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Showing papers in "American Journal of Physiology-regulatory Integrative and Comparative Physiology in 2004"


Journal ArticleDOI
TL;DR: The development of acidosis during intense exercise has traditionally been explained by the increased production of lactic acid, causing the release of a proton and the formation of the acid salt.
Abstract: The development of acidosis during intense exercise has traditionally been explained by the increased production of lactic acid, causing the release of a proton and the formation of the acid salt s...

1,023 citations


Journal ArticleDOI
TL;DR: Current knowledge regarding the sources of endothelial ROS generation, their regulation, their involvement in redox signaling, and the relevance of enhanced ROS generation and redox signaled to the pathophysiology of cardiovascular disorders where endothelial activation and dysfunction are implicated are reviewed.
Abstract: The endothelial generation of reactive oxygen species (ROS) is important both physiologically and in the pathogenesis of many cardiovascular disorders. ROS generated by endothelial cells include su...

749 citations


Journal ArticleDOI
TL;DR: This review describes approaches to the direct and indirect measurement of different reactive metabolites of oxygen and nitrogen and particular attention to a method's applicability for in vivo determinations will be addressed.
Abstract: Facile detection of reactive oxygen and nitrogen species in biologic systems is often problematic. This is a result of the numerous cellular mechanisms, both enzymatic and nonenzymatic involved in their catabolism/decomposition, the complex and overlapping nature of their reactivities, as well as the often limited intracellular access of detector systems. This review describes approaches to the direct and indirect measurement of different reactive metabolites of oxygen and nitrogen. Particular attention to a method's applicability for in vivo determinations will be addressed.

628 citations


Journal ArticleDOI
TL;DR: The sex hormone-induced stimulation of the endothelium-dependent mechanisms of vascular relaxation and inhibition of the mechanisms ofascular smooth muscle contraction may contribute to the gender differences in vascular tone and may represent potential beneficial vascular effects of hormone replacement therapy during natural and surgically induced deficiencies of gonadal hormones.
Abstract: The greater incidence of hypertension and coronary artery disease in men and postmenopausal women compared with premenopausal women has been related, in part, to gender differences in vascular tone and possible vascular protective effects of the female sex hormones estrogen and progesterone. However, vascular effects of the male sex hormone testosterone have also been suggested. Estrogen, progesterone, and testosterone receptors have been identified in blood vessels of human and other mammals and have been localized in the plasmalemma, cytosol, and nuclear compartments of various vascular cells, including the endothelium and the smooth muscle. The interaction of sex hormones with cytosolic/nuclear receptors triggers long-term genomic effects that could stimulate endothelial cell growth while inhibiting smooth muscle proliferation. Activation of plasmalemmal sex hormone receptors may trigger acute nongenomic responses that could stimulate endothelium-dependent mechanisms of vascular relaxation such as the nitric oxide-cGMP, prostacyclin-cAMP, and hyperpolarization pathways. Additional endothelium-independent effects of sex hormones may involve inhibition of the signaling mechanisms of vascular smooth muscle contraction such as intracellular Ca2+ concentration and protein kinase C. The sex hormone-induced stimulation of the endothelium-dependent mechanisms of vascular relaxation and inhibition of the mechanisms of vascular smooth muscle contraction may contribute to the gender differences in vascular tone and may represent potential beneficial vascular effects of hormone replacement therapy during natural and surgically induced deficiencies of gonadal hormones.

611 citations


Journal ArticleDOI
TL;DR: Moderate exercise, started at young age in mice, increased life span, decreased oxidative stress, and prevented the decline of cytochrome oxidase activity and behavioral performance at middle age but not at old age.
Abstract: Moderate exercise in a treadmill (10, 15, and 20 cm/s, for 5 min each, weekly) from 28 to 78 wk of age extended male and female mice life span by 19 and 9% accompanied by 36 and 13% and 13 and 9% increased performance in behavioral assays (tightrope and T-maze tests) at 52 wk of age. Moderate exercise significantly decreased the aging-associated development of oxidative stress by preventing 1) the increase in protein carbonyls and thiobarbituric acid-reactive substances contents of submitochondrial membranes; 2) the decrease in antioxidant enzyme activities (Mn- and Cu,Zn-superoxide dismutase and catalase); and 3) the decrease in mitochondrial NADH-cytochrome-c reductase and cytochrome oxidase activities observed at 52 wk of mice age in brain, heart, liver, and kidney. These effects were no longer significant at 78 wk of age in mice. Moderate exercise, started at young age in mice, increased life span, decreased oxidative stress, and prevented the decline of cytochrome oxidase activity and behavioral performance at middle age but not at old age.

