bluuebunny/crossref_metadata_2025 huggingface dataset:
Stress alters cutaneous permeability barrier homeostasis
Authors: Denda Mitsuhiro , Tsuchiya Toru , Elias Peter M. , Feingold Kenneth R.
Published: December 2017

Recent studies have shown that psychological stress can influence cutaneous barrier function, suggesting that this form of stress could trigger or aggravate skin disease. In the present study, we demonstrate that transfer of hairless mice to a different cage delays barrier recovery rates. Pretreatment with a phenothiazine sedative, chlorpromazine, before transfer of animals restored the kinetics of barrier recovery toward normal, suggesting that psychological stress is the basis for this alteration in barrier homeostasis. To determine the mechanism linking psychological stress to altered barrier recovery, we first demonstrated that plasma corticosterone levels increase markedly after transfer of animals to new cages and that pretreatment with chlorpromazine blocks this increase. Second, we demonstrated that the systemic administration of corticosterone delays barrier recovery. Finally, we demonstrated that pretreatment with the glucocorticoid receptor antagonist RU-486 blocks the delay in barrier recovery produced by systemic corticosterone, change of cage, or immobilization. These results suggest that psychological stress stimulates increased production of glucocorticoids, which, in turn, adversely affects permeability barrier homeostasis.
Daytime naps in darkness phase shift the human circadian rhythms of melatonin and thyrotropin secretion
Authors: Buxton Orfeu M. , L'Hermite-Balériaux Mireille , Turek Fred W. , van Cauter Eve
Published: December 2017

To systematically determine the effects of daytime exposure to sleep in darkness on human circadian phase, four groups of subjects participated in 4-day studies involving either no nap (control), a morning nap (0900–1500), an afternoon nap (1400–2000), or an evening nap (1900–0100) in darkness. Except during the scheduled sleep/dark periods, subjects remained awake under constant conditions, i.e., constant dim light exposure (36 lx), recumbence, and caloric intake. Blood samples were collected at 20-min intervals for 64 h to determine the onsets of nocturnal melatonin and thyrotropin secretion as markers of circadian phase before and after stimulus exposure. Sleep was polygraphically recorded. Exposure to sleep and darkness in the morning resulted in phase delays, whereas exposure in the evening resulted in phase advances relative to controls. Afternoon naps did not change circadian phase. These findings indicate that human circadian phase is dependent on the timing of darkness and/or sleep exposure and that strategies to treat circadian misalignment should consider not only the timing and intensity of light, but also the timing of darkness and/or sleep.
Type of negative feedback controlling sucrose ingestion depends on sucrose concentration
Authors: Davis John D. , Smith Gerard P. , Singh Bramdeo
Published: December 2017

The sham intake of concentrated, but not weak, milk solutions requires up to three sham-feeding tests for intake to reach maximum (7). It is well known that the sham intake of concentrated (0.8 M) sucrose requires three or more sham-feeding tests to reach its maximum (4, 6, 17), but it is not known if this occurs with weaker sucrose solutions. We investigated this question by measuring the sham intake of seven concentrations of sucrose (0.025, 0.05, 0.1, 0.2, 0.4, 0.6, and 0.8 M) during five sham-feeding tests. Sham intake of the three highest concentrations required up to three sham-feeding tests to reach maximum. Sham intake of the four lowest concentrations reached maximum in the first sham-feeding test. Our results show that the type of negative feedback that controls the intake of sucrose depends on its concentration. With weak solutions, intake is limited by a single direct, physiological, negative-feedback signal. When concentrated solutions are ingested, intake is controlled jointly by a direct physiological signal operating in conjunction with a labile one that loses its effectiveness with sham-feeding experience.
AMPA glutamate receptors and respiratory control in the developing rat: anatomic and pharmacological aspects
Authors: Whitney Gina M. , Ohtake Patricia J. , Simakajornboon Narong , Xue Ying-Dan , Gozal David
Published: December 2017

The developmental role of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) glutamate receptors in respiratory regulation remains undefined. To study this issue, minute ventilation (V˙E) was measured in 5-, 10-, and 15-day-old intact freely behaving rat pups using whole body plethysmography during room air (RA), hypercapnic (5% CO2), and hypoxic (10% O2) conditions, both before and after administration of the non- N-methyl-d-aspartate (NMDA) receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzo[f]quinoxaline-7-sulfonamide disodium (NBQX; 10 mg/kg ip). In all age groups,V˙Eduring RA was unaffected by NBQX, despite reductions in breathing frequency ( f) induced by increases in both inspiratory and expiratory duration. During hypoxia and hypercapnia, V˙Eincreases were similar in both NBQX and control conditions in all age groups. However, tidal volume was greater and f lower after NBQX. To determine if AMPA receptor-positive neurons are recruited during hypoxia, immunostaining for AMPA receptor (GluR2/3) and c -fos colabeling was performed in caudal brain stem sections after exposing rat pups at postnatal ages 2, 5, 10, and 20 days, and adult rats to room air or 10% O2for 3 h. GluR2/3 expression increased with postnatal age in the nucleus of the solitary tract (NTS) and hypoglossal nucleus, whereas a biphasic pattern emerged for the nucleus ambiguus (NA). c -fos expression was enhanced by hypoxia at all postnatal ages in the NTS and NA and also demonstrated a clear maturational pattern. However, colocalization of GluR2/3 and c -fos was not affected by hypoxia. We conclude that AMPA glutamate receptor expression in the caudal brain stem is developmentally regulated. Furthermore, the role of non-NMDA receptors in respiratory control of conscious neonatal rats appears to be limited to modest, albeit significant, regulation of breathing pattern.
Is fluid-phase endocytosis conserved in hepatocytes of species acclimated and adapted to different temperatures?
Authors: Padrón David , Bizeau Michael E. , Hazel Jeffrey R.
Published: December 2017

