bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactate transport by rainbow trout white muscle: kinetic characteristics and sensitivity to inhibitors
Authors: Wang Y. , Wright P. M. , Heigenhauser G. J. , Wood C. M.
Published: December 2017

This study used an isolated-perfused tail-trunk preparation of rainbow trout to examine the uptake and release of lactate (Lac) and metabolic protons (delta H+M) in resting and exercised fish white muscle. In exercised muscle, L(+)-Lac efflux was inhibited (approximately 40%) by 5 mM alpha-cyano-4-hydroxycinnamate (CIN), but not by 0.5 mM 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) or 0.1 mM amiloride. These results suggest that Lac release occurs through a Lac(-)-H- symport and the free diffusion of lactic acid (HLac) or Lac-, but not via the Lac-/HCO3(-)-Cl- antiporter. Lac efflux was accompanied by delta H+m influx in all treatments, and increased delta H+m influx occurred after SITS treatment. In resting muscle, Lac uptake rates were greater than Lac efflux rates in the postexercise preparation. L-Lac influx exhibited partial saturation kinetics, whereas D(-)-Lac influx was linearly related to its extracellular concentration (0-32 mM). At 16 mM extracellular L-Lac, with a negligible transmembrane L-HLac gradient and an outwardly directed not driving force on L-Lac-, CIN, and SITS reduced net L-Lac uptake by 75 and 45%, respectively. At 16 mM extracellular concentration, D-Lac influx was 64% of the net L-Lac influx. These results suggest that in trout muscle at 16 mM extracellular L-Lac, the Lac -H+ symport accounts for 30-36%, the Lac-/HCO3(-)-Cl- antiport for 39-45%, and diffusion for 19-25% of uptake, although the latter is probably overestimated and the former underestimated for methodological reasons. Net L-Lac efflux was not affected by extracellular D-Lac concentration and/or D-Lac influx, implying the existence of a concurrent L-Lac efflux during L-Lac influx. The D-Lac influx kinetics data indicated that the Lac-/HCO3 antiport was not saturable in the extracellular D-Lac concentration range of 0-32 mM. This study clearly demonstrates the involvement of carrier-mediated transport in transmembrane Lac movement in fish muscle and supports the "active lactate retention" mechanism proposed by Turner and Wood (J. Exp. Biol. 105: 895-401, 1983).
Muscle enzyme activity in humans: role of substrate availability and training
Authors: Helge J. W. , Kiens B.
Published: December 2017

To study the effect of nutrient intake (substrate flux) and training on muscle enzyme activities, 36 untrained healthy men adapted for 7 wk to a fat-rich or a carbohydrate-rich diet. Ten of the 18 subjects on each diet completed an endurance training program, and the remaining 8 served as controls. Maximal oxygen uptake was increased (11%) in the trained groups (P < 0.05). Irrespective of training, beta-hydroxyacyl-CoA-dehydrogenase activity in the vastus lateralis muscle was significantly increased by an average of 25% after adaptation to a fat-rich diet and was unchanged after adaptation to a carbohydrate-rich diet. In contrast, irrespective of diet, muscle citrate synthase activity and hexokinase activity were increased (P < 0.05) after adaptation to training by 17 and 18% in the group fed the carbohydrate, rich diet and by 17 and 12% in the group fed the fat-rich diet, respectively, and were unchanged in the two control groups. We suggest that diet can affect muscle enzymatic adaptation, presumably through an effect on the substrate flux.
Adrenomedullin microinjection into the area postrema increases blood pressure
Authors: Allen M. A. , Smith P. M. , Ferguson A. V.
Published: December 2017

Adrenomedullin (ADM) circulates in the blood at concentrations comparable to other vasoactive peptides with established roles in cardiovascular regulation. Intravenously administered ADM produces a clear hypotensive effect, whereas intracerebroventricular microinjections result in increases in blood pressure (BP). Recently, we demonstrated that ADM influences neurons of the area postrema (AP), a central nervous system site implicated in cardiovascular control. However, to address directly the physiological significance of the actions of ADM at the AP, an in vivo microinjection study was undertaken. ADM, at two concentrations (1 and 10 microM), in volumes of 50, 100, and 200 nl, was microinjected into the AP or NTS of 21 urethan-anesthetized male Sprague-Dawley rats. Microinjection of 10 microM ADM (100 nl) resulted in significant transient (2-5 min) increases in BP [120 s area under the curve (AUC): 684.3 +/- 268.6 mmHg/s (P < 0.05)], and heart rate (HR) [AUC: 12.5 +/- 4.5 beats/min (P < 0.05)]. The lower concentration of ADM (1 microM) had no effect on either BP (179.1 +/- 143.6 mmHg/s) or HR (0.8 +/- 2.6 beats/min). ADM was also microinjected into the immediately adjacent nucleus of the solitary tract, where it was found to be without effect on either BP or HR. This study demonstrates, for the first time, a physiological role for ADM acting at a specific brain site, the AP, to produce significant cardiovascular responses.
Change from beta- to alpha-adrenergic glycogenolysis induced by corticosteroids in female rat liver
Authors: Moriyama M. , Nakanishi Y. , Tsuyama S. , Kannan Y. , Ohta M. , Sugano T.
Published: December 2017