458 citations


Journal ArticleDOI
TL;DR: The hypothesis that multiorgan dysfunction induced by severe sepsis has a bioenergetic etiology is supported and a long-term, fluid-resuscitated, fecal peritonitis model utilizing male Wistar rats is developed that closely replicates human physiological, biochemical, and histological findings.
Abstract: Although sepsis is the major cause of mortality and morbidity in the critically ill, precise mechanism(s) causing multiorgan dysfunction remain unclear. Findings of impaired oxygen utilization in septic patients and animals implicate nitric oxide-mediated inhibition of the mitochondrial respiratory chain. We recently reported a relationship between skeletal muscle mitochondrial dysfunction, clinical severity, and poor outcome in patients with septic shock. We thus developed a long-term, fluid-resuscitated, fecal peritonitis model utilizing male Wistar rats that closely replicates human physiological, biochemical, and histological findings with a 40% mortality. As with humans, the severity of organ dysfunction and eventual poor outcome were associated with nitric oxide overproduction and increasing mitochondrial dysfunction (complex I inhibition and ATP depletion). This was seen in both vital (liver) and nonvital (skeletal muscle) organs. Likewise, histological evidence of cell death was lacking, suggesting the possibility of an adaptive programmed shutdown of cellular function. This study thus supports the hypothesis that multiorgan dysfunction induced by severe sepsis has a bioenergetic etiology. Despite the well-recognized limitations of laboratory models, we found clear parallels between this long-term model and human disease characteristics that will facilitate future translational research.

434 citations


Journal ArticleDOI
TL;DR: This is the first demonstration of a quantitative relationship between the concentration-dependent rewarding effect of orosensory stimulation by sucrose during eating and the overflow of dopamine in the nucleus accumbens.
Abstract: Although taste can influence meal size and body weight, the neural substrate for these effects remains obscure. Dopamine, particularly in the nucleus accumbens, has been implicated in both natural and nonnatural rewards. To isolate the orosensory effects of taste from possible postingestive consequences, we investigated the quantitative relationship between sham feeding of sucrose and extracellular dopamine in the nucleus accumbens with microdialysis in rats. Sucrose intake linearly increased as a function of concentration (0.03 M, 18.07 ± 2.41 ml; 0.1 M, 30.92 ± 2.60 ml; 0.3 M, 43.28 ± 2.88 ml). Sham feeding also stimulated accumbens dopamine overflow as a function of sucrose solution concentration (0.03 M, 120.76 ± 2.6%; 0.1 M, 140.28 ± 7.8%; 0.3 M, 146.27 ± 5.05%). A second experiment used the same protocol but clamped the amount of sucrose ingested and revealed a similar, concentration-dependent dopamine activation in the nucleus accumbens. This is the first demonstration of a quantitative relationship between the concentration-dependent rewarding effect of orosensory stimulation by sucrose during eating and the overflow of dopamine in the nucleus accumbens. This finding provides new and strong support for accumbens dopamine in the rewarding effect of sucrose.

