Showing papers in "American Journal of Physiology-regulatory Integrative and Comparative Physiology in 2002"
TL;DR: Results show that entropy falls before clinical signs of neonatal sepsis and that missing points are well tolerated, and proposes more informed selection of parameters and reexamination of studies where approximate entropy was interpreted solely as a regularity measure.
Abstract: Abnormal heart rate characteristics of reduced variability and transient decelerations are present early in the course of neonatal sepsis. To investigate the dynamics, we calculated sample entropy, a similar but less biased measure than the popular approximate entropy. Both calculate the probability that epochs of window length m that are similar within a tolerance r remain similar at the next point. We studied 89 consecutive admissions to a tertiary care neonatal intensive care unit, among whom there were 21 episodes of sepsis, and we performed numerical simulations. We addressed the fundamental issues of optimal selection of m and r and the impact of missing data. The major findings are that entropy falls before clinical signs of neonatal sepsis and that missing points are well tolerated. The major mechanism, surprisingly, is unrelated to the regularity of the data: entropy estimates inevitably fall in any record with spikes. We propose more informed selection of parameters and reexamination of studies where approximate entropy was interpreted solely as a regularity measure.
1,151 citations
TL;DR: This review draws on recent experimental findings as well as current models proposed by experts in the chemokine field to present information regarding the structure, expression, and signaling properties of chemokines and their receptors.
Abstract: Chemokines regulate inflammation, leukocyte trafficking, and immune cell differentiation. The role of chemokines in homing of naive T lymphocytes to secondary lymphatic organs is probably the best understood of these processes, and information on chemokines in inflammation, asthma, and neurological diseases is rapidly increasing. Over the past 15 years, understanding of the size and functional complexity of the chemokine family of peptide chemoattractants has grown substantially. In this review, we first present information regarding the structure, expression, and signaling properties of chemokines and their receptors. The second part is a systems physiology-based overview of the roles that chemokines play in tissue-specific homing of lymphocyte subsets and in trafficking of inflammatory cells. This review draws on recent experimental findings as well as current models proposed by experts in the chemokine field.
622 citations
TL;DR: It is demonstrated that an increased body temperature, associated with and independent of internal biological time, is correlated with improved performance and alertness, which supports the hypothesis that body temperature modulates neurobehavioral function in humans.
Abstract: Body temperature has been reported to influence human performance. Performance is reported to be better when body temperature is high/near its circadian peak and worse when body temperature is low/near its circadian minimum. We assessed whether this relationship between performance and body temperature reflects the regulation of both the internal biological timekeeping system and/or the influence of body temperature on performance independent of circadian phase. Fourteen subjects participated in a forced desynchrony protocol allowing assessment of the relationship between body temperature and performance while controlling for circadian phase and hours awake. Most neurobehavioral measures varied as a function of internal biological time and duration of wakefulness. A number of performance measures were better when body temperature was elevated, including working memory, subjective alertness, visual attention, and the slowest 10% of reaction times. These findings demonstrate that an increased body temperature, associated with and independent of internal biological time, is correlated with improved performance and alertness. These results support the hypothesis that body temperature modulates neurobehavioral function in humans.
407 citations
TL;DR: In vitro experiments demonstrated that activation of the caspase cascade in skeletal muscle might be limited by procaspase-9 activation and suggests that subtle changes in apoptosis are involved in sarcopenia.
Abstract: Sarcopenia may be partly due to a loss in total fiber number by apoptosis We have investigated age-related alterations in the mitochondria-mediated pathway leading to apoptosis in the gastrocnemius muscle from 6-mo-old and 24-mo-old male Fisher 344 rats Apoptosis (mono- and oligonucleosome fragmentation) in the gastrocnemius muscle was increased by 50% in the old rats compared with the adult animals Furthermore, there was a significant correlation between cytosolic cytochrome c and caspase-3 activity, although neither cytochrome c nor caspase-3 activity increased significantly with age Furthermore, there was a significant correlation between caspase-3 activity and mono- and oligonucleosome fragmentation in the old rats only Mitochondrial Bcl-2 and Bax were not altered with age In vitro experiments demonstrated that activation of the caspase cascade in skeletal muscle might be limited by procaspase-9 activation This is the first study to explore the role of apoptosis in sarcopenia and suggests that subtle changes in apoptosis are involved
377 citations
TL;DR: A blunted baroreflex gain and impaired heart rate variability are predictive of poor outcome in patients with heart failure and myocardial infarction and may represent an early index of autonomic activation in left ventricular dysfunction.