The conversion of beta- to alpha-adrenergic glycogenolysis by corticosteroids was studied in perfused livers of mature female rats. Isoproterenol stimulated glucose production more effectively in female rats than in male rats, but the difference in its stimulatory effect disappeared in adrenalectomized (ADX) rats, whereas it remained in adrenodemedulated rats. When ADX female rats were treated with dexamethasone sulfate, alpha-responses increased and beta-responses decreased, depending on the concentration of dexamethasone sulfate. The treatment of female rats with 1.5 mg/kg dexamethasone sulfate changed the levels of the alpha- and beta-responses to those observed in male rats, and the changes were associated with changes in the number of receptors. Although periodicity of changes in plasma corticosterone levels was observed in both male and female rats, the extent of circadian variations was significantly lower in female rats during the estrous cycle than in male rats. The variations in plasma corticosterone levels and in both alpha- and beta-responses after ovariectomy approached those in male rats. The results suggest that the level of plasma corticosterone might play an important role in the regulation of the relative levels of alpha- and beta-adrenergic responses in female rats.
Kidneys from normotensive donors lower blood pressure in young transplanted spontaneously hypertensive rats
Authors: Patschan O. , Kuttler B. , Heemann U. , Uber A. , Rettig R.
Published: December 2017

Single transplanted kidneys from spontaneously hypertensive rats (SHR) have been shown to elicit hypertension in genetically normotensive recipients. This study was designed to investigate the effects of single transplanted kidneys from genetically normotensive donors [Biobreeding (BB)/Ottawa Karlsburg (OK) rats] on blood pressure in SHR recipients. The following groups were formed: group 1 (n = 11), SHR donors and SHR recipients; group 2 (n = 15), BB/OK donors and SHR recipients; and group 3 (n = 8), BB/OK donors and BB/OK recipients. Recipients received antihypertensive treatment (hydralazine) from weaning until renal transplantation at the age of 9 wk and immunosuppressive treatment (anti-CD4 antibody and cyclosporine A) for 3 wk starting on the day of transplantation. Six weeks after transplantation, intra-arterially measured blood pressure and heart weight-to-body weight ratio were highest in group 1, intermediate in group 2, and lowest in group 3. There were no significant differences with respect to plasma urea and creatinine concentrations among the three groups. These results support the hypothesis that hypertension in renal-transplanted SHR depends in part on the genetic background of the transplanted kidney.
Metabolic correlates of selection for swim stress-induced analgesia in laboratory mice
Authors: Konarzewski M. , Sadowski B. , Jozwik I.
Published: December 2017

The upper limits of metabolic rates and the links between maximal and resting metabolic rates in vertebrates have recently received a lot of attention, mainly due to their possible relationship to the evolution of endothermy. We measured peak metabolic rates during 3 min swimming in 20 degrees C water (Vo2swim), maximal metabolic rate (Vo2max) in -2.5 degrees C Helox, and basal metabolic rate (BMR) in two lines of mice selected for high (HA) and low (LA) swim stress-induced analgesia (SSIA). We found that exercise combined with heat loss used for producing SSIA also acted as a selection agent, resulting in a 15% HA/LA line difference in Vo2swim. Core body temperature of HA mice (characterized by lower Vo2swim) was also on average 3.2 degrees C lower than that of LA mice. Furthermore, Vo2max of HA mice was lower than that of LA mice by 8% and accompanied by larger hypothermia. Thus mice with exceptionally high (or low) Vo2max tended to have exceptionally high (or low) Vo2swim, resulting in a positive correlation between Vo2swim and Vo2max. All these suggest that selection for SSIA produced genetically correlated responses in both Vo2swim and Vo2max. However, we did not observe HA/LA differences in BMR. Hence, changes in resting and maximum metabolic rates are not necessarily correlated. We hypothesize that the lack of such a correlation was partially due to the modulation of metabolic responses by SSIA.
Peripheral endotoxin increases splenic sympathetic nerve activity via central prostaglandin synthesis
Authors: MacNeil B. J. , Jansen A. H. , Janz L. J. , Greenberg A. H. , Nance D. M.
Published: December 2017

We tested whether prostaglandin synthesis mediates the lipopolysaccharide (LPS)-induced increase in splenic sympathetic nerve activity. Sprague-Dawley rats were pretreated with intravenous or intracerebroventricular injections of indomethacin, and splenic nerve activity was recorded after intravenous injections of LPS. In vehicle-pretreated rats, 100 micrograms LPS induced a 62.8 +/- 5.6% increase in splenic nerve activity beginning 22.7 +/- 2.7 min postinjection. All vehicle-pretreated animals responded to high (100 micrograms, 5 of 5 animals) and low (10 micrograms, 8 of 8 animals) doses of LPS. Both intravenous (15 mg/kg) and intracerebroventricular (50 micrograms) pretreatments with indomethacin delayed (F1.19 = 30.66, P < 0.001) the increase in nerve activity after 100 micrograms LPS. When given intravenously, 50 micrograms indomethacin (the intracerebroventricular dose) did not delay the response to intravenous LPS, indicating that the effects of intracerebroventricular indomethacin pretreatment were restricted to the central nervous system. Importantly, intracerebroventricular indomethacin reduced (2 of 7 animals) or completely blocked (5 of 7 animals) the splenic nerve response to the low dose of LPS (10 micrograms, iv). The indomethacin effects could not be accounted for by central release of vasopressin because intracerebroventricular injection of indomethacin did not alter baseline nerve activity or blood pressure, whereas intracerebroventricular injection of vasopressin rapidly increased both measures. Additionally, central injection of LPS did not elevate splenic nerve activity, whereas intracerebroventricular injection of prostaglandin E2 induced a rapid (2.2 +/- 2.7 min) increase in splenic nerve activity. These data indicate that central prostaglandin synthesis is an intermediate step whereby systemic LPS elicits an increase in sympathetic outflow to an immune organ.
Sex differences in immunocompetence differ between two Peromyscus species
Authors: Klein S. L. , Nelson R. J.
Published: December 2017

