bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of dietary obesity on naloxone disposition in sheep
Authors: Alavi Fereidon K. , McCann Joseph P. , Sangiah Subbiah , Clarke Cyril R.
Published: April 2011

Naloxone is an opioid antagonist used frequently in studies of appetite regulation in lean and obese animals and humans. Body condition may affect plasma and tissue distribution of injected naloxone and thus confound interpretation of responses to naloxone in lean compared with obese subjects. The objective of this experiment was to determine the effect of dietary obesity per se on the pharmacokinetic behavior of iv-injected naloxone (3 mg/kg) in lean (46 kg body weight) and dietary obese (77 kg body weight) sheep that were maintained at equilibrium weight. To this end, an HPLC procedure combined with electrochemical detection was developed for measuring naloxone in sheep plasma. Naloxone disappearance from plasma followed an apparent first-order process, the kinetics of which were described best using a two-compartment open model. Components of the biexponential equations describing the plasma concentration (C) – time (t) curves for naloxone disappearance in lean (Ct = 1814e−0.190t + 413e−0.017t) and obese (Ct = 2282e−0.282t + 573e−0.018t) sheep were similar (p > 0.05). Mean (±SE) elimination half-lifes for naloxone in lean (42.7 ± 4.6 min) and obese (44.3 ± 10.2 min) sheep were similar (p > 0.05). Volume of distribution of naloxone (Vd) was extensive but also similar (p > 0.05) in lean (5.6 ± 0.9 L/kg) and obese (4.1 ± 0.6 L/kg) sheep. Naloxone was distributed extensively throughout the body fluids and trapped or stored in significant amount in extravascular tissues because the naloxone Vd greatly exceeded 100% of body weight in both lean (557 ± 86 mL/100 g) and obese (413 ± 58 mL/100 g) sheep. Whole-body clearance (ClB) of naloxone indexed to body weight (90 ± 7 vs. 69 ± 6 mL∙kg−1∙min−1) and absolute rates for body clearance (4.1 ± 0.3 vs. 5.3 ± 0.6 L/min) of naloxone tended to be greater (p < 0.1) in lean than obese sheep. We conclude that dietary obesity did not alter significantly the pharmacokinetic behavior of iv-injected naloxone in sheep.Key words: naloxone, obesity, sheep, kinetics, HPLC.
Central Neural Mechanisms of Touch and Proprioception
Authors: Kalaska John F.
Published: April 2011

The argument is made that somesthesia is not a strictly passive process, and its central neuronal mechanisms cannot be studied in all their complexity and subtlety by applying passive stimuli to uninterested or unconscious animals. The case is clear for kinesthesia. Peripheral proprioceptive signals are altered by active muscle contractions, and the central mechanisms of kinesthetic sensations should be studied during active movements. A similar case can be made for tactile discrimination. Ascending tactile afferents are subject to modulation during movement. Moreover, the generation of a central neural representation of the mechanical stimulus is only part of the tactile perceptual process. It is also influenced by the behavioral, attentive, and motivational state of the animal, whose effects can only be revealed in awake animals actively participating in discrimination tasks.Key words: tactile discrimination, proprioception, gating, attention, active touch.
A renal vasodilator effect of angiotensin II revealed by dual thromboxane inhibition
Authors: Badahman Al-Hassan , Wilson Thomas W.
Published: April 2011

Angiotensin II (AII) stimulates arachidonate release from renal endothelial and other ceils. Arachidonate is then metabolized by cyclooxygenase to prostaglandin (PG) H2, then PGI2 and thromboxane A2 (TXA2). PGH2 and TXA2 activate the same receptor and should augment AII-mediated vasoconstriction, whereas PGI2 is a vasodilator. We had previously shown that inhibiting TXA2 synthesis with furegrelate (FRG) redirects PGH2 metabolism toward PGI2, causing renal vasodilation. Because TXA2 synthesis inhibition may be incomplete and unmetabolized PGH2 may cause vasoconstriction, we reasoned that adding a PGH2/TXA2 receptor antagonist (BMS 180,290, formerly SQ 29548 (SQ)) to furegrelate should cause further renal vasodilation in the presence of AII Eight groups of 10 Sprague–Dawley rats received 120-min intravenous infusions of vehicle, FRG (2 mg∙kg−1 plus 2 mg∙kg−1∙h−1), SQ (2 mg∙kg−1 plus 2 mg∙kg−1∙h−1), FRG plus SQ, AII (10 ng∙kg−1∙min−1), AII plus FRG, AII plus SQ, or AII plus FRG plus SQ. Mean arterial pressure (MAP), p-[14C]aminohippurate clearance (CPAH), and [3H]insulin clearance were averaged for each rat for the final 90 min in three clearance periods. MAP did not change with any treatment. Estimating renal vascular resistance as MAP/CPAH confirmed a renal vasoconstrictor effect of this dose of AII: 58.1 ± 6.3 vs. 47.3 ± 6.8 (arbitrary units) with the vehicle (p < 0.05). FRG, SQ, or their combination did not affect renal vascular resistance, but adding FRG or SQ to AII prevented AII-mediated renal vasoconstriction. Adding both to AII caused net renal vasodilation to 24.8 ± 2.6 (p < 0.05 vs. vehicle). Inulin clearance changed in the same direction in all groups, but the changes were less marked. We conclude that stimulation of renal arachidonate release by AII combined with TXA2 synthesis inhibition and receptor antagonism results in vasodilation. This renal effect could be due to increased and unopposed renal vasodilator PG (principally PGI2) action.Key words: renal hemodynamics, angiotensin II, prostaglandins, thromboxane.
Aminophylline partially blocks ventilatory depression with hypoxia in the awake cat
Authors: Long W. Q. , Anthonisen N. R.
Published: April 2011

