bluuebunny/crossref_metadata_2025 huggingface dataset:
Additive inhibition of renal bicarbonate reabsorption by maleate plus acetazolamide
Authors: Hoppe A , Gmaj P , Metler M , Angielski S
Published: December 2017

The effects of two potent inhibitors of renal bicarbonate reabsorption--maleate and acetazolamide--were investigated in the rat using clearance techniques. Acetazolamide given in high dose (50 mg/kg body wt) inhibited fractional bicarbonate reabsorption by ca. 30%, maleate (2.58 nmol/kg body wt) by 25%, and maleate plus acetazolamide by 54-72%. GFR was depressed, and urine volume was increased by both drugs in an additive manner. Maleate was equally effective as inhibitor of HCO3- reabsorption in the presence and absence of carbonic anhydrase activity. It is suggested that the site of action of both drugs is predominantly proximal, but they act on different steps in the transcellular HCO3- transport. A hypothetical mechanism of maleate action is presented, which takes into account the changes in passive HCO3- flux through the basolateral membrane.
Response of mouse liver glycogen cycle enzymes to endotoxin treatment
Authors: Giger O , McCallum RE
Published: December 2017

The present study was undertaken to characterize endotoxin-induced changes in carbohydrate metabolism and more specifically, to determine the contribution of glycogenolysis to the loss of liver glycogen. Female ICR mice, fasted overnight, were injected with a median lethal dose (LD50, 9 mg/kg) of endotoxin extracted from Salmonella typhimurium strain SR-11. Glycogen synthase and glycogen phosphorylase activities were measured at 0.5 and 6 h after treatment. Endotoxin treatment did not alter total glycogen synthase activity, but the amount of enzyme present in the active form was significantly lower in endotoxic mice. There was no significant increase in glycogen phosphorylase activity in endotoxin-treated mice. Glycogen phosphorylase was activated to the same extent in control and endotoxic mice by decapitation or intravenous epinephrine (25 or 1 mug/kg). The results of this study indicate no significant increase in glycogen phosphorylase activity in endotoxic mice, contraindicating enhanced glycogenolysis as a mechanism for depletion of carbohydrate following endotoxin injection. Altered activation of glycogen synthase, however, may contribute to the loss of glycogen during endotoxemia.
Hydrolysis of peptides within lumen of small intestine
Authors: Silk DB , Nicholson A , Kim YS
Published: December 2017

The quantitative significance of intraluminal peptide hydrolases in the terminal stages of peptide digestion has been investigated, and the precise origins of these enzymes have been determined. Intestinal contents and mucosae were obtained from rats anethetized with ether. Experiments carried out on pancreaticobiliary secretions and germfree rats show that pancreatic and bacterial enzymes do not contribute significantly toward the luminal digestion of dipeptides. Chemical assay data, thermostability studies, and examination of electrophoretic mobilities of luminal peptide hydrolases indicate that jejunal enzymes originate predominantly from the cytoplasm of intestinal mucosal cells, whereas the brush border of muosal cells is a major source of the enzymes in the ileum. With glycl-L-phenylalanine and L-phenylalanyl-glycine as substrates, jejunal luminal activity was less than 2.6% of mucosal activity. Brush-border peptide hydrolase activity in ileal contents, however, was 11.9% and 40.7% of mucosal brush-border activity for the two substrates. Luminal enzymes thus play an insignifcant role in the terminal digestion of peptides in the jejunum, but have a much more important role in the ileal digestion of peptides.
Effect of adrenal enucleation on sodium excretion in the rat
Authors: Alexander EA , Bengele HH , McNamara ER
Published: December 2017

After the adrenal glands are removed without their capsules, so-called adrenal enucleation, rats initially retain sodium, and, after adrenal regeneration, escape from salt retention. To define the renal mechanisms involved in this alteration in salt handling, we have utilized clearance and micropuncture techniques in three groups of saline-expanded rats that were sham-operated (S), enucleated (AE), or escaped after adrenal regeneration (E.) Sodium excretion was clearly blunted after AE, 5.5 mueq/min vs. 20.5 for S and 18.7 for E. Although glomerular filtration rate (GFR) and filtered load of sodium were lower in AE rats, the delivered load of sodium beyond the late distal tubule was not different among the groups: 0.30 neq/min for AE, 0.42 for S, and 0.40 for E. This was a consequence of strikingly greater sodium reabsorption in the loop of Henle and distal tubule in both the S and E rats. In the collecting duct over 50% of the delivered sodium was reabsorbed by the AE rats while over 30% of the excreted sodium was added in this tubular segment in the other groups. These data demonstrate that the impaired natriuresis after adrenal enucleation appears to be due to striking differences in collecting duct function. Since adrenal regeneration in the escape animals reverses this sodium retention, the effect is probably related to some alteration in adrenal hormone production. Sodium excretion in markedly expanded normal rats also appears to be determined by the net addition of sodium in the collecting duct.
Inhibition of ion transport by bile salts in canine gastric mucosa
Authors: Kuo YJ , Shanbour LL
Published: December 2017

