bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethanol oxidation is not required to attenuate endotoxin-enhanced glucose metabolism
Authors: Molina P. E. , Lang C. H. , Bagby G. J. , Spitzer J. J.
Published: December 2017

Previous studies from our laboratory demonstrated that acute ethanol (EtOH) intoxication, through an unknown mechanism, blunts the endotoxin-enhanced carbohydrate metabolism. The purpose of the present study was to determine whether oxidation of the ethanol moiety is required for the inhibition of the endotoxin-induced changes in carbohydrate metabolism. In vivo glucose kinetics were assessed by the intravenous administration of D-[3-3H]glucose in catheterized conscious unrestrained rats. Escherichia coli endotoxin (200 micrograms/100 g body wt) increased glucose rate of appearance (Ra) and metabolic clearance rate (MCR) by 75 and 50%, respectively. A primed-constant infusion of EtOH (275 mg/100 g + 25 mg.100 g-1.h-1) initiated 2 h before endotoxin challenge attenuated the endotoxin-enhanced glucose kinetics. EtOH intoxication did not prevent endotoxin-induced hyperglycemia but delayed the hyperlactacidemic response. The importance of EtOH metabolism in suppressing the glucose metabolic response to endotoxin was studied by administering 4-methyl-pyrazole (4-MP; 8 mg/100 g), an inhibitor of alcohol dehydrogenase activity. After administration of 4-MP and a bolus injection of EtOH (275 mg/100 g), the plasma EtOH concentration remained constant and matched the level of EtOH in rats receiving a primed-constant infusion of EtOH. Inhibition of EtOH metabolism with 4-MP did not abrogate the ability of EtOH to suppress endotoxin-induced increases in glucose Ra or MCR. Furthermore, the injection of the nonmetabolized alcohol tert-butanol abolished the endotoxin-induced increase in glucose Ra and MCR without preventing the endotoxin-induced hyperglycemia and hyperlactacidemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibition of ANP clearance receptors and endopeptidase 24.11 in maturing rats
Authors: Chevalier R. L. , Garmey M. , Scarborough R. M. , Linden J. , Gomez R. A. , Peach M. J. , Carey R. M.
Published: December 2017

Systemic clearance of atrial natriuretic peptide (ANP) decreases during postnatal development. To determine the relative contribution of ANP clearance (C) receptors and neutral endopeptidase 24.11 (NEP; EC 3.4.24.11) in regulation of plasma ANP concentration ([ANP]) during maturation, 18- to 60-day-old male Sprague-Dawley rats were anesthetized and infused with rat ANP (35 ng.kg-1.min-1). Infusion of the NEP inhibitor phosphoramidon increased [ANP] and urine guanosine 3',5'-cyclic monophosphate (cGMP) excretion in both weanling and adult rats. Infusion of C-ANP, an analogue that binds C receptors selectively, resulted in a greater rise in [ANP] in preweaned than in adult rats, suggesting a maturational decrease in function of C receptors. Despite the increase in [ANP], however, urine flow, cGMP, and sodium excretion failed to increase in preweaned compared with adult rats. Combined infusion of phosphoramidon and C-ANP resulted in a marked increase in [ANP] and cGMP excretion in weanling and adult rats. These results indicate that both C receptors and NEP modulate plasma [ANP] in the physiological range and that each pathway compensates when the other is inhibited. Age-related differences in the renal response to ANP clearance inhibitors may have important physiological implications in the regulation of sodium balance during development.
FNLP injures endotoxin-primed rat lung by neutrophil-dependent and -independent mechanisms
Authors: Anderson Benjamin O. , Bensard Denis D. , Brown James M. , Repine John E. , Shanley Paul F. , Leff Jonathan A. , Terada Lance S. , Banerjee Anirban , Harken Alden H.
Published: December 2017

Pages R413–R420: Benjamin O. Anderson, Denis D. Bensard, James M. Brown, John E. Repine, Paul F. Shanley, Jonathan A. Leff, Lance S. Terada, Anirban Banerjee, and Alden H. Harken. “FNLP injures endotoxin-primed rat lung by neutrophil-dependent and -independent mechanisms.” The symbol μ was inadvertently omitted in the printed paper, suggesting that the doses were 106 times higher than the correct values. The correct doses were as follows: Salmonella typhimurium endotoxin, 500 μg/kg ip; FNLP, 250 μg/kg iv; and vinblastine, 750 μg/kg iv.
Mathematical analysis of perifusion data: models predicting elution concentration
Authors: Smith W. R. , Wake G. C. , McIntosh J. E. , McIntosh R. P. , Pettigrew M. , Kao R.
Published: December 2017

System models are constructed and analyzed for combined convective flow and for dispersion in distorting concentrations of a chemical signal as it passes through a packed column. We derive general analytical solutions for these models. The results have applications to analyses such as in biological experiments involving hormonal stimulation of perifused cells, elution chromatography, adsorption columns, and studies of groundwater flow. The models reveal that the column distorts an incoming signal (such as a change in solute concentration in the flowing liquid) at the inlet. This distortion is greatest at low values of the Peclet number of the flow and is small at larger values. We explore the effects of the approximations inherent in the mathematical models of the system. Specification of the boundary conditions of the problem are shown to be particularly important. With the use of incorrect models, it is possible to obtain accurate interpolations to data obtained from perfusion experiments. However, the parameters derived (in particular the dispersion constant and the peak concentration of a solute concentration pulse) may be considerably in error. This may lead to errors when these parameter estimates are used to predict results in other experimental situations.
Movement of cellular ions during stimulation with isoproterenol in simian eccrine clear cells
Authors: Sato K. T. , Saga K. , Ohtsuyama M. , Takemura T. , Kang W. H. , Sato F. , Suzuki Y. , Sato K.
Published: December 2017