Our primary objective was to determine if rates of fluid-phase endocytosis (FPE) were conserved in hepatocytes from organisms acclimated and adapted to different temperatures. To this aim, the fluorescent dye Lucifer yellow was employed to measure FPE at different assay temperatures (AT) in hepatocytes from 5°C- and 20°C-acclimated trout, Oncorhynchus mykiss (at 5 and 20°C AT), 22°C- and 35°C-acclimated tilapia, Oreochromis nilotica (at 22 and 35°C AT), and the Sprague-Dawley rat (at 10, 20, and 37°C AT). FPE was also studied in rats fed a long-chain polyunsaturated fatty acid (PUFA)-enriched diet (at 10°C AT). Despite being temperature dependent, endocytic rates (values in pl ⋅ cell−1⋅ h−1) in both species of fish were compensated after a period of acclimation. For example, in 20°C-acclimated trout, the rate of endocytosis declined from 1.84 to 1.07 when the AT was reduced from 20 to 5°C; however, after a period of acclimation at 5°C, the rate (at 5°C AT) was largely restored (1.80) and almost perfectly compensated (95%). In tilapia, endocytic rates were also temperature compensated, although only partially (36%). Relatively similar rates obtained at 5°C in 5°C-acclimated trout (1.8), at 20°C in 20°C-acclimated trout (1.84), and at 22°C in 22°C-acclimated tilapia (2.2) suggest that endocytic rates are somewhat conserved in these two species of fish. In contrast, the rate in rat measured at 37°C (16.83) was severalfold greater than in fish at their respective body temperatures. A role for lipids in determining rates of endocytosis was supported by data obtained at 10°C in hepatocytes isolated from rats fed a long-chain PUFA-enriched diet: endocytic rates were higher (5.35 pl ⋅ cell−1⋅ h−1) than those of rats fed a standard chow diet (2.33 pl ⋅ cell−1⋅ h−1). The conservation of endocytic rates in fish may be related to their ability to conserve other membrane characteristics (i.e., order or phase behavior) by restructuring their membrane lipid composition or by modulating the activities of proteins that regulate endocytosis and membrane traffic, whereas the lack of conservation between fish and rat may be due to differences in metabolic rate.
Mg2+-induced endothelium-dependent relaxation of blood vessels and blood pressure lowering: role of NO
Authors: Yang Zhi-Wei , Gebrewold Asefa , Nowakowski Maja , Altura Bella T. , Altura Burton M.
Published: December 2017

In vitro extracellular Mg2+concentration ([Mg2+]0) produces endothelium-dependent and endothelium-independent relaxations in rat aorta in a concentration-dependent manner. These relaxant effects of Mg2+on intact rat aortic rings, but not denuded rat aortic rings, were suppressed by either NG-monomethyl-l-arginine (l-NMMA), Nω-nitro-l-arginine methyl ester (l-NAME), or methylene blue. The inhibitory effects of l-NMMA and l-NAME could be reversed partly by l-arginine. [Mg2+]0-induced dilatation in vivo in rat mesenteric arterioles and venules was almost completely inhibited by NG-nitro-l-arginine andl-NMMA. Removal of extracellular Ca2+concentration ([Ca2+]0) or buffering intracellular Ca2+concentration in endothelial cells, with 10 μM 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid-AM, markedly attenuated the relaxant effects of Mg2+. Mg2+produced nitric oxide (NO) release from the intact aortic rings in a concentration-dependent manner. Removal of [Ca2+]0diminished the increased NO release induced by elevated levels of [Mg2+]0. In vivo infusion of increasing doses (1–30 μM/min) of MgSO4, directly into the femoral veins of anesthetized rats, elicited significant concentration-dependent sustained increases in serum total Mg and concomitant decreases in arterial blood pressure. Before and after employment of various doses of MgSO4, intravenous administration of either l-NMMA (10 mg/kg) orl-NAME (10 mg/kg) increased (i.e., reversed) the MgSO4-lowered blood pressure markedly, and intravenous injection of l-arginine restored partially the increased blood pressure effects of both l-NMMA andl-NAME. Our results suggest that 1) small blood vessels are very dependent on NO release for Mg2+dilatations and 2) the endothelium-dependent relaxation induced by extracellular Mg2+is mediated by release of endothelium-derived relaxing factor-NO from the endothelium, and requires Ca2+and formation of guanosine 3′,5′-cyclic monophosphate.
Isotope recycling in lactating dogs (Canis familiaris)
Authors: Scantlebury Michael , Hynds Waring , Booles Derek , Speakman John R.
Published: December 2017

Isotope-based techniques for the measurement of water turnover, energy expenditure, and milk intake often assume that there is no recycling of isotopes once they have left the labeled animal. In experiments involving lactating females or their suckling offspring, there are several possible routes of isotope recycling. These include the consumption of labeled milk by offspring, the ingestion of labeled excreta, and the rebreathing of exhaled labeled CO2or water vapor by both mother and offspring. Isotope recycling might be especially important during lactation because the offspring are in close contact with each other and their mother for prolonged periods. We show here in 24- to 30-day-old domestic dog Canis familiarispuppies that there was no detectable transfer of18O or2H from labeled to unlabeled pups in two litters (16 pups, 8 labeled, 8 unlabeled) that were weaned early and independent of their mother. However, there was a significant transfer of both isotopes from labeled to unlabeled pups and from labeled pups to their mothers in nine equivalent nursing litters of the same age (27 labeled, 26 unlabeled pups). The increases in enrichment of isotopes in unlabeled offspring were greater than the increases in enrichment of the mothers. This indicates that maternal ingestion of offspring excreta and subsequent transfer of isotope in milk is not the sole pathway of recycling. Additional routes must also be important, such as exchange of isotope between pups on saliva-coated nipples and perhaps direct ingestion of excreta by unweaned young. Recycling is unlikely to be an important factor when determining maternal metabolic rate during peak lactation in domestic dogs. However, experiments that are designed to assess the energy demands of pups and isotope-based estimates of water turnover in offspring may need to take into account any effects of isotope recycling. In a theoretical example, removing the effects of recycling increased the measured energy expenditure in pups by up to 7% and increased the calculated elimination rates of both isotopes by up to 11.1% in18oxygen and 10.9% in2hydrogen.
Regulation of atrial natriuretic peptide gene expression in gastric antrum by fasting
Authors: Gower William R. , Salhab Khaled F. , Foulis Wendy L. , Pillai Nirmala , Bundy Jason R. , Vesely David L. , Fabri Peter J. , Dietz John R.
Published: December 2017

