bluuebunny/crossref_metadata_2025 huggingface dataset:
Capsaicin-treated rats permanently overingest low- but not high-concentration sucrose solutions
Authors: Kelly Lisa , Morales Silvia , Smith Brenda K. , Berthoud Hans-Rudolf
Published: December 2017

The effect of capsaicin-induced chemical ablation of visceral afferents on 1-h liquid sucrose consumption was investigated in food-deprived rats. We first show that although 10% sucrose is permanently overconsumed by capsaicin-treated (CAPs) compared with vehicle-treated (VEHs) control rats, 40% sucrose is only overconsumed during the first but not subsequent 1-h exposures. Furthermore, one group of CAPs lost the overconsumption response at 20% when exposed to progressively increasing sucrose concentrations of 10–40%, and another group recovered the overconsumption response at 10% when exposed to a series of decreasing concentrations. Control rats ingested relatively constant volumes of sucrose over the range of 10, 15, and 20%, resulting in significantly different energy intakes. In contrast, CAPs generally showed a concentration-dependent decrease in volume intake, resulting in relatively constant energy intake. These results suggest that capsaicin-sensitive visceral afferents, likely from gastric distension and other preabsorptive sensors, provide major control over volume ingested. In the absence of these signals, rats initially overconsume, but rapidly learn to use other signals from capsaicin-resistant preabsorptive or postabsorptive sites, to control future intake. This redundant satiety system appears to be sensitive to the osmotic value or caloric content of the unfamiliar food, but only if this is above a threshold of about 15% sucrose.
Testosterone receptor blockade after trauma and hemorrhage attenuates depressed adrenal function
Authors: Ba Zheng F. , Wang Ping , Koo Douglas J. , Zhou Mian , Cioffi William G. , Bland Kirby I. , Chaudry Irshad H.
Published: December 2017

Although the testosterone receptor antagonist flutamide restores the depressed immune function in males after trauma and hemorrhage, it remains unknown whether this agent has any salutary effects on adrenal function. To study this, male rats underwent laparotomy and were bled to and maintained at a blood pressure of 40 mmHg until 40% of the shed blood volume was returned in the form of Ringer lactate. Animals were then resuscitated and flutamide (25 mg/kg body wt) was administered subcutaneously. Plasma adrenocorticotropic hormone (ACTH) and corticosterone, as well as adrenal corticosterone and cAMP were measured 20 h after resuscitation. In additional animals, ACTH was administered and ACTH-induced corticosterone release and adrenal cAMP were determined. The results indicate that adrenal contents of corticosterone and cAMP were significantly decreased and morphology was altered after hemorrhage. Administration of flutamide improved corticosterone content, restored cAMP content, and attenuated adrenal morphological alterations. Flutamide also improved the diminished ACTH-induced corticosterone release and adrenal cAMP response at 20 h after hemorrhage and resuscitation. Furthermore, the diminished corticosterone response to ACTH stimulation in the isolated adrenal preparation was improved with flutamide. These results suggest that flutamide is a useful adjunct for improving adrenal function in males following trauma and hemorrhage.
Short-term modulation of the exercise ventilatory response in goats: effects of 8-OH-DPAT and MPPI
Authors: Henderson Daniel R. , Mitchell Gordon S.
Published: December 2017

Increased respiratory dead space increases the exercise ventilatory response, a response known as short-term modulation (STM). We hypothesized that STM results from a spinal, serotonin (5-HT)-dependent mechanism. Because 5-HT1Aautoreceptors on caudal brain stem raphe neurons inhibit 5-HT release, we hypothesized that 5-HT1A-receptor agonists would inhibit, whereas 5-HT1A-receptor antagonists would enhance, STM. Ventilatory and arterial blood-gas measurements were made at rest and during exercise (4.0–4.5 km/h, 5% grade) in goats with the respiratory mask alone or with increased dead space (0.20–0.25 liter), before and after intravenous administration of the 5-HT1A-receptor agonist 8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT; 0.1 mg/kg) or the antagonist 4-iodo- N-{2-[4-(methoxyphenyl)-1-piperazinyl]ethyl}- N-2-pyridinylbenzamide (MPPI; 0.08 mg/kg). 8-OH-DPAT increased the slope of the arterial Pco2vs. metabolic CO2production relationship and decreased the ventilation vs. metabolic CO2production relationship during exercise with increased dead space (not with the mask alone), indicating an impairment of STM. In contrast, MPPI had minimal effects on any measured variable. Although nonspecific effects of 8-OH-DPAT cannot be ruled out, impaired STM is consistent with the hypothesis that STM requires active raphe serotonergic neurons and 5-HT release.
Characterization of RyR1-slow, a ryanodine receptor specific to slow-twitch skeletal muscle
Authors: Morrissette Jeffery , Xu Le , Nelson Alexandra , Meissner Gerhard , Block Barbara A.
Published: December 2017