The ionic mechanism of beta-adrenergic sweating is unknown. In isolated rhesus eccrine secretory coils, K efflux was determined by an extracellular K electrode and cellular monovalent ions by X-ray microanalysis. Isoproterenol (Iso) induced a small (dose-dependent propranolol-inhibitable) K efflux followed by net K reuptake. Similar K response was seen with forskolin, theophylline, or isobutyl-methylxanthine (IBMX). The net K uptake often exceeded the net K efflux, causing a small net accumulation of K. Bumetanide (BT) and ouabain not only abolished the Iso (with or without IBMX) -induced net K uptake but increased the Iso-induced initial K efflux about threefold. BT and ouabain drastically decreased K and Cl concentrations in the clear cell (by X-ray microanalysis) only in the presence of Iso plus IBMX, suggesting that adenosine 3',5'-cyclic monophosphate (cAMP) may simultaneously stimulate both KCl efflux (by unknown mechanisms) and K reuptake (presumably by BT-sensitive cotransporters and ouabain-sensitive Na pumps). Thus the cAMP-mediated ion movement is different from the cholinergic mechanism that is characterized by the net KCl loss, cell shrinkage (Saga et al., J. Membr. Biol. 107: 13-24, 1989; Takemura et al., J. Membr. Biol. In press), and no augmentation of methacholine-induced K efflux by BT or ouabain.
Activation of brown adipose tissue thermogenesis in recovery from anesthetic hypothermia in rats
Authors: Shimizu Y. , Saito M.
Published: December 2017

Changes of brown adipose tissue (BAT) thermogenesis in the recovery from anesthetic hypothermia were studied by measuring the temperatures of the interscapular BAT and rectum or the tissue uptake of 2-deoxyglucose (2-DG) in rats. After intraperitoneal injection of pentobarbital sodium (50 mg/kg), rectal temperature decreased to reach a steady level of approximately 33 degrees C (steady phase) and then increased gradually (recovery phase). The temperature of the interscapular BAT was significantly higher than rectal temperature in the recovery phase. The uptake of 2-DG in vivo in BAT was low in the steady phase but increased greatly in the recovery phase. The increase in 2-DG uptake was suppressed after surgical sympathetic denervation or when rectal temperature was maintained at approximately 37.5 degrees C. In the heart, skeletal muscle, and white adipose tissue, there was no appreciable change in 2-DG uptake except a slight increase in the heart. beta-Adrenergic blockade attenuated the changes in BAT temperature and 2-DG uptake seen during the recovery phase. It was concluded that BAT significantly contributes to heat production in recovery from anesthetic hypothermia.
Myocardial aging: antioxidant enzyme systems and related biochemical properties
Authors: Ji L. L. , Dillon D. , Wu E.
Published: December 2017

The effects of aging on myocardial antioxidant enzyme activity, lipid peroxidation, and other related biochemical properties were investigated in male Wistar-Furth rats at 4, 26, and 31 mo of age at rest and after an acute exercise bout. The results showed that resting heart cytosolic superoxide dismutase (CuZn SOD) activity was significantly decreased in the heart with aging (66 +/- 6.5 U/mg protein at 4 mo vs. 49 +/- 3.8 U/mg protein at 31 mo) and was elevated in all age groups after exercise. Mitochondrial Mn SOD activity was almost doubled in both 26- and 31-mo-old rats compared with that at 4 mo. Myocardial catalase and cytosolic glutathione peroxidase (GPX) activities were significantly decreased with age, whereas mitochondrial GPX was 29% higher (P less than 0.05) in 31- than 4-mo-old rats. Glutathione S-transferase activity in the heart also declined with age (P less than 0.05 at 31 mo). Malondialdehyde contents in both heart homogenate and mitochondria were significantly increased at old age. Activity of several enzymes related to myocardial energy production, e.g., citrate synthase, malate dehydrogenase, and lactate dehydrogenase, as well as myocardial protein content showed an age-related decline. These data indicate that myocardial antioxidant capacity is weakened during aging and that the compensatory increases of mitochondrial SOD and GPX may be an important mechanism in coping with free radical damage in senescent heart. Findings in the present investigation seem to support the free radical theory of aging.
Natriuretic peptides inhibit rat astroglial proliferation: mediation by C receptor
Authors: Levin E. R. , Frank H. J.
Published: December 2017

The processing and secretion of atrial natriuretic peptide (ANP) from neurons and the expression of high-affinity receptors on astroglia from primary cultures of fetal rat diencephalon have recently been demonstrated. Thus natriuretic peptides may play a role in neuronal-glial signaling, but a physiological role has not been characterized. In these studies, we show that ANP and brain natriuretic peptide significantly (P less than 0.05) decrease the incorporation of [3H]thymidine into astroglia in the presence of fetal bovine serum and inhibit the proliferation of these cells in the presence or absence of serum. These effects were evident at concentrations of natriuretic peptides (10(-10) M) characteristic of the receptor Kd and were not seen in cultured bovine brain capillary endothelial cells, another brain cell expressing high-affinity receptors for the natriuretic peptides. The antiproliferative effects were potently produced by ANP-(4-23), a ring-deleted analogue of ANP-(1-28), which at the concentrations used in this study binds only to the C or low-molecular-weight natriuretic peptide receptor. Thymidine incorporation was not affected by adenosine 3',5'-cyclic monophosphate (cAMP), the inhibition of which has been proposed to mediate postbinding signaling of the C receptor. Epidermal growth factor (10(-9) M) produced an 87% increase in thymidine incorporation, which was not significantly inhibited by either form of ANP. Thus natriuretic peptides in the brain may serve as antigrowth factors for glia through binding to a receptor previously felt to function solely in peptide clearance. The inhibitory effects are not the result of inhibiting the proliferative effects of an endogenous growth factor and are cAMP independent.
Skeletal muscle amino acid and myofibrillar protein mRNA response to thermal injury and infection
Authors: Fong Y. M. , Minei J. P. , Marano M. A. , Moldawer L. L. , Wei H. , Shires G. T. , Shires G. T. , Lowry S. F.
Published: December 2017