Atrial natriuretic peptide (ANP) gene expression was localized in the rat gastric antrum using immunohistochemistry and in situ hybridization to mucosal cells in the lower portion of the antropyloric glands. Colocalization of immunoreactive ANP, long-acting natriuretic peptide, i.e., proANP-(1—30), and serotonin in these cells identified them to be enterochromaffin cells. Fasting for 72 h in 8-mo-old (adult) rats produced a significant ( P < 0.05) decrease in the levels of ANP prohormone mRNA, immunoreactive proANP-(1–30) and ANP to ∼33% of that of fed rats. Fasting in 1-mo-old rats had no effect on these parameters. Transcripts for natriuretic peptide receptor subtypes NPR-A, NPR-B, and NPR-C were found in both mucosa and muscle tissues of the antrum. ANP, brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) stimulated the production of cGMP in antral mucosa in vitro with a potency of ANP > BNP >> CNP, suggesting that these receptors were functional. We conclude that fasting decreases ANP prohormone mRNA and its gene products, long-acting natriuretic peptide, and ANP in the antrum of adult rats.
Exogenous growth hormone induces somatotrophic gene expression in neonatal liver and skeletal muscle
Authors: Lewis A. J. , Wester T. J. , Burrin D. G. , Dauncey M. J.
Published: December 2017

The extent to which the local somatotrophic axis is functional in extrahepatic tissues in the neonate is unclear. We therefore determined the expression of growth hormone (GH) receptor (GHR), and insulin-like growth factors I and II (IGF-I and IGF-II) mRNA in liver and skeletal muscle (longissimus) of neonatal pigs given daily intramuscular injections of either recombinant porcine GH (1 mg/kg body wt; n = 6) or saline ( n = 5) for 7 days. Exogenous GH increased plasma concentrations of GH 30-fold and IGF-I threefold. Abundances of specific mRNA in liver and muscle were measured by RNase protection assays (values are arbitrary density units). In liver, GH treatment increased GHR (6.0 vs. 9.7; P< 0.01) and IGF-I (5.2 vs. 49.0; P < 0.001) but not IGF-II (19.5 vs. 17.2) mRNA. In muscle, GH treatment increased IGF-I mRNA (13.3 vs. 22.8; P < 0.05) but not GHR (8.3 vs. 9.5) or IGF-II (16.1 vs. 16.9). These results demonstrate that exogenous GH can induce local somatotrophic function predominantly in liver but also in muscle of newborn pigs. Our novel finding on the selective increase in muscle IGF-I but not GHR gene expression suggests differences in posttranscriptional regulation and/or intracellular signaling mechanisms.
Involvement of H+-ATPase and carbonic anhydrase in inorganic carbon uptake for endosymbiont photosynthesis
Authors: Furla Paola , Allemand Denis , Orsenigo Maria-Novella
Published: December 2017

Symbiotic cnidarians absorb inorganic carbon from seawater to supply intracellular dinoflagellates with CO2for their photosynthesis. To determine the mechanism of inorganic carbon transport by animal cells, we used plasma membrane vesicles prepared from ectodermal cells isolated from tentacles of the sea anemone, Anemonia viridis. H14[Formula: see text] uptake in the presence of an outward NaCl gradient or inward H+gradient, showed no evidence for a Cl−- or H+- driven [Formula: see text] transport. H14[Formula: see text] and36Cl−uptakes were stimulated by a positive inside-membrane diffusion potential, suggesting the presence of [Formula: see text] and Cl−conductances. A carbonic anhydrase (CA) activity was measured on plasma membrane (4%) and in the cytoplasm of the ectodermal cells (96%) and was sensitive to acetazolamide (IC50= 20 nM) and ethoxyzolamide (IC50= 2.5 nM). A strong DIDS-sensitive H+-ATPase activity was observed (IC50= 14 μM). This activity was also highly sensitive to vanadate and allyl isothiocyanate, two inhibitors of P-type H+-ATPases. Present data suggest that [Formula: see text]absorption by ectodermal cells is carried out by H+secretion by H+-ATPase, resulting in the formation of carbonic acid in the surrounding seawater, which is quickly dehydrated into CO2by a membrane-bound CA. CO2then diffuses passively into the cell where it is hydrated in[Formula: see text] by a cytosolic CA.
Kinins in humans
Authors: Duncan Ann-Maree , Kladis Athena , Jennings Garry L. , Dart Anthony M. , Esler Murray , Campbell Duncan J.
Published: December 2017