Two distinct skeletal muscle ryanodine receptors (RyR1s) are expressed in a fiber type–specific manner in fish skeletal muscle (11). In this study, we compare [3H]ryanodine binding and single channel activity of RyR1-slow from fish slow-twitch skeletal muscle with RyR1-fast and RyR3 isolated from fast-twitch skeletal muscle. Scatchard plots indicate that RyR1-slow has a lower affinity for [3H]ryanodine when compared with RyR1-fast. In single channel recordings, RyR1-slow and RyR1-fast had similar slope conductances. However, the maximum open probability (Po) of RyR1-slow was threefold less than the maximum Poof RyR1-fast. Single channel studies also revealed the presence of two populations of RyRs in tuna fast-twitch muscle (RyR1-fast and RyR3). RyR3 had the highest Poof all the RyR channels and displayed less inhibition at millimolar Ca2+. The addition of 5 mM Mg-ATP or 2.5 mM β,γ-methyleneadenosine 5′-triphosphate (AMP-PCP) to the channels increased the Poand [3H]ryanodine binding of both RyR1s but also caused a shift in the Ca2+dependency curve of RyR1-slow such that Ca2+-dependent inactivation was attenuated. [3H]ryanodine binding data also showed that Mg2+-dependent inhibition of RyR1-slow was reduced in the presence of AMP-PCP. These results indicate differences in the physiological properties of RyRs in fish slow- and fast-twitch skeletal muscle, which may contribute to differences in the way intracellular Ca2+is regulated in these muscle types.
Mechanisms of vascular instability in a transgenic mouse model of sickle cell disease
Authors: Nath K. A. , Shah V. , Haggard J. J. , Croatt A. J. , Smith L. A. , Hebbel R. P. , Katusic Z. S.
Published: December 2017

We investigated a transgenic mouse model of sickle cell disease, homozygous for deletion of mouse β-globin and containing transgenes for human βSand βS-antillesglobins linked to the transgene for human α-globin. In these mice, basal cGMP production in aortic rings is increased, whereas relaxation to an endothelium-dependent vasodilator, A-23187, is impaired. In contrast, aortic expression of endothelial nitric oxide synthase (NOS) is unaltered in sickle mice, whereas expression of inducible NOS is not detected in either group; plasma nitrate/nitrite concentrations and NOS activity are similar in both groups. Increased cGMP may reflect the stimulatory effect of peroxides (an activator of guanylate cyclase), because lipid peroxidation is increased in aortae and in plasma in sickle mice. Despite increased vascular cGMP levels in sickle mice, conscious systolic blood pressure is comparable to that of aged-matched controls; sickle mice, however, evince a greater rise in systolic blood pressure in response to nitro-l-arginine methyl ester, an inhibitor of NOS. Systemic concentrations of the vasoconstrictive oxidative product 8-isoprostane are increased in sickle mice. We conclude that vascular responses are altered in this transgenic sickle mouse and are accompanied by increased lipid peroxidation and production of cGMP; we suggest that oxidant-inducible vasoconstrictor systems such as isoprostanes may oppose nitric oxide-dependent and nitric oxide-independent mechanisms of vasodilatation in this transgenic sickle mouse. Destabilization of the vasoactive balance in the sickle vasculature by clinically relevant states may predispose to vasoocclusive disease.
Cerebral artery KATP- and KCa-channel activity and contractility: changes with development
Authors: Long Wen , Zhang Lubo , Longo Lawrence D.
Published: December 2017

The present study was designed to test the hypothesis that in cerebral arteries of the fetus, ATP-sensitive (KATP) and Ca2+-activated K+channels (KCa) play an important role in the regulation of intracellular Ca2+concentration ([Ca2+]i) and that this differs significantly from that of the adult. In main branch middle cerebral arteries (MCA) from near-term fetal (∼140 days) and nonpregnant adult sheep, simultaneously we measured norepinephrine (NE)-induced responses of vascular tension and [Ca2+]iin the absence and presence of selective K+-channel openers/blockers. In fetal MCA, in a dose-dependent manner, both the KATP-channel opener pinacidil and the KCa-channel opener NS 1619 significantly inhibited NE-induced tension [negative logarithm of the half-maximal inhibitory concentration (pIC50) = 5.0 ± 0.1 and 8.2 ± 0.1, respectively], with a modest decrease of [Ca2+]i. In the adult MCA, in contrast, both pinacidil and NS 1619 produced a significant tension decrease (pIC50= 5.1 ± 0.1 and 7.6 ± 0.1, respectively) with no change in [Ca2+]i. In addition, the KCa-channel blocker iberiotoxin (10−7to 10−6M) resulted in increased tension and [Ca2+]iin both adult and fetal MCA, although the KATP-channel blocker glibenclamide (10−7to 3 × 10−5M) failed to do so. Of interest, administration of 10−7M iberiotoxin totally eliminated vascular contraction and increase in [Ca2+]iseen in response to 10−5M ryanodine. In precontracted fetal cerebral arteries, activation of the KATPand KCachannels significantly decreased both tension and [Ca2+]i, suggesting that both K+channels play an important role in regulating L-type channel Ca2+flux and therefore vascular tone in these vessels. In the adult, KATPand the KCachannels also appear to play an important role in this regard; however, in the adult vessel, activation of these channels with resultant vasorelaxation can occur with no significant change in [Ca2+]i. These channels show differing responses to inhibition, e.g., KCa-channel inhibition, resulting in increased tension and [Ca2+]i, whereas KATP-channel inhibition showed no such effect. In addition, the KCachannel appears to be coupled to the sarcoplasmic reticulum ryanodine receptor. Thus differences in plasma membrane K+-channel activity may account, in part, for the differences in the regulation of contractility of fetal and adult cerebral arteries.
High-fat diet-induced muscle insulin resistance: relationship to visceral fat mass
Authors: Kim Jong-Yeon , Nolte Lorraine A. , Hansen Polly A. , Han Dong-Ho , Ferguson Kevin , Thompson Paul A. , Holloszy John O.
Published: December 2017