Males generally exhibit reduced immunocompetence and greater susceptibility to disease than females. The explanations for why males may be more susceptible to disease than females fall into two categories: 1) the proximate mechanisms mediating immunity, such as hormonal mechanisms, and 2) variation in reproductive success between the sexes. The present study examined the extent to which these factors contribute to sex differences in cell-mediated immune function in polygynous Peromyscus maniculatus and monogamous Peromyscus californicus. Prevailing hypotheses suggest that, because variation in male and female reproductive success is greater among polygynous than monogamous species, sex differences in immunocompetence should be greater among polygynous than monogamous species as well. In contrast to these predictions, sex differences in cell-mediated immunity and body mass were only observed among monogamous P. californicus, in which females exhibited higher splenocyte proliferation in response to the T cell mitogen, concanavalin A, and weighed less than male conspecifics. Male P. maniculatus had higher serum testosterone concentrations than male P. californicus, but females of the two species did not differ in circulating estradiol concentrations. Sex steroid concentrations were not correlated with either immunocompetence or body mass; however, large P. californicus males exhibited reduced immune responses. Taken together, these results do not support the hypothesis that sex differences in immunocompetence are more pronounced among polygynous compared with monogamous species. Furthermore, these data suggest that circulating testosterone does not mediate sex differences in immuno-competence or body mass in P. californicus.
Vasodilation and glomerular binding of adrenomedullin in rabbit kidney are not CGRP receptor mediated
Authors: Hjelmqvist H. , Keil R. , Mathai M. , Hubschle T. , Gerstberger R.
Published: December 2017

The polypeptide adrenomedullin (ADM) was infused systemically to conscious rabbits to elucidate its actions on overall circulation and especially the renovascular bed and the formation and/or release of hormones important for body fluid homeostasis, including adrenocortical steroids. ADM lowered mean arterial pressure from 71.5 +/- 3.2 to 64.7 +/- 3.2 mmHg only at the highest dose of 25 pmol.min-1.kg-1 infused intravenously for 20 min and concomitantly induced tachycardia, possibly due to both baroreflex activation and direct cardiostimulatory effects. Renal blood flow (RBF) determined in rabbits chronically equipped with a perivascular ultrasonic flow probe increased from 55.4 +/- 2.1 to 67.4 +/- 2.7 and from 58.2 +/- 3.5 to 75.2 +/- 6.0 ml/min at ADM infusions of 5 and 25 pmol.min-1.kg-1, respectively. The elevation in RBF persisted even in the presence of the calcitonin gene-related peptide (CGRP1 receptor antagonist CGRP-(8-37). Of all osmoregulatory hormones tested, only corticosterone (Cort) plasma concentration increased in response to the highest ADM dose from 17.6 +/- 3.1 to 38.9 +/- 6.2 ng/ml, probably due to haroreflex activation. Subdepressor doses of ADM, however, caused a mild reduction in circulating Cort. Expression of functional high-affinity binding sites specific for ADM in vitro could be demonstrated for the renal artery and outer cortical glomeruli using 125I-labeled rat ADM as radioligand and determination of cellular adenosine 3',5'-cyclic monophosphate (cAMP) formation within the glomeruli. The ineffectiveness of CGRP-(8-37) to displace radiolabeled ADM from its binding sites, to inhibit ADM-induced glomerular cAMP formation, and to prevent ADM-induced renal vasodilation supports the hypothesis of ADM altering renal hemodynamics by interacting with ADM- and not CGRP-specific membrane receptors.
Evidence for reset of regulated cortisol in pregnancy: studies in adrenalectomized ewes
Authors: Keller-Wood Maureen
Published: December 2017

These studies test the hypothesis that the increased adrenocorticotropic hormone (ACTH) and cortisol in pregnancy reflect a reset of regulated plasma cortisol concentrations. Ewes were sham operated (Sham) or adrenalectomized (ADX) at ∼108 days gestation. Adrenalectomized ewes were replaced with aldosterone (3 μg ⋅ kg−1 ⋅ day−1) and with cortisol at either of two doses (ADX + 0.6 and ADX + 1.0 mg ⋅ kg−1 ⋅ day−1); the ewes were also studied postpartum. Plasma cortisol concentrations in ADX + 0.6 ewes (5.3 ± 1.3 ng/ml) were similar to the Sham ewes postpartum (5.5 ± 0.6 ng/ml), whereas ADX + 1.0 concentrations (8.9 ± 1.0 ng/ml) were similar to pregnant Sham ewes (9.5 ± 1.9 ng/ml). Plasma ACTH concentrations were significantly increased in the pregnant ADX + 0.6 ewes (273 ± 44 pg/ml) relative to pregnant Sham ewes (84 ± 9 pg/ml) or the same ewes postpartum (42 ± 9 pg/ml). Plasma ACTH concentrations were not different among the groups postpartum. Acute increases in plasma cortisol to 15–25 ng/ml produced similar inhibition in all groups. These results suggest that pregnancy resets the basal cortisol concentration required for normalization of basal ACTH concentration.
Effect of antenatal glucocorticoids on sympathetic nerve activity at birth in preterm sheep
Authors: Segar Jeffrey L. , Lumbers Eugenie R. , Nuyt Anne Monique , Smith Oliva J. , Robillard Jean E.
Published: December 2017

