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Human Physiology (human + physiology)
Selected AbstractsPlasma IL-6 concentration is inversely related to insulin sensitivity, and acute-phase proteins associate with glucose and lipid metabolism in healthy subjectsDIABETES OBESITY & METABOLISM, Issue 6 2005M. K. Heliövaara Aim:, It has been shown that atherosclerosis is an inflammatory disease. Recent data suggest that inflammation precedes type 2 diabetes. Hence, we wanted to study the interrelationship between IL-6, insulin sensitivity, lipids and numerous acute-phase proteins. Methods:, Twenty-one healthy individuals [16 males/5 females, age 27.9 ± 1.8 years, body mass index (BMI) 24.1 ± 0.8 kg/m2] participated in the study. Each patient went through a 4-h hyperinsulinaemic (40 mU/m2/min) euglycaemic clamp and 4-h saline infusion. Blood samples were taken before and at the end of the infusions. Results:, Plasma interleukin (IL)-6 concentration correlated inversely with insulin sensitivity (M -value) (r = ,0.49, p < 0.05). Moreover, the plasma levels of IL-6 associated with c-peptide (r = 0.49, p < 0.05), fat% (r = 0.43, p < 0.05) and diastolic blood pressure (r = 0.46, p < 0.05). ,-1-acid glycoprotein was related to HbA1c (r = 0.47, p < 0.05), insulin (r = 0.55, p < 0.01), diastolic blood pressure (r = 0.58, p < 0.01), systolic blood pressure (r = 0.58, p < 0.01) and triglycerides (r = 0.58, p < 0.01). Haptoglobin was correlated with insulin (r = 0.46, p < 0.05), total cholesterol (r = 0.61, p < 0.01), BMI (r = 0.58, p < 0.01), fat% (r = 0.63, p < 0.01) and lipid oxidation during clamp (r = 0.43, p < 0.05). Diastolic blood pressure decreased during the clamp (from 78.3 ± 1.9 to 72.1 ± 2.0 mmHg, p = 0.001). Insulin infusion did not affect the serum levels of most acute-phase proteins. Conclusions:, Our study suggests that low grade inflammation, as reflected by IL-6, A1GP and haptoglobin contributes to the regulation of insulin sensitivity, lipid metabolism and blood pressure in normal human physiology. [source] Isolating endogenous visuo-spatial attentional effects using the novel visual-evoked spread spectrum analysis (VESPA) techniqueEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2007Edmund C. Lalor Abstract In natural visual environments, we use attention to select between relevant and irrelevant stimuli that are presented simultaneously. Our attention to objects in our visual field is largely controlled endogenously, but is also affected exogenously through the influence of novel stimuli and events. The study of endogenous and exogenous attention as separate mechanisms has been possible in behavioral and functional imaging studies, where multiple stimuli can be presented continuously and simultaneously. It has also been possible in electroencephalogram studies using the steady-state visual-evoked potential (SSVEP); however, it has not been possible in conventional event-related potential (ERP) studies, which are hampered by the need to present suddenly onsetting stimuli in isolation. This is unfortunate as the ERP technique allows for the analysis of human physiology with much greater temporal resolution than functional magnetic resonance imaging or the SSVEP. While ERP studies of endogenous attention have been widely reported, these experiments have a serious limitation in that the suddenly onsetting stimuli, used to elicit the ERP, inevitably have an exogenous, attention-grabbing effect. Recently we have shown that it is possible to derive separate event-related responses to concurrent, continuously presented stimuli using the VESPA (visual-evoked spread spectrum analysis) technique. In this study we employed an experimental paradigm based on this method, in which two pairs of diagonally opposite, non-contiguous disc-segment stimuli were presented, one pair to be ignored and the other to be attended. VESPA responses derived for each pair showed a strong modulation at 90,100 ms (during the visual P1 component), demonstrating the utility of the method for isolating endogenous visuo-spatial attention effects. [source] The emotions in war: fear and the British and American military, 1914,45HISTORICAL RESEARCH, Issue 185 2001Joanna Bourke In modern warfare, technological innovations are applied to terrifying effect. On the machine-dominated battlefields of the twentieth century, the ability of individuals to master their emotions is crucial to the whole martial enterprise. Fear has widely been recognized as the most fraught of all emotions: it may stimulate combatants to fight and it may cause them to flee. This article examines the proliferation of theories about the nature of this emotion within the British and American forces during the First and Second World Wars. The military recognized the impact of new technologies upon human physiology and psychology, elaborated ways of interpreting the particular threat