The kinin peptide system in humans is complex. Whereas plasma kallikrein generates bradykinin peptides, glandular kallikrein generates kallidin peptides. Moreover, a proportion of kinin peptides is hydroxylated on proline3 of the bradykinin sequence. We established HPLC-based radioimmunoassays for nonhydroxylated and hydroxylated bradykinin and kallidin peptides and their metabolites in blood and urine. Both nonhydroxylated and hydroxylated bradykinin and kallidin peptides were identified in human blood and urine, although the levels in blood were often below the assay detection limit. Whereas kallidin peptides were more abundant than bradykinin peptides in urine, bradykinin peptides were more abundant in blood. Bradykinin and kallidin peptide levels were higher in venous than arterial blood. Angiotensin-converting enzyme inhibition increased blood levels of bradykinin, but not kallidin, peptides. Reactive hyperemia had no effect on antecubital venous levels of bradykinin or kallidin peptide levels. These studies demonstrate differential regulation of the bradykinin and kallidin peptide systems, and indicate that blood levels of bradykinin peptides are more responsive to angiotensin-converting enzyme inhibition than blood levels of kallidin peptides.
Dose-dependent effects of endotoxin on human sleep
Authors: Mullington Janet , Korth Carsten , Hermann Dirk M. , Orth Armin , Galanos Chris , Holsboer Florian , Pollmächer Thomas
Published: December 2017

The role of the central nervous system in the host response to infection and inflammation and modulation of these responses by the hypothalamic-pituitary-adrenal system are well established. In animals, activation of host defense mechanisms increases non-rapid eye movement (NREM) sleep amount and intensity, which, in turn, are thought to support host defense, or the body's ability to defend itself against challenges to its immune system. In humans, the evidence is conflicting. Therefore, we investigated the effects of three placebo-controlled doses of endotoxin on host response, including nocturnal sleep in healthy volunteers. Administered before nocturnal sleep onset, endotoxin dose dependently increased rectal temperature, heart rate, and the plasma levels of tumor necrosis factor (TNF)-α, soluble TNF receptors, interleukin (IL)-1 receptor antagonist, IL-6, and cortisol. The lowest dose reliably increased circulating levels of cytokines and soluble cytokine receptors, but it did not affect rectal temperature, heart rate, or cortisol. This subtle host defense activation increased deep NREM sleep amount, often referred to as slow-wave sleep (stages 3 and 4), and intensity (delta power). Conversely, the highest dose of endotoxin disrupted sleep. Whereas it is well established that the endocrine and thermoregulatory systems are very sensitive to endotoxin, this study shows that human sleep-wake behavior is even more sensitive to activation of host defense mechanisms.
Functional and morphological modifications of the urinary bladder in aging female rats
Authors: Lluel P. , Palea S. , Barras M. , Grandadam F. , Heudes D. , Bruneval P. , Corman B. , Martin D. J.
Published: December 2017

In female Wistar/Rij rats, 10 and 30 mo old, the micturition profiles in conscious animals, the contractile responses of the isolated urinary bladder, and the histology of the vesical tissue have been investigated. During cystomanometry, 60% of conscious senescent rats, but only 25% of young adult rats, showed spontaneous contractions during the bladder-filling phase. In aging rats, micturition pressure and duration of micturition were significantly higher by ∼40–50%. In contrast, bladder capacity, bladder compliance, micturition volume, and residual volume were not modified with age. In vitro, the contractile responses of the bladder body to KCl, carbachol, arecoline, and α,β-MeATP were similar in tissues from young adult and senescent rats. In contrast, maximum responses to noradrenaline, but not phenylephrine, were two times greater in the older rats. Isoprenaline exhibited the same potency in relaxing KCl-precontracted bladder body of 10- and 30-mo-old animals. Morphometric analysis showed a significant increase in the mean thickness of the muscularis layer with age, whereas the collagen density significantly decreased in the muscularis and in the lamina propria layers. The fact that the majority of senescent rats displayed bladder instability and increased response to α-adrenergic agonists suggests that this strain of rat seems a good model for the aged human. However, other characteristics of the aging human urinary tract (urinary frequency, decreased cystometric capacity, and decreased detrusor contractility associated with fibrosis) are not present.
Production and functional roles of nitric oxide in the proximal tubule
Authors: Liang Mingyu , Knox Franklyn G.
Published: December 2017

A significant role for nitric oxide (NO) in proximal tubule physiology and pathophysiology has been revealed by a series of in vivo and in vitro studies. Whether the proximal tubule produces NO under basal conditions is still controversial; however, evidence suggests that the proximal tubule is constantly exposed to NO that might include NO from nonproximal tubule sources. When challenged with a variety of stimuli, including hypoxia, the proximal tubule is able to produce large quantities of NO. In vivo studies generally indicate that NO inhibits fluid and sodium reabsorption by the proximal tubule. However, the final effect of NO on proximal tubular reabsorption appears to depend on the concentration of NO and involve interaction with other regulatory mechanisms. NO regulates Na+-K+-ATPase, Na+/H+exchangers, and paracellular permeability of proximal tubular cells, which may contribute to its effect on proximal tubular transport. Enhanced production of NO, perhaps depending on macrophage type inducible NO synthase, participates in hypoxic/ischemic proximal tubular injury. In conclusion, NO plays a fundamental role in both physiology and pathophysiology of the proximal tubule.
Angiotensin stimulates respiration in spontaneously hypertensive rats
Authors: Jennings Donald B. , Lockett Heather J.
Published: December 2017