Studies were conducted with in vivo and in vitro canine stomach preparations. Instillation of 5, 10, and 20 mM bile salts in TES bufer (pH 7.4) into the nonsecreting stomach in vivo caused a progressive decrease in electrical potential difference (PD) and an increase in electrical resitance (R). The rate of acid secretion, determined by the pH-stat method in the histamine-stimulated stomach, decreased with 5 and 20 mM bile salts. Mucosal adenosine triphosphate (ATP) content of the nonsecreting or secreting stomach was reduced by bile salts. In vitro flux studies demonstrated that within the first hour after 1 mM bile salts were added to the mucosal side of the chamber, PD decreased, R increased, and net sodium transport decreased. In the second hour, unidirectional fluxes of sodium increased, indicating an increase in permeability of the gastric mucosa to sodium. These results demonstrate that the initial action of bile salts is inhibition of ion transport, which is followed by an increase in permeability.
Properties of immobilized guinea pig hindlimb muscles
Authors: Maier A , Crockett JL , Simpson DR , Saubert CW IV , Edgerton VR
Published: December 2017

Guinea pig hindlimbs were unilaterally immobilized at resting length to evaluate histochemical, biochemical, and contractile properties of immobilized muscle. Contralateral limbs remained unrestrained. Four weeks later contractile properties were measured under chloral hydrate anesthesia. Average time-to-peak tension of the immobilized soleus was 30% less, whereas that of the gastrocnemius was not significantly changed relative to contralateral muscles. Immobilized soleus muscles acquired as much as 25% fibers with high alkaline myofibrillar adenosine triphosphatase activity; these fibers do not occur in the normal muscle. Neither the immobilized soleus nor gastrocnemius fatigued more quickly than their contralateral counterparts. In the immobilized gastrocnemius myofibrillar protein (mg/g muscle) decreased to 76% and maximum tetanic tension to 70% of contralateral values. However, tetanic tension per gram wet muscle weight or 100 mg myofibrillar protein was significantly greater in the immobilized gastrocnemius. No specific factor responsible for the increased tetanic tension could be identified.
Inhibition of transmembrane K transfer in ureter-ligated dogs infused with KCl
Authors: Hiatt N , Chapman LW , Davidson MB , Sheinkopf JA , Miller A
Published: December 2017

In anuric dogs loaded with K by infusion with 2 meq KCl/kg per h until prelethal hyperkalemic cardiotoxicity appears, the extent of transmembrane K transfer depends on the origin of the anuria. Animals with bilateral ureter ligation transfer a mean of 1.2 meq/kg to intracellular fluid, while those with bilateral nephrectomy transfer more than 2.5 times as much (3.1 meq/kg). Further, if dogs with functioning kidneys are ureter ligated or nephrectomized after approximately 45 min of K loading, K transfer ultimately falls as infusion continues. The fall is precipitate and over 90% in ligated animals; but it is gradual, and only 10% in those that are nephrectomized. Finally, K transfer, because of the absence of insulin, is negligible in K-loaded pancreatectomized dogs with bilateral ureter ligation, but fairly substantial in pancreatectomized animals with bilateral nephrectomy. The data suggest that ureter ligation and hyperkalemia activate a renal mechanism that interferes with the transfer of infused K to intracellular fluid. The mechanism may involve the renin-angiotensin II-aldosterone system to a limited degree.
Hemodynamic pulmonary edema in dogs with acute and chronic lymphatic ligation
Authors: Magno M , Szidon JP
Published: December 2017

The effect of lymphatic ligation on relative lung water (g H2O/g dry lung) was studied in dogs. Raising left atrial pressure to 20 mmHg for 2 h in chronically lymphatic-ligated dogs (4 days) caused a significantly greater increase in relative lung water than the same hemodynamic challenge did in sham-operated and acutely lymphatic-ligated dogs. There was no significant difference in relative lung water between the acutely lymphatic-ligated and sham-operated dogs. At normal left atrial pressures, there was no significant difference in relative lung water between the sham-operated and chronically lymphatic-ligated dogs. Since the combined effects of chronic lymphatic ligation and left atrial hypertension is greater than the sum of the individual effects, it appears that chronic lymphatic ligation increases the susceptibility of the lung to hemodynamic edema, we suggest that chronic lymphatic ligation may have produced increases in the interstitial volume and protein mass that are undetectable by our technique. These increases, in turn, could lead to a reduction in tissue safety factors against hemodynamic pulmonary edema.
Influence of oxygen and glucose on the water and ion content of swine aorta
Authors: Harrrison RG , Massaro TA
Published: December 2017

The swelling properties of isolated swine arterial tissue have been studied to determine their effect on diffusion and hydraulic permeability measurements. Tissue potassium and sodium content were also measured to obtain an index of tissue metabolic activity. When oxygen and glucose were present in the incubation medium, a 5% decrease in tissue water content was observed over an incubation period of approximately 3.5 h. Under these conditions the tissue potassium content was higher and the sodium content was lower than when oxygen and/or glucose were omitted from the medium. When both oxygen and glucose were omitted, the potassium and sodium levels were significantly altered, suggesting a disturbance in the sodium-potassium transport system due to depletion of necessary metabolities.
Antioxidant enzyme expression in rat lungs during hyperoxia
Authors: Ho Y. S. , Dey M. S. , Crapo J. D.
Published: December 2017