posed by ,fear' in modern conflicts, and prescribed ways of disciplining the emotional lives of combatants. [source] Circuitry of nuclear factor ,B signalingIMMUNOLOGICAL REVIEWS, Issue 1 2006Alexander Hoffmann Summary:, Over the past few years, the transcription factor nuclear factor (NF)-,B and the proteins that regulate it have emerged as a signaling system of pre-eminent importance in human physiology and in an increasing number of pathologies. While NF-,B is present in all differentiated cell types, its discovery and early characterization were rooted in understanding B-cell biology. Significant research efforts over two decades have yielded a large body of literature devoted to understanding NF-,B's functioning in the immune system. NF-,B has been found to play roles in many different compartments of the immune system during differentiation of immune cells and development of lymphoid organs and during immune activation. NF-,B is the nuclear effector of signaling pathways emanating from many receptors, including those of the inflammatory tumor necrosis factor and Toll-like receptor superfamilies. With this review, we hope to provide historical context and summarize the diverse physiological functions of NF-,B in the immune system before focusing on recent advances in elucidating the molecular mechanisms that mediate cell type-specific and stimulus-specific functions of this pleiotropic signaling system. Understanding the genetic regulatory circuitry of NF-,B functionalities involves system-wide measurements, biophysical studies, and computational modeling. [source] A minipig model of high-fat/high-sucrose diet-induced diabetes and atherosclerosisINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2004Shoumin Xi Summary Type 2 diabetes is a major risk factor of the development of atherosclerosis in humans. However, studies examining mechanisms underlying diabetes-accelerated atherosclerosis have been limited by the lack of suitable humanoid animal models. Pigs have a cardiovascular system that is very similar to that of humans and is useful as a model for human physiology and pathophysiology. In this study, we established a new miniature pig model for studying dyslipidaemia and atherosclerosis in diabetes. Chinese Guizhou minipigs were fed a normal control diet or a high-fat/high-sucrose diet (HFSD) for 6 months. Plasma total cholesterol (TC), high-density lipoprotein cholesterol, triglyceride (TG), insulin and glucose were quantified at monthly intervals. The induction of insulin resistance and dysfunction of the pancreatic ,-cell were assessed by oral glucose tolerance test and insulin sensitivity test. The aortic fatty streak lesions were quantified following lipid staining with Sudan IV. During the feeding period, mild high plasma TC and TG were induced. At the end of 6 months, in HFSD-fed animals, the adipocytes were hypertrophic, fat deposit in the liver was observed, loss of pancreatic ,-cells was observed, and the aortic fatty streak lesions were clearly present in the animals' aortas. Our study established that miniature pigs that were fed a HFSD without adding dietary cholesterol developed insulin resistance, mild diabetes and atherosclerotic lesions. HFSD-fed miniature pigs may be good animal models for research on the treatment of diabetic dyslipidaemia complicated with atherosclerosis. [source] Porcine induced pluripotent stem cells may bridge the gap between mouse and human iPSIUBMB LIFE, Issue 4 2010Miguel A. Esteban Abstract Recently, three independent laboratories reported the generation of induced pluripotent stem cells (iPSCs) from pig (Sus scrofa). This finding sums to the growing list of species (mouse, human, monkey, and rat, in this order) for which successful reprogramming using exogenous factors has been achieved, and multiple others are possibly forthcoming. But apart from demonstrating the universality of the network identified by Shinya Yamanaka, what makes the porcine model so special? On one side, pigs are an agricultural commodity and have an easy and affordable maintenance compared with nonhuman primates that normally need to be imported. On the other side, resemblance (for example, size of organs) of porcine and human physiology is striking and because pigs are a regular source of food the ethical concerns that still remain in monkeys are not applicable. Besides, the prolonged lifespan of pigs compared with other domestic species can allow exhaustive follow up of side effects after transplantation. Porcine iPSCs may thus fill the gap between the mouse model, which due to its ease is preferred for mechanistic studies, and the first clinical trials using iPSCs in humans. However, although these studies are relevant and have created significant interest they face analogous problems that we discuss herein together with potential new directions. © 2010 IUBMB IUBMB Life, 62(4): 277,282, 2010 [source] Ion channels in toxicologyJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2010Iván Restrepo-Angulo Abstract Ion channels play essential roles in human physiology and toxicology. Cardiac contraction, neural transmission, temperature sensing, insulin release, regulation of apoptosis, cellular pH and oxidative stress, as well as detection of active compounds from chilli, are some of the processes in which ion channels have an important role. Regulation of ion channels by several chemicals including those found in air, water and soil represents an interesting potential link between environmental pollution and human diseases; for instance, de novo expression of ion channels in response to exposure to carcinogens is being considered as a potential tool for cancer diagnosis and therapy. Non-specific binding of several drugs to ion channels is responsible for a huge number of undesirable side-effects, and testing guidelines for several drugs now require ion channel screening for pharmaceutical safety. Animal toxins targeting human ion channels have serious effects on the population and have also provided a remarkable tool to study the molecular structure and function of ion channels. In this review, we will summarize the participation of ion channels in biological processes extensively used in toxicological studies, including cardiac function, apoptosis and cell proliferation. Major findings on the adverse effects of drugs on ion channels as well as the regulation of these proteins by different chemicals, including some pesticides, are also reviewed. Association of ion channels and toxicology in several biological processes strongly suggests these proteins to be excellent candidates to follow the toxic effects of xenobiotics, and as potential early indicators of life-threatening situations including chronic degenerative diseases. Copyright © 2010 John Wiley & Sons, Ltd. [source] MicroRNAs: Master Regulators of Ethanol Abuse and Toxicity?ALCOHOLISM, Issue 4 2010Rajesh C. Miranda Ethanol exerts complex effects on human physiology and health. Ethanol is not only addictive, but it is also a fetal teratogen, an adult neurotoxin, and an etiologic agent in hepatic and cardiovascular disease, inflammation, bone loss, and fracture susceptibility. A large number of genes and signaling mechanisms have been implicated in ethanol's deleterious effects leading to the suggestion that ethanol is a "dirty drug." An important question is, are there cellular "master-switches" that can explain these pleiotropic effects of ethanol? MicroRNAs (miRNAs) have been recently identified as master regulators of the cellular transcriptome and proteome. miRNAs play an increasingly appreciated and crucial role in shaping the differentiation and function of tissues and organs in both health and disease. This critical review discusses new evidence showing that ethanol-sensitive miRNAs are indeed regulatory master-switches. More specifically, miRNAs control the development of tolerance, a crucial component of ethanol addiction. Other drugs of abuse also target some ethanol-sensitive miRNAs suggesting that common biochemical mechanisms underlie addiction. This review also discusses evidence that miRNAs mediate several ethanol pathologies, including disruption of neural stem cell proliferation and differentiation in the exposed fetus, gut leakiness that contributes to endotoxemia and alcoholic liver disease, and possibly also hepatocellular carcinomas and other gastrointestinal cancers. Finally, this review provides a perspective on emerging investigations into potential roles of miRNAs as mediators of ethanol's effects on inflammation and fracture healing, as well as the potential for miRNAs as diagnostic biomarkers and as targets for therapeutic interventions for alcohol-related disorders. [source] Descartes's Passions of the SoulPHILOSOPHY COMPASS (ELECTRONIC), Issue 3 2006Lisa Shapiro While Descartes's Passions of the Soul has been taken to hold a place in the history to human physiology, until recently philosophers have neglected the work. In this research summary, I set Descartes's last published work in context and then sketch out its philosophical significance. From it, we gain further insight into Descartes's solution to the Mind,Body Problem , that is, to the problem of the ontological status of the mind,body union in a human being, to the nature of body,mind causation, and to the way body-caused thoughts represent the world. In addition, the work contains Descartes's developed ethics, in his account of virtue and of the passion of générosité in particular. Through his taxonomy of the passions and the account of their regulation, we also learn more about his moral psychology. [source] Docosahexaenoic acid biosynthesis and dietary contingency: Encephalization without aquatic constraintAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 4 