414 citations


Journal ArticleDOI
TL;DR: The discrepancies between procedures show that the choice of parameters and data handling should be considered before BRS estimation, and new techniques with this set of results are needed.
Abstract: This study compared spontaneous baroreflex sensitivity (BRS) estimates obtained from an identical set of data by 11 European centers using different methods and procedures. Noninvasive blood pressure (BP) and ECG recordings were obtained in 21 subjects, including 2 subjects with established baroreflex failure. Twenty-one estimates of BRS were obtained by methods including the two main techniques of BRS estimates, i.e., the spectral analysis (11 procedures) and the sequence method (7 procedures) but also one trigonometric regressive spectral analysis method (TRS), one exogenous model with autoregressive input method (X-AR), and one Z method. With subjects in a supine position, BRS estimates obtained with calculations of alpha-coefficient or gain of the transfer function in both the low-frequency band or high-frequency band, TRS, and sequence methods gave strongly related results. Conversely, weighted gain, X-AR, and Z exhibited lower agreement with all the other techniques. In addition, the use of mean BP instead of systolic BP in the sequence method decreased the relationships with the other estimates. Some procedures were unable to provide results when BRS estimates were expected to be very low in data sets (in patients with established baroreflex failure). The failure to provide BRS values was due to setting of algorithmic parameters too strictly. The discrepancies between procedures show that the choice of parameters and data handling should be considered before BRS estimation. These data are available on the web site (http://www.cbi.polimi.it/glossary/eurobavar.html) to allow the comparison of new techniques with this set of results.

338 citations


Journal ArticleDOI
TL;DR: Increased activity of the adipose and systemic RAS in obesity-related hypertension is demonstrated and a selective increase in angiotensinogen gene expression in retroperitoneal adipose tissue from OP vs. OR and LF rats is demonstrated.
Abstract: In obesity-related hypertension, activation of the renin-angiotensin system (RAS) has been reported despite marked fluid volume expansion. Adipose tissue expresses components of the RAS and is mark...

325 citations


Journal ArticleDOI
TL;DR: It is suggested that release of oxytocin from a descending pPVN-to-NTS pathway contributes to leptin's attenuation of food intake by a mechanism that involves the activation of pPvN oxytoc in neurons by leptin, resulting in increased sensitivity of NTS neurons to satiety signals.
Abstract: Hindbrain projections of oxytocin neurons in the parvocellular paraventricular nucleus (pPVN) are hypothesized to transmit leptin signaling from the hypothalamus to the nucleus of the solitary trac...

312 citations


Journal ArticleDOI
TL;DR: The results suggest that poly I:C induces fever, but not anorexia, through an IL-1 and prostaglandin-dependent mechanism.
Abstract: Polyinosinic:polycytidylic acid (poly I:C) is a synthetic double-stranded RNA that is used experimentally to model viral infections in vivo. Previous studies investigating the inflammatory properti...

Journal ArticleDOI
TL;DR: A strong relationship between feeding and the diurnal rhythm of leptin is suggested and that feeding also fundamentally modulates the di nighttime rhythm of ghrelin.
Abstract: To determine the relationships among plasma ghrelin and leptin concentrations and hypothalamic ghrelin contents, and sleep, cortical brain temperature (Tcrt), and feeding, we determined these parameters in rats in three experimental conditions: in free-feeding rats with normal diurnal rhythms, in rats with feeding restricted to the 12-h light period (RF), and in rats subjected to 5-h of sleep deprivation (SD) at the beginning of the light cycle. Plasma ghrelin and leptin displayed diurnal rhythms with the ghrelin peak preceding and the leptin peak following the major daily feeding peak in hour 1 after dark onset. RF reversed the diurnal rhythm of these hormones and the rhythm of rapid-eye-movement sleep (REMS) and significantly altered the rhythm of Tcrt. In contrast, the duration and intensity of non-REMS (NREMS) were hardly responsive to RF. SD failed to change leptin concentrations, but it promptly stimulated plasma ghrelin and induced eating. SD elicited biphasic variations in the hypothalamic ghrelin contents. SD increased plasma corticosterone, but corticosterone did not seem to influence either leptin or ghrelin. The results suggest a strong relationship between feeding and the diurnal rhythm of leptin and that feeding also fundamentally modulates the diurnal rhythm of ghrelin. The variations in hypothalamic ghrelin contents might be associated with sleep-wake activity in rats, but, unlike the previous observations in humans, obvious links could not be detected between sleep and the diurnal rhythms of plasma concentrations of either ghrelin or leptin in the rat.

