Response of skeletal muscle mitochondria to hypoxia. (1/7)

This review explores the current concepts relating the structural and functional modifications of skeletal muscle mitochondria to the molecular mechanisms activated when organisms are exposed to a hypoxic environment. In contrast to earlier assumptions it is now established that permanent or long-term exposure to severe environmental hypoxia decreases the mitochondrial content of muscle fibres. Oxidative muscle metabolism is shifted towards a higher reliance on carbohydrates as a fuel, and intramyocellular lipid substrate stores are reduced. Moreover, in muscle cells of mountaineers returning from the Himalayas, we find accumulations of lipofuscin, believed to be a mitochondrial degradation product. Low mitochondrial contents are also observed in high-altitude natives such as Sherpas. In these subjects high-altitude performance seems to be improved by better coupling between ATP demand and supply pathways as well as better metabolite homeostasis. The hypoxia-inducible factor 1 (HIF-1) has been identified as a master regulator for the expression of genes involved in the hypoxia response, such as genes coding for glucose transporters, glycolytic enzymes and vascular endothelial growth factor (VEGF). HIF-1 achieves this by binding to hypoxia response elements in the promoter regions of these genes, whereby the increase of HIF-1 in hypoxia is the consequence of a reduced degradation of its dominant subunit HIF-1a. A further mechanism that seems implicated in the hypoxia response of muscle mitochondria is related to the formation of reactive oxygen species (ROS) in mitochondria during oxidative phosphorylation. How exactly ROS interfere with HIF-1a as well as MAP kinase and other signalling pathways is debated. The current evidence suggests that mitochondria themselves could be important players in oxygen sensing.  (+info)

Forty years of stress research: principal remaining problems and misconceptions. (2/7)

An overview of the main problems and misconceptions in the clinical application and theoretic evaluation of the stress concept reveals that the same 10 problems appear to cause the greatest difficulties in its application, irrespective of the specialty in which it is used: (1) the correct definition of stress, stressors and the general adaptation syndrome; (2) the concept of nonspecificity in biology and medicine; (3) the conditioning of stress responses by diverse endogenous (mainly genetically determined) and exogenous (environmental) factors; (4) the relation between the genral and the local adaptation syndromes; (5) the difference between direct and indirect pathogens; (6) the definition of the morbid lesions in whose pathogenesis stress plays a particularly prominent role--the so-called diseases of adaptation; (7) the role of genetics versus that of factors under voluntary self-control in mastering biologic stress; (8) the mode of action of syntoxic and catatoxic hormones, drugs and behavioural attitudes; (9) the so-called first mediator of the stress response, which carries the message that a state of stress exists from the directly affected area to the neurohormonal regulatory centres; and (10) the prophylaxis and treatment of stress-induced damage by pharmacologic and behavioural techniques.  (+info)

Neurosteroids in the context of stress: implications for depressive disorders. (3/7)

Animal models indicate that the neuroactive steroids 3alpha,5alpha-THP (allopregnanolone) and 3alpha,5alpha-THDOC (allotetrahydroDOC) are stress responsive, serving as homeostatic mechanisms in restoring normal GABAergic and hypothalamic-pituitary-adrenal (HPA) function following stress. While neurosteroid increases to stress are adaptive in the short term, animal models of chronic stress and depression find lower brain and plasma neurosteroid concentrations and alterations in neurosteroid responses to acute stressors. It has been suggested that disruption in this homeostatic mechanism may play a pathogenic role in some psychiatric disorders related to stress. In humans, neurosteroid depletion is consistently documented in patients with current depression and may reflect their greater chronic stress. Women with the depressive disorder, premenstrual dysphoric disorder (PMDD), have greater daily stress and a greater rate of traumatic stress. While results on baseline concentrations of neuroactive steroids in PMDD are mixed, PMDD women have diminished functional sensitivity of GABA(A) receptors and our laboratory has found blunted allopregnanolone responses to mental stress relative to non-PMDD controls. Similarly, euthymic women with histories of clinical depression, which may represent a large proportion of PMDD women, show more severe dysphoric mood symptoms and blunted allopregnanolone responses to stress versus never-depressed women. It is suggested that failure to mount an appropriate allopregnanolone response to stress may reflect the price of repeated biological adaptations to the increased life stress that is well documented in depressive disorders and altered allopregnanolone stress responsivity may also contribute to the dysregulation seen in HPA axis function in depression.  (+info)

The representation of stimulus orientation in the early stages of somatosensory processing. (4/7)

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Immunological and inflammatory responses to organic dust in agriculture. (5/7)

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Stress reactivity and corticolimbic response to emotional faces in adolescents. (6/7)

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The stress analogy. (7/7)

The author calls attention to the advantages of using the engineering meaning of stress and strain when applying these terms to describe the effects of social and physical forces on people. Such an analogy opens up the possibility of measuring the amount of damage from excess stresses existing in people, as well as estimating their limits and remaining strengths. It also explains why some people are more affected by a given stressor than other people.  (+info)