Renal sympathetic nerve activity (RSNA) increases rapidly after delivery of term fetal sheep and parallels the rise in heart rate (HR) and arterial pressure. To examine the RSNA response at birth in immature lambs, experiments were performed in chronically instrumented preterm fetal sheep (118- to 125-day gestation, term 145 days) before and after delivery by cesarean section. HR remained unchanged from fetal values at 1 and 4 h after birth, whereas mean arterial blood pressure (MABP) decreased significantly ( P < 0.05) by 4 h after delivery. RSNA significantly decreased after premature birth in all animals studied ( n = 6), achieving only 39 ± 17% of fetal RSNA ( P< 0.05; all results are mean ± SE). Because cardiovascular function after premature birth is improved by the use of antenatal corticosteroids, we also tested the hypothesis that corticosteroid administration would evoke a more pronounced sympathetic response in prematurely delivered lambs ( n = 7, 118- to 125-day gestation). After maternal administration of dexamethasone (5 mg im, 48 and 24 h before delivery), RSNA increased after birth in six of seven fetuses to 166 ± 32% of the fetal RSNA value. Dexamethasone treatment also decreased the sensitivity of baroreflex-mediated changes in HR in response to increases in MABP. Because the sympathetic response at birth is depressed in preterm compared with term lambs, we performed an additional study ( n = 8) to determine if immature sheep are capable of mounting a sympathetic response to cold. In utero cooling produced rapid and sustained increases in MABP (20 ± 4%), HR (26 ± 6%), and RSNA (282 ± 72%) (all P < 0.05), consistent with a generalized sympathoexcitation. These results suggest that sympathoexcitation is absent after premature delivery despite the presence of functional descending autonomic pathways. Furthermore, exogenous corticosteroids appear to have a maturational effect on the sympathetic response at birth, which may be one mechanism by which maternal steroid administration improves postnatal cardiovascular homeostasis.
Glucocorticoid negative feedback on the HPA axis in five inbred rat strains
Authors: Gómez Francisca , De Kloet E. Ronald , Armario Antonio
Published: December 2017

The aim of the present work was to study the influence of altering glucocorticoid negative feedback on both basal activity of the hypothalamic-pituitary-adrenal (HPA) axis and its response to acute stress (tail shock) in five inbred rat strains known to differ in some depression-like behaviors: Brown Norway (BN), Fischer 344 (F344), Lewis (Lew), spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY) rats. Two complementary approaches were used: 1) enhancement of negative feedback by administration of 0.05 and 0.2 mg/kg dexamethasone (Dex) and 2) attenuation of negative feedback by pharmacological adrenalectomy (PhADX). The results indicate that 1) Lew rats consistently show adrenocorticotropic hormone (ACTH) and corticosterone hyporesponsiveness to stress, 2) interstrain differences in the effect of Dex on the HPA axis were very weak and not related apparently to differences in the metabolism of the steroid, 3) the suppressive effect of the highest dose of Dex on basal corticosterone levels was lower in BN rats than in the other strains, and 4) after PhADX, an increase in ACTH levels was observed in response to acute stress in BN, F344, and WKY but not in Lew and SHR rats, suggesting possible interstrain differences in pituitary sensitivity to neural stimuli induced by stress. In summary, our results indicate that there are differences among the strains with regard to both 1) the suppressive effect of Dex on the HPA axis, BN rats showing a certain degree of resistance, and 2) the capability of PhADX rats to respond to acute stress, which suggests a defective release of ACTH in Lew and SHR rats. The biological meaning of these alterations of corticosteroid negative feedback among the five inbred strains studied remains to be established.
Myocardial and plasma renin-angiotensinogen dynamics during pressure-induced cardiac hypertrophy
Authors: Heller Lois J. , Opsahl John A. , Wernsing Shane E. , Saxena Retu , Katz Stephen A.
Published: December 2017

Plasma and left ventricular (LV) renin and angiotensinogen concentrations were assessed in a rat model of pressure-overload cardiac hypertrophy to determine if myocardial levels remained proportional to plasma levels over time. Three days after subdiaphragmatic aortic constriction (AC), LV hypertrophy was evident and renin concentrations in both plasma and LV, although not significantly elevated, were positively correlated with relative cardiac mass. After 42 days AC, LV hypertrophy remained, plasma and LV renin and angiotensinogen levels were not different from shams, and there was no correlation between renin and relative cardiac mass. Furthermore, LV renin and angiotensinogen concentrations remained at ∼25 and 4%, respectively, of those in plasma throughout the experiment. Myocytes from 3-day AC and sham-treated rats contained little renin as did LV from 48-h anephric rats. Incubations using calculated concentrations of myocardial interstitial renin and angiotensinogen revealed significant angiotensin I generation. These data suggest that LV renin in this model varies directly with plasma renin, is confined to the interstitial space, and can generate significant intramyocardial angiotensin I.
Differential selectivity of cardiac neurons in separate intrathoracic autonomic ganglia
Authors: Armour J. A. , Collier K. , Kember G. , Ardell J. L.
Published: December 2017