In humans and cats, the ventilatory response to 30 min of moderate hypoxia is biphasic, an initial increase being followed by a decrease in ventilation to levels that are often less than halfway between the initial response and the air-breathing control level. The decrease, or hypoxic depression, is thought to be of central origin. In humans, intravenous aminophylline, an adenosine blocker, blunts hypoxic depression and may completely block it in anesthetized cats. We studied 11 adult cats while awake, measuring ventilation and end-tidal [Formula: see text] and [Formula: see text] during 30 min of isocapnic hypoxia ([Formula: see text] 32 Torr (1 Torr = 133.3 Pa), [Formula: see text] 60 Torr) after intravenous aminophylline on 1 day and saline on another. On the saline day hypoxia initially produced a 75% increase in ventilation, which declined at 30 min to 110% of control, largely owing to a decrease in tidal volume. With aminophylline, room-air ventilation was slightly increased, and hypoxia initially produced a 50% increase in ventilation, which then declined to 130% of control at 30 min. Late in hypoxia, ventilation was significantly greater with aminophylline than with saline. The degree of hypoxic depression was not related to blood theophylline levels and was similar after aminophylline doses of 10 and 13 mg/kg. We conclude that hypoxic depression is at least partially due to adenosine accumulation, the effect of aminophylline being likely due to central adenosine blockade.Key words: adenosine, hypoxic depression.
Temporal changes in left ventricular function after massive sympathetic nervous system activation
Authors: Lang Sally A. , Maron Michael B. , Bosso Frank J. , Pilati Charles F.
Published: April 2011

Intense activation of the sympathetic nervous system (SNS) decreases the contractile state of the rabbit left ventricle (LV). In this study, we determined the time course of LV dysfunction after massive central activation of the SNS in dogs. Veratrine (40–80 μg/kg) was injected intracisternally to activate the SNS in six chloralose-anesthetized dogs, and LV end-diastolic pressure (LVEDP), cardiac output, heart rate, and aortic pressure (Pa) were measured at 30-min intervals for 3 h. Pa increased from 147 ± 8 (SE) to 272 ± 7 mmHg (1 mmHg = 133.3 Pa) within 15 min, then declined to 148 ± 16 mmHg by 1 h. LV function curves (stroke work versus LVEDP or stroke work versus LV transmural pressure) showed a marked decrease in slope and a shift to the right within minutes after activating the SNS, which persisted for the duration of the experiment. These data indicate that LV contractility was diminished in these animals. No changes in LV function were observed in three dogs serving as time-matched controls. In three additional dogs, LV pressure was raised to a degree similar to that observed after SNS activation by constricting the ascending aorta for 1 h. These animals exhibited only modest shifts in the LV function curve during and after aortic constriction. Mean plasma catecholamine concentration increased by one to two orders of magnitude in animals after SNS activation, but only minor changes were observed in the other two groups. We conclude that myocardial contractility declines markedly soon after massive SNS activation and is not solely a function of the initial hypertensive period.Key words: left ventricle contractility, heart failure, neurogenic pulmonary edema, sympathetic nervous system, catecholamines, veratrine.
Effect of potassium-induced cortical spreading depression on prostaglandin-induced fever in conscious and urethane-anesthetized rats
Authors: Komaromi I. , Malkinson T. J. , Veale W. L. , Rosenbaum G. , Cooper K. E. , Pittman Q. J.
Published: April 2011

Potassium-induced cortical spreading depression (CSD) on prostaglandin E1 (PGE1) induced fever has been investigated in a dose-responsive experimental design in both conscious and urethane-anesthetized adult male Sprague–Dawley rats. While CSD in itself had no effect on nonfebrile body temperature even under cold ambient conditions, CSD significantly suppressed small but not large fevers induced by intracerebroventricular PGE1. The increased oxygen consumption during fever was also reduced. We also explored the possible involvement of the antipyretic peptide arginine vasopressin, in the CSD-induced suppression of fever. Long term castrated rats have significantly reduced ventral septal levels of this peptide, yet CSD was effective in suppressing the initial 40 min of PGE1 fever in these animals. Thus we conclude that increased release of ventral septal arginine vasopressin is probably not involved in the action of CSD on fever.Key words: fever, cortical spreading depression, prostaglandin, potassium, cytokines, interleukin, anesthesia, urethane.
Intracellular calcium concentrations during metabolic inhibition in the motoneuron cell line NSC-19
Authors: Hasham M. I. , Naumann D. , Kim S. U. , Cashman N. R. , Quamme G. A. , Krieger C.
Published: April 2011