To understand the molecular mechanisms that upregulate the activities of pulmonary antioxidant enzymes in adult rats during exposure to 85% oxygen, the relative contents of corresponding mRNA in normal and hyperoxic lungs were determined. Hyperoxic exposure drastically induced the expression of lung manganese-containing superoxide dismutase (MnSOD) mRNA. Maximal induction of MnSOD mRNA occurred at days 3 and 5 of exposure to hyperoxia, reaching a 600 and a 340% increase over the levels of air-exposed rats, respectively. In addition, hyperoxia induced lung mRNA for glucose-6-phosphate dehydrogenase, glutathione peroxidase, glyceraldehyde-3-phosphate dehydrogenase, alpha-tubulin, and gamma-actin to different extends at various days of exposure. Hyperoxia had little or no effect on the levels of mRNA for copper/zinc-containing superoxide dismutase (CuZnSOD), catalase, heat shock protein (HSP70), and creatine kinase. Nuclear run-on experiments showed that the transcriptional rate of the MnSOD gene is enhanced in hyperoxic rat lungs by approximately 400% at day 3 of exposure compared with that of controls. The specific activities of CuZnSOD and MnSOD in these lung samples per unit of lung protein or DNA were also determined. The activity of CuZnSOD in hyperoxic lungs was found to be unchanged compared with controls, except a 20% decrease at day 7 of exposure when standardized against protein content of lung homogenate. Changes of CuZnSOD activity were more dramatic in hyperoxic lungs (a 40% increase at days 3, 5, 7, and 14 of exposure) when enzyme activity was normalized using lung DNA content. Surprisingly, no proportional increase of lung MnSOD enzyme activity was observed at days 3 and 5 of oxygen exposure. The increase of MnSOD activity per unit of lung protein also did not parallel the increase in MnSOD protein content at days 5, 7, and 14 of exposure. These data suggest that, in addition to transcriptional activation, translational and/or posttranslational regulation of the MnSOD gene expression may play a critical role in controlling lung MnSOD activity on hyperoxic exposure.
Early expression of β- and γ-subunits of epithelial sodium channel during human airway development
Authors: Gaillard Dominique , Hinnrasky Jocelyne , Coscoy Sylvie , Hofman Paul , Matthay Michael A. , Puchelle Edith , Barbry Pascal
Published: December 2017

The amiloride-sensitive epithelial Na+channel (ENaC) is an apical membrane protein complex involved in active Na+absorption and in control of fluid composition in airways. There are no data reporting the distribution of its pore-forming α-, β-, and γ-subunits in the developing human lung. With use of two different rabbit polyclonal antisera raised against β- and γ-ENaC, immunohistochemical localization of the channel was performed in fetal (10–35 wk) and in adult human airways. Both subunits were detected after 17 wk of gestation on the apical domain of bronchial ciliated cells, in glandular ducts, and in bronchiolar ciliated and Clara cells. After 30 wk, the distribution of β- and γ-subunits was similar in fetal and adult airways. In large airways, the two subunits were detected in ciliated cells, in cells lining glandular ducts, and in the serous gland cells. In the distal bronchioles, β- and γ-subunits were identified in ciliated and Clara cells. Ultrastructural immunogold labeling confirmed the identification of β- and γ-ENaC proteins in submucosal serous cells and bronchiolar Clara cells. Early expression of ENaC proteins in human fetal airways suggests that Na+absorption might begin significantly before birth, even if secretion is still dominant.
Prenyltransferase inhibitors block superoxide production by pulmonary vascular smooth muscle
Authors: Boota Ahmad , Johnson Bruce , Lee Kee-L , Blaskovich Michelle A. , Liu Shang-Xi , Kagan Valerian E. , Hamilton Andrew , Pitt Bruce , Sebti Saïd M. , Davies Paul
Published: December 2017

We recently showed that the farnesyltransferase inhibitor FTI-277 blocks interleukin 1β (IL-1β)-induced nitric oxide production in pulmonary vascular smooth muscle cells (SMC), whereas the geranylgeranyltransferase inhibitor GGTI-298 enhances this effect. Here we show that IL-1β and platelet-derived growth factor (PDGF) stimulate superoxide production by pulmonary vascular SMC and that this effect is blocked by both FTI-277 and GGTI-298, suggesting that farnesylated and geranylgeranylated proteins are required for superoxide production. We also show that FTI-277 and GGTI-298 block superoxide production stimulated by constitutively active mutant H-Ras. Furthermore, superoxide production by IL-1β, PDGF factor, and constitutively activated Ras is blocked by diphenyleneiodonium, implicating NAD(P)H oxidase as the generating enzyme. Given the role of oxidant radicals in vascular reactivity and injury, the action of both FTI-277 and GGTI-298 in suppressing superoxide generation by an inflammatory cytokine as well as by a potent smooth muscle mitogen may be therapeutically useful.
Lamellar body membrane turnover is stimulated by secretagogues
Authors: Bates Sandra R. , Tao Jian-Qin , Schaller Susanne , Fisher Aron B. , Shuman Henry
Published: December 2017

Lamellar bodies are specialized cellular organelles used for storage of surfactant by alveolar type II cells of the lung. We utilized monoclonal antibody (MAb) 3C9, which recognizes an integral lamellar body-limiting membrane protein of 180 kDa, to follow lamellar body trafficking.125I-labeled MAb 3C9 bound to the surface of type II cells and was internalized by the cells in a time- and concentration-dependent manner that was inhibitable by excess unlabeled antibody. The internalized antibody remained undegraded over a 4-h time period. The L2 rat lung cell line that does not have lamellar bodies did not bind iodinated 3C9. Exposure of type II cells to the secretagogues ATP, phorbol 12-myristate 13-acetate, and cAMP resulted in a 1.5- to 2-fold enhancement of binding and uptake of MAb 3C9. Calphostin C inhibited phorbol 12-myristate 13-acetate-stimulated phospholipid secretion and also reduced binding and uptake of MAb 3C9 by type II cells. Treatment of type II cells with phenylarsine oxide to obstruct clathrin-mediated endocytosis had no effect on the internalization of MAb 3C9 while markedly blocking the uptake of surfactant protein A and transferrin. An actin-mediated process was important for lamellar body membrane uptake because incubation with cytochalasin D partially inhibited MAb 3C9 incorporation by type II cells. These studies are compatible with enhanced lamellar body membrane turnover associated with surfactant secretion and indicate that this process can be monitored by the trafficking of the antigen reporter MAb 3C9.
Role of the Na/H antiport in pH-dependent cell death in pulmonary artery endothelial cells
Authors: Cutaia M. , Tollefson K. , Kroczynski J. , Parks N. , Rounds S.
Published: December 2017