Journal ArticleDOI
TL;DR: The present review will provide an overview of the understanding of the etiology, pathophysiology, and treatment of obesity hypertension in humans, with a focus on the state of knowledge in humans.
Abstract: The association between obesity and hypertension is well documented, although the exact nature of this relation remains unclear. Sympathetic nervous and renin-angiotensin-aldosterone system activation appear to play an important role in the sodium and water retention, rightward shift in the pressure-natriuresis, and blood pressure elevation observed in obese individuals. Visceral obesity and the ectopic deposition of adipose tissue may be important in the activation of these systems and in the target organ damage that ensues. Weight loss is critical in the effective management of obesity hypertension and the accompanying target organ damage, although recidivism rates are high. However, prevention of weight gain should be the major priority for combating hypertension and its consequences in the future. The present review will provide an overview of our understanding of the etiology, pathophysiology, and treatment of obesity hypertension. Our focus is on the state of knowledge in humans. The potential role of abdominal obesity is considered throughout our review. We refer to relevant animal literature for supportive evidence and where little or no data in humans are available.

Journal ArticleDOI
TL;DR: A subpopulation of brain mitochondria with increased size and fragility was differentiated in aging rats, whereas liver showed a homogeneous mitochondrial population, as assayed by mitochondrial marker enzyme activities in the postmitochondrial supernatant.
Abstract: The mitochondrial mass of rat brain and liver remained unchanged on aging in young adults, old adults, and senescent animals (28, 60, and 92 wk of age); the values were 15–17 and 29–31 mg protein/g...

Journal ArticleDOI
TL;DR: A working hypothesis is proposed in which any activity or condition that limits the availability of oxidizable fuels can inhibit both gonadotropin-releasing hormone (GnRH)/luteinizing hormone secretion and female copulatory behaviors, and disruption of these signaling processes allows normal reproduction to proceed in the face of energetic deficits.
Abstract: Natural selection has linked the physiological controls of energy balance and fertility such that reproduction is deferred during lean times, particularly in female mammals. In this way, an energetically costly process is confined to periods when sufficient food is available to support pregnancy and lactation. Even in the face of abundance, nutritional infertility ensues if energy intake fails to keep pace with expenditure. A working hypothesis is proposed in which any activity or condition that limits the availability of oxidizable fuels (e.g., undereating, excessive energy expenditure, diabetes mellitus) can inhibit both gonadotropin-releasing hormone (GnRH)/luteinizing hormone secretion and female copulatory behaviors. Decreases in metabolic fuel availability appear to be detected by cells in the caudal hindbrain. Hindbrain neurons producing neuropeptide Y (NPY) and catecholamines (CA) then project to the forebrain where they contact GnRH neurons both directly and also indirectly via corticotropin-releasing hormone (CRH) neurons to inhibit GnRH secretion. In the case of estrous behavior, the best available evidence suggests that the inhibitory NPY/CA system acts primarily via CRH or urocortin projections to various forebrain loci that control sexual receptivity. Disruption of these signaling processes allows normal reproduction to proceed in the face of energetic deficits, indicating that the circuitry responds to energy deficits and that no signal is necessary to indicate that there is an adequate energy supply. While there is a large body of evidence to support this hypothesis, the data do not exclude nutritional inhibition of reproduction by other pathways and processes, and the full story will undoubtedly be more complex than this.