Abstract: The arterial baroreflex contributes importantly to the short-term regulation of blood pressure and cardiovascular variability. A number of factors (including reflex, humoral, behavioral, and environmental) may influence gain and effectiveness of the baroreflex, as well as cardiovascular variability. Many central neural structures are also involved in the regulation of the cardiovascular system and contribute to the integrity of the baroreflex. Consequently, brain injuries or ischemia may induce baroreflex impairment and deranged cardiovascular variability. Baroreflex dysfunction and deranged cardiovascular variability are also common findings in cardiovascular disease. A blunted baroreflex gain and impaired heart rate variability are predictive of poor outcome in patients with heart failure and myocardial infarction and may represent an early index of autonomic activation in left ventricular dysfunction. The mechanisms mediating these relationships are not well understood and may in part be the result of cardiac structural changes and/or altered central neural processing of baroreflex signals.
312 citations
TL;DR: Gene-targeted mice carrying deletions in the genes encoding for individual alpha(2)-receptor subtypes have added important new insight into the physiological significance of adrenergic receptor diversity and two different strategies have emerged to regulate adrenergic signal transduction.
Abstract: α2-Adrenergic receptors mediate part of the diverse biological effects of the endogenous catecholamines epinephrine and norepinephrine. Three distinct subtypes of α2-adrenergic receptors, α2A, α2B,...
297 citations
TL;DR: NPY expression and food intake are less sensitive to the leptin's suppressive effects in DIO rats, and they defended their higher body weight after only 1 wk on a 31% fat high-energy (HE) diet.
Abstract: On low-fat chow diet, rats prone to diet-induced obesity (DIO) have increased arcuate nucleus neuropeptide Y (NPY) expression but similar leptin levels compared with diet-resistant (DR) rats (19). Here, body weight and leptin levels rose in DIO rats, and they defended their higher body weight after only 1 wk on a 31% fat high-energy (HE) diet. However, DIO NPY expression did not fall to DR levels until 4 wk when plasma leptin was 168% of DR levels. When switched to chow, DIO rats lost carcass fat (18). By 10 wk, leptin levels fell to 148% and NPY expression again rose to 150% of DR levels. During 4 wk of food restriction, DIO leptin fell by ∼50% while NPY increased by 30%. While both returned to control levels by 8 wk, DIO rats still regained all lost weight when fed ad libitum. Finally, the anorexic effect of intracerebroventricular leptin (10 μg) was inversely correlated with subsequent 3-wk weight gain on HE diet. Thus NPY expression and food intake are less sensitive to the leptin's suppressive effects in DIO rats. While this may predispose them to develop DIO, it does not fully explain their defense of a higher body weight on HE diet.
273 citations
TL;DR: Under in vivo conditions, LPS increased the plasma concentration of TNF-alpha and IL-6 and stimulated the accumulation of their mRNAs in multiple tissues including skeletal muscle from wild-type mice.
Abstract: The purpose of the present study was to examine the regulation of tumor necrosis factor (TNF)-α and interleukin (IL)-6 by lipopolysaccharide (LPS) in C2C12 myoblasts and mouse skeletal muscle. LPS ...
246 citations
TL;DR: Regional variation in adipogenesis depends on differences at the level of transcription factor expression and is a trait conferred on daughter cells.
Abstract: Fat distribution varies among individuals with similar body fat content. Innate differences in adipose cell characteristics may contribute because lipid accumulation and lipogenic enzyme activities...
243 citations
TL;DR: The cumulative toxic effects of oxyradicals are considered the molecular mechanism of the behavioral deficits observed on aging.
Abstract: Behavioral tests, tightrope success, and exploratory activity in a T maze were conducted with male and female mice for 65 wk. Four groups were defined: the lower performance slow males and slow females and the higher performance fast males and fast females. Fast females showed the longest life span and the highest performance, and slow males showed the lowest performance and the shortest life span. Oxidative stress and mitochondrial electron transfer activities were determined in brain of young (28 wk), adult (52 wk), and old (72 wk) mice in a cross-sectional study. Brain thiobarbituric acid reactive substances (TBARS) were increased by 50% in old mice and were ∼15% higher in males than in females and in slow than in fast mice. Brain Cu,Zn-superoxide dismutase (SOD) activity was increased by 52% and Mn-SOD by 108% in old mice. The activities of mitochondrial enzymes NADH-cytochrome c reductase, cytochrome oxidase, and citrate synthase were decreased by 14–58% in old animals. The cumulative toxic effects of oxyradicals are considered the molecular mechanism of the behavioral deficits observed on aging.
