule of Llywelyn, known as Llywelyn the Great, is explored in detail in this thesis. The grandson of Owain Gwynedd, ruler of North Wales from 1137-1170, Llywelyn grew up during the period of turmoil following Owain’s death. After wresting control of Gwynedd from his rival family members in the latter decade of the 12th century, he proceeded to gain recognition as the foremost representative of Wales on the political stage.
Although viewed as a legendary hero in Welsh history, poetry and culture, Llywelyn's route to power is more complex than that. The thesis explores the development of the man from rebel and warlord, to leader and spokesman, to statesman, traces the expansion of his hegemony throughout Wales, and discusses the methods he used to gain and maintain power. Particular attention is paid to his use of family, marriage, allies, rivals and the church to achieve his goals. These insights can be derived from the surviving charters, letters, and other acta of Llywelyn and the Royal Chancery of England, the titles accorded therein, Welsh and English chronicles, as well as, occasionally, Venedotian Poetry. Finally, this thesis seeks to address the limitations on Llywelyn’s successes, in light of succeeding events and concludes with a discussion of Llywelyn’s legendary status in the modern world
Detecting intestinal ischemia using near infrared spectroscopy
No full textBlood supply to the intestine can suddenly be interrupted. Acute mesenteric intestinal ischemia often requires invasive surgery to restore blood supply to the intestine. Early correction of vascular insufficiency is the most important factor in improving patient survival when confronted with acute mesenteric intestinal ischemia. A prolonged loss of blood flow results in irreversible damage to the intestine that can lead to death. It is also imperative that dead segments of the intestines be removed. Several subjective criteria are relied upon to differentiate viable from non-viable tissue, unfortunately, these criteria can lead to an inaccurate assessment. A porcine model of intestinal ischemia was used to determine the efficacy of using near infrared (NIR) spectroscopy to find ischemic segments of the intestine and detect the onset of reperfusion following resolution of vascular occlusion. Nine segments of intestine were identified and six were assigned to three treatment groups; (1) segments undergoing no vascular manipulations, (2) segments undergoing arterial/venous occlusion and (3) segments undergoing arterial/venous occlusion followed by reperfusion. The remaining segments were used as spacers and interposed between each of the ischemia segments. A classification model, using partial least square discriminant analysis, was built on the spectra collected from the segments with no vascular manipulations and the segments that were solely subjected to arterial/venous occlusion. The spectra collected from the intestinal segments that experienced both occlusion and reperfusion were used to test the classification model. The model was able to detect and distinguish ischemic intestinal tissue with a specificity and sensitivity exceeding 80% with an overall classification accuracy of 89%. The method appears to be well suited as an intra-operative assessment method when intestinal ischemia is a concern.Michael G. Sowa, Elicia Kohlenberg, Jeri R. Payette, Lorenzo Leonardi, Michelle A. Levasseur and Christopher B. Rile
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