Analyses of activity generated by neurons in middle cervical or stellate ganglia versus intrinsic cardiac ganglia were performed to determine how neurons in different intrathoracic ganglia, which are involved in cardiac regulation, interact. Discharges of 19% of intrathoracic extracardiac neurons and 32% of intrinsic cardiac neurons were related to cardiodynamics. Epicardial touch increased the activity generated by ∼80% of intrinsic cardiac neurons and ∼60% of extracardiac neurons. Both populations responded similarly to epicardial chemical stimuli. Activity generated by neurons in intrinsic cardiac ganglia demonstrated no consistent short-term relationships to neurons in extracardiac ganglia. Myocardial ischemia influenced extracardiac and intrinsic cardiac neurons similarly. Carotid artery baroreceptors influenced neurons in ipsilateral extracardiac ganglia. After decentralization from the central nervous system, intrinsic cardiac neurons received afferent inputs primarily from cardiac chemosensitive neurites, whereas middle cervical ganglion neurons received afferent inputs primarily from cardiac mechanosensory neurites. It is concluded that the populations of neurons in different intrathoracic ganglia can display differential reflex control of cardiac function. Their redundancy in function and noncoupled behavior minimizes cardiac dependency on a single population of intrathoracic neurons.
Corticotropin-releasing hormone-binding protein in brain and pituitary of food-deprived obese (fa/fa) Zucker rats
Authors: Timofeeva Elena , Deshaies Yves , Picard Frédéric , Richard Denis
Published: December 2017

The present study was conducted to verify whether experimental conditions such as obesity and food deprivation, which promote food intake and reduce thermogenesis, could modify the expression of the corticotropin-releasing hormone (CRH)-binding protein (BP) in the rat brain. In situ hybridization, histochemistry, and immunohistochemistry were used to assess the expression of CRH-BP in lean ( Fa/?) and obese ( fa/fa) Zucker rats that were fed ad libitum, food deprived for 24 h, or food deprived for 24 h and refed for 6 h. In both lean and obese rats, food deprivation led to a reduction in body weight that was accompanied by a reversible increase in plasma corticosterone levels. Food deprivation and, to a lesser degree, obesity induced the expression of CRH-BP mRNA in the dorsal part of the medial preoptic area (MPOA). This induction of the CRH-BP gene led to by food deprivation was confirmed by the appearance in the dorsal part of the MPOA of neurons immunoreactive to CRH-BP. Food deprivation (in particular) and obesity also increased the levels of CRH-BP mRNA in the basolateral amygdala (BLA). The enhanced CRH-BP expression in the MPOA and BLA in response to food deprivation was reversed by refeeding. In lean Fa/? rats, the CRH-BP mRNA level in the pituitary cells was significantly decreased after food deprivation and restored after refeeding. When food was provided ad libitum, the number of cells expressing CRH-BP in the anterior pituitary was significantly higher in lean rats than in obese animals. Food deprivation for 24 h decreased dramatically the number of pituitary cells expressing CRH-BP in lean rats. Altogether, the present results demonstrate that food deprivation and, to a lesser extent, obesity can selectively affect the expression of CRH-BP. Given both the inactivating effect of CRH-BP on the CRH system and the potential roles played by the MPOA and BLA in the thermogenic and anorectic effects of CRH, it can be argued that the induction of the CRH-BP gene in obesity and after food deprivation occurs as a mechanism to reduce energy expenditure and to stimulate food intake.
Differential role of melanocortins in mediating leptin's central effects on feeding and reproduction
Authors: Hohmann John G. , Teal Thomas H. , Clifton Donald K. , Davis James , Hruby Victor J. , Han Guoxia , Steiner Robert A.
Published: December 2017

Leptin serves as a humoral link coupling the status of energy reserves to the functional activity of the reproductive system. Leptin is thought to act through melanocortinergic pathways in the brain to regulate ingestive behaviors; however, whether melanocortins mediate leptin's actions on the neuroendocrine-reproductive axis is unknown. We tested this hypothesis first by determining whether the effects of leptin on feeding behavior and reproduction in the ob/ob mouse could be blocked by the melanocortin receptor (MC-R) antagonist SHU9119 and second, by examining the effects of the MC-R agonist MTII on feeding and the endocrine-reproductive system. Administered by intracerebroventricular injections, leptin inhibited food intake, raised plasma gonadotropin levels, and increased seminal vesicle weights compared with controls; SHU9119 (intracerebroventricularly) attenuated leptin's effects on food intake and body weight but did not alter leptin's stimulatory effect on the reproductive axis. MTII (intracerebroventricularly and intraperitoneally) decreased food intake and increased body temperature compared with controls but had no effect on the reproductive-endocrine axis. These results suggest that although leptin acts centrally through melanocortinergic pathways to inhibit ingestive behaviors and stimulate metabolism, leptin's activational effect on the reproductive axis is likely to be mediated by other, unknown neuroendocrine circuits.
Leptin effect in ob/ob mice under thermoneutral conditions depends not necessarily on central satiation
Authors: Rafael Johannes , Herling Andreas W.
Published: December 2017

Energy expenditure in ob/ob mice kept at thermoneutrality was quantified from food intake and body composition of mice treated with leptin over 15 and 75 days, respectively. Energy expenditure in response to 15 days of treatment with leptin was twice as high as under pair-feeding conditions, indicating extensive breakdown of adipose tissue independent of a centrally mediated satiation. Leptin-induced reduction of food intake ceased during treatment with leptin over 75 days, when the lipid reserves of the mice were depleted and energy expenditure became similar to that in lean mice. Energy mobilized in leptin-treated ob/ob mice from endogenous lipid resources and similar to the food energy consumed in hyperphagic ob/ob controls may cause satiation. Maximal energy expenditure in both groups may correspond to their energy supply: energy expenditure in ob/ob mice was shown to be correlated to the food intake in the absence of leptin. Leptin effects observed in ob/ob mice under thermoneutral conditions may modify the traditional view of the functionality of the hormone.
NMDA receptor participation in control of food intake by the stomach
Authors: Covasa Mihai , Ritter Robert C. , Burns Gilbert A.
Published: December 2017