It has been variously hypothesized that the insulin resistance induced in rodents by a high-fat diet is due to increased visceral fat accumulation, to an increase in muscle triglyceride (TG) content, or to an effect of diet composition. In this study we used a number of interventions: fish oil, leptin, caloric restriction, and shorter duration of fat feeding, to try to disassociate an increase in visceral fat from muscle insulin resistance. Substituting fish oil (18% of calories) for corn oil in the high-fat diet partially protected against both the increase in visceral fat and muscle insulin resistance without affecting muscle TG content. Injections of leptin during the last 4 days of a 4-wk period on the high-fat diet partially reversed the increase in visceral fat and the muscle insulin resistance, while completely normalizing muscle TG. Restricting intake of the high-fat diet to 75% of ad libitum completely prevented the increase in visceral fat and muscle insulin resistance. Maximally insulin-stimulated glucose transport was negatively correlated with visceral fat mass ( P < 0.001) in both the soleus and epitrochlearis muscles and with muscle TG concentration in the soleus ( P < 0.05) but not in the epitrochlearis. Thus we were unable to dissociate the increase in visceral fat from muscle insulin resistance using a variety of approaches. These results support the hypothesis that an increase in visceral fat is associated with development of muscle insulin resistance.
Spaceflight induces changes in splenocyte subpopulations: effectiveness of ground-based models
Authors: Pecaut Michael J. , Simske Steven J. , Fleshner Monika
Published: December 2017

Spaceflight produces changes in the immune system. The mechanisms for the alterations in immune function after spaceflight remain unclear due in part to the difficulties associated with conducting spaceflight research. The purpose of the following studies, therefore, was to create a ground-based protocol that can reproduce the immunological changes found after spaceflight, i.e., changes in splenic lymphocyte populations. Rats were exposed to either flight aboard the Space Shuttle Endeavor (STS-77) or ground-based simulations of various components of the spaceflight experience. The ground-based mock spaceflight was comprised of exposure to launch and landing loads and unloading of the hindlimbs. In addition, each component of this ground-based mock spaceflight was tested separately. The results were that spaceflight reduced splenic CD4+T (helper/inducer) cells and CD11b+(neutrophils/macrophages) cells. The ground-based simulations of spaceflight did not reproduce the same pattern of splenocyte changes. In fact, exposure to landing loads alone increased splenic CD4+T (helper/inducer) cells. These findings support the conclusion that the ground models tested did not induce similar changes in the immune system as did spaceflight. It is possible, therefore, that stressors/factors unique to the spaceflight experience impact the immune system in ways that cannot be currently, fully modeled on the ground.
Sleep-related c-Fos protein expression in the preoptic hypothalamus: effects of ambient warming
Authors: Gong Hui , Szymusiak Ronald , King Janice , Steininger Teresa , McGinty Dennis
Published: December 2017

Preoptic area (POA) neuronal activity promotes sleep, but the localization of critical sleep-active neurons is not completely known. Thermal stimulation of the POA also facilitates sleep. This study used the c-Fos protein immunostaining method to localize POA sleep-active neurons at control (22°C) and mildly elevated (31.5°C) ambient temperatures. At 22°C, after sleep, but not after waking, we found increased numbers of c-Fos immunoreactive neurons (IRNs) in both rostral and caudal parts of the median preoptic nucleus (MnPN) and in the ventrolateral preoptic area (VLPO). In animals sleeping at 31.5°C, significantly more Fos IRNs were found in the rostral MnPN compared with animals sleeping at 22°C. In VLPO, Fos IRN counts were no longer increased over waking levels after sleep at the elevated ambient temperature. Sleep-associated Fos IRNs were also found diffusely in the POA, but counts were lower than those made after waking. This study supports a hypothesis that the MnPN, as well as the VLPO, is part of the POA sleep-facilitating system and that the rostral MnPN may facilitate sleep, particularly at elevated ambient temperatures.
Second messengers mediating mechanical responses to the FaRP GYIRFamide in the flukeFasciola hepatica
Authors: Graham M. K. , Fairweather I. , McGeown J. G.
Published: December 2017

Spontaneous phasic contractions recorded from isolated body strips of Fasciola hepatica were increased in frequency and amplitude by GYIRFamide, an FMRFamide-related peptide (FaRP). Superfusion with guanosine 5′-O-(2-thiodiphosphate) (100 μM, n = 5) reduced the effects of GYIRFamide on both frequency (by 82%) and amplitude (by 75%). The adenylate cyclase inhibitor MDL-12330A (25 μM) increased spontaneous activity. MDL-12330A completely inhibited the frequency response to GYIRFamide and reduced the amplitude response by 66% as measured relative to this elevated basal activity ( n = 6). Inhibition of phospholipase C (PLC) with neomycin sulfate (1 mM) had no direct effect on activity but reduced the frequency response to GYIRFamide by 64% and the amplitude increase by 95% ( n = 9). The protein kinase C (PKC) inhibitor chelerythrine chloride (10 μM) also reduced frequency and amplitude responses by 98 and 99%, respectively, without affecting basal contractility ( n = 5). Phorbol 12-myristate 13-acetate, an activator of PKC, increased contraction frequency and amplitude ( n = 6). It was concluded that GYIRFamide stimulates mechanical activity in F. hepatica through a G protein, via a PLC- and PKC-dependent second messenger pathway.
Role of suprachiasmatic nuclei in circadian and light-entrained behavioral rhythms of lizards
Authors: Bertolucci Cristiano , Sovrano Valeria Anna , Magnone Maria Chiara , Foà Augusto
Published: December 2017