We investigated the role of intracellular pH (pHi) and Na/H exchange in cell death in human pulmonary artery endothelial cells (HPAEC) following a metabolic insult (inhibition-oxidative phosphorylation, glycolysis). Metabolic inhibition in medium at pH 7.4 decreased viability (0–15% live cells) over 6 h. Cell death was attenuated by maneuvers that decreased pHiand inhibited Na/H exchange (acidosis, Na/H antiport inhibitors). In contrast, cell death was potentiated by maneuvers that elevated pHior increased Na/H exchange (monensin, phorbol ester treatment) before the insult. HPAEC demonstrated a biphasic pHiresponse following a metabolic insult. An initial decrease in pHiwas followed by a return to baseline over 60 min. Maneuvers that protected HPAEC and inhibited Na/H exchange (acidosis, Na+-free medium, antiport inhibitors) altered this pattern. pHidecreased, but no recovery was observed, suggesting that the return of pHito normal was mediated by antiport activation. Although Na/H antiport activity was reduced (55–60% of control) following a metabolic insult, the cells still demonstrated active Na/H exchange despite significant ATP depletion. Phorbol ester pretreatment, which potentiated cell death, increased Na/H antiport activity above the level observed in monolayers subjected to a metabolic insult alone. These results demonstrate that HPAEC undergo a pH-dependent loss of viability linked to active Na/H exchange following a metabolic insult. Potentiation of cell death with phorbol ester treatment suggests that this cell death pathway involves protein kinase C-mediated phosphorylation events.
MCP-1 in pleural injury: CCR2 mediates haptotaxis of pleural mesothelial cells
Authors: Nasreen Najmunnisa , Mohammed Kamal A. , Galffy Gabriella , Ward Melissa J. , Antony Veena B.
Published: December 2017

Pleural injury results in the death of mesothelial cells and denudation of the mesothelial basement membrane. Repair of the mesothelium without fibrosis requires proliferation and migration of mesothelial cells into the injured area. We hypothesized that monocyte chemoattractant protein-1 (MCP-1) induces proliferative and haptotactic responses in pleural mesothelial cells (PMCs) and that the MCP-1 binding receptor CCR2 mediates the pleural repair process. We demonstrate that PMCs exhibited MCP-1-specific immunostaining on injury. MCP-1 induced proliferative and haptotactic responses in PMCs. PMCs express CCR2 in a time-dependent manner. Fluorescence-activated cell sorting analysis demonstrated that interleukin (IL)-2 upregulated CCR2 protein expression in PMCs, whereas lipopolysaccharide (LPS) downregulated the response at the initial period compared with that in resting PMCs. However, the inhibitory potential of LPS was lost after 12 h and showed a similar response at 24 and 48 h. Haptotactic migration was upregulated in PMCs that were cultured in the presence of IL-2. The increased haptotactic capacity of mesothelial cells in the presence of IL-2 correlated with increased CCR2 mRNA expression. PMCs cultured in the presence of LPS showed decreased haptotactic activity to MCP-1. Blocking the CCR2 with neutralizing antibodies decreased the haptotactic response of PMCs to MCP-1. These results suggest that the haptotactic migration of mesothelial cells in response to MCP-1 are mediated through CCR2, which may play a crucial role in reepithelialization of the denuded basement membrane at the site of pleural injury and may thus contribute to the regeneration of the mesothelium during the process of pleural repair.
Total body water and the exchangeable hydrogen. II. A review of comparative data from animals based on isotope dilution and desiccation, with a report of new data from the rat
Authors: Culebras J. M. , Fitzpatrick G. F. , Brennan M. F. , Boyden C. M. , Moore F. D.
Published: December 2017

Total body water (TBW) determination by tritium space could be factitiously elevated by exchangeable H+ contained within water-soluble chemical configurations. Should this nonaqueous (molecular) exchangeable H+ turn out to be a large fraction of total exchangeable H+, TBW measurement by tritiated water (THO) dilution would display a systematic upward and non-random error. TBW was measured by THO dilution and subsequently by total body desiccation in 21 rats (weight 227+/-83 g, mean+/-SD). TBW was 71.38+/-2.4% by THO dilution and 70.20+/-1.5% by body desiccation. Analysis of variance of TBW vs. body weight showed a highly significant correlation both with desiccation (P less than 0.0005, r=-0.78) and dilution (P less than 0.03, r= -0.50). Convariance analysis of both methods showed no difference in slope (P greater than 0.9). There was a difference in variance (P less than 0.001) and means (P less than 0.03). Tritium space is 1.2% of body weight larger than TBW measured by desiccation. TBW measured by THO dilution gives a 1.71% overestimation of TBW as measured by desiccation. TBW measurement by THO dilution is accurate within less than 2% error. These findings have particular significance in the light of our theoretical model of the total nonaqueous exchangeable H+ in fat, protein, and carbodhydrate in the living vertebrate.
Coupling of signals to brown fat: alpha- and beta-adrenergic responses in intact rats
Authors: Flaim K. E. , Horwitz B. A. , Horowitz J. M.
Published: December 2017