We previously reported that MK-801 (dizocilpine), an antagonist of N-methyl-d-aspartate (NMDA)-type glutamate receptors, increased meal size and duration in rats. MK-801 did not increase sham feeding or attenuate reduction of sham feeding by intraintestinal nutrient infusions. These results suggested that the MK-801-induced increase in meal size did not depend on antagonism of postgastric satiety signals. Consequently, we hypothesized that the NMDA antagonist might increase food intake by directly antagonizing gastric mechanosensory signals or by accelerating gastric emptying, thereby reducing gastric mechanoreceptive feedback. To test this hypothesis, we recorded intake of 15% sucrose in rats implanted with pyloric cuffs that could be closed to prevent gastric emptying. Sucrose intake was increased when the pyloric cuffs were open, allowing the stomach to empty. However, intake was not increased when the pyloric cuffs were inflated, causing gastric retention of all ingested sucrose. Direct measurements of gastric emptying revealed that MK-801 accelerated the emptying of 5-ml loads of 0.9% NaCl and 15% sucrose. Furthermore, MK-801 also accelerated the rate of emptying of freely ingested sucrose regardless of the volume ingested. Taken together with our previous findings, these results indicate that blockade of NMDA receptors with MK-801 does not increase food intake by antagonizing gastric mechanosensation. Rather, it accelerates gastric emptying, and thereby may indirectly reduce gastric mechanoreceptive cues, resulting in prolongation of eating. Modulation of gastric emptying rate by NMDA receptors could play an important role in the control of meal sizes.
Role of the locus ceruleus in baroreceptor regulation of supraoptic vasopressin neurons in the rat
Authors: Grindstaff Ryan J. , Grindstaff Regina R. , Sullivan Margaret J. , Cunningham J. Thomas
Published: December 2017

The goal of this study was to identify the source of baroreceptor-related noradrenergic innervation of the diagonal band of Broca (DBB). Male Sprague-Dawley rats underwent sinoaortic denervation (SAD, n = 13) or sham SAD surgery ( n = 13). We examined Fos expression produced by baroreceptor activation and dopamine-β-hydroxylase immunofluorescence in hindbrain regions that contain noradrenergic neurons. Baroreceptors were stimulated by increasing blood pressure >40 mmHg with phenylephrine (10 μg · kg−1· min−1 iv) in sham SAD and SAD rats. Controls were infused with 0.9% saline. Only the locus ceruleus (LC) demonstrated a baroreceptor-dependent increase in Fos immunoreactivity in dopamine-β-hydroxylase-positive neurons. In a second experiment, normal rats received rhodamine-labeled microsphere injections in the DBB ( n = 12) before phenylephrine or vehicle infusion. In these experiments, only the LC consistently contained Fos-positive cells after phenylephrine infusion that were retrogradely labeled from the DBB. Finally, we lesioned the LC with ibotenic acid and obtained extracellular recordings from identified vasopressin neurons in the supraoptic nucleus. LC lesions significantly reduced the number of vasopressin neurons that were inhibited by acute baroreceptor stimulation. Together, these results suggest that noradrenergic neurons in the LC participate in the baroreflex activation of the DBB and may thus be important in the baroreflex inhibition of vasopressin-releasing neurons in the supraoptic nucleus.
Curt Richter and regulatory physiology
Authors: Moran Timothy H. , Schulkin Jay
Published: December 2017

Curt Richter made seminal contributions to our understanding of a number of issues regarding the relationships between physiology and behavior. He was the first to conceptualize behavior as an aspect of regulatory physiology. These ideas developed from his work on behavioral responses to a variety of physiological perturbations. The classic example is Richter's demonstration of the development of avid sodium ingestion in response to urinary sodium loss after adrenalectomy. Some of Richter's ideas on the nature and underlying physiology of specific appetites maintain their influence and continue to stimulate active investigation. Others, focused on abilities to self-select balanced diets, have not borne the test of time or experimental challenge. As current research takes a more molecular focus, Richter's ideas on behavior in the service of the internal milieu maintain their currency, and the search for the molecular bases for these relationships should serve as a research focus.
Motility studies of isolated antral pouches before and after vagus denervation
Authors: Wohlrabe Donald E. , Kelly William D.
Published: December 2017

The motility responses of vagus innervated and denervated antral pouches to electrical stimulation of the vagus nerves and to insulin hypoglycemia were determined. Electrical stimulation appears to be a reliable method of demonstrating the presence or absence of vagus nerve supply to the antrum both in acute studies and in preparations of several months' duration. The motility response of the antral pouch to insulin hypoglycemia was found to be a less reliable method of determining the presence or absence of vagal innervation largely because spontaneous hypermotility may occur and there is more room for difference of opinion in interpretation of the results obtained. The administration of glucose after an appropriate time interval, however, added significantly to the reliability of the test. By the methods employed the antral branches of the vagus nerves were found to be the only sources of vagus innervation of the antrum. No evidence was obtained to suggest effective parasympathetic innervation of the antrum via a pyloric nerve, via the greater curvature mesenteric attachment or via an intramural gastric pathway.