To establish whether the suprachiasmatic nuclei (SCN) of the Ruin lizard ( Podarcis sicula) play a role in entrainment of circadian rhythms to light, we examined the effects of exposure to 24-h light-dark (LD) cycles on the locomotor behavior of lizards with SCN lesions. Lizards became arrhythmic in response to complete SCN lesion under constant temperature and constant darkness (DD), and they remained arrhythmic after exposure to LD cycles. Remnants of SCN tissue in other lesioned lizards were sufficient to warrant entrainment to LD cycles. Hence, the SCN of Ruin lizards are essential both to maintain locomotor rhythmicity and to mediate entrainment of these rhythms to light. We also asked whether light causes expression of Fos-like immunoreactivity (Fos-LI) in the SCN. Under LD cycles, the SCN express a daily rhythm in Fos-LI. Because Fos-LI is undetectable in DD, the rhythm seen in LD cycles is caused by light. We further showed that unilateral SCN lesions in DD induce dramatic period changes. Altogether, the present data support the existence of a strong functional similarity between the SCN of lizards and the SCN of mammals.
Role of NO and cytochromeP-450-derived eicosanoids in ET-1-induced changes in intrarenal hemodynamics in rats
Authors: Hercule H. C. , Oyekan A. O.
Published: December 2017

Endothelin-1 (ET-1) produces potent renal effects that we have previously shown to be dependent on cytochrome P-450 (CYP450) metabolites of aracidonic acid (24) This study evaluated the role of these metabolites in the effects produced by ET-1 on renal blood flow (RBF), cortical blood flow (CBF), medullary blood flow (MBF), and mean arterial blood pressure (MBP). ET-1 (20–200 pmol/kg) increased MBP, renal vascular resistance (RVR), and MBF but reduced CBF and RBF in a dose-dependent manner. The decreases in CBF and RBF, and increases in MBP and RVR were blunted by BMS-182874, an ETareceptor antagonist or BQ-788, an ETbreceptor antagonist. Similarly, indomethacin, an inhibitor of cyclooxygenase activity, or 12,12-dibromododecenoic acid (DBDD), a CYP450-dependent inhibitor of production of 20-hydroxyeicosatetraenoic acid (20-HETE), blunted these effects. ET-3 elicited dose-related reduction in CBF and increase in MBF. Indomethacin accentuated the reduction in CBF and attenuated the increase in MBF, as did DBDD. ET-1-induced increase in MBF was attenuated by BQ-788, Nω-nitro-l-arginine methyl ester (l-NAME), an inhibitor of nitric oxide (NO) synthesis, indomethacin, or DBDD. DBDD inhibited the hemodynamic effects ofl-NAME. Miconazole, the inhibitor of CYP450-dependent epoxygenase activity, was without effect. These results indicate that hemodynamic changes produced by ET-1 are mediated by vasoconstrictor prostanoids and/or prostanoid-like substances, possibly, 20-HETE via activation of ETaand ETbreceptors. However, the increase in MBF is mediated by vasodilator prostanoids or by NO via ETbreceptor activation.
Role of NO and PAF in the impairment of skeletal muscle contractility induced by TNF-α
Authors: Alloatti Giuseppe , Penna Claudia , Mariano Filippo , Camussi Giovanni
Published: December 2017

The role of platelet-activating factor (PAF) and nitric oxide (NO) as mediators of the effects of tumor necrosis factor-α (TNF-α) on skeletal muscle contractility was studied in guinea pig extensor digitorum longus (EDL) muscle. TNF-α (5–10 ng/ml) reduced contractility at every stimulation frequency (1–200 Hz) and shifted the force-frequency relationship to the right. The role of NO and PAF as mediators of TNF-α was suggested by the protective effect of NG-nitro-l-arginine methyl ester (l-NAME; 1 mM), but not of NG-nitro-d-arginine methyl ester (d-NAME; 1 mM), and by the inhibitory effect of the PAF-receptor antagonist WEB-2170 (3 μM). TNF-α increased the production of PAF and NO. Similar to TNF-α, both S-nitroso- N-acetylpenicillamine (0.5–1 μM), an NO-generating compound, and PAF (10–20 nM) reduced EDL contractility. l-NAME, but not d-NAME, blocked the negative effect of PAF. Blockade of phospholipase A2, which is required for PAF synthesis, significantly reduced the effects of TNF-α. WEB-2170 inhibited NO synthesis induced by TNF-α and PAF-stimulated NO production. These results suggest that both PAF and NO contribute to the development of the mechanical alterations induced by TNF-α and that NO production is downstream to the synthesis of PAF.
Bacterial translocation can increase plasma corticosterone and brain catecholamine and indoleamine metabolism
Authors: Ando Tetsuya , Brown Rhonda F. , Berg Rodney D. , Dunn Adrian J.
Published: December 2017

The potential contribution of stress-induced bacterial translocation to the activation of the hypothalamo-pituitary-adrenocortical (HPA) axis and brain biogenic amines was assessed. Mice were restrained for various periods, and brain concentrations of tryptophan, catecholamines, serotonin, and their metabolites, plasma corticosterone, and the translocation of viable bacteria from the gastrointestinal tract to the mesenteric lymph nodes, spleen, and liver were measured. Restraint induced the translocation of indigenous gram-positive bacteria in only a small proportion of animals, but translocation of gram-negative bacteria did not occur. Restraint induced short-lived increases in plasma corticosterone and brain amine metabolism, whereas bacterial translocation was slower and persisted long after the HPA axis and neurochemical responses had dissipated. When mice were infected with Salmonella typhimurium, spontaneous translocation occurred and plasma corticosterone, interleukin-6 concentrations, and brain catecholamine and indoleamine metabolism were elevated. These findings indicate that the translocation of indigenous gastrointestinal bacteria did not contribute to the HPA axis and neurochemical changes induced by restraint. However, translocation of nonindigenous S. typhimurium with or without restraint did induce HPA and neurochemical responses.
Blood and brain magnesium in inbred mice and their correlation with sleep quality
Authors: Chollet Didier , Franken Paul , Raffin Yvette , Malafosse Alain , Widmer Jean , Tafti Mehdi
Published: December 2017