Skeletal muscle changes associated with severe injury were investigated in male Wistar rats subjected to 30% full thickness scald injury (burn) and thermal injury followed by immediate colonization with 10(8) colony-forming units of Pseudomonas aeruginosa (BI). Freely fed animals (FF) and animals pair fed to the BI animals (PF) served as controls. Thermal injury in conjunction with infection produced a rapid and sustained muscle cellular membrane depolarization (transmembrane potential difference at 12 h after injury: FF 92.1 +/- 0.3 and BI 85.2 +/- 2.3 mV; P less than 0.05). This was followed by body weight loss and skeletal muscle protein wasting (gastrocnemius protein at 7 days: FF 0.35 +/- 0.01 and BI 0.16 +/- 0.03 g; P less than 0.05) and intracellular high-energy phosphate depletion (ATP at 10 days: FF 6.6 +/- 0.4 and BI 4.5 +/- 0.4 mumol/g tissue; P less than 0.05). These body and cellular changes were not accounted for by the anorexia alone. Marked alterations in intracellular free amino acids were also noted in the BI group characterized by increases in levels of all amino acids (total intracellular free amino acids at 7 days: FF 51 +/- 7 and BI 91 +/- 12 mM; P less than 0.05) except intracellular glutamine (at 7 days: FF 6.0 +/- 0.2 and BI 2.4 +/- 0.6 mM; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Insulin suppression is associated with hypersomatostatinemia and hyperglucagonemia in glucose-injected rainbow trout
Authors: Harmon J. S. , Eilertson C. D. , Sheridan M. A. , Plisetskaya E. M.
Published: December 2017

Rainbow trout, Oncorhynchus mykiss, were used to evaluate the effects of carbohydrate loading on plasma levels of pancreatic hormones and associated changes in metabolic indexes in a carnivorous fish. Glucose (3,000 mg/dl, 10 microliters/g body wt) was injected intraperitoneally into fish (mean wt 54 +/- 5 g) that were killed 0.5-24 h after administration. Glucose injection resulted in hyperglycemia with maximum glucose levels of 306 +/- 13 mg/dl observed 60 min after injection. Glucose administration also resulted in hyperlipidemia. Plasma fatty acids increased twofold in glucose-injected animals. Alterations in plasma metabolites reflected changes in energy stores. Although total lipid concentration was unaffected by glucose injection, lipolytic enzyme activity in the liver was enhanced. Biosynthetic capacity, as indicated by NADPH production from glucose-6-phosphate dehydrogenase, was decreased by glucose injection. Liver glycogen content was reduced in glucose-injected animals 1 h after injection. Glucose injection was attended by increases in the plasma levels of gene II somatostatin-25 (predominant form of pancreatic somatostatin in salmonids) and of glucagon. Insulin levels were initially suppressed after glucose injection. These results indicate that metabolic adjustments caused by glucose administration can be related to the regulatory action of pancreatic hormones. Furthermore, these results suggest that the somatostatin-secreting cells of the trout are sensitive to glucose and that somatostatin-suppressed insulin secretion contributes to the glucose intolerance of trout.
Effect of V2 antagonist on clearance of arginine vasopressin by isolated perfused rat kidneys
Authors: Keeler R. , Sato A. K. , Claybaugh J. R. , Wilson N.
Published: December 2017

Isolated rat kidneys were perfused with Krebs-Henseleit-bovine serum albumin solution at a mean pressure of 99 +/- 2.6 mmHg. After control periods, arginine vasopressin (AVP) was added to the perfusate at a final calculated concentration of 25 pg/ml (2.5 x 10(-11) M). Urine and perfusate samples were collected at 15-min intervals for the following 60 min to measure kidney function and the renal clearance of immunoreactive AVP (irAVP). At 15-30 min after the addition of AVP, total renal clearance of irAVP was 1,623 +/- 190 microliters.min-1.g kidney wt-1. Glomerular filtration accounted for 35 +/- 3.0% of the total clearance, and 65 +/- 10.3% was cleared by peritubular pathways. Of the filtered irAVP, 48 +/- 4.8% was recovered in the urine. To investigate the importance of V2 receptors in the metabolism of AVP, clearance measurements were made in the presence of the V2 antagonist [d(CH2)5,D-Ile2,Ile4,Arg8]AVP (5 x 10(-9) M). Total renal clearance of irAVP was reduced by 48% to 848 +/- 79 microliters.min-1.g-1. This reduction was entirely accounted for by the complete inhibition of peritubular clearance of irAVP. In the presence of the V2 antagonist, irAVP was cleared only by filtration. The proportion of filtered AVP recovered in the urine (53 +/- 8.7%) was not significantly altered by the presence of the V2 antagonist. We conclude that a major component of the renal clearance of AVP depends on receptor-mediated uptake of AVP in the kidney cells.
Contribution of renal medullary mitochondrial density to urinary concentrating ability in mammals
Authors: Abrahams S. , Greenwald L. , Stetson D. L.
Published: December 2017