Spontaneously hypertensive rats (SHR) have an activated brain angiotensin system. We hypothesized 1) that ventilation (V˙) would be greater in conscious SHR than in control Wistar-Kyoto (WKY) rats and 2) that intravenous infusion of the ANG II-receptor blocker saralasin would depress respiration in SHR, but not in WKY. Respiration and oxygen consumption (V˙o2) were measured in conscious aged-matched groups ( n = 16) of adult female SHR and WKY. For protocol 1, rats were habituated to a plethysmograph and measurements obtained over 60–75 min. After installation of chronic intravenous catheters, protocol 2consisted of 30 min of saline infusion (∼14 μl ⋅ kg−1⋅ min−1) followed by 40 min of saralasin (1.3 μg ⋅ kg−1⋅ min−1).V˙, tidal volume (VT), inspiratory flow [VT/inspiratory time (Ti)], breath expiratory time, and V˙o2were higher, and breath Ti was lower in “continuously quiet” SHR. In SHR, but not in WKY rats, ANG II-receptor block decreasedV˙, VT, and VT/Ti and increased breath Ti. During ANG II-receptor block, an average decrease in V˙o2in SHR was not significant. About one-half of the higherV˙ in SHR appears to be accounted for by an ANG II mechanism acting either via peripheral arterial receptors or circumventricular organs.
Regulation of protein breakdown and adrenocortical response to stress in birds during migratory flight
Authors: Jenni Lukas , Jenni-Eiermann Susanne , Spina Fernando , Schwabl Hubert
Published: December 2017

During long-term fasting at rest, protein utilization is maintained at low levels until it increases at a threshold adiposity. This study examines 1) whether such a shift in energy substrate use also occurs during endurance exercise while fasting, 2) the role of corticosterone, and 3) the adrenocortical response to an acute stressor. Ten species of migrating birds caught after an endurance flight over at least 500 km were examined. Plasma uric acid and corticosterone levels were low in birds with fat stores >5% of body mass and high in birds with smaller fat stores. Corticosterone levels were very high in birds with no visible fat stores and emaciated breast muscles. Corticosterone levels increased with handling time only in birds with large fat stores. These findings suggest that 1) migrating birds with appreciable fat stores are not stressed by endurance flight, 2) a metabolic shift (increased protein breakdown), regulated by an endocrine shift (medium corticosterone levels), occurs at a threshold adiposity, as observed in birds at rest, 3) adrenocortical response to an acute stressor is inhibited after this shift, and 4) an adrenocortical response typical for an emergency situation (high corticosterone levels) is only reached when muscle protein is dangerously low.
An endogenous monocarboxylate transport inXenopus laevisoocytes
Authors: Tosco M. , Orsenigo M. N. , Gastaldi G. , Faelli A.
Published: December 2017

We investigated the existence of an endogenous system for lactate transport in Xenopus laevis oocytes.36Cl-uptake studies excluded the involvement of a DIDS-sensitive anion antiporter as a possible pathway for lactate movement.l-[14C]lactate uptake was unaffected by superimposed pH gradients, stimulated by the presence of Na+in the incubating solution, and severely reduced by the monocarboxylate transporter inhibitor p-chloromercuribenzenesulphonate (pCMBS). Transport exhibited a broad cation specificity and was cis inhibited by other monocarboxylates, mostly by pyruvate. These results suggest that lactate uptake is mediated mainly by a transporter and that the preferred anion is pyruvate. [14C]pyruvate uptake exhibited the same pattern of functional properties evidenced for l-lactate. Kinetic parameters were calculated for both monocarboxylates, and a higher affinity for pyruvate was revealed. Various inhibitors of monocarboxylate transporters reduced significantly pyruvate uptake. These studies demonstrate that Xenopus laevis oocytes possess a monocarboxylate transport system that shares some functional features with the members of the mammalian monocarboxylate cotransporters family, but, in the meanwhile, exhibits some particular properties, mainly concerning cation specificity.
Lipopolysaccharide andd-galactosamine-induced hepatic injury is mediated by TNF-α and not by Fas ligand
Authors: Josephs Michael D. , Bahjat F. Rena , Fukuzuka Kunitaro , Ksontini Riadh , Solorzano Carmen C. , Edwards Carl K. , Tannahill Cynthia L. , MacKay Sally L. D. , Copeland Edward M. , Moldawer Lyle L.
Published: December 2017

Tumor necrosis factor (TNF)-α and Fas ligand (FasL) are trimeric proteins that induce apoptosis through similar caspase-dependent pathways. Hepatocytes are particularly sensitive to inflammation-induced programmed cell death, although the contribution of TNF-α and/or FasL to this injury response is still unclear. Here, we report that d-galactosamine and lipopolysaccharide-induced liver injury in C57BL/6 mice is associated with increased hepatic expression of both TNF-α and FasL mRNA. Pretreatment of mice with a TNF-binding protein improved survival, reduced plasma aspartate aminotransferase concentrations, and attenuated the apoptotic liver injury, as determined histologically and by in situ 3′ OH end labeling of fragmented nuclear DNA. In contrast, pretreatment of mice with a murine-soluble Fas fusion protein (Fasfp) had only minimal effect on survival, and apoptotic liver injury was either unaffected or exacerbated depending on the dose of Fasfp employed. Similarly, mice with a spontaneous mutation in FasL (B6Smn.C3H- Faslgldderived from C57BL/6) were equally sensitive tod-galactosamine/lipopolysaccharide-induced shock. We conclude that the shock and apoptotic liver injury afterd-galactosamine/lipopolysaccharide treatment are due primarily to TNF-α release, whereas increased FasL expression appears to contribute little to the mortality and hepatic injury.
Neutrophil depletion prevents intestinal mucosal permeability alterations in burn-injured rats
Authors: Sir Özcan , Fazal Nadeem , Choudhry Mashkoor A. , Gamelli Richard L. , Sayeed Mohammed M.
Published: December 2017