A strong genetic component in the regulation of blood magnesium (Mg) levels has been demonstrated. The regulation and distribution of brain Mg levels, however, have never been assessed. Herein we report on the genetic variation of peripheral and central Mg levels in six inbred strains of mice. In addition, the possible involvement of Mg in sleep regulation was assessed by establishing correlations between Mg and sleep parameters obtained before and after a 6-h sleep deprivation. Although genotype strongly determined blood Mg levels, it did not affect brain Mg, suggesting that central and peripheral Mg are regulated differently. Central Mg displayed a highly structure-specific distribution with frontal cortex having the highest and brain stem the lowest values. Whereas for the amount and distribution of baseline sleep only marginal correlations with Mg were found, Mg contents in four of nine brain structures were highly positively correlated with the length of slow-wave sleep episodes during recovery. This relationship suggests that higher levels of Mg in specific brain sites promote sleep quality as part of a recovery process.
Arginase I: a limiting factor for nitric oxide and polyamine synthesis by activated macrophages?
Authors: Kepka-Lenhart Diane , Mistry Sanjay K. , Wu Guoyao , Morris Sidney M.
Published: December 2017

Because arginase hydrolyzes arginine to produce ornithine and urea, it has the potential to regulate nitric oxide (NO) and polyamine synthesis. We tested whether expression of the cytosolic isoform of arginase (arginase I) was limiting for NO or polyamine production by activated RAW 264.7 macrophage cells. RAW 264.7 cells, stably transfected to overexpress arginase I or β-galactosidase, were treated with interferon-γ to induce type 2 NO synthase or with lipopolysaccharide or 8-bromo-cAMP (8-BrcAMP) to induce ornithine decarboxylase. Overexpression of arginase I had no effect on NO synthesis. In contrast, cells overexpressing arginase I produced twice as much putrescine after activation than did cells expressing β-galactosidase. Cells overexpressing arginase I also produced more spermidine after treatment with 8-BrcAMP than did cells expressing β-galactosidase. Thus endogenous levels of arginase I are limiting for polyamine synthesis, but not for NO synthesis, by activated macrophage cells. This study also demonstrates that it is possible to alter arginase I levels sufficiently to affect polyamine synthesis without affecting induced NO synthesis.
A model for influence of exercise on formation and growth of tissue bubbles during altitude decompression
Authors: Foster Philip P. , Feiveson Alan H. , Glowinski Roland , Izygon Michael , Boriek Aladin M.
Published: December 2017

In response to exercise performed before or after altitude decompression, physiological changes are suspected to affect the formation and growth of decompression bubbles. We hypothesized that the work to change the size of a bubble is done by gas pressure gradients in a macro- and microsystem of thermodynamic forces and that the number of bubbles formed through time follows a Poisson process. We modeled the influence of tissue O2 consumption on bubble dynamics in the O2transport system in series against resistances, from the alveolus to the microsystem containing the bubble and its surrounding tissue shell. Realistic simulations of experimental decompression procedures typical of actual extravehicular activities were obtained. Results suggest that exercise-induced elevation of O2 consumption at altitude leads to bubble persistence in tissues. At the same time, exercise-enhanced perfusion leads to an overall suppression of bubble growth. The total volume of bubbles would be reduced unless increased tissue motion simultaneously raises the rate of bubble formation through cavitation processes, thus maintaining or increasing total bubble volume, despite the exercise.
Predicting time to decompression illness during exercise at altitude, based on formation and growth of bubbles
Authors: Foster Philip P. , Feiveson Alan H. , Boriek Aladin M.
Published: December 2017

For altitude decompressions, we hypothesized that reported onset times of limb decompression illness (DCI) pain symptoms follow a probability distribution related to total bubble volume [Vb·( t)] as a function of time. Furthermore, we hypothesized that the probability of ever experiencing DCI during a decompression is associated with the cumulative volume of bubbles formed. To test these hypotheses, we first used our previously developed formation-and-growth model ( Am J Physiol Regulatory Integrative Comp Physiol 279: R2304–R2316, 2000) to simulate Vb·(t) for 20 decompression profiles in which 334 human subjects performed moderate repetitive skeletal muscle exercise (827 kJ/h) in an altitude chamber. Using survival analysis, we determined that, for a controlled condition of exercise, the fraction of the subject population susceptible to DCI can be approximately expressed as a power function of the formation-and-growth model-predicted cumulative volume of bubbles throughout the altitude exposure. Furthermore, for this fraction, the probability density distribution of DCI onset times is approximately equal to the ratio of the time course of formation-and growth-modeled total bubble volume to the predicted cumulative volume.
Metallothionein gene expression and secretion in white adipose tissue
Authors: Trayhurn Paul , Duncan Jacqueline S. , Wood Anne M. , Beattie John H.
Published: December 2017