240 citations
TL;DR: At the level of the cross bridge, the effects of short-term resistance training were quantitative (fiber hypertrophy and proportional increases in fiber P(o) and absolute power) rather than qualitative (no change in P(O)/CSA, V(o), or power/fiber volume).
Abstract: The aim of this study was to assess the relationships between human muscle fiber hypertrophy, protein isoform content, and maximal Ca2+-activated contractile function following a short-term period ...
TL;DR: It is concluded that large intakes of fluid, equal to and greater than 8 x 8, are advisable for the treatment or prevention of some diseases and certainly are called for under special circumstances, such as vigorous work and exercise, especially in hot climates.
Abstract: Despite the seemingly ubiquitous admonition to “drink at least eight 8-oz glasses of water a day” (with an accompanying reminder that beverages containing caffeine and alcohol do not count), rigoro...
TL;DR: Because of the relative ease with which combinatorial studies can be performed, the zebrafish may eventually be particularly valuable in understanding the functional interaction between subtle gene defects that cause polygenic disorders.
Abstract: This brief review summarizes features of the zebrafish, Danio rerio, that make it a suitable model organism for studies of regulatory physiology. The review presents the argument that random mutagenesis screens are a valuable gene-finding strategy to identify genes of functional importance and that their utility, although well established for developmental issues, will extend to a variety of topics of interest to the regulatory physiologist. Particular attention is drawn to the range of functional responses amenable to mutagenesis screens in larval zebrafish. Other virtues of the organism, the range of genomic tools, the potential for innovative optical methods, and the tractability for genetic and other experimental manipulations, are also described. Finally, the review provides examples of functional studies in zebrafish, including studies in sensory neurons, cardiac rhythm disturbances, gastrointestinal function, and studies of the developing kidney, that illustrate potential applications. Because of the relative ease with which combinatorial studies can be performed, the zebrafish may eventually be particularly valuable in understanding the functional interaction between subtle gene defects that cause polygenic disorders.
TL;DR: The decreased endothelium-dependent mechanisms of vascular relaxation and the enhanced mechanism of vascular smooth muscle contraction represent plausible causes of the increased vascular resistance and arterial pressure associated with preeclampsia.
Abstract: Normal pregnancy is associated with reductions in total vascular resistance and arterial pressure possibly due to enhanced endothelium-dependent vascular relaxation and decreased vascular reactivit...
TL;DR: Intracerebroventricular infusions of prostaglandin E(2) provoked arousal from hibernation and induced fever, suggesting that neural signaling pathways that mediate febrile responses are functional during hibernation.
Abstract: Golden-mantled ground squirrels (Spermophilus lateralis) undergo seasonal hibernation during which core body temperature (Tb) values are maintained 1–2°C above ambient temperature. Hibernation is n...
TL;DR: It is indicated that chronic unloading of carotid baroreceptors can produce neurogenic hypertension and provide strong evidence that arterial bar Koreceptors are involved in the long-term control of blood pressure.
Abstract: We developed a new model to examine the role of arterial baroreceptors in the long-term control of mean arterial pressure (MAP) in dogs. Baroreceptors in the aortic arch and one carotid sinus were ...
TL;DR: Results obtained from experiments studying autonomic blockade suggest that cardiovascular alterations in the chronic mild stress model are mediated by elevated sympathetic tone to the heart, which has implications for the study of pathophysiological links between affective disorders and cardiovascular disease.
Abstract: Depressed patients with and without a history of cardiovascular pathology display signs, such as elevated heart rate, decreased heart rate variability, and increased physiological reactivity to environmental stressors, which may indicate a predisposition to cardiovascular disease. The specific physiological mechanisms associating depression with such altered cardiovascular parameters are presently unclear. The current study investigated cardiovascular regulation in the chronic mild stress rodent model of depression and examined the specific autonomic nervous system mechanisms underlying the responses. Sprague-Dawley rats exposed to a series of mild, unpredictable stressors over 4 wk displayed anhedonia (an essential feature of human depression), along with elevated resting heart rate, decreased heart rate variability, and exaggerated pressor and heart rate responses to air jet stress. Results obtained from experiments studying autonomic blockade suggest that cardiovascular alterations in the chronic mild stress model are mediated by elevated sympathetic tone to the heart. The present findings have implications for the study of pathophysiological links between affective disorders and cardiovascular disease.
TL;DR: The capa gene is the first to be shown to encode neuropeptides that act on renal fluid production through nitric oxide and is shown to be not synergistic, implying that both act on the same pathways in tubules.