In mammals, the length of the loops of Henle increases with increasing body size without a concomitant rise in urinary concentrating ability. Because mass-specific metabolic rate falls with increasing body mass, this study sought to determine the extent to which this decline in metabolic rate could explain the low urinary concentrating ability of large mammals with long loops of Henle. Mitochondrial ultrastructural parameters were measured in the medullary thick ascending limbs (mTALs) of a series of nine mammalian genera ranging in body mass from 0.011 kg (bats) to approximately 400 kg (horses). The volume of mitochondria as a percent of mTAL cellular volume declined with increasing body mass (Mb-0.056). Inner mitochondrial membrane area per volume of mitochondrion also declined with increasing body mass (Mb-0.034), as did basolateral membrane area per unit mTAL cellular volume (Mb-0.075). Thus, not only do mitochondria occupy more volume of mTAL cells of smaller mammals, but those mitochondria are also more densely packed with cristae. Inner mitochondrial membrane area per unit volume of mTAL cell cytoplasm scaled as Mb-0.092. The decline in inner mitochondrial membrane area and basolateral membrane area per volume of mTAL cell may explain at least in part the relationship between body mass and renal concentrating ability in mammals of different sizes.
Diurnal rhythms in fetal urine flow, vascular pressures, and heart rate in sheep
Authors: Brace R. A. , Moore T. R.
Published: December 2017

Conflicting indirect data exist as to whether diurnal variations occur in fetal urine flow rate. In addition, the extent of diurnal rhythms in fetal venous pressure or arterial pressure is unknown, although 24-h rhythms do exist in fetal heart rate. In the present study, we used on-line computer techniques to continuously monitor these variables in chronically catheterized ovine fetuses. Fetal urine flow rate and vascular pressures were successfully recorded in 6 of 11 animals over a 24-h period on 21 days out of a total of 45 days of monitoring. We found highly significant diurnal variations in fetal urine flow rate (P less than 10(-6). Hourly means displayed a maximum at 2130 h and a minimum at 1330 h with a maximum amplitude of 28 +/- 5% of the 24-h mean. A secondary maximum (at 0630 h) and minimum (at 0330 h) of smaller amplitude also occurred. There were simultaneous and highly significant (P less than 0.0001) diurnal rhythms in fetal arterial pressure (+/- 2%), venous pressure (+/- 7%), and heart rate (+/- 5%). The maxima in arterial pressure and heart rate occurred within 1 h of the maximum in urine flow, while venous pressure changes were opposite those in arterial pressure. Hourly mean urine flow correlated significantly with arterial pressure but not venous pressure or heart rate, suggesting that the observed 24-h variations in fetal urine flow rate may be partially mediated by a pressure diuresis.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes in small intestinal mucosa morphology and cell renewal in suckling, prolonged-suckling, and weaned lambs
Authors: Attaix D. , Meslin J. C.
Published: December 2017

No information concerning the effect of weaning on intestinal cell proliferation is currently available in large species with early intestinal morphogenesis, a group including most domestic animals and humans. Changes in intestinal morphology and epithelial cell renewal were investigated in 1-, 5-, and 8-wk-old suckling and 8-wk-old weaned lambs after injection of [3H]thymidine. In suckling lambs a gradual increase in crypt depth occurred with age, especially in the proximal intestine, whereas villus height was significantly reduced in the distal regions. At 8 wk of age weaned and prolonged-suckling lambs exhibited no significant differences in crypt depth throughout the intestine and in villus height proximally. However, weaned lambs had shorter villi in the jejunum and ileum. The highest enterocyte migration rates (4.4-9.7 microns/h) were observed in 1-wk-old lambs. In suckling animals, migration rates decreased with age by 60, 51, and 11% in the duodenum, jejunum, and ileum, respectively. Weaned and prolonged-suckling 8-wk-old lambs had a similar rate of enterocyte migration in the ileum. Furthermore, ruminating animals exhibited only slightly higher migration rates in the duodenum and the jejunum (53 and 15%, respectively). In suckling lambs, epithelial cell renewal required 2.1-4.0, 4.5-6.3, and 4.0-5.3 days at 1, 5, and 8 wk of age, respectively, whereas labeled cells reached the tips of the villi within 3.0-3.1 days in weaned animals. These data suggest that the suckling period corresponds to a gradual and important phase of postnatal intestinal adaptation in the sheep, a species with early patterns of intestinal cell replacement.(ABSTRACT TRUNCATED AT 250 WORDS)
Prostanoids attenuate pial arteriolar dilation induced by cortical spreading depression in rabbits
Authors: Shibata M. , Leffler C. W. , Busija D. W.
Published: December 2017

The role of prostanoids in mediating cerebrovascular responses to cortical spreading depression (CSD) was examined in anesthetized rabbits. CSD was elicited by KCl microinjection, and its propagation was monitored electrophysiologically. Pial arterial diameter was determined using a closed cranial window and intravital microscopy, and regional cerebral blood flow (rCBF) was determined using laser flowmetry. Levels of peri-arachnoid cerebrospinal fluid prostanoids were determined by radioimmunoassay. CSF increased pial arteriolar diameter 62% and rCBF 354% over the baseline levels. Locations of propagating CSD, dilating pial arteriole, and increased rCBF were always closely associated spatiotemporally. Cerebrospinal fluid prostanoid levels increased during single CSD-induced arteriolar dilation, and they were further augmented during multiple CSDs. Indomethacin enhanced both CSD-induced vasodilation (88%) and rCBF increase (580%), but it decreased the cerebrospinal fluid levels of prostanoids below the baseline levels and prevented their increase during CSD-induced vasodilation. These results indicate that prostanoids are synthesized from neurons or glial cells and/or the brain vessels and, as the net result, counteract pial arteriolar dilation and rCBF increase during CSD. In addition, they support the hypothesis that the vasodilation is caused primarily by neurogenic factors associated with CSD.
Oxygen pressure-dependent control of carbonic anhydrase synthesis in chick embryonic erythrocytes
Authors: Million D. , Zillner P. , Baumann R.
Published: December 2017