White adipose tissue (WAT) has been examined to determine whether the gene encoding metallothionein (MT), a low-molecular-weight stress response protein, is expressed in the tissue and whether MT may be a secretory product of adipocytes. The MT-1 gene was expressed in epididymal WAT, with MT-1 mRNA levels being similar in lean and obese ( ob/ ob) mice. MT-1 mRNA was found in each of the main adipose tissue sites (epididymal, perirenal, omental, subcutaneous), and there was no major difference between depots. Separation of adipocytes from the stromal-vascular fraction of WAT indicated that the MT gene (MT-1 and MT-2) was expressed in adipocytes themselves. Treatment of mice with zinc had no effect on MT-1 mRNA levels in WAT, despite strong induction of MT-1 expression in the liver. MT-1 gene expression in WAT was also unaltered by fasting or norepinephrine. However, administration of a β3-adrenoceptor agonist, BRL-35153A, led to a significant increase in MT-1 mRNA. On differentiation of fibroblastic preadipocytes to adipocytes in primary culture, MT was detected in the medium, suggesting that the protein may be secreted from WAT. It is concluded that WAT may be a significant site of MT production; within adipocytes, MT could play an antioxidant role in protecting fatty acids from damage.
Intraspecific variation in aerobic metabolism and glycolytic enzyme expression in heart ventricles
Authors: Podrabsky Jason E. , Javillonar Chris , Hand Steven C. , Crawford Douglas L.
Published: December 2017

A previous phylogenetic analysis among 15 taxa of the teleost fish Fundulussuggested that there should be thermal-adaptive differences in heart metabolism among populations. To test this hypothesis, the rate of oxygen consumption and the activities of all 11 glycolytic enzymes were measured in isolated heart ventricle from two populations of Fundulus heteroclitus. Heart ventricular metabolism is greater in a northern population versus a southern population of these fish. Analysis of the amount of glycolytic enzymes indicates that 87% of the variation in cardiac metabolism within and between populations is explained by the variation in three enzymes (pyruvate kinase, glyceraldehyde-3-phosphate dehydrogenase, and lactate dehydrogenase). These enzymes are the same three enzymes that were predicted to be important based on previously determined phylogenetic patterns of expression. Our data indicate that near-equilibrium enzymes, as well as classically defined rate-limiting enzymes, can also influence metabolism.
Survival of water stress in annual fish embryos: dehydration avoidance and egg envelope amyloid fibers
Authors: Podrabsky Jason E. , Carpenter John F. , Hand Steven C.
Published: December 2017

Diapausing embryos of Austrofundulus limnaeus survive desiccating conditions by reducing evaporative water loss. Over 40% of diapause II embryos survive 113 days of exposure to 75.5% relative humidity. An early loss of water from the perivitelline space occurs during days 1–2, but thereafter, rates of water loss are reduced to near zero. No dehydration of the embryonic tissue is indicated based on microscopic observations and the retention of bulk (freezable) water in embryos as judged by differential scanning calorimetry. Such high resistance to desiccation is unprecedented among aquatic vertebrates. Infrared spectroscopy indicates frequent intermolecular contacts via β-sheet (14%) in hydrated egg envelopes (chorions). These β-sheet contacts increase to 36% on dehydration of the egg envelope. Interestingly, the egg envelope is composed of protein fibrils with characteristics of amyloid fibrils usually associated with human disease. These features include a high proportion of intermolecular β-sheet, positive staining and green birefringence with Congo red, and detection of long, unbranched fibrils with a diameter of 4–6 nm. The high resistance of diapause II embryos to water stress is not correlated with ontogenetic changes in the egg envelope.
Transplantation of metanephroi across the major histocompatibility complex in rats
Authors: Rogers Sharon A. , Liapis Helen , Hammerman Marc R.
Published: December 2017

To determine whether transplanted metanephroi grow, differentiate, and function in hosts that differ in major histocompatibility complex loci (RT1 loci in rats) from donors in a defined way, we implanted metanephroi from embryonic day( E) 15 PVG (RT1c) rat embryos into the omentum of nonimmunosupressed uninephrectomized PVG-RT1avl (host) rats. By 4 wk posttransplantation, metanephroi had grown and differentiated such that glomeruli, proximal and distal tubules, and collecting ducts had normal structure and ultrastructure. At 12 wk posttransplantation, weights of metanephroi were 54 ± 8 mg. Inulin clearances were 0.9 ± 0.3 μl · min−1 · 100 g rat wt−1. In vitro, splenocytes from PVG rats stimulated the proliferation of cells originating from both PVG-RT1avlrats in which a transplant had been performed and PVG-RT1avl rats with no transplant. Full-thickness PVG-RT1avl skin engrafted normally on PVG-RT1avl rats in which PVG metanephroi had been previously implanted and metanephroi retained a normal appearance. In contrast, skin from PVG rats sloughed, and the tubular architecture of metanephroi was obliterated by a mononuclear cell infiltrate consistent with acute rejection. Here we show for the first time that functional chimeric kidneys develop from metanephroi transplanted across the MHC into nonimmunosupressed hosts and provide evidence that a state of peripheral immune tolerance secondary to T cell “ignorance” permits their survival.
Cold-induced changes in thyroid function in a poikilothermic mammal, the naked mole-rat
Authors: Buffenstein Rochelle , Woodley Ryan , Thomadakis Cleopatra , Daly T. Joseph M. , Gray David A.
Published: December 2017

Cold acclimation induces very divergent responses in thyroid function in reptiles and mammals reflective of their different thermoregulatory modes. Naked mole-rats, unlike other small mammals, are unable to effectively employ endothermy and are operatively poikilotherms. We therefore investigated changes in their thyroid status with chronic cold exposure. Under simulated burrow conditions, free thyroxine (T4; 0.39 ± 0.09 ng/dl) and thyroid stimulating hormone (TSH; 1.12 ± 0.56 μIU/ml) levels fell within the reptilian range, one order of magnitude lower than mammalian levels. However, cold induced typical mammalian responses: free T4levels (0.55 ± 0.09 ng/dl) and thyroid follicular cell height were significantly greater. Although TSH levels (1.28 ± 0.83 μIU/ml) were not significantly elevated, thyrotrophs exhibited ultrastructural signs of increased secretory activity. Low thyroid hormone concentrations may contribute substantially to the unusual thermoregulatory mode exhibited by naked mole-rats.
A single bout of exercise induces β-adrenergic desensitization in human adipose tissue
Authors: Marion-Latard Fabrice , De Glisezinski Isabelle , Crampes Francois , Berlan Michel , Galitzky Jean , Suljkovicova Hana , Riviere Daniel , Stich Vladimir
Published: December 2017