Cutaneous thermal injury increases intestinal mucosal permeability. The mechanisms of this functional disturbance are not fully understood. We investigated whether accumulation of neutrophils in the intestine contributes to the increase in mucosal permeability. Labeled and unlabeled lactulose and mannitol were infused into a segment of rat ileum or jejunum. Blood concentrations of [3H]lactulose and [14C]mannitol were measured after 30, 60, and 90 min. On day 1 postburn, lactulose permeability increased fourfold in the ileum and twofold in the jejunum compared with sham-burned rats; mannitol permeability increased twofold in the ileum and 1.5-fold in the jejunum. A greater increase in permeability occurred on day 3 postburn in the ileum, but not in the jejunum. The depletion of neutrophils in burned rats prevented the increase in permeability in both segments on day 1 postburn. Histological studies of intestines from burned, with or without neutrophil depletion, and sham-burned rats showed similar morphology. However, numerous neutrophils were found in the extravascular compartment in day 1 postburn, but not in neutrophil-depleted and sham-burned rats. These findings support the concept that the burn-induced increase in mucosal permeability is produced during the accumulation of neutrophils in the intestine and can be abrogated by the depletion of neutrophils.
Eccentric ergometry: increases in locomotor muscle size and strength at low training intensities
Authors: LaStayo P. C. , Pierotti D. J. , Pifer J. , Hoppeler H. , Lindstedt S. L.
Published: December 2017

Lengthening (eccentric) muscle contractions are characterized by several unusual properties that may result in unique skeletal muscle adaptations. In particular, high forces are produced with very little energy demand. Eccentrically trained muscles gain strength, but the specific nature of fiber size and composition is poorly known. This study assesses the structural and functional changes that occur to normal locomotor muscle after chronic eccentric ergometry at training intensities, measured as oxygen uptake, that do not influence the muscle when exercised concentrically. Male subjects trained on either eccentric or concentric cycle ergometers for 8 wk at a training intensity starting at 54% and ending at 65% of their peak heart rates. The isometric leg strength increased significantly in the eccentrically trained group by 36%, as did the cross-sectional area of the muscle fiber by 52%, but the muscle ultrastructure remained unchanged. There were no changes in either fiber size, composition, or isometric strength in the concentrically trained group. The responses of muscle to eccentric training appear to be similar to resistance training.
Effect of acute adrenalectomy on sympathetic responses to peripheral lipopolysaccharide or central PGE2
Authors: MacNeil B. J. , Jansen A. H. , Greenberg A. H. , Nance D. M.
Published: December 2017

The impact of plasma corticosterone levels on the sympathetic nervous system (SNS) response to intravenous lipopolysaccharide (LPS) or intracerebroventricular injections of PG was studied in anesthetized (urethan-chloralose) male Sprague-Dawley rats. For this, electrophysiological recordings of splenic and renal nerves were completed in control or adrenalectomized (ADX) rats. LPS (10 μg iv) similarly increased splenic and renal nerve activity in control rats with a shorter onset latency for the splenic nerve. Acute ADX enhanced the response of both nerves to LPS ( P < 0.005) and reduced the onset latency of the renal nerve ( P < 0.05). PGE2 (2 μg icv) rapidly increased the activity of both nerves but preferentially (magnitude and onset latency) stimulated the renal nerve ( P < 0.05). The magnitude of the splenic nerve response to PGE2 was unaffected by ADX. Unexpectedly, PGE2 was less effective at stimulating renal nerve activity in ADX animals relative to intact controls ( P < 0.05). Pretreatment of ADX rats with a CRF antagonist {[d-Phe12, Nle21,38, Cα-MeLeu37]CRF-(12—41)} reversed this effect such that the renal nerve responded to central PGE2 to a greater extent than the splenic nerve ( P< 0.05), as was the case in non-ADX rats. These data indicate that enhanced sensitivity of central sympathetic pathways does not account for the enhanced SNS responses to LPS in ADX rats. Also, a CRF-related process appears to diminish renal sympathetic outflow in ADX rats.
Mechanisms regulating hypoxic respiratory depression during fetal and postnatal life
Authors: Bissonnette John M.
Published: December 2017

Selected topics in the respiratory response to acute hypoxia in the fetus and newborn are reviewed. Peripheral chemoreceptors acting through ionotrophic glutamate receptors play an important role in affecting the initial augmentation phase. Whether fall off in peripheral chemoreceptor activity contributes to the secondary depressive phase remains controversial. A number of approaches including permanent electrolytic and reversible cooling lesions, Fos protein activation, and double-labeling immunohistochemistry has converged to show that an area in and around the locus ceruleus in the rostral pons affects the central depression. There is evidence that this is mediated by catecholamines acting at α2-adrenergic receptors. Tonic activity in early expiratory (postinspiratory) neurons may contribute to hypoxia-induced apneic episodes in the fetus and newborn. Desensitization of α-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptors has been demonstrated in respiratory-related neurons both in vivo and in vitro. The role that this process might play in the depressive phase of the hypoxic ventilatory response has not been established. In vitro experiments with isolated brain stem-spinal cord preparations or transverse brain stem slices usually involve anoxia, whereas whole animal experiments use 8–15% O2. Therefore, caution must be exercised in attempting to construct a unifying framework from these two approaches.
Baroreceptor afferent discharge in the pregnant rat
Authors: Hines Tina
Published: December 2017