The present study examines the effects of alpha- and beta-adrenergic antagonists (phentolamine and propranolol, respectively) and agonists (phenylephrine, isoproterenol) on the neurally induced temperature changes and membrane potentials of interscapular brown adipocytes. These studies, performed in vivo with anesthetized rats, indicate that both alpha- and beta-adrenergic components are associated with the biphasic temperature changes observed following sympathetic activation of the tissue. Specifically, the initial transient temperature decrease seen after brown fat stimulation appeared to reflect vasoconstriction mediated primarily via alpha-receptors, while the subsequent rise in tissue temperature was associated primarily (though perhaps not entirely) with beta-adrenergic pathways. In contrast, the redistribution of ions across the membrane of the brown adipocyte, a phenomenon manifested as a membrane depolarization, was elicited by phenylephrine (an alpha-agonist) as well as by isoproterenol (a beta-agonist), with the magnitude of the isoproterenol-induced depolarization being comparable to that of the phenylephrine-induced effect.
Epinephrine effects on branchial water and urea flux in rainbow trout
Authors: Haywood G. P. , Isaia J. , Maetz J.
Published: December 2017

In isolated trout heads, perfused at constant pressure, epinephrine (10(-6) M) was found to double water and urea efflux but increased Ringer perfusion rate by only 33%. Drastic changes in perfusion rate (by clamping) produced smaller changes of both efflux rates. Epinephrine-stimulated increase in water and urea efflux, and perfusion rate, was blocked by propranolol (beta-blocker) but not by phentolamine (alpha-blocker). Both blockers together canceled out all epinephrine effects. Epinephrine increased water influx across isolated unperfused gill arches, the effect again being blocked by propranolol but not by phentolamine. Both blockers together canceled any epinephrine effect. We conclude that epinephrine alters branchial vascular flow and functional surface area via alpha- and beta-adrenergic receptors, but also increases branchial permeability to water and probably urea, via beta-adrenergic receptors. To test the validity of the perfused head technique, water and urea efflux rates were compared with in vivo values.
Model for transport in the central nervous system
Authors: Spector R. , Spector A. Z. , Snodgrass S. R.
Published: December 2017

A pharmacokinetic model relating the flux of substances between blood, the compartment consisting of the cerebrospinal fluid (CSF)-extracellular space (ECS) of brain, and brain was developed. Transport equations for diffusion, active transport, and bulk flow of CSF between these three compartments were postulated, and kinetic constants were experimentally obtained. The appropriate differential equations were solved on a digital computer to predict concentrations in CSF and brain as a function of the plasma concentration. The ability of the model to predict correctly CSF and brain concentrations of ascorbic acid and mannitol with only knowledge of the plasma concentrations in both steady-state and nonsteady-state conditions was experimentally tested in rabbits. Ascorbic acid was chosen as a model substance that is actively transported into the CSF-ECS of brain and also into brain cells whereas mannitol enters CSF and brain by diffusion. The model made accurate predictions when the assumptions were not violated. Second, the model showed that the experimentally determined Michaelis-Menten transport constant (KT = 0.8 mg=dl-1) for ascorbate transport from blood into the CSF-ECS of brain optimizes ascorbate homeostasis in brain.
Impact of centrally applied biogenic amines upon the energy balance of fowl
Authors: Hillman P. E. , Scott N. R. , van Tienhoven A.
Published: December 2017

The impact of intraventricular injections of 100 microng of the biogenic amines, norepinephrine or dopamine, upon the energy balance of white leghorn hens Gallus domesticus was examined. Both drugs reduce metabolic heat production (about 35% at 9 and 20 degrees C, and about 15% at 35 degrees C) by inhibiting shivering or by reducing activity or both. Also the drugs inhibit the opposing thermal response, evaporative heat loss (about 3% at 9 and 20 degrees C, and about 20% at 35 degrees C) by reducing respiration rate. The relative balance of inhibiting these opposing responses by the drugs results in hypothermia at 9 and 20 degrees C, and hyperthermia or no change in body temperature at 35 degrees C. Both drugs usually caused an initial vasodilation of the feet and comb at all temperatures tested but did not persist long enough to have much of an impact on body temperature. It was concluded that differing ambient temperatures do not alter the action of the biogenic amines upon the modes of physical thermoregulation in chickens even though the direction of body temperature change is reversed at different ambient temperatures.
Oxygen exchange in a simulated trout gill secondary lamella
Authors: Smith D. G. , Johnson D. W.
Published: December 2017

The complex blood flow patterns occurring in a trout secondary lamella were computed from a theoretical electrical model consisting of a two-dimensional array of unitary resistances representing the blood channels of the lamella. Estimates of oxygen uptake from water to blood were made by means of the standard conductance equations for oxygen and values from the literature for blood and water PO2's in trout. The results were plotted as contour charts of blood and water PO2, O2 transfer, and blood flow. According to the results of various manipulations of this model, oxygen exchange across a given lamella will be largely unaffected by changes in the overall shape of the lamella. However, the model predicted that oxygen exchange would be greatly reduced if 1) the basal pillar cell channels were denied access to the respiratory water flow, 2) pillar cell contraction were to force blood into the larger-diameter marginal channels, or 3) the blood flow rate were to be increased, regardless of a concomitant increase in water flow. These predictions are discussed in terms of current theories of gas exchange in teleost gills.
Evidence for enhanced uptake of ATP by liver and kidney in hemorrhagic shock
Authors: Chaudry I. H. , Sayeed M. M. , Baue A. E.
Published: December 2017