This study was designed to assess whether physiological activation of the sympathetic nervous system induced by exercise changes adipose tissue responsiveness to catecholamines in humans. Lipid mobilization in abdominal subcutaneous adipose tissue was studied with the use of a microdialysis method in 11 nontrained men (age: 22.3 ± 1.5 yr; body mass index: 23.0 ± 1.6). Adipose tissue adrenergic sensitivity was explored with norepinephrine, dobutamine (β1-agonist), or terbutaline (β2-agonist) perfused during 30 min through probes before and after 60-min exercise (50% of the maximal aerobic power). The increase in extracellular glycerol concentration during infusion was significantly lower after the exercise when compared with the increase observed before the exercise ( P < 0.05, P < 0.02, and P < 0.01, respectively, for norepinephrine, dobutamine, and terbutaline). In a control experiment realized without exercise, no difference in norepinephrine-induced glycerol increase between the two infusions was observed. To assess the involvement of catecholamines in the blunted β-adrenergic-induced lipolytic response after exercise, adipose tissue adrenergic sensitivity was explored with two 60-min infusions of norepinephrine or epinephrine separated by a 60-min interval. With both catecholamines, the increase in glycerol was significantly lower during the second infusion ( P < 0.05). The findings suggest that aerobic exercise, which increased adrenergic activity, induces a desensitization in β1- and β2-adrenergic lipolytic pathways in human subcutaneous adipose tissue.
Endothelial-derived nitric oxide and angiotensinogen: blood pressure and metabolism during mouse pregnancy
Authors: Hefler Lukas A. , Tempfer Clemens B. , Moreno Rene M. , O'Brien William E. , Gregg Anthony R.
Published: December 2017

The regulation of blood pressure during pregnancy involves several biological pathways. Candidate genes implicated in hypertensive diseases during pregnancy include those of the renin-angiotensin system and nitric oxide synthase (NOS). We evaluated blood pressure and metabolic characteristics during pregnancy in mutant mice. These included mice with a null mutation in the endothelial NOS (eNOS) gene ( Nos3−/−), four copies of the angiotensinogen gene ( Agt2/2), and mutations in both genes [four copies of Agt and heterozygous deficient for eNOS (Agt2/2Nos3+/−), four copies of Agt and homozygous deficient for eNOS ( Agt2/2Nos3−/−)]. Blood pressure measurements of nulliparous females from mutant strains were compared with two common laboratory strains C57Bl6/J and SV129 throughout their first pregnancy. Serum and urine analysis for the evaluation of renal and liver physiology were measured in the prepregnant state and during the third trimester of pregnancy. Throughout pregnancy blood pressures in all mutant strains were higher compared with controls. Agt2/2Nos3−/−showed the highest blood pressures and C57Bl6/J the lowest. Control mice, but not mutant mice, showed a second trimester decline in blood pressure. No immediate differences were noted regarding behavioral characteristics, renal or liver function parameters. Mice deficient for eNOS, mice with overexpression of Agt, and mice with mutations in both genes demonstrated higher blood pressure throughout pregnancy. There was no evidence of renal dysfunction, liver dysfunction, or hemolysis among any of the strains studied. We conclude that Nos3 and Agt are important genes in the regulation of blood pressure during pregnancy.
Sex steroid hormones enhance immune function in male and female Siberian hamsters
Authors: Bilbo Staci D. , Nelson Randy J.
Published: December 2017

Immune function is better in females than in males of many vertebrate species, and this dimorphism has been attributed to the presence of immunosuppressive androgens in males. We investigated the influence of sex steroid hormones on immune function in male and female Siberian hamsters. Previous studies indicated that immune function was impaired in male and female hamsters housed under short-day photoperiods when androgen and estrogen concentrations were virtually undetectable. In experiment 1, animals were gonadally intact, gonadectomized (gx), or gx with hormone replacement. Females exhibited the expected increase in antibody production over males, independent of hormone treatment condition, whereas male and female gx animals exhibited decreased lymphocyte proliferation to the T cell mitogen, phytohemagglutinin (PHA) compared with intact animals, and this effect was reversed in gx hamsters following testosterone and estradiol treatment, respectively. In experiment 2, testosterone, dihydrotestosterone, and estradiol all enhanced cell-mediated immunity in vitro, suggesting that sex steroid hormones may be enhancing immune function through direct actions on immune cells. In experiment 3, an acute mitogen challenge of lipopolysaccharide significantly suppressed lymphocyte proliferation to PHA in intact males but not females, suggesting that males may be less reactive to a subsequent mitogenic challenge than females. Contrary to evidence in many species such as rats, mice, and humans, these data suggest that sex steroid hormones enhance immunity in both male and female Siberian hamsters.
Acute hypertension inhibits thirst stimulated by ANG II, hyperosmolality, or hypovolemia in rats
Authors: Stocker Sean D. , Stricker Edward M. , Sved Alan F.
Published: December 2017