Pregnancy is associated with blunted reflex responses to cardiac and arterial baroreceptor stimulation. We tested the hypothesis that arterial baroreceptor afferent discharge is attenuated in response to a pressure stimulus in pregnant rats. Multifiber aortic depressor nerve activity (ADNA), mean arterial pressure (MAP), and heart rate were measured in anesthetized (pentobarbital sodium, 35 mg/kg ip) late-pregnant and virgin rats in response to increases [phenylephrine (PE), 1.5–24 μg ⋅ kg− 1 ⋅ min− 1and 1–16 μg/kg] and decreases [sodium nitroprusside (SNP), 5–80 μg ⋅ kg− 1 ⋅ min− 1and 0.05–16 μg/kg] in MAP. Resting MAP was lower in pregnant rats, but changes in MAP were similar to those in virgin rats during both PE and SNP administration. ADNA was significantly attenuated in pregnant animals during both PE and SNP infusions ( P < 0.05) due to a more rapid adaptation to the pressure stimulus. Bolus drug administration evoked similar changes in MAP and ADNA in both groups; however, the maximum decrease in ADNA was achieved at the lowest dose of SNP in pregnant rats. Thus baroreceptor afferent discharge is attenuated in pregnant rats, and this involves a more rapid adaptation to a pressure stimulus.
Characterization ofl-arginine transporters in rat renal inner medullary collecting duct
Authors: Wu Feng , Cholewa Brian , Mattson David L.
Published: December 2017

Previous work from our laboratory has demonstrated that the inner medullary collecting duct (IMCD) expresses a large amount of nitric oxide synthase (NOS) activity. The present study was designed to characterize the transport of NOS substrate,l-arginine, in a suspension of bulk-isolated IMCD cells from the Sprague-Dawley rat kidney. Biochemical transport studies demonstrated an l-arginine transport system in IMCD cells that was saturable and Na+independent ( n = 6).l-Arginine uptake by IMCD cells was inhibited by the cationic amino acids l-lysine, l-homoarginine, and l-ornithine (10 mmol/l each) and unaffected by the neutral amino acids l-leucine, l-serine, andl-glutamine. Both l-ornithine ( n = 6) and l-lysine ( n = 6) inhibited NOS enzymatic activity in a dose-dependent manner in IMCD cells, supporting the important role of l-arginine transport for NO production by this tubular segment. Furthermore, RT-PCR of microdissected IMCD confirmed the presence of cationic amino acid transporter CAT1 mRNA, whereas CAT2A, CAT2B, and CAT3 were not detected. These results indicate that l-arginine uptake by IMCD cells occurs via system y+, is encoded by CAT1, and may participate in the regulation of NO production in this renal segment.
Effects of leptin and cholecystokinin in rats with a null mutation of the leptin receptorLepr fak
Authors: Wildman H. F. , Chua S. , Leibel R. L. , Smith G. P.
Published: December 2017

The Koletsky (“corpulent”) obese rat is homozygous for an autosomal recessive mutation of the leptin receptor (Lepr) that results in hyperphagia, obesity, and hyperlipidemia. Unlike the Lepr mutation that characterizes the fatty Zucker rat ( Lepr fa ), the Koletsky mutation ( Lepr fak ) is null. Because the Leprfak mutation is null, exogenous leptin should have no effect on body weight or food intake in fak/fa k rats. We confirmed that prediction: murine leptin, administered into the third ventricle for 5 consecutive days, did not affect daily food intake or body weight in fak/fa k rats but produced dose-related inhibitions of food intake and body weight in +/+ and +/fa k rats. Although fak/fa k rats did not respond to leptin, their response to CCK-8 (4 μg/kg ip) injected before 30-min test meals of 10% sucrose was not different from that of +/+ or +/fak rats. These results demonstrate that the fak/fa k rat is a good model in which to analyze the controls of food intake, energy expenditure, and energy storage in the absence of leptin effects.
Bone and shell contribution to lactic acid buffering of submerged turtlesChrysemys picta belliiat 3°C
Authors: Jackson Donald C. , Crocker Carlos E. , Ultsch Gordon R.
Published: December 2017

To evaluate shell and bone buffering of lactic acid during acidosis at 3°C, turtles were submerged in anoxic or aerated water and tested at intervals for blood acid-base status and plasma ions and for bone and shell percent water, percent ash, and concentrations of lactate, Ca2+, Mg2+, Pi, Na+, and K+. After 125 days, plasma lactate concentration rose from 1.6 ± 0.2 mM (mean ± SE) to 155.2 ± 10.8 mM in the anoxic group but only to 25.2 ± 6.4 mM in the aerated group. The acid-base state of the normoxic animals was stable after 25 days of submergence. Plasma calcium concentration ([Ca2+]) rose during anoxia from 3.2 ± 0.2 to 46.0 ± 0.6 mM and [Mg2+] from 2.7 ± 0.2 to 12.2 ± 0.6 mM. Both shell and bone accumulated lactate to concentrations of 135.6 ± 35.2 and 163.6 ± 5.1 mmol/kg wet wt, respectively, after 125 days anoxia. Shell and bone [Na+] both fell during anoxia but the fate of this Na+is uncertain because plasma [Na+] also fell. No other shell ions changed significantly in concentration, although the concentrations of both bone calcium and bone potassium changed significantly. Control shell water (27.8 ± 0.6%) was less than bone water (33.6 ± 1.1%), but neither changed during submergence. Shell ash (44.7 ± 0.8%) remained unchanged, but bone ash (41.0 ± 1.0%) fell significantly. We conclude that bone, as well as shell, accumulate lactate when plasma lactate is elevated, and that both export sodium carbonate, as well as calcium and magnesium carbonates, to supplement ECF buffering.
Metabolic inhibitors synergistically decrease hepatic energy status and increase food intake
Authors: Ji Hong , Graczyk-Milbrandt Grazyna , Friedman Mark I.
Published: December 2017