It has been shown that infusion of ATP-MgCl2 proved beneficial in the treatment of shock; however, it is not known whether this effect is due to improvement in the microcirculation or direct provision of energy or a combination of the above or other effects. To elucidate the mechanism of the salutary effect of ATP-MgCl2, we have now examined the in vitro uptake of ATP by liver and kidney of animals in shock. Rats were bled to a mean arterial pressure of 40 Torr and so maintained for 2 hrs. After the rats were killed, liver and kidney were removed and slices of tissue (0.3-0.5 mm thick) were incubated for 1 h in 1.0 ml of Krebs-HCO3 buffer containing 10 mM glucose, 5 mM MgCl2, and 5 mM [8-14C]ATP or 5 mM [8-14C]ADP, or 5 mM [8-14C]AMP, or 5 mM [8-14C]adenosine in 95% O2-5% CO2 and then homogenized. Tissue and medium samples were subjected to electrophoresis to separate and measure the various nucleotides. The uptake of [14C]ATP but not that of [14C]ADP or [14C]adenosine by liver and kidney slices from animals in shock was 2.5 times greater than the corresponding uptake by control slices. Thus, the beneficial effect of ATP-MgCl2 in shock could be due to provision of energy directly to tissue in which ATP levels were lowered.
Fitting straight lines to experimental data
Authors: Brace R. A.
Published: December 2017

The problem associated with use of statistical methods for determining a best linear relationship of the form Y = AX +B have been examined for a condition quite prevalent with experimental research, i.e., when the values of both variables are subject to essentially unknown errors. Under this condition standard least-squares regression analysis underestimates the value of the slope A. A very simple method for determining the best value of the slope and intercept has been introduced which can be used when errors are present in both variables. With this proposed method, the calculated slope is equal to the standard error of Y divided by the standard error of X (with the appropriate sign) and the intercept is found from the mean values of X and Y, i.e., B = Y - AX. The best estimate of the slope is also equal to the slope found with the conventional regression method divided by the absolute value of the correlation coefficient. The line determined with the suggested method can be considered to be a line of symmetry through the data.
Water transport in perfused scorpion ileum
Authors: Ahearn G. A. , Hadley N. F.
Published: December 2017

Water transport in desert scorpion ileum involves two independent transfer pathways operating in parallel: 1) paracellular flow occurs through intercellular spaces in response to transmural osmotic or ionic gradients; and 2) transcellular water transport occurs across apical and basal cell membranes in response to a basal, energy-requiring sodium efflux process. The tissue exhibits no osmotic rectification over the range of transepithelial osmotic gradients imposed (Lp = hydraulic conductivity), Lp = 95 x 10(-7) cm - s-1 - atm-1), but displays apparent asymmetric ion permeability in response to transmural ion gradients, as determined by codiffusional water movements across the preparation. Osmotic permeability ((Pos), Pos = 1.13 x 10(-3) cm - s-1) of the tissue exceeds diffusional permeability ((Pd), Pd = 1.45 x 10(-5) cm - s-1) by almost two orders of magnitude. In the absence of osmotic or hydrostatic pressure gradients, transmural water transport requires cellular metabolism, is sodium-dependent, is inhibited by potassium, and produces an apparent strongly hypotonic absorbate. This water transport process appears to be adaptive, as scorpion dehydration results in alterations of luminal ion concentrations that favor increased net flow of water to the hemolymph.
Observations in energy balance in man during spaceflight
Authors: Rambaut P. C. , Leach C. S. , Leonard J. I.
Published: December 2017

An investigation was undertaken of the changes in metabolic energy balance which occur in weightlessness. Daily energy intake was determined each day throughout the 28-, 59-, and 84-day flights for each of the nine Skylab astronauts. The energy content of the urine and feces was also measured. Changes in body composition were inferred from measurements of weight, volume, water, and total exchangeable potassium before and after flight. During flight changes were followed by a daily measurement of body mass and by metabolic balance. Examination of the data reveal losses in body weight during the 1st and 2nd mo of flight, a loss in body water and protein during the 1st mo, and a loss of fat during the 1st, 2nd, and 3rd mo of flight. The energy input was about 41.7 kcal/kg per day on the ground, and 43.7 kcal/kg per day after 3 mo in space. The increase in net energy input of about 1.6% per mo is significant (P less than 0.05). When the net energy input is expressed on the basis of total body potassium, the increase in the resulting “noramlized” net energy input of about 3.7% per mo is also significant (P less than 0.05).
Arterial pressure-urinary output relationship in hypertensive rats
Authors: Norman R. A. , Enobakhare J. A. , DeClue J. W. , Douglas B. H. , Guyton A. C.
Published: December 2017

The steady-state relationship between mean arterial pressure (AP) and output of sodium and water was determined for one-kidney control (1KC), one-kidney Goldblatt (1KG), normotensive Wistar-Kyoto (WKY), and Okamoto spontaneously hypertensive rats (SHR). Control fluid intake (given by intravenous infusion) was set at approximately 30 ml/day Ringer solution. The infusion rate was then increased progressively to 2, 4, and 8 times control for 24- to 48-h periods each. Control AP averaged 115 Torr in 1KC, 152 Torr in 1KG, 120 Torr in WKY, and 158 Torr in SHR. The eightfold increase in salt and water intake was accompanied by almost equal increase in salt and water output and increases in AP to 157 Torr in 1KC, 190 Torr in 1KG, 126 Torr in WKY, and 166 Torr in SHR. The arterial pressure-urinary output relationship in 1KG is parallel to that of 1KC but shifted to higher AP levels. Similarly, this relationship in SHR is parallel to that of WKY but shifted to higher AP levels. This parallel shift is indicative of uniform renal vasoconstriction but normal functional renal mass in the SHR.
Changes in serotonin contents in brain affect metabolic heat production of rabbits in cold
Authors: Lin M. T. , Pang I. H. , Chern S. I. , Chia W. Y.
Published: December 2017