Changes in the concentrations of intracellular free calcium ([Ca2+]i) and adenine nucleotides were determined in response to metabolic inhibitors in the motoneuron cell line NSC-19. The NADH dehydrogenase inhibitor amobarbital (Amytal) and the mitochondrial uncoupler carbonylcyanide m-chlorophenylhydrazone (CCCP) were used to alter energy metabolism. Exposure of cells to 5 mM Amytal did not significantly change ATP concentrations but produced transient elevations of [Ca2+]i of approximately 80 nM, which were reduced by 32% when cells were studied in Ca2+-free solutions. CCCP (10 μM) caused a transient reduction in ATP concentration of 33%. CCCP also produced sustained elevations of [Ca2+]i of about 280 nM, which were reduced by 47% when in Ca2+-free solutions. In spite of the sustained elevation of [Ca2+]i induced by CCCP, NSC-19 showed no reduction in cell viability after 48 h compared with controls. Ruthenium red, a blocker of Ca2+ uptake by mitochondria, had little effect on the CCCP-induced [Ca2+]i increment. KCl or glutamate did not produce significant changes in [Ca2+]i, indicating that these cells do not possess significant numbers of voltage-dependent Ca2+ channels or excitatory amino acid receptor-gated channels. [Ca2+]i values in these cells were modified by changes in extracellular Ca2+ concentrations. In Ca2+-containing solutions, inhibition of Na+/Ca2+ exchange by amiloride and bepridil led to increased [Ca2+]i, as did blockade of Ca2+ ATPase by vanadate, suggesting that membrane transporters are important in Ca2+ efflux in NSC-19. The present studies indicate that exposure of NSC-19 cells to Amytal and CCCP produces Ca2+ increments by release from internal stores, as well as by transmembrane influx. These results demonstrate that small increments in [Ca2+]i can be produced by metabolic inhibitors or other compounds and that such changes are not associated with immediate cell death. Changes in [Ca2+]i could potentially result in abnormal cell function secondary to altered action of Ca2+-dependent enzymes.Key words: calcium, ATP, amobarbital, carbonylcyanide m-chlorophenylhydrazone, mitochondria, motoneurons, cell death.
Insulin potentiates norepinephrine-induced vascular tone by activation of protein kinase C and tyrosine kinase
Authors: Henrion Daniel , Laher Ismail
Published: April 2011

Insulin might play a role in the hypertension occurring in insulin-resistant diabetes. In addition, insulin has recently been shown to potentiate norepinephrine (NE) induced vascular tone. We used ring segments of the rabbit facial artery mounted in a myograph to test the hypothesis that potentiation of NE-induced tone by insulin may be related to activation of protein kinase C (PKC) and tyrosine kinase (TK). NE-induced contractions in the presence of insulin (1 mU/mL) were 200% (NE 0.1 and 0.3 μM), 252% (NE 1 μM), and 129% (NE 3 μM) of control. Insulin (1 mU/mL) had no effect on NE (10 and 100 μM) induced contractions. The potentiation by insulin of NE-induced tone was not altered by endothelium removal and could be mimicked by phorbol-12-myristate-13-acetate (PMA, 0.1 μM). Histamine-induced contractions were not altered by insulin (1 mU/mL). Insulin potentiation of NE-induced tone was suppressed by pretreatment of the rabbit facial artery with the PKC inhibitor calphostin C (0.1 μM) or the TK inhibitor genistein (10 μM). 45Ca2+ influx due to NE (3 μM) did not change in the presence of insulin (1 mU/mL) or PMA (0.1 μM) despite a higher contractile response, so that wall force per unit of 45Ca2+ influx was increased by insulin (1 mU/mL) and PMA (0.1 μM). Calphostin C (0.1 μM) and genistein (10 μM) both prevented the increase in wall force per unit of 45Ca2+ influx due to insulin (1 mU/mL). Our study shows that insulin potentiates NE-induced tone through a TK- and PKC-dependent mechanism.Key words: insulin, potentiation, norepinephrine, protein kinase C, tyrosine kinase, calphostin C, genistein, vascular reactivity.
Effects of Buthus martensii Karsch scorpion venom on the release of noradrenaline from in vitro and in vivo rat preparations
Authors: Foucart Sylvain , Wang Rui , Moreau Pierre , Sauvé Rémi , Champlain Jacques de , Yamaguchi Nobuharu , Bai Lin , Lu Xin-Ran
Published: April 2011

The aim of this study was to test the neuronal effects of the Chinese Buthus martensii Karsch (BMK) scorpion venom in vivo and in vitro in order to understand the mechanism involved in the cardiovascular pressor effect of this venom. In conscious unrestrained rats, administration of 100 μg/kg i.v. BMK venom induced an increase in blood pressure, which was associated with a significant increase in plasma noradrenaline. In isolated atria, BMK also induced an increase in the stimulation-induced release of [3H]noradrenaline in a dose-dependent manner. The modulatory effect of agents acting at sympathetic prejunctional adrenoceptors on [3H]noradrenaline release was not altered by BMK venom administration. Finally, it was observed that 100 μg/mL BMK venom increased the intracellular calcium concentration in acutely dissociated sympathetic neurons from adult rat superior cervical ganglion. This action appeared to be mainly due to an influx of extracellular calcium. BMK venom induced a small rise in intracellular calcium in the absence of external calcium, indicating that it may also mobilize calcium from intracellular stores. The results observed in this study suggest that BMK venom may induce pressor responses by releasing noradrenaline from the sympathetic nerve terminals and that activation of neuronal calcium channels may be involved in that process.Key words: scorpion venom, noradrenaline release, presynaptic modulation, intracellular calcium.
Dietary calcium, defective cellular Ca2+ handling, and arterial pressure control
Authors: McCarron David A. , Hatton Daniel , Roullet Jean-Baptiste , Roullet Chantal
Published: April 2011

