bluuebunny/crossref_metadata_2025 huggingface dataset:
PAF-induced synthesis of tetraenoic and pentaenoic leukotrienes in the isolated rabbit lung
Authors: Grimminger Friedrich , Mayer Konstantin , Kiss Ladislau , Walmrath Dieter , Seeger Werner
Published: December 2017

In an isolated rabbit lung model, we tested the hypothesis that platelet-activating factor (PAF)-induced leukotriene (LT) synthesis is critically dependent on the free precursor fatty acid supply and the possible substitution of arachidonic acid (AA) by eicosapentaenoic acid (EPA). To augment the intravascular polymorphonuclear neutrophils (PMNs) in the isolated lung, human PMNs were infused into the pulmonary artery. LTs and hydroxyeicosatetra(penta)enoic acids were quantified with HPLC techniques. Application of PAF (5 μM) or AA (10 μM) provoked the generation of limited quantities of 4-series LTs and 5-hydroxyeicosatetraenoic acid (total sum of 5-lipoxygenase products ≈7 and ≈27 pmol/ml in lungs both with and without infused PMNs, respectively). Combined administration amplified 5-lipoxygenase product formation, with a predominance of cysteinyl-LT synthesis in lungs both without (total sum ≈ 67 pmol/ml) and, much more strikingly, with (total sum ≈308 pmol/ml) an infusion of neutrophils. EPA (10 μM) elicited exclusive generation of 5-series LTs and 5-hydroxyeicosapentaenoic acid (total sum ≈ 82 pmol/ml). Dual stimulation with PAF and EPA provoked amplification of EPA-derived 5-lipoxygenase product formation, again with predominance of cysteinyl-LTs in lungs without (total sum ≈224 pmol/ml) and, in particular, with (total sum ≈545 pmol/ml) preceding microvascular PMN entrapment. Combined application of PAF, AA, and EPA resulted in the synthesis of LTs derived from both fatty acids, with a predominance of 5-series products. We conclude that the PAF-evoked 5-lipoxygenase product formation in the neutrophil-harboring lung capillary bed is critically dependent on intravascular precursor fatty acid supply, with EPA representing the preferred substrate compared with AA. PMN-related transcellular eicosanoid synthesis is suggested to underlie the predominant generation of cysteinyl-LTs. The supply of n-3 versus n-6 precursor fatty acid may thus have a major impact on inflammatory mediator generation.
Immunopathology of a two-hit murine model of acid aspiration lung injury
Authors: Nemzek J. A. , Call D. R. , Ebong S. J. , Newcomb D. E. , Bolgos G. L. , Remick D. G.
Published: December 2017

In a two-hit model of acid aspiration lung injury, mice were subjected to nonlethal cecal ligation and puncture (CLP). After 48 h, intratracheal (IT) acid was administered, and mice were killed at several time points. Recruitment of neutrophils in response to acid was documented by myeloperoxidase assay and neutrophil counts in bronchoalveolar lavage (BAL) fluid and peaked at 8 h post-IT injection. Albumin in BAL fluid, an indicator of lung injury, also peaked at 8 h. When the contributions of the two hits were compared, neutrophil recruitment and lung injury occurred in response to acid but were not greatly influenced by addition of another hit. Neutrophil sequestration was preceded by elevations in KC and macrophage inflammatory protein-2α in plasma and BAL fluid. KC levels in BAL fluid were higher and peaked earlier than macrophage inflammatory protein-2α levels. When KC was blocked with specific antiserum, neutrophil recruitment was significantly reduced, whereas albumin in BAL fluid was not affected. In conclusion, murine KC mediated neutrophil recruitment but not lung injury in a two-hit model of aspiration lung injury.
Sodium nitroprusside augments human lung fibroblast collagen gel contraction independently of NO-cGMP pathway
Authors: Liu X. D. , Skold C. M. , Umino T. , Spurzem J. R. , Romberger D. J. , Rennard S. I.
Published: December 2017