Elevating serotonin (5-HT) contents in brain with 5-hydroxytryptophan (5-HTP) reduced rectal temperature (Tre) in rabbits after peripheral decarboxylase inhibition with the aromatic-L-amino-acid decarboxylase inhibitor R04-4602 at two ambient temperatures (Ta), 2 and 22 degrees C. The hypothermia was brought about by both an increase in respiratory evaporative heat loss (Eres) and a decrease in metabolic rate (MR) in the cold. At a Ta of 22 degrees C, the hypothermia was achieved solely due to an increase in heat loss. Depleting brain contents of 5-HT with intraventricular, 5,7-dihydroxytryptamine (5,7-DHT) produced an increased Eres and ear blood flow even at Ta of 2 degrees C. Also, MR increased at all but the Ta of 32 degrees C. However, depleting the central and peripheral contents of 5-HT with p-chlorophenylalanine (pCPA) produced lower MR accompanied by lower Eres in the cold compared to the untreated control. Both groups of pCPA-treated and 5,7-DHT-treated animals maintained their Tre within normal limits. The data suggest that changes in 5-HT content in brain affects the MR of rabbits in the cold. Elevating brain content of 5-HT tends to depress the MR response to cold, while depleting brain content of 5-HT tends to enhance the MR response to cold.
Humoral and mechanical factors modulating neural input to the renal vasculature
Authors: Carlson D. E. , Schramm L. P.
Published: December 2017

The velocity and magnitude of neurally elicited renal vasoconstrictions decrease with reduction of renal arterial pressure. We investigated the relative roles of humoral and mechanical factors in this decrease. Cats were anesthetized with chloralose. Renal arterial pressure was controlled with an aortic cuff. Vasoconstrictions were elicited by electrical stimulation of the renal nerves until renal vascular resistance stabilized. Renal blood flow autoregulation was maintained during stimulation. Competitive blockade of angiotensin II did not affect the decrease in renal vascular responsiveness to neural input at reduced renal arterial pressure. A mathematical model suggested that a major portion of the decrease in the velocity of vasoconstrictions was a mechanical consequence of autoregulatory vasodilation. However, the model was only able to account for the experimental findings after the blockade of prostaglandin synthesis, and this blockade significantly increased the velocity of vasoconstrictions at renal arterial pressures of 75 Torr or below. These results suggested that prostaglandins as well as mechanical factors played a role in the autoregulatory decrease in responsiveness to sympathetic input.
Regulation of glycogen resynthesis in muscles of rats following exercise
Authors: Conlee R. K. , Hickson R. C. , Winder W. W. , Hagberg J. M. , Holloszy J. O.
Published: December 2017

Following a strenuous bout of exercise, glycogen repletion occurred most rapidly in the fast-twitch red type of muscle, least rapidly in fast-twitch white, and at an intermediate rate in slow-twitch red muscle. There was a linear correlation between glycogen synthase I activity and the rate of glycogen synthesis in the three types of muscle. This finding helps explain the differences between the rates of glycogen resynthesis in the three muscle types, and supports the view that glycogen synthase activity is the most important factor determining the rate of glycogen synthesis when substrate supply is adequate. There was an inverse correlation between muscle glycogen concentration and percent glycogen synthase I. Plasma insulin concentration was low and norepinephrine and glucagon concentrations were elevated in the postexercise period. The finding that rapid glycogen synthesis occurred despite a hormonal milieu conducive to glycogenolysis provides evidence that a low glycogen concentration is a potent stimulus to glycogen synthesis that overrides the effects of low insulin, and high norepinephrine and glucagon levels.
Feeding responses of rats with dorsomedial hypothalamic lesions given ip 2DG or glucose
Authors: Bellinger L. L. , Bernardis L. L. , Brooks S.
Published: December 2017

The glucoprivation effects of 2-deoxy-D-glucose (2DG) on feeding behavior were studied in rats with bilateral lesions of the dorsomedial hypothalamic nucleus (DMN) and sham-operated controls. The lesioned and sham-operated rats were injected intraperitoneally with 2DG (5% wt/vol) at doses of either 150 mg/kg, 300 mg/kg, or 500 mg/kg, or with saline ("control days"). At all doses significantly more sham-operated rats ate and showed an increased food consumption during the first few hours after 2DG injection when compared to saline control days. However, their 24-h food consumption was normal or less than normal, depending on the dose of 2DG. On the other hand, rats with DMN lesions (DMN-L) did not increase their food consumption during the 4 h after the injection at any of the 2DG doses. In a second experiment DMN-L and sham-operated controls were injected intraperitoneally with glucose (1.36 g/kg body wt or 2.72 g/kg body wt) or saline after an overnight fast. Glucose loads, compared to saline injections, significantly depressed the controls' food consumption only during the first hour of refeeding. On the other hand, glucose injections did not depress food intake of the DMN-L rats. It is suggested that DMN lesions may have either destroyed glucoreceptors in the DMN that monitor glucose or the glucoprivation effects caused by 2DG and/or glucoreceptive pathways that pass through the DMN.
A mathematical simulation of the hyperneas of metabolic CO2 production and inhalation
Authors: Yamamoto W. S.
Published: December 2017