The association between dietary calcium intake, calcium metabolism, and blood pressure form the basis of this review. Epidemiologic data consistently show an inverse relationship between dietary calcium and blood pressure. Clinical trials of calcium supplementation have not been as consistent in outcome. Approximately two-thirds of the supplementation studies have found a beneficial effect of calcium on blood pressure. The lack of consistency in outcome from the clinical trials relative to the epidemiological literature may be related to calcium intake. The epidemiological literature indicates an inverse relationship between calcium intake and blood pressure, with those individuals with the lowest calcium intake (< 700 mg/day) having the highest blood pressure. Clinical studies utilizing patients with high baseline calcium levels (> 700 mg/day) may not see an effect of calcium supplementation on blood pressure because of a ceiling effect. Supplemental calcium appears to correct a defect in calcium handling characterized by a renal calcium leak, increased circulating parathroid hormone, and increased intracellular calcium levels. In part, the deficit in cellular calcium homeostasis may be a consequence of abnormal calmodulin activity. Specifically, it appears that calmodulin activity is diminished in experimental hypertension and that increasing dietary calcium may improve calmodulin activity in the spontaneously hypertensive rat. The deficit in calmodulin activity has the potential to interfere with a number of cellular processes crucial to the regulation of cell function and maintenance of appropriate vascular tone. It is concluded that additional research should be directed toward understanding the ramifications of altered calmodulin activity in hypertension and the influence that dietary calcium can have on the activity of calmodulin.Key words: hypertension, dietary Ca2+, calmodulin, Ca2+ metabolism, calcium channel blockers.
The physicochemistry of [H+] and respiratory control: roles of , strong ions, and their hormonal regulators
Authors: Jennings Donald B.
Published: April 2011

I describe how the dietary intake of strong ions potentially affects the regulation of ventilation and the [Formula: see text] of body fluids in two ways. First, changing the dietary intake of NaCl can alter the concentration difference between strong cations and strong anions (the [SID] of Stewart) of body fluids. Experimental observations indicate that the [SID] in brain fluids or cerebrospinal fluid ([SID]CSF) could be the stimulus to central chemoreceptors. [SID]CSF consistently predicts ventilatory regulation of [Formula: see text], whereas [H+]CSF does not. [Formula: see text] acts as a stimulus to ventilation independently of [SID]CSF and possibly at higher as well as lower centers of the nervous system. I relate the concept of [SID] regulation of arterial [Formula: see text] to the alphastat hypothesis of protein function, respiratory control, and [H+] homeostasis. Second, altering the dietary intake of NaCl changes the levels of hormones involved in salt and water balance. Angiotensin II acts centrally to stimulate ventilation. Evidence for the roles of both the renal and brain rennin–angiotensin systems in respiratory control, and the modulation of respiratory control by vasopressin are reviewed. These peptide systems probably act via circumventricular organs of the brain to affect respiratory control and (or) by changing strong ion concentrations in brain fluids. Questions to be resolved on the role of [SID]CSF and hormones in respiratory adaptations, and experiments required to improve our understanding of the control of ventilation, are addressed in the concluding comments.Key words: respiratory control, dietary NaCl, strong ion difference, alphastat hypothesis, angiotensin II, arginine vasopressin, circumventricular organs.
Immune changes induced by exercise in an adverse environment
Authors: Shephard Roy J
Published: April 2011

Both physical activity and exposure to environmental stressors such as cold, heat, and high altitudes modify various components of immune function: T cell counts, natural killer (NK) cell counts, and cytolytic activity, cytokine secretion, lymphocyte proliferation and immunoglobulin levels. Light physical activity or a moderate level of environmental stress stimulate the immune response, but exhausting physical activity or more severe environmental stress have a suppressant effect, manifested by a temporary increase in susceptibility to viral infections. Combinations of physical activity and environmental stress generally have at least an additive effect. Thus, an intensity of physical activity or of environmental stress that is beneficial in itself can readily cause immunosuppression if the body is challenged by the two stimuli simultaneously.Key words: cold exposure, environmental stress, heat exposure, high altitudes, immunosuppression.
Changes in resting membrane potential induced by active sensitization in the guinea-pig vas deferens
Authors: Noireaud J , Souilem O , Baudet S , Bidon J -C , Gogny M , Jondet A
Published: April 2011

Smooth muscles hyperresponsiveness is a common feature in anaphylaxis and allergic diseases. The aim of the present work was to investigate whether the enhanced reactivity of sensitized guinea-pig vas deferens was associated with changes in the resting membrane potential (Er) of the smooth muscle cells. Active sensitization was performed by subcutaneous injection of egg albumen. Er was measured in vitro in isolated vas deferens with conventional KCl-filled microelectrodes. Quantification of [3H]ouabain binding sites, measurements of 86Rb efflux, and measurements of Na and K contents were also performed. In normal physiological solution, at 35°C, Er was a mean of -54.1 ± 0.3 mV (mean ± SEM) in control vas deferens. Sensitization resulted in depolarizing Er by about 7 mV. In control and sensitized preparations, the 3H-ouabain binding site concentration, the efflux of 86Rb, and the K content were similar. In guinea-pig vas deferens, active sensitization induced a partial depolarization of the resting membrane potential of the smooth muscle cells, which did not result from a downregulation of Na+-K+ pump sites.Key words: hyperreactivity, sensitization, Na+-K+ ATPase, guinea-pig, vas deferens, smooth muscle.
HCO3- secretion by bullfrog duodenum: dependence on nutrient Na+ during secretory stimulation
Authors: Goddard Philip J , Takahashi Shin'ichi , Milbank Aaron J , Silen William , Soybel David I
Published: April 2011