Submitted on July 7, 1958
Esophageal and pleural pressures in man, upright and supine
Authors: Mead Jere , Gaensler E. A.
Published: December 2017

To assess the reliability of esophageal sampling of pleural pressure, both pressures were recorded simultaneously in seven subjects in the upright posture and, in five of these, in the supine posture. Esophageal pressure was obtained with air-containing latex balloons and pleural pressure was recorded from catheters introduced into the intrapleural space. Pneumothorax volumes were estimated to be between 5 and 350 ml. The closest correspondence between the pressures was observed in the upright posture. Expressing the difference in the amplitude of the respiratory excursions as the percentage of deviation of esophageal from pleural pressures, in the upright posture individual values ranged from +20 to -18, while the average value for the group did not differ significantly from 0. On the other hand, in the supine position individual variation was greater (range +60 to -25) and, on the average, esophageal pressure amplitudes were larger (average +27 during quiet breathing) than pleural pressure amplitudes.

Submitted on August 22, 1958
Combined ventilatory and breath-holding evaluation of sensitivity to respiratory gases
Authors: Stroud Robert C.
Published: December 2017

Direct measurements of the ventilatory response to variations in CO2 tension independent of changes in O2 tension are easily obtained by breathing mixtures of carbon dioxide in 100% oxygen. Direct determination of the respiratory response to O2, however, is not possible due to alternations in CO2 tension resulting from changes in ventilation. Therefore, an attempt has been made to determine this response empirically by a combined analysis of breath-holding and ventilatory data. Comparison of experimentally determined responses to various combinations of O2 and CO2 tensions agree quite well with those predicted by this approach and indicate that oxygen plays a small but definite role in the regulation of eupnic breathing at sea level.

Submitted on October 22, 1958
Extreme warmth and sensorimotor coordination
Authors: Pepler R. D.
Published: December 2017

Six subjects were exposed for 30 minutes on three occasions at 48-hour intervals to a very warm, humid climate with a wet bulb temperature of 105℉ (41℃). During the second and third exposures the subjects worked continuously to keep a pointer aligned with a target mark, as it moved erratically from side to side. Accuracy of alignment was normal at first, but deteriorated rapidly and progressively. Movement of the pointer was greater than usual right from the start and changed little thereafter. Rectal temperature rose steadily during the exposures. Failures to correct progressively greater misalignments of the pointer were thought to indicate a growing inattentiveness to the task and a general deterioration in the organization of performance.

Submitted on September 2, 1958
Effects of oral glycine during cold exposure in man
Authors: Beavers William R. , Covino Benjamin G.
Published: December 2017

Six male human subjects were given 30 gm oral glycine. Oxygen consumption, skin and rectal temperatures, and forefinger blood flows were measured during an interval in a warm room and then during 75 minutes cold exposure (0°F). The same subjects receiving 30 gm glucose served as controls. Glycine increased heat production at rest in a warm room and also during cold exposure. The subjects when receiving glycine had a slightly higher rectal temperature and higher skin temperatures in areas other than fingers during the cold exposure period.

Submitted on August 1, 1958
Effect of restraint on altitude tolerance in the rat
Authors: Bartlett R. G. , Altland P. D.
Published: December 2017

Young adult male and female Sprague-Dawley rats were exposed to a simulated altitude of 33,500 ft. both with and without restraint. The exposure was begun immediately upon the restraint of the experimental animals. The restrained animals died significantly sooner than did the nonrestrained controls. The possible relation of colonic temperature, oxygen consumption and emotional stress to the decreased altitude tolerance is discussed. It is suggested that the data serve as a warning for caution in the use of restraint for convenience in altitude tolerance experiments.

Submitted on August 6, 1958
EEG amplitude and reaction time during sleep
Authors: Coleman Paul D. , Gray Florence E. , Watanabe Kyozo
Published: December 2017

Amplitude of the electroencephalogram was evaluated as a measure of sleep. EEG amplitude during sleep was found to be a) significantly and positively correlated with reaction time, b) inversely related to the duration of periods during which no gross body movement occurred and c) only slightly negatively related to heart rate.

Submitted on August 11, 1958
Distribution of fluoride in the normal dog femur
Authors: Gardner Dwight E. , Smith Frank A. , Hodge Harold C. , Brudevold Finn , Eldredge Donald McG.
Published: December 2017

Longitudinal sections and concentric layers of normal dog femurs were analyzed for their fluoride contents. Longitudinally, fluoride is deposited in greatest concentrations in the epiphyseal regions, i.e. the regions of vascularity and active growth. Concentrations in these regions are approximately twofold greater than at the mid-point of the diaphysis. In cross section, fluoride is also deposited in greater concentrations in the areas of more rapid growth and better blood supply, i.e. on the periosteal and endosteal surfaces of the shaft. The pattern of deposition is similar in adult and young bone, though fluoride concentrations are appreciably greater in the adult bone. The pattern of distribution conforms with the accepted principles of deposition of other boneseeking elements.

Submitted on November 17, 1958
Solubility of inert gases in human lung tissue
Authors: Cander Leon
Published: December 2017

Solubilities of the relatively insoluble inert gases, sulfur hexafluoride (SF6) and helium (He), the moderately soluble inert gases, nitrous oxide (N2O) and acetylene (C2H2), and the very soluble inert gas, diethyl ether, were determined in blood-free homogenates of human lung tissue at 37℃ by techniques employing the manometric and volumetric van Slyke apparatuses. The values, reported as Bunsen solubility coefficients at 37℃, were 0.0068, 0.0092, 0.407, 0.768 and 13.4 for SF6, He, N2O, C2H2 and diethyl ether, respectively.