During chick embryonic development carbonic anhydrase (CA) expression of erythrocytes is kept at a very low level until the last week of incubation (i.e., up to day 14). We have previously obtained evidence that hypoxia is the physiological stimulus for rapid onset of CA synthesis before hatching. Looking for putative signals we have carried out in vitro incubations of embryonic erythrocytes, screening a large number of hormones and second messengers, which were all ineffective, with the exception of the A1 agonist N6-phenylisopropyladenosine (adenosine had no effect). However, incubation with embryonic plasma (10%) from embryos greater than 6 days caused a 10-fold increase of the CA activity during 24 h. This increase was not observed when the incubation was carried out with the addition of actinomycin D, cycloheximide, aluminum fluoride, pertussis toxin, or heat-inactivated plasma. Mammalian plasma had no effect on CA activity. Filtration experiments show that the molecular mass of the factor is less than 2,000 Da. We conclude that embryonic plasma contains a heat-labile factor which stimulates CA synthesis via activation of transcription and whose receptor is coupled to a pertussis toxin-sensitive G protein. In vivo the action of the plasma factor is suppressed as long as blood Po2 is high, suggesting the presence of an inhibitor molecule whose synthesis is controlled by the Po2.
Channel arrest: implications from membrane resistance in turtle neurons
Authors: Doll C. J. , Hochachka P. W. , Reiner P. B.
Published: December 2017

A widespread defense strategy used by hypoxia-tolerant animals is metabolic depression. One possible mechanism for metabolic depression is "channel arrest." This hypothesis predicts that ion leakage through plasma membrane leakage channels is reduced during an anoxic episode. The decreased ion flux would result in the conservation of energy through the reduction of ATP-demanding ion pumping. We tested this hypothesis with the anoxia-tolerant turtle (Chrysemys picta) as a model system. With intracellular recording used in cortical slices, whole cell input resistance and specific membrane resistivity were monitored under control and anoxic conditions. There were no significant changes in resistance, indicating that the channel arrest defense mechanism was not utilized for energy conservation during short-term anoxia (less than or equal to 120 min).
Low salt mimics effects of dark pulses on circadian pacemaker in cultured chick pineal cells
Authors: Zatz M. , Wang H. M.
Published: December 2017

Chick pineal cells in static culture display a persistent photosensitive circadian rhythm of melatonin production and release. Pulses of white light or darkness, in otherwise constant red light, induce phase shifts in subsequent cycles whose magnitude and direction depend on the phase at which the pulse is given. Such "phase-dependent phase shifts" are mediated by effects on the underlying pacemaker. We reported previously that inhibiting the Na-K-ATPase with ouabain or salt solutions lacking potassium evokes phase shifts with the same phase dependence as those induced by pulses of darkness. One of the consequences of inhibiting the sodium pump is cell swelling. To test the relevance of this effect, we exposed chick pineal cells to pulses of medium containing reduced concentrations of NaCl, which should cause cell swelling. These hypotonic solutions induced phase shifts in the melatonin rhythm with the same phase dependence as those caused by pulses of ouabain or darkness. The size of the phase shifts varied with degree of dilution, and phase shifting was prevented by replacement of NaCl. In view of previous results showing that hypertonic media mimicked the phase-shifting effects of light, these results suggest that cell swelling may mediate the darklike effects of ouabain on the circadian pacemaker in chick pineal cells.
Metabolic fate of lactate after vigorous activity in the leopard frog, Rana pipiens
Authors: Fournier P. A. , Guderley H.
Published: December 2017

Although the ability of isolated frog muscle to synthesize glycogen from lactate has long been known, it has never been demonstrated that this metabolic activity occurs in the intact frog. Our results clearly indicate that lactate glycogenesis in frog muscle occurs to a significant extent in vivo. During recovery from strenuous exercise, most of the lactate accumulated by frogs seems to be recycled into muscle glycogen because the lactate that disappears during recovery could account nearly stoichiometrically for the glycogen that accumulates in muscle. Furthermore, the decrease in body lactate and the increase in muscle glycogen follow corresponding time courses, suggesting a precursor-product relationship between lactate and glycogen. During recovery from intense exercise, hepatectomized and normal frogs have nearly identical extents of lactate elimination and glycogen synthesis. This suggests that muscle is the main tissue responsible for the recycling of lactate into muscle glycogen and that liver plays a negligible role in lactate disposal. The negligible hepatic contribution to lactate recycling results in part from the liver's incapacity to produce glucose from lactate. In support of this proposition, we show that frog liver perfused in vitro is unable to incorporate any detectable labeled lactate into glucose despite its excellent physiological integrity. Changes in dietary status, training state, season at which the experiments were done, exercise status, and composition of the perfusion media (pH, hormonal composition, physiological saline vs. culture medium) did not give rise to lactate gluconeogenesis. Because frog liver contains all the regulatory enzymes of the gluconeogenic pathway, its inability to synthesize glucose from lactate is not due to an absence of pyruvate carboxylase. A limited ability for lactate uptake may explain why frog liver cannot produce glucose from lactate.
Area postrema stimulation induces differential renal hemodynamics with two anesthetics
Authors: Hartle D. K. , Soliman A. S.
Published: December 2017