Abstract: ADrosophila gene (capability, capa) at 99D on chromosome 3R potentially encodes three neuropeptides: GANMGLYAFPRV-amide (capa-1), ASGLVAFPRV-amide (capa-2), and TGPSASSGLWGPRL-amide (capa-3). Capa-...
TL;DR: Genetic background, diet composition, and palatability interact to produce disparate levels of defended body weight and central neuropeptide expression in Sprague-Dawley rats selectively bred for diet-induced obesity.
Abstract: Sprague-Dawley rats selectively bred for diet-induced obesity (DIO) or diet resistance (DR) were characterized on diets of differing energy content and palatability. Over 10 wk, DR rats on a high-energy (HE) diet (31% fat) gained weight similarly to DR rats fed chow (4.5% fat), but they became obese on a palatable liquid diet (Ensure). DIO rats gained 22% more weight on an HE diet and 50% more on Ensure than chow-fed DIO rats. DIO body weight gains plateaued when switched from HE diet to chow. But, Ensure-fed DIO rats switched to chow spontaneously reduced their intake and weight to that of rats switched from HE diet to chow. They also reduced their hypothalamic proopiomelanocortin and dynorphin but not neuropeptide Y mRNA expression by 17-40%. When reexposed to Ensure after 7 wk, they again overate and matched their body weights to rats maintained on Ensure throughout. All Ensure-fed rats had a selective reduction in dynorphin mRNA in the ventromedial hypothalamic nucleus. Thus genetic background, diet composition, and palatability interact to produce disparate levels of defended body weight and central neuropeptide expression.
TL;DR: This review focuses on studies that indicate oxygen radicals can cause renal vasconstriction, mediate the vasoconstriction of other agonists, and modulate nitric oxide-dependent actions in the normal kidney.
Abstract: The renal microvasculature is an important component in the regulation of kidney function. Recent studies suggest that oxygen radicals can contribute to the modulation of renal cortical and medullary microvascular function under normal conditions as well as in pathophysiological conditions such as diabetes mellitus and hypertension. This review focuses on studies that indicate oxygen radicals can cause renal vasoconstriction, mediate the vasoconstriction of other agonists, and modulate nitric oxide-dependent actions in the normal kidney. Hypertension and diabetes mellitus are associated with oxidative stress. Recent investigations suggest that oxygen radicals may contribute to the enhanced renal vascular tone, increased sensitivity to vasoconstrictors, impaired endothelium-dependent vasodilation, and enhanced tubuloglomerular feedback found in these pathophysiological conditions.
TL;DR: This is the first study to report cytochrome c release from the mitochondria and alterations in Bcl-2 with age in vivo, providing a potential mechanism for the increase in apoptosis seen in the aging heart.
Abstract: There is a loss of myocytes in the aging heart due to necrosis and apoptosis. Oxidative stress, an apoptosis-inducing signal, may also increase in the aging heart. Cytosol and mitochondria isolated from the left and right ventricle of the hearts of 6-, 16-, and 24-mo-old male Fischer 344 rats were used to measure key markers of apoptosis and to assess oxidative stress. Cytosolic cytochrome c content was significantly elevated in the 16- and 24-mo-old animals compared with the 6-mo-old animals. Furthermore, Bcl-2, an antiapoptotic protein, showed a strong tendency to decrease with age, whereas Bax, a proapoptotic protein, remained unchanged. Apoptotic protease-activating factor 1 levels and caspase-3 activities were not different among the three age groups. Indicative of the chronic oxidative stress with age, heart mitochondria from old animals showed increases in manganese superoxide dismutase and glutathione peroxidase activity and increases in lipid peroxidation. This is the first study to report cytochrome c release from the mitochondria and alterations in Bcl-2 with age in vivo, providing a potential mechanism for the increase in apoptosis seen in the aging heart.
TL;DR: Results indicate that micro-CT is a promising method to evaluate renal vascular architecture in the intact rodent kidney relative to physiological and pathological function.
Abstract: Appropriate nephron function is dependent on the intrarenal arrangement of blood vessels. The preferred and primary means to study the architecture of intrarenal circulation has been by filling it with opaque substances such as india ink, radio-opaque contrast material, or various polymers for study by light or scanning electron microscopy. With such methodologies, superficial vessels may obscure deep vessels and little quantitative information may be obtained. Serial-section microtomy has not been practical because of problems relating to alignment and registration of adjacent sections, lost sections, and preparation time and effort. Microcomputed tomography (micro-CT) overcomes such limitations and provides a means to study the three-dimensional architecture of filled vessels within an intact rodent kidney and to obtain more quantitative information. As an example of micro-CT's capabilities, we review the use of micro-CT to study the alterations in renal microvasculature caused by the development of liver cirrhosis after chronic bile duct ligation. In this example, micro-CT evidence shows a selective decrease in cortical vascular filling in the kidney, with a maintenance of medullary vascular filling. These changes may contribute to the salt and water retention that accompanies cirrhosis. These results indicate that micro-CT is a promising method to evaluate renal vascular architecture in the intact rodent kidney relative to physiological and pathological function.