Journal ArticleDOI
TL;DR: A preexisting reduction in hypothalamic but not brain stem leptin signaling might contribute to the development of DIO when dietary fat and caloric density are increased.
Abstract: Rats selectively bred to develop diet-induced obesity (DIO) were compared with those bred to be diet resistant (DR) on a 31% fat high-energy diet with regard to their central leptin signaling and blood-brain barrier (BBB) transport. Peripheral leptin injection (15 mg/kg ip) into lean 4- to 5-wk-old rats produced 54% less anorexia in DIO than DR rats. DIO rats also had 21, 63, and 64% less leptin-induced immunoreactive phosphorylated signal transducer and activator of transcription 3 (pSTAT3) expression in the hypothalamic arcuate, ventromedial, and dorsomedial nuclei, respectively. However, hindbrain leptin-induced nucleus tractus solitarius pSTAT3 and generalized sympathetic (24-h urine norepinephrine) activation were comparable. Reduced central leptin signaling was not due to defective BBB transport since transport did not differ between lean 4- to 5-wk-old DIO and DR rats. Conversely, DIO leptin BBB transport was reduced when they became obese at 23 wk of age on low-fat chow or after 6 wk on high-energy diet. In addition, leptin receptor mRNA expression was 23% lower in the arcuate nuclei of 4- to 5-wk-old DIO compared with DR rats. Thus a preexisting reduction in hypothalamic but not brain stem leptin signaling might contribute to the development of DIO when dietary fat and caloric density are increased. Defects in leptin transport appear to be an acquired defect associated with the development of obesity and possibly age.

Journal ArticleDOI
TL;DR: Understanding oxygen and tissue-specific regulation of EPO production is of high relevance for physiology and might be useful for new therapies to treat human diseases.
Abstract: Hypoxia-inducible expression of the gene encoding for the glycoprotein hormone erythropoietin (EPO) is the paradigm of oxygen-regulated gene expression. EPO is the main regulator of red blood cell production and more than 100 years of research on the regulation of EPO production have led to the identification of a widespread cellular oxygen sensing mechanism. Central to this signaling cascade is the transcription factor complex hypoxia-inducible factor-1 (HIF-1). Meanwhile, it is known that HIF-1 controls more than 50 oxygen-dependent genes and is now recognized as the main regulator of oxygen homoeostasis in the body. In addition to hypoxic induction, expression of the EPO gene is tightly regulated in a tissue-specific manner. During ontogeny, production of EPO required for erythropoiesis is switched from the fetal liver to the kidneys. Here EPO is mainly synthesized in adulthood. Production of EPO has also been found in organs where it has nonerythropoietic functions: EPO is important for development of the brain and is neuroprotective, whereas it stimulates angiogenesis in the reproductive tract and possibly in other organs. Understanding oxygen and tissue-specific regulation of EPO production is of high relevance for physiology. Moreover, this knowledge might be useful for new therapies to treat human diseases.

Journal ArticleDOI
TL;DR: There are major differences in the effects of intraduodenal C12 and C10, administered at 0.375 kcal/min, on appetite, energy intake, antropyloroduodanal PWs, and gut hormone release in humans.
Abstract: The gastrointestinal effects of intraluminal fats may be critically dependent on the chain length of fatty acids released during lipolysis. We postulated that intraduodenal administration of lauric...

Journal ArticleDOI
TL;DR: In the presence of regional myocardial ischemia, components within the intrinsic cardiac nervous system undergo pathological change that alters its spatially and temporally organized reflexes such that populations of neurons, acting in isolation, may destabilize efferent neuronal control of regional cardiac electrical and/or mechanical events.
Abstract: The cardiac neuronal hierarchy can be represented as a redundant control system made up of spatially distributed cell stations comprising afferent, efferent, and interconnecting neurons. Its peripheral and central neurons are in constant communication with one another such that, for the most part, it behaves as a stochastic control system. Neurons distributed throughout this hierarchy interconnect via specific linkages such that each neuronal cell station is involved in temporally dependent cardio-cardiac reflexes that control overlapping, spatially organized cardiac regions. Its function depends primarily, but not exclusively, on inputs arising from afferent neurons transducing the cardiovascular milieu to directly or indirectly (via interconnecting neurons) modify cardiac motor neurons coordinating regional cardiac behavior. As the function of the whole is greater than that of its individual parts, stable cardiac control occurs most of the time in the absence of direct cause and effect. During altered cardiac status, its redundancy normally represents a stabilizing feature. However, in the presence of regional myocardial ischemia, components within the intrinsic cardiac nervous system undergo pathological change. That, along with any consequent remodeling of the cardiac neuronal hierarchy, alters its spatially and temporally organized reflexes such that populations of neurons, acting in isolation, may destabilize efferent neuronal control of regional cardiac electrical and/or mechanical events.