Mathematical models of the CO2 responsive controller for ventillatory responses to CO2 inhaled and to CO2 introduced in the perpheral tissues are formulated in the context of a controlled system that is a compartmented tissue system with a lung undergoing breathing movements. Equations representing the system are either ordinary difference-differential equations or algebraic equations. If the controller contains three components simulating, respectively, a proportional controller with a set point, a mechanism sensitive to trans-membrane CO2 gradients, and a mechanism responsive to the autocovariance difference in arterial carbon dioxide tension (PaCO2) about 1.2 s apart; and if the neural tissues produce CO2 as a result of their own activity (positive feedback), the entire system responds to metabolic production of CO2 by increasing ventilation in proportion to metabolism while maintaining a constant PaCO2. The same system responds to inhaled CO2 mixtures with ventilation increasing in proportion to increases in PaCO2. The behavior of the model is used to postulate a spatiotemporal hypothesis for the humoral component of respiratory regulation of CO2 exchanges.
Circulatory effects on osmotic water exchange in Rana pipiens
Authors: Mahany T. M. , Parsons R. H.
Published: December 2017

Page R172: T. M. Mahany and R. H. Parsons. “Circulatory effects on osmotic water exchange in Rana pipiens.” Page R173: the second equation should read

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Inhibition of osmotic thirst by electric stimulation of the basal forebrain in dogs
Authors: Szczepanska-Sadowska E. , Sobocinska J. , Sadowski B. , Kosowski S.
Published: December 2017

The effect of electrical brain stimulation (ESB; 50 Hz, 50-150 microA sine wave, 5 s on/5 s off) on osmotic thirst was examined in 10 conscious dogs chronically implanted with electrodes aimed at the anteromedial part of the basal forebrain. Suppression of osmotic thirst (SOT) was observed during stimulation through 18 of 41 electrodes located in the olfactory tubercle, the nucleus accumbens, the caudate nucleus, the medial septum, and the lateral preoptic-anterolateral hypothalamic area (PrA/ALH). Mean increment in plasma osmolality necessary to cause drinking rose from 9.0 +/- 1.5 mosmol (X +/- SE; n = 15) under control conditions to 15.8 +/- 2.6 mosmol (n = 18) during ESB in SOT placements. Threshold cellular dehydration eliciting drinking increased from 2.70 +/- 0.50% of intracellular water (ICW;n = 16) to 4.77 +/- 0.68% of ICW (n = 18), respectively. The strongest SOT was found during ESB in the nucleus accumbens, and the PrA/ALH. The same stimulation failed to inhibit feeding, support self-stimulation or produce appreciable changes of dog's gross behavior. The results give evidence for the existence in the basal forebrain of the dog a widely distributed neural system suppressing osmotic thirst. The nucleus accumbens and the PrA/ALH seem to play an important role in this system.
Acid-base equilibrium during acute long-lasting experiments in artificially ventilated cats
Authors: Galletti C. , Maioli M. G. , Sanseverino E. R.
Published: December 2017

Experiments were carried out to study blood acid-base equilibrium in the cat during experiments with artificial ventilation. Blood acid-base equilibrium was examined in the arterial and venous blood by analyzing pH, carbon dioxide and oxygen partial pressure, and plasma bicarbonates. Artificial ventilation was regulated on the basis of this analysis; CO2 concentration in expired air was monitored throughout the experiment. An attempt was made to verify if artificial ventilation could be regulated indirectly only on the basis of CO2 concentration in expired air. The most appropriate acid-base equilibrium was maintained when CO2 concentration in expired air was kept within the range of 3.9-4.1%.
Evaluation of in vivo brain site perfusion with the push-pull cannula
Authors: Honchar M. P. , Hartman B. K. , Sharpe L. G.
Published: December 2017

The effect of tissue site perfusion with push-pull cannulas on the integrity of brain tissue was evaluated during in vivo studies in conscious New Zealand rabbits. The mean rate of perfusion-induced tissue disruption was 1.09 microgram tissue wet wt/min as estimated from the perfusate levels of endogenous nervous system specific proteins (S-100 and 14-3-2). The level of intravenously injected 125I-labeled bovine serum albumin recovered in perfusate samples indicated that approximately 2.0 nl serum/min penetrated the vascular barrier into the perfused tissue site. The appearance of intraventricularly injected solutes in perfusate samples was subjected to regression analysis.It was demonstrated that nonspecific variations in the appearance of one substance in the perfusate could be controlled for by a regression on the levels of another concurrently recovered inert substance. The experiments demonstrate that tissue site perfusion can provide useful access to brain extracellular fluid when suitable controls are incorporated for recovery variation and blood-brain barrier seepage.
Fixed interval feeding does not entrain the circadian pacemaker in blind rats
Authors: Gibbs F. P.
Published: December 2017

Male and female rats were blinded by orbital enucleation at 1 or 21 days of age and were housed along with intact controls in a temperature- and light-controlled room (22 +/- 2 degrees C, LD 12:12). At 40 days of age the rats were transferred to running wheel cages connected to an event recorder and their activity patterns were monitored for the next 11--16 wk. After 4--6 wk in the running wheels, the rats were subjected to a fixed interval feeding (FIF) schedule lasting 23 days followed by 4--6 wk of ad libitum feeding and watering. Of 19 blind rats with interpretable activity records, 14 showed no change in their activity patterns associated with the FIF other than the addition of a large component of activity before and after the feeding period every day. It was concluded that, in contrast to the squirrel monkey, FIF is not an important zeitgeber for blind rats.