2007Bryce A. Carlson Reconstructing evolutionary processes in the distant past is necessarily an inductive endeavor, typically appealing to numerous considerations thought to be relevant to the veracity of a particular conclusion. In this respect, it is essential that the considerations invoked to support hypotheses are in turn well-established truths. It is with these concerns that we sought to examine the nutritional, physiological, and archeological premises underlying the perspective that access to an aquatic diet rich in docosahexaenoic acid (DHA, 22:6n -3) was critical to human brain evolution (Carlson and Kingston [2007]: Am J Hum Biol 19:132,141). In our report investigating links between omega-3 (n -3) fatty acids and hominin encephalization, we concluded that the regular consumption of aquatic resources rich in preformed DHA may not have been essential given a varied diet of wild terrestrial foods (Carlson and Kingston [2007]). This assessment was based primarily on evidence of potential physiological adaptations in modern humans to ensure sufficient availability of DHA during critical periods of brain growth. While modern human physiology provides critical information regarding DHA as a constraint in evolving a large brain, it is also important to consistently contextualize interpretations within a framework of eclectic foraging diets rather than nutritionally limited modern agricultural populations or even modern foragers. We contend that current interpretations of Pleistocene hominin nutritional ecology do not uniquely support a shore-based foraging niche as claimed by Cunnane et al. ([2007]: Am J Hum Biol, 19:578,581). Specific issues raised in response to our article by Cunnane et al. and Joordens et al. ([2007]: Am J Hum Biol, 19:582,584) are addressed here. Am. J. Hum. Biol. 19:585,588, 2007. © 2007 Wiley-Liss, Inc. [source] Endurance exercise performance: the physiology of championsTHE JOURNAL OF PHYSIOLOGY, Issue 1 2008Michael J. Joyner Efforts to understand human physiology through the study of champion athletes and record performances have been ongoing for about a century. For endurance sports three main factors , maximal oxygen consumption , the so-called ,lactate threshold' and efficiency (i.e. the oxygen cost to generate a give running speed or cycling power output) , appear to play key roles in endurance performance. and lactate threshold interact to determine the ,performance , which is the oxygen consumption that can be sustained for a given period of time. Efficiency interacts with the performance to establish the speed or power that can be generated at this oxygen consumption. This review focuses on what is currently known about how these factors interact, their utility as predictors of elite performance, and areas where there is relatively less information to guide current thinking. In this context, definitive ideas about the physiological determinants of running and cycling efficiency is relatively lacking in comparison with and the lactate threshold, and there is surprisingly limited and clear information about the genetic factors that might pre-dispose for elite performance. It should also be cautioned that complex motivational and sociological factors also play important roles in who does or does not become a champion and these factors go far beyond simple physiological explanations. Therefore, the performance of elite athletes is likely to defy the types of easy explanations sought by scientific reductionism and remain an important puzzle for those interested in physiological integration well into the future. [source] Affective response to 5 µT ELF magnetic field-induced physiological changesBIOELECTROMAGNETICS, Issue 2 2007Paul Stevens Abstract Research into effects of weak magnetic fields (MFs) at biologically relevant frequencies has produced ambiguous results. Although they do affect human physiology and behaviour, the direction of effects is inconsistent, with a range of complex and unrelated behaviours being susceptible. A possible explanation is that these effects, rather than being directly caused, are instead related to changes in affective state. A previous study showed that MFs altered the affective content of concurrent perceptions, but it was unclear whether the emotional response was direct or indirect. Here it is shown that exposure to a 0,5 µT MF (DC-offset sinudsoidal wave form) within EEG ,-band frequencies (8,12 Hz), results in a reported change in emotional state. This relates to a decrease global field power but lacks the frontal ,-asymmetry that would physiologically indicate a directly induced emotional state, suggesting that participant experiences are due to an interpretation of the effects of MF exposure. Bioelectromagnetics © 2006 Wiley-Liss, Inc. [source] Robert F. Furchgott, Nobel laureate (1916,2009) , a personal reflectionBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2009William