The effect of area postrema stimulation (APS) on blood pressure, renal blood flow (RBF), and renal vascular resistance was compared in urethan-anesthetized and pentobarbital sodium-anesthetized Sprague-Dawley rats. Mean arterial pressure (MAP) increased in a frequency-dependent manner during APS in both urethan- and pentobarbital-anesthetized rats. Although no significant differences occurred in the maximum percent change in MAP between groups, marked differences occurred in RBF and calculated renal vascular resistance (RVR) changes. In urethan-anesthetized rats, RBF and MAP increased during APS, but RVR did not change. In contrast, APS significantly decreased RBF (-26.5 +/- 1.9%) while increasing RVR (+99.4 +/- 11.4%) in pentobarbital-anesthetized rats. The increase in RVR in the pentobarbital-anesthetized group during APS was eliminated by prior ganglionic blockade. It was concluded that the anesthetic agent employed can significantly alter the degree to which APS can activate renal vasomotion in the rat.
Altered gene expression in fast-twitch muscle induced by chronic low-frequency stimulation
Authors: Pette D. , Dusterhoft S.
Published: December 2017

Increased neuromuscular activity via chronic low-frequency stimulation induces multiple fast-to-slow transitions in phenotypic properties that ultimately lead to fiber type conversions in the fast-twitch muscle of small mammals. Most of these alterations occur in an ordered sequence and result from the sequentially altered expression of myofibrillar and other protein isoforms. These changes relate to altered levels of specific mRNAs, followed by alterations in protein synthesis. As shown by the exchange of myosin heavy chain isoforms, protein degradation may be an additional control factor involved in the rearrangement of the myofibrillar apparatus. The degree of the various fast-to-slow transitions is species dependent and may be related to differences in thyroid hormone levels. It is suggested that the drastically and persistently depressed phosphorylation potential of the ATP system possibly serves to trigger the transformation process.
Modulation of the spinobulbospinal micturition reflex pathway in cats
Authors: Kruse M. N. , Mallory B. S. , Noto H. , Roppolo J. R. , de Groat W. C.
Published: December 2017

Micturition, which is mediated by a spinobulbospinal reflex pathway, can be modulated by various spinal and supraspinal mechanisms. This study examined modulation of the micturition reflex in decerebrate unanesthetized cats. Electrical stimulation of the pontine micturition center (PMC) elicited two types of bladder responses: small-amplitude short-duration responses due to direct activation of the bulbospinal pathway (PS-direct contractions) and large-amplitude long-duration reflex responses induced by PS-direct contractions but maintained by afferent feedback (PS-reflex contractions). Rectal and vaginal-cervical stimulation inhibited the PS-direct contractions, indicating inhibition of the descending or efferent limb of the micturition pathway. Stimulation of the central end of a transected S2 ventral root elicited recurrent inhibition of PS-reflex contractions but not of PS-direct contractions, indicating that recurrent inhibition does not directly affect the descending pathway. Continuous electrical stimulation (20 Hz) of the PMC decreased (53 +/- 21%) bladder capacity, presumably by affecting transmission in the pons or ascending input to the pons. Thus the micturition reflex could be modulated at several sites: the pons, the ascending or descending pathways, or spinal interneuronal sites.
Inhibition of Ca2+ and K+ currents by "antifreeze" proteins
Authors: Rubinsky B. , Mattioli M. , Arav A. , Barboni B. , Fletcher G. L.
Published: December 2017

For the last two decades, the research on fish “antifreeze” proteins has focused exclusively on their ability to depress noncolligatively blood plasma freezing points, presumably by binding to ice crystals. We report evidence that antifreeze polypeptides from the winter flounder (Pseudopleuronectes americanus) have another special property, the ability to block ion channels. In experiments with porcine granulosa cells we show, using the patch-clamp technique in the whole cell configuration, that these proteins suppress effectively calcium and potassium currents. The results of dose-response studies indicate a protein-protein interaction mechanism.
Long-term decrease in body fat and in brown adipose tissue in capsaicin-desensitized rats
Authors: Cui J. , Himms-Hagen J.
Published: December 2017

Previous studies showed that atrophy of brown adipose tissue (BAT) of capsaicin-desensitized rats occurs rapidly and persists for up to 28 days. The rats do not, however, become any more obese than control rats, despite the frequent association of atrophied BAT with obesity. The objective of the present study was to assess longer-term effects of capsaicin desensitization on BAT and on energy balance. Rats were studied at 2.5, 3.5, and 8 mo after treatment. Major effects at 8 mo, mostly seen to a lesser extent at 3.5 mo but not at 2.5 mo, were a marked reduction in body weight that was largely attributable to a reduction in body fat but also to some stunting of growth and an atrophy or lack of growth of BAT (reduced weight and content of protein, DNA, cytochrome oxidase, and uncoupling protein). Resting metabolic rates and food intake at 8 mo were reduced in proportion to the smaller body size. We suggest that the lack of trophic influence of sensory neuropeptides on BAT proposed previously may extend to other organs, including white adipose tissue, and contribute to the reduced adiposity and the smaller body size of capsaicin-desensitized rats.
Human thermoregulatory responses during heat exposure after artificially induced sunburn
Authors: Pandolf K. B. , Gange R. W. , Latzka W. A. , Blank I. H. , Kraning K. K. , Gonzalez R. R.
Published: December 2017