HCO3- secretion across in vitro duodenal mucosa of Rana catesbeiana was investigated under baseline conditions and during secretory stimulation. Baseline secretion was abolished by removal of CO2-HCO3- and reduced - 60% by removal of nutrient Na+, but was not sensitive to changes in Cl- or K+. Baseline secretion was not directly altered by exposure to 10-3 M amiloride or 10-3 M H2DIDS (dihydro-4,4prime-diisothiocyanostilbene-2,2prime-disulfonic acid) in the nutrient solution and only mildly reduced by acetazolamide. Following removal and restoration of Na+, recovery of secretion was impaired by exposure to acetazolamide (5 × 10-4 M) or H2DIDS (5 × 10-4 M) in the nutrient solution. Secretion stimulated by glucagon (10-6 M) or 16,16-dimethyl prostaglandin E2 (10 mu g·mL-1) was markedly attenuated by removal of Na+ or by exposure to H2DIDS, but secretion was not altered by acetazolamide (5 × 10-4 M) or nutrient amiloride (1 mM). Thus, the HCO3- that is secreted under nonstimulated conditions derives partly from basolateral Na+-dependent uptake and partly from cellular CO2 hydration. Secretagogue-stimulated secretion by duodenal surface epithelium depends on stilbene-sensitive Na+(HCO3-)n uptake across the basolateral membrane.Key words: duodenum, duodenal mucosa, bicarbonate ion, ion transport, amphibian, acetazolamide, sodium-bicarbonate cotransport, chloride-bicarbonate exchange.
Stimulation and inhibition of resting muscle thermogenesis by vasoconstrictors in perfused rat hind limb
Authors: Newman JMB , Clark M G
Published: April 2011

Angiotensin (AII) and serotonin (5-HT) are both vasoconstrictors of the constant-flow perfused rat hind limb that have opposite effects on thermogenesis, possibly the result of differing effects on vascular flow distribution between nutritive and non-nutritive pathways. In the present study interaction between the two opposing agents was examined with the expectation that the combined presence would show additive effects on pressure and mutually neutralizing effects on thermogenesis. Thus doses of AII and 5-HT that gave similar, but opposite, quantitative effects on thermogenesis were infused alone, in combination one after the other, or in combination with the order reversed, and the effects on perfusion pressure (PP) and thermogenesis (oxygen uptake, VO2) were compared. AII (3 nM) alone increased PP by 15 ± 1 mmHg (1 mmHg = 133.3 Pa) and VO2 by 3.1 ± 0.2 mu mol·h-1·g-1, whereas 5-HT (1 mu M) alone increased PP by 75 ± 6 mmHg and inhibited VO2 by 3.9 ± 0.2 mu mol·h-1·g-1. When added in combination, the outcome depended on the order of addition. Following AII, infusion of 5-HT further increased PP by 160 ± 11 mmHg and decreased VO2 by 6.3 ± 0.2 mu mol·h-1·g-1. Following 5-HT, infusion of AII further increased PP by 28 ± 4 mmHg and increased VO2 by only 1.8 ± 0.3 mu mol·h-1·g-1. The prior presence of 5-HT (1 mu M) shifted the AII dose-response curves for VO2 and pressure to the right and left, respectively. The prior infusion of AII increased the dose-dependent response to 5-HT in terms of both the inhibition of VO2 and the increase in PP. At low doses of 5-HT (10-8-10-7 M), but not alpha-methyl serotonin alphaMT), there was a marked vasodilatation-associated inhibition of AII-mediated increase in VO2. Overall the data show that the combined effect of AII and 5-HT differed from the simple addition of each separately. Since the order of addition appears to be critical in terms of thermogenic outcome, it is concluded that each vasoconstrictor exerts a specific hemodynamic action to affect access of the other to vascular receptor sites. These findings are consistent with the previously reported effects of these vasoconstrictors on substrate and insulin access to muscle of the perfused rat hind limb.Key words: flow distribution, skeletal muscle, vasoconstrictors, non-nutritive flow, nutritive flow, thermogenesis.
Effect of cycloheximide and tunicamycin on the gonadotrophin-releasing hormone stimulated distal glycosylation of luteinizing hormone by rat pituitary cells
Authors: Pérez Gabriela T , Apfelbaum Marta E
Published: April 2011

We have previously demonstrated that gonadotrophin-releasing hormone (GnRH) induces not only changes in quantity but also in quality on secreted luteinizing hormone (LH), by increasing [14C]Leu (translation) and [3H]Gal (distal glycosylation) incorporation into newly synthesized hormone. In the present report, we have further examined the GnRH-induced [3H]Gal-LH synthesis and release by treating anterior pituitary cells with polypeptide synthesis and glycosylation inhibitors (cycloheximide and tunicamycin, respectively). Pituitary cells from ovariectomized adult rats were cultured for 4 days and then incubated for different periods (0-5 h) in medium containing [14C]Leu plus [3H]Man or [14C]Leu plus [3H]Gal in the absence (basal) or presence of 10 nmol/L GnRH with or without (control) cycloheximide (1.0 and 4.0 µg/mL) or tunicamycin (0.5 and 2.0 µg/mL). At the end of each incubation period, the cells and the medium were separated and processed for DNA uptake and newly synthesized LH (labeled LH, by immunoprecipitation with a-betaLH) determinations. The velocity of synthesis and release (between 0 and 2 h, and between 2 and 5 h) was calculated by regression analysis and the statistical significance of differences was determined by the slope test. GnRH enhanced the rates of synthesis and release of [14C]Leu-, [3H]Man-, and [3H]Gal-LH to 157 and 237; 164 and 190; and 272 and 508% of basal values, respectively. Cycloheximide totally blocked synthesis and release of [14C]Leu-LH and greatly reduced those of [3H]Man-LH, resulting in the loss of cellular responsiveness to GnRH. Addition of tunicamycin to the pituitary cells inhibited the rates of synthesis and release of [3H]Man-LH which had been induced by GnRH, without altering those of [14C]Leu-LH. These findings indicate that glycosylation is not a condition for GnRH-stimulated LH translation. The GnRH-increased [3H]Gal-LH rates of synthesis and release were affected to a lesser extent by the inhibitors. Thus, GnRH stimulation of distal glycosylation can occur, albeit at a reduced rate, even though protein synthesis and glycosylation are blocked. In conclusion, the present results corroborate that GnRH stimulates the addition of galactose residues into LH molecule. This effect is not simply the consequence of stimulating LH polypeptide chain synthesis. In addition, it is shown that GnRH-increased LH translation is independent of glycosylation.Key words: gonadotrophin-releasing hormone, luteinizing hormone, glycosylation, cycloheximide, tunicamycin.
Increased neural damage to global hemispheric hypoxic ischemia (GHHI) in febrile but not nonfebrile lipopolysaccharide Escherichia coli injected rats
Authors: Thornhill Jim , Asselin Johanne
Published: April 2011