Previous studies indicate that administration of the metabolic inhibitor, 2,5-anhydro-d-mannitol (2,5-AM) or methyl palmoxirate (MP), induces feeding behavior in rats by lowering hepatic energy status. Combined treatment with these agents synergistically increases food intake. The present study was designed to investigate whether combined treatment also has a synergistic effect on hepatic energy status. Rats treated with both inhibitors increased feeding behavior compared with the controls, whereas those treated with 2,5-AM or MP alone did not. Although 2,5-AM alone lowered hepatic ATP content regardless of MP treatment, only the combination resulted in decreases in hepatic ATP/ADP ratio and phosphorylation potential. MP treatment did not affect the uptake of 2,5-AM into liver. These results suggest that a reduction in hepatic energy status is the common triggering signal for eating behavior induced by 2,5-AM and MP and provide additional evidence for an integrated metabolic control of food intake.
Subthreshold aortic nerve inputs to neurons in nucleus of the solitary tract
Authors: Zhang Jing , Mifflin Steven W.
Published: December 2017

Subthreshold aortic nerve (AN) inputs to neurons receiving a monosynaptic AN-evoked input (MSNs: respond to each of two AN stimuli separated by 5 ms) and neurons receiving a polysynaptic AN input (PSNs) in the nucleus of the solitary tract (NTS) were identified in anesthetized rats. In extracellular recordings from 24 MSNs and 49 PSNs, 12% of MSNs and 29% of PSNs only responded to AN stimulation during the application of excitatory amino acids. In intracellular recordings from 24 MSNs and 22 PSNs, 12% of MSNs and 14% of PSNs responded to AN stimulation with excitatory postsynaptic potentials that did not evoke action potential discharge. Reductions in arterial pressure produced minimal changes in the spontaneous discharge of suprathreshold AN-evoked neurons, suggesting that these neurons receive excitatory inputs from nonbaroreceptor sources. The results suggest that some baroreflex-related NTS neurons exist in a “reserve state” and can be changed to an active state or vice versa. This will change the number of neurons involved in baroreflex circuits and provides a novel mechanism for regulating baroreflex function independently of alterations in peripheral afferent input.
Renal Na excretion in dehydrated and rehydrated adrenalectomized sheep maintained with aldosterone
Authors: McKinley Michael J. , Evered Mark D. , Mathai Michael L.
Published: December 2017

The effect of water deprivation for 19 h on renal Na excretion of conscious adrenalectomized (ADX) sheep maintained on a constant intravenous infusion of aldosterone and cortisol (ADX-constant steroid sheep) was investigated. Both ADX and normal sheep showed large increases in renal Na excretion when they were deprived of water. ADX-constant steroid sheep also exhibited a normal postprandial natriuresis 3–6 h after feeding, whether or not water was available to drink. In another experiment, sheep deprived of water for 41 h were then allowed to drink water. Both normal and ADX-constant steroid sheep exhibited a large reduction of renal Na excretion in the 6 h after rehydration. Changes in plasma Na and K concentration and osmolality were similar in normal and ADX-constant steroid sheep during periods of dehydration and rehydration. These results show that change in aldosterone secretion is not a major factor in causing either dehydration-induced or postprandial natriuresis. Neither is it a major cause of rehydration-induced renal Na retention.
Effects of ambient temperature on metabolic rate, respiratory quotient, and torpor in an arctic hibernator
Authors: Buck C. Loren , Barnes Brian M.
Published: December 2017

Arctic ground squirrels ( Spermophilus parryii) overwinter in hibernaculum conditions that are substantially below freezing. During torpor, captive arctic ground squirrels displayed ambient temperature (Ta)-dependent patterns of core body temperature (Tb), metabolic rate (TMR), and metabolic fuel use, as determined by respiratory quotient (RQ). At Ta 0 to −16°C, Tb remained relatively constant, and TMR rose proportionally with the expanding gradient between Tb and Ta, increasing >15-fold from a minimum of 0.0115 ± 0.0012 ml O2 · g−1 · h−1. At Ta 0–20°C, Tbincreased with Ta; however, TMR did not change significantly from Tb 0 to 12°C, indicating temperature-independent inhibition of metabolic rate. The overall change in TMR from Tb 4 to 20° equates to a Q10 of 2.4, but within this range of Tb, Q10 changed from 1.0 to 14.1. During steady-state torpor at Ta 4 and 8°C, RQ averaged 0.70 ± 0.013, indicating exclusive lipid catabolism. At Ta −16 and 20°C, RQ increased significantly to >0.85, consistent with recruitment of nonlipid fuels. RQ was negatively correlated with maximum torpor bout length. For Ta values <0°C, this relationship supports the hypothesis that availability of nonlipid metabolic fuels limits torpor duration in hibernating mammals; for Ta values >0°C, hypotheses linked to body temperature are supported. Because anterior body temperatures differ from core, overall, the duration torpor can be extended in hibernating mammals may be dependent on brain temperature.
Na+-K+-ATPase is distributed to microvillous and basal membrane of the syncytiotrophoblast in human placenta
Authors: Johansson M. , Jansson T. , Powell T. L.
Published: December 2017

Despite its importance for placental function, syncytiotrophoblast Na+-K+-ATPase has not been studied in detail. We purified syncytiotrophoblast microvillous (MVM) and basal (BM) membranes from full-term human placenta. Western blotting with isoform-specific antibodies demonstrated the presence of the α1-subunit, but not the α2- or α3-subunits, in MVM and BM. Relative density per unit membrane protein in BM was 48 ± 1% (mean ± SE, n = 4, P < 0.02) of that in the MVM. The activity of Na+-K+-ATPase was lower in BM (1.4 ± 0.14 μmol · mg−1· min−1, n = 8, P < 0.02) than in MVM (3.9 ± 0.25 μmol · mg−1· min−1). Immunocytochemistry confirmed the distribution of Na+-K+-ATPase to MVM and BM. These findings suggest that the syncytiotrophoblast represents a type of transporting epithelium different from the classical epithelia found in the small intestine and kidney, where Na+-K+-ATPase is confined to the basolateral membrane only. This unique polarization of the Na+pump does not, however, preclude a net transcellular transport of Na+to the fetus.