Thermoregulatory responses in the heat (ambient temperature 49 degrees C, 20% relative humidity, 1 m/s wind) were investigated in 10 unacclimated men during 50 min of cycle ergometer exercise (approximately 53% of maximal aerobic power) after a 10-min rest before as well as 24 h and 1 wk after twice the minimal erythemal dose of UV-B radiation that covered approximately 85% of the body surface area. In 7 subjects esophageal temperature (Tes) was recorded while in all 10 subjects five-site skin and rectal temperatures, heart rate, and back, left forearm, and shielded (12 cm2 area) right forearm sweating rates (msw) were recorded at 15-s intervals. Venous blood was collected before and after exercise-heat stress. Mean skin temperature, Tes, rectal temperature, heart rate, and total body sweating rate were not significantly (P greater than 0.05) affected by sunburn. Pre- and postexercise values of hematocrit, hemoglobin, plasma protein, plasma volume, and plasma osmolality were also not affected (P greater than 0.05) by sunburn. Analysis of presunburn and post-sunburn data showed that the Tes intercept for sweating (degrees C) was unaffected (P greater than 0.05), but msw/Tes and final msw from the left forearm (msw/Tes 0.24 +/- 0.02 vs. 0.17 +/- 0.01 mg.cm-2.min-1. degrees C-1, P less than 0.05; msw 0.60 +/- 0.05 vs. 0.37 +/- 0.02, mg.cm-2.min-1, P less than 0.05) and back (msw/Tes 0.43 +/- 0.03 vs. 0.36 +/- 0.01 mg.cm-2.min-1. degrees C-1, P = 0.052; msw 1.08 +/- 0.09 vs. 0.74 +/- 0.05 mg.cm-2.min-1, P less than 0.05) were significantly reduced 24 h postsunburn.(ABSTRACT TRUNCATED AT 250 WORDS)
Accelerated reproductive development in juvenile male ground squirrels fed a high-fat diet
Authors: Dark J. , Ruby N. F. , Wade G. N. , Licht P. , Zucker I.
Published: December 2017

Male golden-mantled ground squirrels held at 23 degrees C were fed high-fat (HF) or standard (chow) diets. In December, ambient temperature was reduced to 6 degrees C, food was removed, and frequency and duration of torpor bouts were monitored continuously by radiotelemetry. Reproductive condition and body composition were assessed upon terminal arousal in the spring. Juvenile males fed the HF diet weighed more than chow-fed controls before and throughout the hibernation season and had significantly greater lipid masses at terminal arousal. Testes masses and plasma testosterone concentrations were substantially higher in HF than in chow-fed juveniles. The accelerated reproductive development of fatter squirrels was not contingent upon increases in the total number of days spent in torpor, number of torpor bouts, or the average duration of each arousal from torpor. Access to the HF diet had no effect on body mass, adiposity, or reproductive status of adult male ground squirrels in spring. Threshold levels of white adipose tissue and associated differences in availability of metabolic fuels may be permissive for testicular growth during the hibernation season. Juveniles exceed this threshold only when fed the HF diet.
Evidence against a humoral control mechanism in adrenal catecholamine secretion during insulin-induced hypoglycemia
Authors: Lamarche L. , Yamaguchi N. , Peronnet F. , Guitard F.
Published: December 2017

The present study tested the hypothesis that a humoral control mechanism is involved in the enhanced adrenal catecholamine secretion during insulin-induced hypoglycemia. The experiments were carried out in anesthetized dogs in which neuronal and humoral components were simultaneously determined by measuring catecholamine output from the right innervated and the left acutely denervated adrenal gland, respectively. Different levels of hypoglycemia were induced by intravenous injection of insulin with doses of 0.075 (n = 6), 0.150 (n = 6), and 0.300 IU/kg (n = 6) in three separate groups of dogs. Catecholamine output in the right innervated gland increased dose dependently (P less than 0.05), reaching a maximum level 45 min after insulin administration. By contrast, catecholamine output from the left denervated adrenal gland remained unchanged at all doses tested. In sham-denervated animals (n = 7), catecholamine output from the left adrenal gland increased to a magnitude similar to that observed in the right innervated gland after insulin administration. Plasma glucose concentration significantly decreased in a dose-dependent manner, reaching a nadir 30 min after insulin administration. Maximum decreases in plasma glucose concentration could be strongly correlated with maximum increases in catecholamine output from the right innervated adrenal gland (r = -0.66, n = 18, P = 0.011), but not with those from the left denervated gland (r = -0.32, n = 18, P = 0.455). The present results do not support the functional existence of a humoral mechanism permitting the release of adrenal catecholamines during insulin-induced hypoglycemia.
Acute effects of captopril, an angiotensin-converting enzyme inhibitor, on the pregnant ewe and fetus
Authors: Lumbers E. R. , Kingsford N. M. , Menzies R. I. , Stevens A. D.
Published: December 2017

After control measurements had been made, 15 chronically catheterized pregnant ewes (gestational age 123-141 days) were given 15 mg of captopril intravenously followed by an infusion of 6 mg/h. These doses blocked the pressor responses of both ewes and fetuses to 5 micrograms of angiotensin I. After captopril, maternal mean arterial pressure fell from 94 +/- 3.5 to 88 +/- 3.6 (SE) mmHg (P less than 0.0001) and pulse interval fell (P = 0.008). Maternal flow to the cotyledons fell from 766 +/- 118 to 525 +/- 77 ml/min (P = 0.002), as did flow to the remainder of the maternal placenta, i.e., the caruncles and their underlying myoendometrium (control flow 188 +/- 35 ml/min, flow 10-15 min after captopril 166 +/- 36.1 ml/min; P = 0.021). Flow to the rest of the myometrium did not change. Fetal arterial pressure fell from 46.9 +/- 1.6 to 44.1 +/- 1.6 mmHg (P less than 0.009), and fetal placental blood flow fell from 639.9 +/- 93.2 to 413.1 +/- 53.9 ml/min (P = 0.025). Flow to the fetal membranes declined also, from 53.2 +/- 6.5 to 35.6 +/- 3.3 ml/min (P less than 0.005). Maternal and fetal renal blood flows and fetal adrenal blood flows were unchanged. Fetal arterial PO2 was initially 19.5 +/- 0.8 mmHg; after captopril, it was 17.7 +/- 0.9 mmHg (P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
Alpha 2-adrenergic regulation of galanin and norepinephrine release from canine pancreas
Authors: Scheurink A. J. , Mundinger T. O. , Dunning B. E. , Veith R. C. , Taborsky G. J.
Published: December 2017