Experiments were conducted to compare the impact of febrile versus nonfebrile lipopolysaccharide (LPS) induced bacterial infection at the time of global hemispheric hypoxic ischemia (GHHI) on the neural damage evoked by the GHHI insult. In the first study acute intraperitoneal (i.p.) sterile saline (SS) or LPS Escherichia coli (60 µg/kg) was given to groups of male, conscious Long Evans rats, and core (colonic, Tc) temperatures were monitored over 6 h postinjection. Peak febrile response occurred ~5 h after the LPS E. coli was injected. Upon sacrifice 7 days later, no hemispheric or regional brain damage occurred in the saline or LPS-injected groups of this first study. In the second study, GHHI was applied (ligation of right common carotid artery + 35 min of 12% O2) in groups of anesthetized, male Long Evans rats previously given an acute i.p. injection of sterile saline or 60 µg/kg LPS E. coli 5 h earlier. Temperatures (Tc) were monitored before, during, and 1.5 and 24 h following GHHI. The LPS-injected group was subdivided into a febrile (Tc > 38°C before and (or) after GHHI) and nonfebrile (Tc < 38°C before and after GHHI) subgroups. A significant correlation was found between the peak temperature rise from preinjection control values following drug administration of either saline or LPS E. coli and the resultant hemispheric damage caused by GHHI. Moreover, upon sacrifice 7 days later ipsilateral hemispheric and regional (i.e., hippocampal, thalamic) damage to GHHI of the febrile LPS E. coli group was significantly increased from respective hemispheric, hippocampal, and thalamic damage of the saline and nonfebrile, LPS groups given the same ischemic insult. Results suggest that the heightened Tc of a LPS infection at the time of global ischemia exacerbated the neural damage of GHHI, a finding similar to that reported with heightened core temperatures induced by external heating.Key words: febrile infection, stroke, temperature, neural damage.
Modulation of vasomotion in resistance arteries of JCR:LA-cp rats: a model of insulin resistance
Authors: O'Brien Sheila F , Russell James C , Davidge Sandra T
Published: April 2011

Obesity and insulin resistance are strongly associated with an increased risk of vascular disease. Vasomotion is the cyclic variation in the diameter of arteries and is a general feature of the vasculature that may have important physiological consequences. We tested the hypothesis that obesity - insulin resistance is associated with abnormal vasomotion by comparing obese, insulin-resistant JCR:LA-cp rats, known to develop vasculopathy, atherosclerosis, and ischemic lesions of the heart, with lean insulin-sensitive animals from the same strain. Vasomotion was assessed using isolated mesenteric arteries on a myograph system after preconstriction to 50% of maximal constriction with norepinephrine. The amplitude of vasomotion was enhanced by the presence of meclofenamate, a prostaglandin H synthase inhibitor, and was diminished by NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor. Removal of the endothelium essentially abolished vasomotion, and meclofenamate had no effect on de-endothelialized arteries. Frequency was not altered by either L-NAME or meclofenamate. Although pharmacological inhibition of nitric oxide and eicosanoid production clearly altered vasomotion, there was no difference in the amplitude or frequency of vasomotion in arteries from obese rats compared with lean rats. These results indicate that the endothelium plays a central role in modulating vasomotion, involving both enhancing and inhibiting effects, and that vasomotion is similar between obese, insulin-resistant and lean, insulin-sensitive rats.Key words: insulin resistance, vasomotion, resistance arteries, JCR:LA-cp rats.
Zidovudine (AZT) induced alterations in mitochondrial biogenesis in rat striated muscles
Authors: Freyssenet Damien , DiCarlo Martino , Escobar Patricia , Grey Janice , Schneider Jeremy , Hood David A
Published: April 2011

Zidovudine (AZT) and didanosine (ddI), two drugs used in the treatment of AIDS, are also known to cause mitochondrial abnormalities. We investigated the physiological relevance of the mitochondrial defects by measuring in situ skeletal muscle performance and cytochrome c oxidase (CYTOX) enzyme activity in heart muscle, red high-oxidative (RG) and white low-oxidative (WG) portions of the gastrocnemius muscle of control (n = 17), AZT- (n = 14), or ddI-treated (n = 11) rats for 28 days. We also evaluated the hypothesis that AZT treatment could alter the expression of the mitochondrial transcription factor A (mtTFA), a key molecule involved in mitochondrial DNA (mtDNA) replication and transcription. AZT had a pronounced effect on blood pressure and skeletal muscle performance, which were significantly decreased during contractile activity at 2 and 5 Hz, compared with control. A significant decrease in CYTOX activity in heart and RG, but not WG muscles, was also evident. In the heart, this was accompanied by an apparent compensatory increase in mtTFA mRNA level that could not be attributed to enhanced transcriptional activation mediated by nuclear respiratory factor 1 (NRF-1). In contrast with AZT, no effect of ddI was found on the extent of fatigue or muscle enzyme activity. These results indicate that AZT induces mitochondrial defects primarily in muscles with the highest oxidative capacities (heart and RG). The long-term effects of AZT on mitochondrial biogenesis have the potential to reduce muscle performance, but the effects on performance in this short-term study were likely due to an inability of the AZT-treated animals to maintain blood pressure during contractile activity.Key words: mitochondrial myopathy, endurance performance, cytochrome c oxidase, mitochondrial transcription factor A, zidovudine, didanosine.
Haloperidol-mediated phosphoinositide hydrolysis via direct activation of α1-adrenoceptors in frontal cerebral rat cortex
Authors: Borda Tania Gabriela , Cremaschi Graciela , Sterin-Borda Leonor
Published: April 2011