Journal ArticleDOI
TL;DR: The findings suggest that maternal infections may lead to an unbalanced inflammatory reaction in the fetal environment that activates the fetal stress axis.
Abstract: Perinatal infections are a risk factor for fetal neurological pathologies, including cerebral palsy and schizophrenia. Cytokines that are produced as part of the inflammatory response are proposed ...

Journal ArticleDOI
TL;DR: Differences in origins of the sympathetic outflow to WAT and functional differences in the WAT SNS innervation that could contribute to the differential propensity for fat cell proliferation across WAT depots in vivo are suggested.
Abstract: White adipose tissue (WAT) is innervated by the sympathetic nervous system (SNS), and the central origins of this innervation have been demonstrated for inguinal and epididymal WAT (iWAT and eWAT, respectively) using a viral transneuronal tract tracer, the pseudorabies virus (PRV). Although the more established role of this sympathetic innervation of WAT is as a major stimulator of lipid mobilization, this innervation also inhibits WAT fat cell number (FCN); thus, local denervation of WAT leads to marked increases in WAT mass and FCN. The purpose of this study was to extend our understanding of the SNS regulation of FCN using neuroanatomical and functional analyses. Therefore, we injected PRV into retroperitoneal WAT (rWAT) to compare the SNS outflow to this pad from what already is known for iWAT and eWAT. In addition, we tested the ability of local unilateral denervation of rWAT or iWAT to promote increases in WAT mass and FCN vs. their contralateral neurally intact counterparts. Although the overall pattern of innervation was more similar than different for rWAT vs. iWAT or eWAT, its SNS outflow appeared to involve more neurons in the suprachiasmatic and solitary tract nuclei. Denervation produced significant increases in WAT mass and FCN for both iWAT and rWAT, but FCN was increased significantly more in iWAT than in rWAT. These data suggest differences in origins of the sympathetic outflow to WAT and functional differences in the WAT SNS innervation that could contribute to the differential propensity for fat cell proliferation across WAT depots in vivo.

Journal ArticleDOI
TL;DR: The data suggest that exercise may help to facilitate circadian adaptation to schedules requiring a delay in the sleep-wake cycle, and that the closer to the DLMO(25%), the greater the phase shift.
Abstract: Shift workers and transmeridian travelers are exposed to abnormal work-rest cycles, inducing a change in the phase relationship between the sleep-wake cycle and the endogenous circadian timing syst...

Journal ArticleDOI
TL;DR: In this review some aspects of HIF-1 pathway activation in tumors and the consequences for pathophysiology and treatment of neoplasia are discussed.
Abstract: For most organisms oxygen is essential for life. When oxygen levels drop below those required to maintain the minimum physiological oxygen requirement of an organism or tissue it is termed hypoxia. To counteract possible deleterious effects of such a state, an immediate molecular response is initiated causing adaptation responses aimed at cell survival. This response is mediated by the hypoxia-inducible factor-1 (HIF-1), which is a heterodimer consisting of an α- and a β-subunit. HIF-1α protein is stabilized under hypoxic conditions and therefore confers selectivity to this response. Hypoxia is characteristic of tumors, mainly because of impaired blood supply resulting from abnormal growth. Over the past few years enormous progress has been made in the attempt to understand how the activation of the physiological response to hypoxia influences neoplastic growth. In this review some aspects of HIF-1 pathway activation in tumors and the consequences for pathophysiology and treatment of neoplasia are discussed.

Journal ArticleDOI
TL;DR: Because NaHS has substantial vasoactive effects at physiological plasma concentrations, it is proposed that its soluble derivative, H(2)S, is a tonically active endogenous vasoregulator in trout.
Abstract: Hydrogen sulfide (H2S) is an endogenous vasodilator in mammals, but its presence and function in other vertebrates is unknown. We generated H2S from NaHS and examined the effects on isolated effere...