We found previously that electrical stimulation of the mixed autonomic pancreatic nerves (MPNS) is anesthesized dogs elicits marked and rapid increases of pancreatic output of both norepinephrine (NE) and galanin, and on that basis hypothesized a role for galanin as a sympathetic cotransmitter in the endocrine pancreas. In the present study, direct evidence was sought for the co-release of galanin and NE from canine pancreas by determining whether pancreatic galanin output is subject to modulation by presynaptic alpha 2-adrenergic mechanisms as has been established for NE. During MPNS (8 Hz, 1 ms, 10 mA, 10 min) in anesthesized dogs, both pancreatic NE and galanin outflow were increased with similar temporal patterns during consecutive stimulations. Blockade of presynaptic alpha 2-adrenoceptors with yohimbine increased and stimulation of presynaptic alpha 2-adrenoceptors with clonidine reduced NE and galanin outflow. Over all experiments, pancreatic spillover of galanin was highly correlated with that of NE. It is concluded that presynaptic alpha 2-adrenergic mechanisms modulate not only NE but also pancreatic galanin release, suggesting that galanin is co-released with NE from noradrenergic nerves in the endocrine pancreas.
Seasonal variation in the human circadian rhythm: dissociation between sleep and temperature rhythm
Authors: Honma K. , Honma S. , Kohsaka M. , Fukuda N.
Published: December 2017

The circadian rhythms of sleep-wakefulness, rectal temperature, and plasma melatonin were measured in 10 healthy male subjects for five consecutive seasons. To minimize direct effects of seasonally changing environmental factors, the subjects stayed in a living facility for 4 days in each season, where ambient temperature, humidity, and social contacts were controlled, while the light intensity of the living room was substantially influenced by natural daylight. Seasonal variations were found in the timing of sleep, the mean body temperature, the phases of circadian temperature and melatonin rhythms, and the phase relation between sleep and the rectal temperature rhythm. The subjects went to bed earliest in summer, intermediate in spring and autumn, and latest in winter. A similar but more pronounced seasonality was observed in the wake-up time, which was earlier in summer than in winter. The acrophases of the rectal temperature and plasma melatonin rhythms, which were calculated by fitting a cosine curve, were located in an earlier time of day in summer than in winter. The phase-angle difference of the rectal temperature rhythm to sleep varied seasonally and was more positive in summer than in winter. These findings indicate that not only the external (to the local time) but also the internal (between circadian rhythms) phase relations of the human circadian rhythms depend on season.
The 10-Hz rhythm in sympathetic nerve discharge
Authors: Barman S. M. , Gebber G. L. , Zhong S.
Published: December 2017

Frequency-domain analysis was used to characterize the relationships among the rhythmic discharges recorded simultaneously from two to four sympathetic nerves in unanesthetized decerebrate cats. The major new findings were as follows. 1) The 10-Hz rhythmic discharges of different nerves cohered strongly in baroreceptor-innervated and -denervated cats. 2) The interval between the discharges of two nerves was frequency dependent in the 10-Hz band in some cats, supporting the view that the 10-Hz rhythm is generated by multiple central circuits that are coupled. 3) In some cases the central circuits responsible for the 10-Hz rhythms nonuniformly affected different nerves. 4) In baroreceptor-innervated cats the coherence values for the cardiac-related discharges of any two nerves were significantly higher than those for the 10-Hz rhythms. 5) In baroreceptor-denervated cats the 10-Hz rhythmic discharges of different nerves cohered more strongly than the 2- to 6-Hz rhythms. 6) The 10-Hz rhythm usually was not a harmonic of the 2- to 6-Hz or cardiac-related rhythm. Thus these rhythms are generated independently.
Dietary obesity in nine inbred mouse strains
Authors: West D. B. , Boozer C. N. , Moody D. L. , Atkinson R. L.
Published: December 2017

The effect of 7 wk consumption of a diet containing 32.6% of kilocalories as fat [condensed milk (CM) diet] on body composition and energy intake was evaluated in nine strains of inbred mice (AKR/J, C57L/J, A/J, C3H/HeJ, DBA/2J, C57BL/6J, SJL/J, I/STN, and SWR/J). Control animals were fed a high-carbohydrate diet containing 11.6% of energy as fat (Purina Rodent Chow diet). Relative to Chow diet controls, the CM diet significantly increased carcass lipid content in six strains (AKR/J, C57L/J, A/J, C3H/HeJ, DBA/2J, and C57BL/6J), but had no or a marginal effect on adiposity in three strains of mice (SJL/J, I/STN, and SWR/J). The obesity produced by the CM diet in six strains was not due to hyperphagia. Only one of six (AKR/J) of the strains that increased adiposity on the CM diet consumed more energy than controls during the 7 wk of the experiment. The identification of inbred mouse strains that are sensitive to dietary obesity, vs. others that are resistant, provides a useful tool to pursue the metabolic and genetic basis of this trait in the mouse.