In addition to its effect on D2 dopamine receptor blockades, haloperidol is able to interact with multiple neurotransmitters (NTs). Its action on phosphoinositide (PI) turnover was studied on cerebral cortex preparations. It induces an increase in inositol phosphate (IP) accumulation, which was only blunted by the α1-adrenoceptor blocker prazosin. Haloperidol maximal effect (Emax) was less than the effect of the full agonist norepinephrine (NE), and dose-response curves for both NE in the presence of submaximal doses of haloperidol and haloperidol in the presence of Emax doses of NE showed that haloperidol behaves as a partial agonist of cerebral α1-adrenoceptors. Its effect on PI hydrolysis is mediated through phospholipase C activation, as 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (NCDC) and 1-[6-([(17β)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino)hexyl]-1H-pyrrole-2,5-dione) (U-73122) were able to abrogate both haloperidol and NE actions. Further, the typical neuroleptic exerts a direct activation of α1-adrenoceptors as its actions were not modified by cocaine and persisted in spite of chemical rat cerebral denervation with 6-hydroxydopamine (6-OHDA). The possibility that this agonistic action on α1-adrenoceptors would be involved in haloperidol side effects is also discussed.Key words: haloperidol, neuroleptics, α1-adrenoceptor, phosphoinositide hydrolysis, cerebral frontal cortex.
Local distribution of Oligocottus maculosus Girard and other tidepool cottids of the west coast of Vancouver Island, British Columbia
Authors: Green John M.
Published: April 2011

The study was concerned with the distribution pattern at low tide of Oligocottus maculosus Girard and other cottid fishes inhabiting tidepools on the west coast of Vancouver Island, B.C. Five species (O. maculosus, O. rimensis, Clinocottus acuticeps, C. embryum, and C. globiceps) have their centers of distribution in the intertidal zone. Seven species (Hemilepidotus hemilepidotus, Artedius lateralis, A. fenestralis, Ascelichthys rhodorus, O. snyderi, Enophrys bison, and Leptocottus armatus) inhabit tidepools but are most abundant in the subtidal zone.O. maculosus is the most abundant and widely distributed tidepool cottid in the intertidal zone. Only three other species (C. acuticeps, C. embryum, and C. globiceps) regularly inhabit tidepools above LLHW (lowest lower high water). The primary environmental factor correlated with the distribution of O. maculosus is exposure to wave action. In exposed transects this species is restricted to the upper intertidal zone, while in sheltered transects it inhabits the tidepools throughout the intertidal zone. Observations show that O. maculosus responds to water turbulence by retreating to cover. It is concluded that to inhabit a given tidepool O, maculosus must have a minimum period of low turbulent conditions. This species has 'capitalized' on the tidepool habitat to invade the open coast environment.
Sexual attraction in the free-living nematode Panagrellus silusiae (Cephalobidae)
Authors: Cheng Ronald , Samoiloff M. R.
Published: April 2011

Female Panagrellus silusiae produce a substance that attracts males. Males do not produce attractant, nor is there homosexual attraction. The attractant is water borne and forms a gradient in agar. The attractant is first produced by females during the fourth juvenile stage and males first respond to the attractant during the fourth juvenile stage. Female Cephalobus persegnis also produce an attractant, but the attractants of each species only attract males of that species.
Coccidia of Rocky Mountain bighorn sheep in Western Canada
Authors: Uhazy Leslie S. , Mahrt Jerome L. , Holmes John C.
Published: April 2011

A survey of coccidia in the Rocky Mountain bighorn sheep (Ovis. c. canadensis) in Alberta and Kootenay National Park, British Columbia, was conducted from the winter of 1967 to the spring of 1969. Ninety percent of 510 fecal samples examined were positive for coccidia. The species recovered, in order of prevalence, were Eimeria ovina (syn., E. arloingi) (56%), E. parva (35%), E. crandallis (34%), E. ahsata (33%), E. ninakohlyakimovae (19%), E. faurei (6%), E. intricata (5%) and E. granulosa (1%). Coccidiosis was not encountered in the field; however, evidence which suggests the magnitude of pathogenic infections is presented.
Correlates of reproductive success in a population of nine-banded armadillos
Authors: Loughry W J , Prodöhl Paulo A , McDonough Colleen M , Nelson W S , Avise John C
Published: April 2011

We used microsatellite DNA markers to identify the putative parents of 69 litters of nine-banded armadillos (Dasypus novemcinctus) over 4 years. Male and female parents did not differ in any measure of body size in comparisons with nonparents. However, males observed paired with a female were significantly larger than unpaired males, although paired females were the same size as unpaired females. Females categorized as possibly lactating were significantly larger than females that were either definitely lactating or definitely not lactating. There was no evidence of assortative mating: body-size measurements of mothers were not significantly correlated with those of fathers. Nine-banded armadillos give birth to litters of genetically identical quadruplets. Mothers (but not fathers) of female litters were significantly larger than mothers of male litters, and maternal (but not paternal) body size was positively correlated with the number of surviving young within years, but not cumulatively. There were no differences in dates of birth between male and female litters, nor were there any significant relationships between birth date and maternal body size. Body size of either parent was not correlated with the body sizes of their offspring. Cumulative and yearly reproductive success did not differ between reproductively successful males and females. Average reproductive success (which included apparently unsuccessful individuals) also did not differ between males and females. The majority of adults in the population apparently failed to produce any surviving offspring, and even those that did usually did so in only 1 of the 4 years. This low reproductive success is unexpected, given the rapid and successful range extension of this species throughout the southeastern United States in this century.
Survival of juvenile hares during a cyclic population increase
Authors: Gillis Elizabeth A
Published: April 2011