Nitric oxide (NO) relaxes vascular smooth muscle in part through an accumulation of cGMP in the target cells. We hypothesized that a similar effect may also exist on collagen gel contraction mediated by human fetal lung (HFL1) fibroblasts, a model of wound contraction. To evaluate this, HFL1 cells were cultured in three-dimensional type I collagen gels and floated in serum-free DMEM with and without various NO donors. Gel size was measured with an image analyzer. Sodium nitroprusside (SNP, 100 μM) significantly augmented collagen gel contraction by HFL1 cells (78.5 ± 0.8 vs. 58.3 ± 2.1, P < 0.01), whereas S-nitroso- N-acetylpenicillamine, 5-amino-3-(4-morpholinyl)-1,2,3-oxadiazolium chloride, NONOate, and NG-monomethyl-l-arginine did not affect the contraction. Sodium ferricyanide, sodium nitrate, or sodium nitrite was not active. The augmentory effect of SNP could not be blocked by 1 H-[1,2,4]-oxadiazolo-[4,3- a]-quinoxalin-1-one, whereas it was partially reversed by 8-(4-chlorophenylthio) (CPT)-cGMP. To further explore the mechanisms by which SNP acted, fibronectin and PGE2production were measured by immunoassay after 2 days of gel contraction. SNP inhibited PGE2production and increased fibronectin production by HFL1 cells in a concentration-dependent manner. CPT-cGMP had opposite effects on fibronectin and PGE2production. Addition of exogenous PGE2blocked SNP-augmented contraction and fibronectin production by HFL1 cells. Therefore, SNP was able to augment human lung fibroblast-mediated collagen gel contraction, an effect that appears to be independent of NO production and not mediated through cGMP. Decreased PGE2production and augmented fibronectin production may have a role in this effect. These data suggest that human lung fibroblasts in three-dimensional type I collagen gels respond distinctly to SNP by mechanisms unrelated to the NO-cGMP pathway.
Plasma proteins modified by tyrosine nitration in acute respiratory distress syndrome
Authors: Gole Madhura D. , Souza Jose M. , Choi Irene , Hertkorn Caryn , Malcolm Stuart , Foust Raymond F. , Finkel Barbara , Lanken Paul N. , Ischiropoulos Harry
Published: December 2017

The present study identifies proteins modified by nitration in the plasma of patients with ongoing acute respiratory distress syndrome (ARDS). The proteins modified by nitration in ARDS were revealed by microsequencing and specific antibody detection to be ceruloplasmin, transferrin, α1-protease inhibitor, α1-antichymotrypsin, and β-chain fibrinogen. Exposure to nitrating agents did not deter the chymotrypsin-inhibiting activity of α1-antichymotrypsin. However, the ferroxidase activity of ceruloplasmin and the elastase-inhibiting activity of α1-protease inhibitor were reduced to 50.3 ± 1.6 and 60.3 ± 5.3% of control after exposure to the nitrating agent. In contrast, the rate of interaction of fibrinogen with thrombin was increased to 193.4 ± 8.5% of the control value after exposure of fibrinogen to nitration. Ferroxidase activity of ceruloplasmin and elastase-inhibiting activity of the α1-protease inhibitor in the ARDS patients were significantly reduced (by 81 and 44%, respectively), whereas α1-antichymotrypsin activity was not significantly altered. Posttranslational modifications of plasma proteins mediated by nitrating agents may offer a biochemical explanation for the reported diminished ferroxidase activity, elevated levels of elastase, and fibrin deposits detected in patients with ongoing ARDS.
Thermoregulatory responses to altering hypothalamic temperature in the harbor seal
Authors: Hammel H. T. , Elsner R. W. , Heller H. C. , Maggert J. A. , Bainton C. R.
Published: December 2017

The rostral brainstem of the harbor seal Phoca vitulina was cooled and heated 33-41 degrees C while oxygen consumption and rectal, hypothalamic, flipper and dorsal skin temperatures were measured. These experiments were made on restrained seals at ambient temperatures -15 to 30 degrees C. Cooling the preoptic and hypothalamic (POH) tissue increased oxygen consumption in a way that could be approximated by a linear regression line with slope and threshold temperature at which the metabolic rate was minimal. The slope of the regression line was a function of ambient temperature and rectal temperature. At each ambient temperature, the slope was significantly higher for lower rectal temperature. At all rectal temperatures, the slope was significantly higher for lower ambient temperature. The threshold hypothalamic temperatures did not very consistently or significantly with either rectal temperature or ambient temperature. These results on the harbor seal are explicable by suggesting that the thermal-sensitive and reference neurons in the POH which regulate body temperature are inhibited equally by extrahypothalamic cold transducing neural elements.
Physiological inhibition and facilitation of adrenocortical response to hemorrhage
Authors: Gann D. S. , Cryer G. L. , Pirkle J. C.
Published: December 2017