Submitted on December 4, 1958
Factor X phenomenon
Authors: Spaet Theodore H. , Kropatkin Mona
Published: December 2017

Storage of human serum at refrigerator temperature yields a reagent which poorly supports thromboplastin generation. Although the degree of this defect showed no correlation with the serum prothrombin content, a high serum prothrombin was found to preserve activity. The clotting defect in stored serum was shown to be different from that in Stuart factor-deficient serum, as determined by mixing studies in both prothrombin and thromboplastin generation procedures. It is concluded that the factor X phenomenon is unique, although these studies do not establish factor X as a chemical entity.

Submitted on November 28, 1958
Physical fitness of oarsmen and rugby players before and after training
Authors: Sloan A. W. , Keen E. N.
Published: December 2017

Resting pulse rates and fitness indexes by the Harvard step test were ascertained in 100 healthy male University students. The subjects included members of the University rowing and rugby clubs, who were about to undergo systematic training, and a third group of students not engaged in any such activity. The observations were repeated on 58 of the students after a period of 2–4 months. The mean resting pulse rates of the three groups were not originally significantly different but after training the pulse rate was significantly lower in the athletic groups than in the controls. At the beginning of the training period the oarsmen and rugby players already had higher fitness indexes than the controls and thereafter they showed significant improvement with training. A significant negative correlation between resting pulse rate and fitness index was found only in the athletic groups.

Submitted on October 16, 1958
Pulmonary surface tension
Authors: Brown Elwyn S. , Johnson Rudolph P. , Clements John A.
Published: December 2017

The surface tension of the lung decreases markedly on compression resulting from deflation, as calculated from P-V data, and follows a force-area path very similar to that of several mucus surfaces. With changes in surface area of less than 50%, lung extract and mucus bubble surfaces are mechanically reversible. For decrease in area greater than 50%, surface tension approaches a lower limiting tension of 10–15 d/cm. On re-expansion of the surface, an upper limiting tension of 40–50 d/cm is approached. Hysteresis of considerable magnitude occurs and indicates a major alteration of the surface materials compressed beyond 50%. Estimates of lung surface area based on these considerations accord with histologic estimates.

Submitted on December 4, 1958
Evaluation of use of left coronary artery inflow and O2 content of coronary sinus blood as a measure of left ventricular metabolism
Authors: Rayford C. R. , Khouri E. M. , Lewis F. B. , Gregg D. E.
Published: December 2017

Experiments reported here show that the coronary sinus blood is derived almost entirely from the left coronary artery inflow and is not significantly contaminated with blood from other myocardial territories. The special cannula used for cannulating the coronary sinus permits drainage of all veins which empty into the coronary sinus. In consequence, the percentage of left coronary artery inflow recovered in the coronary sinus is high (usually 80–90%) and reasonably constant during changes in coronary perfusion pressure, aortic constriction, administration of epinephrine or norepinephrine, hemorrhage and reinfusion, induced ventricular fibrillation, and pulmonary artery constriction. The use of the arteriovenous oxygen difference between the arterial and coronary sinus blood in combination with left coronary artery inflow as a precise measure of left ventricular metabolism is validated under these experimental conditions.

Submitted on January 29, 1959
Role of ferritin in nutritional edema
Authors: Srikantia S. G. , Gopalan C.
Published: December 2017

The sequence of changes that occur in induced protein malnutrition has been studied in nine monkeys, three of which received an aureomycin supplement of 25 mg/kg per day from the first day of the experimental period. Serial estimations of serum protein and albumin levels, response to water load, thiocyanate space and the presence of active ferritin in circulation were determined in all nine monkeys. All the monkeys developed edema between the 13th and 16th week of the experiment, except two of the three aureomycin-supplemented animals. While no correlation was observed between serum albumin levels or impairment of response to water load on the one hand and edema on the other, there was a striking relationship between the appearance of active ferritin in circulation and the subsequent formation of edema. The increase in thiocyanate space was invariably preceded by the presence of ferritin in the blood. During nutritional rehabilitation, ferritin disappeared from circulation before the thiocyanate space returned to normal levels. It is significant that aureomycin, which prevented the appearance of ferritin in the blood, also prevented the development of edema. The results of the investigation strongly suggest a causal relationship between ferritin and nutritional edema.

Submitted on August 13, 1958
Evaluation of use of left coronary artery inflow and O2 content of coronary sinus blood as a measure of left ventricular metabolism
Authors: Rayford C. R. , Khouri E. M. , Lewis F. B. , Gregg D. E.
Published: December 2017

Page 817: C. R. Rayford, E. M. Khouri, F. B. Lewis and D. E. Gregg, “Evaluation of use of left coronary artery inflow and O2 content of coronary sinus blood as a measure of left ventricular metabolism.” Under methods line 12 should read: After the coronary sinus was carefully dissected, a suture was passed around it for cannulation. The suture was placed distal to the orifices of the coronary veins which drain near the mouth of the coronary sinus (verified at autopsy).
O2 diffusion in lung of the anesthetized cat
Authors: Duke Helen N. , Stedeford R. D.
Published: December 2017

In cats under chloralose anesthesia, the mean diffusing capacity for O2 (Do2) was 0.91 (S.D. ± 0.29). The mean Do2/m2 body surface was 3.26 (S.D. ± 1.30). Under the experimental conditions described, the Do2 was linearly related to the O2 consumption/body weight or surface area of the animal. The Do2 was reduced by bronchial occlusion in approximate proportion to the blocked area. Cooling the animal also reduced the Do2. Epinephrine and 5-hydroxytryptamine given by constant intravenous infusion had slight effects on the Do2. Dissociation curves for cats' blood are reported.

Submitted on December 5, 1958