Martin Robert F. Furchgott, pharmacologist and joint winner of the Nobel Prize for Medicine or Physiology (1998) died on the 12th of May 2009 aged 92. By unlocking the astonishingly diverse biological actions of nitric oxide, Furchgott leaves behind a rich legacy that has both revolutionized our understanding of human physiology and stimulated new and exciting opportunities for drug development in a wide range of pathological conditions. In this article, William Martin, who worked with Furchgott for 2 years (1983,1985), following the exciting discovery of endothelium-derived relaxing factor/nitric oxide, pays tribute to his close friend and colleague. [source] Lowering of blood pressure during chronic suppression of central sympathetic outflow: Insight from computer simulationsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 2 2010Radu Iliescu Summary 1. Chronic electrical stimulation of the carotid sinuses has provided unique insight into the mechanisms that cause sustained reductions in blood pressure during chronic suppression of central sympathetic outflow. 2. Because renal denervation does not abolish the sustained fall in arterial pressure in response to baroreflex activation, this observation has seemingly challenged the concept that the kidneys play a critical role in the long-term control of arterial pressure during chronic changes in sympathetic activity. The aim of the present study was to use computer simulations to provide a more comprehensive understanding of physiological mechanisms that mediate sustained reductions in arterial pressure during prolonged baroreflex-mediated suppression of central sympathetic outflow. 3. Physiological responses to baroreflex activation under different conditions were simulated by an established mathematical model of human physiology (QHP2008; see Supporting Information (Appendix S1) provided in the online version of this article and/or http://groups.google.com/group/modelingworkshop). The model closely reproduced empirical data, providing important validation of its accuracy. 4. The simulations indicated that baroreflex-mediated suppression of renal sympathetic nerve activity does chronically increase renal excretory function but that, in addition, hormonal and haemodynamic mechanisms also contribute to this natriuretic response. The contribution of these redundant natriuretic mechanisms to the chronic lowering of blood pressure is of increased importance when suppression of renal adrenergic activity is prevented, such as after renal denervation. Activation of these redundant natriuretic mechanisms occurs at the expense of excessive fluid retention. 5. More broadly, the present study illustrates the value of numerical simulations in elucidating physiological mechanisms that are not obvious intuitively and, in some cases, not readily testable in experimental studies. [source] Human in vivo study of the renin,angiotensin,aldosterone system and the sympathetic activity after 8 weeks daily intake of fermented milkCLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, Issue 2 2010Lotte Usinger Summary Objective:, Milk fermented by lactic acid bacteria is suggested to have antihypertensive effect in humans. In vitro and animal studies have established an angiotensin-converting enzyme (ACE) inhibitor effect of peptides in fermented milk. However, other modes of action must be considered, because until today no human studies have confirmed an ACE inhibition in relation to the intake of fermented milk. Materials and methods:, We undertook a double-blinded randomized placebo-controlled study including 94 borderline-hypertensive persons to study the effect on human physiology of Lactobacillus helveticus fermented milk. The subjects were randomized into three groups: Cardi04-300 ml, Cardi04-150 ml or placebo. All components of the renin,angiotensin,aldosterone system were measured several times. Sympathetic activity was estimated by plasma noradrenaline and cardiovascular response to head-up tilt at baseline and after 8 weeks of intervention. Results:, No ACE inhibition of the fermented milk was demonstrated, as none of the components of the renin,angiotensin,aldosteron system changed. Plasma noradrenaline response to tilt test after intervention stayed unchanged between groups (P = 0·38), but declined in the group Cardi04-300 from 2·01 ± 0·93 nmol l,1 at baseline to 1·49 ± 0·74 nmol l,1 after 8 weeks (P = 0·002). There was no change in 24-h ambulatory blood pressure or heart rate between groups. Conclusions:, Despite a known ACE inhibitory effect in vitro and in animals, milk fermented with Lb. helveticus did not inhibit ACE in humans. Our results suggest that the intake of fermented milk decreases sympathetic activity, although not to an extent mediating reductions of blood pressure and heart rate in borderline-hypertensive subjects. [source] | ||||||||||||||||