Snowshoe hares (Lepus americanus) are multilittered synchronous breeders that produce up to four distinct litters of young each summer. I used radiotelemetry to determine the effects of juvenile cohort (i.e., litter group) and food availability on postweaning survival of hares in the southwestern Yukon during the increase phase of a hare cycle. During the study, I monitored 86 juvenile hares from control areas and areas in which supplemental food was provided. Twenty-eight-day survival did not differ between food addition and control areas for any juvenile cohort, and survival rates of juveniles (all cohorts combined) did not differ significantly from those of adults (juveniles: 0.91 per 28 days; adults: 0.93 per 28 days). However, when examined by juvenile cohort, survival of third and fourth litters was significantly lower than that of adults and first and second litters. These differences were the result of differential survival among the juvenile cohorts during a 3-month period in the fall (September-November). Predation was the primary proximate cause of death for weaned juvenile hares, accounting for 86% of deaths.
Adiponectin opposes endothelin-1-mediated vasoconstriction in the perfused rat hindlimb
Authors: Bussey Carol T. , Kolka Cathryn M. , Rattigan Stephen , Richards Stephen M.
Published: April 2011

Recent studies have shown that adiponectin is able to increase nitric oxide (NO) production by the endothelium and relax preconstricted isolated aortic rings, suggesting that adiponectin may act as a vasodilator. Endothelin-1 (ET-1) is a potent vasoconstrictor, elevated levels of which are associated with obesity, type 2 diabetes, hypertension, and cardiovascular disease. We hypothesized that adiponectin has NO-dependent vascular actions opposing the vasoconstrictor actions of ET-1. We studied the vascular and metabolic effects of a physiological concentration of adiponectin (6.5 μg/ml) on hooded Wistar rats in the constant-flow pump-perfused rat hindlimb. Adiponectin alone had no observable vascular activity; however, adiponectin pretreatment and coinfusion inhibited the increase in perfusion pressure and associated metabolic stimulation caused by low-dose (1 nM) ET-1. Adiponectin was not able to oppose vasoconstriction when infusion was commenced after ET-1. This is in contrast to the NO donor sodium nitroprusside, which significantly reduced the pressure due to established ET-1 vasoconstriction, suggesting dissociation of the actions of adiponectin and NO. In addition, adiponectin had no effect on vasoconstriction caused by either high-dose (20 nM) ET-1 or low-dose (50 nM) norepinephrine. Our findings suggest that adiponectin has specific, apparently NO-independent, vascular activity to oppose the vasoconstrictor effects of ET-1. The hemodynamic actions of adiponectin may be an important aspect of its insulin-sensitizing ability by regulating access of insulin and glucose to myocytes. Imbalance in the relationship between adiponectin and ET-1 in obesity may contribute to the development of insulin resistance and cardiovascular disease.
Weight Gain after Tonsillectomy
Authors: Wei Julie L.
Published: April 2011

Excessive weight gain after tonsillectomy has been described by a handful of studies since as early as 1988 and, in recent years, mostly with variable study design, methods, and baseline weight of the subjects. Although most otolaryngologists have likely been asked whether tonsillectomy may lead to weight gain by parents and caretakers, there has been very limited research on this issue, and certainly no causal effect has been established by existing research. Awareness and counseling based on what has been described are relevant as a part of preoperative counseling. However, it is critical that our national epidemic of excessive weight gain in children and adolescents not be simply reduced to a matter of tonsillectomy but be understood as a multifactorial and complex issue. To study this topic well requires commitment to well‐designed studies assessing caloric intake and expenditure, metabolic changes, and prospective growth measurements. Mechanisms for weight gain, even if excessive during the 12 months after tonsillectomy surgery, are far from being elucidated.
Smad1 signaling restricts hematopoietic potential after promoting hemangioblast commitment
Authors: Cook Brandoch D. , Liu Susanna , Evans Todd
Published: April 2011

Bone morphogenetic protein (BMP) signaling regulates embryonic hematopoiesis via receptor-mediated activation of downstream SMAD proteins, including SMAD1. In previous work, we showed that Smad1 expression is sufficient to enhance commitment of mesoderm to hemangioblast fate. We also found indirect evidence to support a subsequent repressive function for Smad1 in hematopoiesis. To test this hypothesis directly, we developed a novel system allowing temporal control of Smad1 levels by conditional knockdown in embryonic stem cell derivatives. Depletion of Smad1 in embryoid body cultures before hemangioblast commitment limits hematopoietic potential because of a block in mesoderm development. Conversely, when Smad1 is depleted in FlK1+ mesoderm, at a stage after hemangioblast commitment, the pool of hematopoietic progenitors is expanded. This involves enhanced expression levels for genes specific to hematopoiesis, including Gata1, Runx1 and Eklf, rather than factors required for earlier specification of the hemangioblast. The phenotype correlates with increased nuclear SMAD2 activity, indicating molecular cross-regulation between the BMP and TGF-β signaling pathways. Consistent with this mechanism, hematopoiesis was enhanced when Smad2 was directly expressed during this same developmental window. Therefore, this study reveals a temporally defined function for Smad1 in restricting the expansion of early hematopoietic progenitors.