The present study sought to determine whether increases in arterial blood pressure inhibited drinking behavior evoked by ANG II, hyperosmolality, or hypovolemia in rats. Cumulative water intakes in 60- or 90-min tests and latency to the first lick were recorded as indexes of thirst. During intravenous infusions of 100 ng · kg−1 · min−1 ANG II, attenuation of the induced increases in arterial pressure with the arteriolar vasodilator diazoxide resulted in greater water intakes and shorter latencies to drink. Drinking behavior stimulated by intravenous infusion of hypertonic saline was significantly inhibited by increases in arterial pressure caused by intravenous infusion of phenylephrine or endothelin-1, and this inhibition of drinking was proportional to the induced increase in pressure. Upon termination of the phenylephrine infusion, mean arterial pressure returned to basal values, and drinking was restored. Phenylephrine-induced increases in arterial pressure also inhibited drinking behavior in response to hypovolemia that could not be explained by differences in plasma renin activity, plasma protein concentration, or plasma osmolality. Thus increases in arterial pressure inhibit water drinking behavior in response to each of these three thirst stimuli in rats.
Estimation of growth hormone secretion rate: impact of kinetic assumptions intrinsic to the analytical approach
Authors: Langendonk Janneke G. , Veldhuis Johannes D. , Burggraaf Jacobus , Schoemaker Rik C. , Cohen Adam F. , Edo Meinders A. , Pijl Hanno
Published: December 2017

We compared four common mathematical techniques to determine daily endogenous growth hormone (GH) secretion rates from diurnal plasma GH concentration profiles in 24 women (16 upper- or lower-body obese and 8 normal-weight individuals). Two forms of deconvolution analysis and two techniques based on a priori determined GH clearance estimates were employed. Deconvolution analyses revealed significant differences in the 24-h GH secretion rate between normal-weight and upper-body obese women, whereas the other two techniques did not. Moreover, deconvolution analyses predicted that the reduction in mean plasma GH concentrations in upper-body obese women was accounted for by impaired GH secretion, whereas the other methods suggested that obesity increases GH metabolic clearance. Thus we infer that disparate conclusions concerning GH secretion can be drawn from the same primary data set. The different inferences likely reflect dissimilar kinetic assumptions and the particular limitations intrinsic to each analytical approach. Accordingly, we urge caution in the facile comparison of calculated GH secretion data in humans, especially when kinetic and secretion measurements are performed under different conditions. The most appropriate way to determine the GH secretion rate in humans must be balanced by the exact intent of the experiment and the acceptability of different assumptions in that context.
Differential alterations in cardiac adrenergic signaling in chronic hypoxia or norepinephrine infusion
Authors: León-Velarde F. , Bourin M.-C. , Germack R. , Mohammadi K. , Crozatier B. , Richalet J.-P.
Published: December 2017

Norepinephrine (NE)-induced desensitization of the adrenergic receptor pathway may mimic the effects of hypoxia on cardiac adrenoceptors. The mechanisms involved in this desensitization were evaluated in male Wistar rats kept in a hypobaric chamber (380 Torr) and in rats infused with NE (0.3 mg · kg−1 · h−1) for 21 days. Because NE treatment resulted in left ventricular (LV) hypertrophy, whereas hypoxia resulted in right (RV) hypertrophy, the selective hypertrophic response of hypoxia and NE was also evaluated. In hypoxia, α1-adrenergic receptors (AR) density increased by 35%, only in the LV. In NE, α1-AR density decreased by 43% in the RV. Both hypoxia and NE decreased β-AR density. No difference was found in receptor apparent affinity. Stimulated maximal activity of adenylate cyclase decreased in both ventricles with hypoxia (LV, 41%; RV, 36%) but only in LV with NE infusion (42%). The functional activities of Gi and Gs proteins in cardiac membranes were assessed by incubation with pertussis toxin (PT) and cholera toxin (CT). PT had an important effect in abolishing the decrease in isoproterenol-induced stimulation of adenylate cyclase in hypoxia; however, pretreatment of the NE ventricle cells with PT failed to restore this stimulation. Although CT attenuates the basal activity of adenylate cyclase in the RV and the isoproterenol-stimulated activity in the LV, pretreatment of NE or hypoxic cardiac membranes with CT has a less clear effect on the adenylate cyclase pathway. The present study has demonstrated that 1) NE does not mimic the effects of hypoxia at the cellular level, i.e., hypoxia has specific effects on cardiac adrenergic signaling, and 2) changes in α- and β-adrenergic pathways are chamber specific and may depend on the type of stimulation (hypoxia or adrenergic).
c-Fos generation in the dorsal vagal complex after systemic endotoxin is not dependent on the vagus nerve
Authors: Hermann G. E. , Emch G. S. , Tovar C. A. , Rogers R. C.
Published: December 2017

The present study used activation of the c-Fos oncogene protein within neurons in the dorsal vagal complex (DVC) as a marker of neuronal excitation in response to systemic endotoxin challenge [i.e., lipopolysaccharide (LPS)]. Specifically, we investigated whether vagal connections with the brain stem are necessary for LPS cytokine- induced activation of DVC neurons. Systemic exposure to LPS elicited a significant activation of c-Fos in neurons in the nucleus of the solitary tract (NST) and area postrema of all thiobutabarbital-anesthetized rats examined, regardless of the integrity of their vagal nerves. That is, rats with both vagi cervically transected were still able to respond with c-Fos activation of neurons in the DVC. Unilateral cervical vagotomy produced a consistent but small reduction in c-Fos activation in the ipsilateral NST of all animals within this experimental group. Given that afferent input to the NST is exclusively excitatory, it is not surprising that unilateral elimination of all vagal afferents would diminish NST responsiveness (on the vagotomized side). These data lead us to conclude that the NST itself is a primary central nervous system detector of cytokines.