Journal ArticleDOI
TL;DR: It is concluded that IGF-I is more effective than insulin in stimulating glucose and alanine uptake in rainbow trout myosatellite cells and that the degree of stimulation changes when cells differentiate to myotubes.
Abstract: The relative function of IGF-I and insulin on fish muscle metabolism and growth has been investigated by the isolation and culture at different stages (myoblasts at day 1, myocytes at day 4, and my...

Journal ArticleDOI
TL;DR: The results suggest that 1) EEG markers of sleep homeostasis appear in the first postnatal months, and 2) sleepHomeostasis goes through a period of maturation.
Abstract: The development of nocturnal sleep and the sleep electroencephalogram (EEG) was investigated in a longitudinal study during infancy. All-night polysomnographic recordings were obtained at home at 2 wk and at 2, 4, 6, and 9 mo after birth (analysis of 7 infants). Total sleep time and the percentage of quiet sleep or non-rapid eye movement sleep (QS/NREMS) increased with age, whereas the percentage of active sleep or rapid eye movement sleep (AS/REMS) decreased. Spectral power of the sleep EEG was higher in QS/NREMS than in AS/REMS over a large part of the 0.75- to 25-Hz frequency range. In both QS/NREMS and AS/REMS, EEG power increased with age in the frequency range 17 Hz. The largest rise occurred between 2 and 6 mo. A salient feature of the QS/NREMS spectrum was the emergence of a peak in the sigma band (12-14 Hz) at 2 mo that corresponded to the appearance of sleep spindles. Between 2 and 9 mo, low-frequency delta activity (0.75-1.75 Hz) showed an alternating pattern with a high level occurring in every other QS/NREMS episode. At 6 mo, sigma activity showed a similar pattern. In contrast, theta activity (6.5-9 Hz) exhibited a monotonic decline over consecutive QS/NREMS episodes, a trend that at 9 mo could be closely approximated by an exponential function. The results suggest that 1) EEG markers of sleep homeostasis appear in the first postnatal months, and 2) sleep homeostasis goes through a period of maturation. Theta activity and not delta activity seems to reflect the dissipation of sleep propensity during infancy.

Journal ArticleDOI
TL;DR: Two common forms of metabolic acidosis (hyperchloremic and lactic acidosis) are associated with dramatically different patterns of immune response in LPS-stimulated RAW 2647 cells.
Abstract: Metabolic acidosis frequently complicates sepsis and septic shock and may be deleterious to cellular function. Different types of metabolic acidosis (e.g., hyperchloremic and lactic acidosis) have ...

Journal ArticleDOI
TL;DR: In this paper, the effect of no exercise (Nex; control) and high exercise level (Hex; ∼4 MJ/day) and two dietary manipulations [a high-fat diet (HF; 50% of energy, 700 kJ/100 g) and low fat diet (LF;...
Abstract: We assessed the effect of no exercise (Nex; control) and high exercise level (Hex; ∼4 MJ/day) and two dietary manipulations [a high-fat diet (HF; 50% of energy, 700 kJ/100 g) and low-fat diet (LF; ...

Journal ArticleDOI
TL;DR: The influence of relaxin on renal hemodynamics and glomerular filtration rate, as well as on other peripheral circulations, is highlighted and on the basis of its potent vasodilatory and matrix-degrading attributes, the therapeutic potential of Relaxin in renal and cardiovascular diseases is speculated.
Abstract: Although traditionally associated with reproductive processes, relaxin is emerging as an important player in renal and cardiovascular function. Much of our recently acquired understanding of relaxi...

Journal ArticleDOI
TL;DR: In vitro results suggest that the hyperglycemia-induced increase in NO in retinal Müller cells and endothelial cells increases production of cytotoxic prostaglandins via COX-2 and that inhibition of retinopathy by aminoguanidine or aspirin is due at least in part to inhibition of this NO/COX- 2 axis.
Abstract: A nonselective inhibitor of cyclooxygenase (COX; high-dose aspirin) and a relatively selective inhibitor of inducible nitric oxide synthase (iNOS; aminoguanidine) have been found to inhibit develop...