In a search for physiological feedback inhibition, secretion rates of cortisol were measured in intact dogs before and after sequential hemorrhages. The sucond of two sequential hemorrhages of 10 ml/kg separated by 90 min evoked significantly less increase of secretion rate of cortisol than did the first. This result was not explained by differential hemodynamic effects. Exhaustion of pituitary or adrenal capacities was excluded, since dogs responded normally to a second, larger hemorrhage. However, no attenuation response to a second 10 ml/kg hemorrhage was seen after a larger, 20 ml/kg, first hemorrhage. This led in turn to a search for a physiological facilitatory mechanism which might offset the feedback effect. The second of two rapid sequential hemorrhages to isovolemia following preexpansion of plasma volume evoked significantly greater increase of secretion rate of cortisol than did the first. This result also was not explained by differential hemodynamic effects. The results support the hypothesis that hemorrhage elicits both physiological feedback and facilitatory effects which interact and which are (different) functions of the intensity of stimulus.
Glucose turnover in kelp bass (Paralabrax sp.): in vivo studies with [6-3H,6-14C]glucose
Authors: Bever K. , Chenoweth M. , Dunn A.
Published: December 2017

[6-3H,6-14C]glucose was injected via an indwelling arterial cannula in free-swimming, fed, and fasted kelp bass to determine hepatic glucose production, peripheral glucose uptake, minimal glucose mass, mean transit time, and the percent of carbon recycling under the two different nutritional states. Mean plasma glucose levels remained unchanged in fed and fasted fish (48+/-8 vs. 43+/-8 mg/100 ml). During steady-state conditions, glucose replacement rates of fed and fasted fish determined with [6-3H]glucose are similar (0.035+/-0.006 vs. 0.025+/-0.003 mg/min per 100 g) and do not differ from rates determined with [6-14C]glucose (0.035+/-0.005 vs. 0.026+/-0.002). The minimal glucose masses and the mean transit tim-s determined with both isotopes are also similar suggesting that plasma glucose levels and glucose turnover are maintained in fish fasted up to 40 days with no apparent increase in carbon recycling. Nonsteady-state isotope experiments suggest that these fish can alter rates of hepatic glucose production and peripheral uptake in response to hyper- and hypoglycemia.
Electroimmunoassay of alpha-2-opsonic protein during reticuloendothelial blockade
Authors: Blumenstock F. , Weber P. , Saba T. M. , Laffin R.
Published: December 2017

Physiological regulation of reticuloendothelial (RE) phagocytic activity by a plasma opsonic factor has been documented. In the recent study, serum levels of this alpha-2-opsonic protein in rats during colloid-induced RE blockade were measured utilizing an electroimmunoassay (Rocket immunoelectrophoresis) with monospecific antiserum to the purified alpha-2-glycoprotein. RE blockade was produced by the intravenous injection of the gelatinized "RE-test-lipid emulsion" at a dose of 50 mg/100 g body wt. The opsonic activity of serum at various intervals during colloid-induced RE blockade as measured by tissue slice bioassay manifested a high correlation (r = 0.98) with the serum opsonic protein concentration as measured by the electroimmunoassay. During RE blockade (30 min), there was a rapid depletion of the opsonic alpha-2-glycoprotein to 20% of the initial preinjection levels. Serum concentration of this glycoprotein remained low for at least 2-3 h after which time its concentration progressively increased with approximation of normal values by 6 h postblockade. Opsonic protein concentration at 24 h postinjection were significantly (P less than 0.05) elevated above controls. Thus, colloid-induced RE blockade is associated with the removal of this glycoprotein from the serum and recovery from RE blockade is accompanied by a restoration of opsonin levels. The electroimmunoassay can provide a sensitive technique to monitor this humoral factor known to exert a physiological control on the RE system.
Involvement of a humoral factor in regulation of body weight in parabiotic rats
Authors: Parameswaran S. V. , Steffens A. B. , Hervey G. R. , de Ruiter L.
Published: December 2017