TL;DR: The data confirm that the diminution in muscle function displayed after 2 wk of unloading is mainly due to neural, rather than contractile, disturbances, and endocrine environment favorable to muscle atrophy.
Abstract: Strength decrements observed after extended (4–6 wk) periods of muscle unloading are associated with significant atrophy Because early (up to 2 wk) strength gains from resistance exercise are rela
TL;DR: NP-induced lipolysis is a primate specificity, and adipocytes from ANP-nonresponsive species present a predominance of "clearance" receptors and very low expression of "biologically active" receptors.
Abstract: We have recently demonstrated that natriuretic peptides (NPs), which are known for regulation of blood pressure via membrane guanylyl cyclase (GC) receptors, are lipolytic in human adipose tissue. ...
TL;DR: The high magnitude of upregulation of mPGES and sPLA(2)-IIA (1,257-fold and 133-fold, respectively) makes these enzymes attractive targets for anti-inflammatory therapy.
Abstract: The febrile response to lipopolysaccharide (LPS) consists of three phases (phases I–III), all requiring de novo synthesis of prostaglandin (PG) E2. The major mechanism for activation of PGE2-synthe...
TL;DR: In conclusion, salt-sensitive hypertension in the S rat is accompanied by marked decreases in renal medullary SOD and greater renal oxidative stress and renal damage than in R rats.
Abstract: The roles of oxidative stress and renal superoxide dismutase (SOD) levels and their association with renal damage were studied in Dahl salt-sensitive (S) and salt-resistant (R)/Rapp strain rats dur...
TL;DR: By reducing circulatory costs, hyperoxia improves aerobic scope but is unable to shift the breakpoint in pH regulation or lethal limits, Hyperoxia appears beneficial at sublethal temperatures, but no longer beyond when cellular or molecular functions become disturbed.
Abstract: The hypothesis of an oxygen-limited thermal tolerance was tested in the Antarctic teleost Pachycara brachycephalum. With the use of flow-through respirometry, in vivo31P-NMR spectroscopy, and MRI, ...
TL;DR: It is suggested that acute and chronic elevations in circulating ANG II levels increase the formation of 20- HETE in the kidney and peripheral vasculature and that 20-HETE contributes to the acute and Chronic pressor effects of ANG II.
Abstract: The present study examined the effects of ANG II on the renal synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) and its contribution to the renal vasoconstrictor and the acute and chronic pres...
TL;DR: The data suggest that OT terminals in the solitary vagal complex modulate reflex control of the heart, acting to facilitate vagal outflow and the slowdown of theheart.
Abstract: Previous work demonstrated that oxytocinergic projections to the solitary vagal complex are involved in the restraint of exercise-induced tachycardia (2). In the present study, we tested the idea t...
TL;DR: It is found that 48 h without food (24 h beyond normal 24-h fasting period) produced no significant change in Hcrt-1 levels nor did feeding after the deprivation, and the amount of increase was correlated with the level of motor activity during the sleep-deprivation procedure.
Abstract: Hypocretins (orexins) are recently discovered hypothalamic neuropeptides that have been implicated in the etiology of narcolepsy. The normal behavioral functions of these peptides are unclear, although a role in feeding has been suggested. We measured hypocretin-1 (Hcrt-1) in the cerebrospinal fluid of dogs during a variety of behaviors. We found that 48 h without food (24 h beyond normal 24-h fasting period) produced no significant change in Hcrt-1 levels nor did feeding after the deprivation. In contrast, 24 h of sleep deprivation produced on average a 70% increase in Hcrt-1 level compared with baseline levels. The amount of increase was correlated with the level of motor activity during the sleep-deprivation procedure. A 2-h period of exercise in the same dogs produced a 57% increase in Hcrt-1 levels relative to quiet waking levels, with the magnitude of the increase being highly correlated with the level of motor activity. The strong correlation between motor activity and Hcrt-1 release may explain some of the previously reported behavioral, physiological, and pathological phenomena ascribed to the Hcrt system.