Excessive food intake and obesity was induced in one member of parabiotic pairs by electrical stimulation (three 30-min sessions/day for 2 wk) of the lateral hypothalamus (LH). The nonstimulated partners reduced spontaneous food intake the fatter the stimulated animals became. This reduced food intake resulted in a decreased body weight, fat content, and fat-free solid body mass. The decrease of food intake was not due to changed social behavior of the obese partner. It must be attributed to transmission of a humoral satiety factor. The very first stimulation of the LH in the stimulated partners resulted in a large increase in blood glucose and glucagon level without much change in the insulin level. These changes in blood parameters were probably due to strong sympathetic arousal. In the nonstimulated animals there were practically no changes in these parameters. One week of fattening resulted in increased basal glucose and insulin levels in the stimulated animals and decreased glucose levels in the nonstimulated partners, in which the basal insulin levels remained nearly normal. Basal glucagon levels were the same in both partners and did not differ from the prefattening situation. At that time during stimulation the obese animals showed a large increase in glucose and glucagon levels and a decrease in insulin level. On the other hand the nonstimulated animals showed a slow gradual increase in glucose and insulin level due to transmission from their fat partners because of the large gradient in these substances between the animals. These phenomena were still more pronounced after 2 wk of fattening. It is tentatively concluded that the humoral satiety factor is neither circulating insulin nor glucagon nor one of the major circulating nutrients.
Impairment in fluid ingestion in rats with lesions of the zona incerta
Authors: Evered M. D. , Mogenson G. J.
Published: December 2017

Rats with lesions of the zona incerta (ZI) dorsal to the lateral hypothalamus drink as much water as controls following intracellular or extracellular dehydration but restrict their daily water intake to minimal requirements for fluid balance, suggesting a specific impairment in secondary drinking. Following water deprivation, however, rats with ZI lesions responded to changes in palatability of the water as if they were experiencing slightly greater difficulty or aversiveness in drinking than controls. The cause appears to be an impairment in the ability to lick fluids from a spout. When water was available ad libitum or when water or liquid diet were provided after water or food deprivation, rats with ZI damage were unable to obtain as much fluid per lick as controls. It is concluded that lesions in this region of the brain impair the motor act of drinking and that the subsequent reduction in the efficiency of drinking is the cause of the attenuation of excessive water intake.
Parabrachial pons mediates hypothalamically induced renal vasoconstriction
Authors: Ward D. G. , Adair J. R. , Schramm L. P. , Gann D. S.
Published: December 2017

The role of the parabrachial region of the dorsal rostral pons (PB) in mediating control of renal blood flow and of systemic arterial blood pressure was investigated in nine cats anesthetized with chloralose-urethan. Electrical stimulation through electrodes placed stereotaxically in lateral and medial positions in the hypothalamus (LH and MH) in PB and in ventrolateral reticular formation (VLRF) of each cat elicited pronounced systemic arterial pressor responses and renal vasoconstrictions. Stimulation parameters were adjusted so that renal flow responses elicited from each site were equal. Following a unilateral lesion in the PB, responses of renal vasoconstriction induced by hypothalamic stimulation were attenuated, but responses of arterial pressure were not altered. Stimulation of the VLRF, posterior to the lesion, consistently produced undiminished systemic pressor responses and renal vasoconstriction throughout the durations of the experiments excluding decay of renal vascular responsiveness. Thus, the data suggest that pathways mediating renal vasoconstriction in response to hypothalamic stimulation was discrete and pass through the parabrachial region, whereas pathways mediating systemic vasoconstriction in response to hypothalamic stimulation are distinct or less compact.
Sodium transport in the freshwater mussel, Carunculina texasensis (Lea)
Authors: Dietz T. H.
Published: December 2017

Freshwater bivalves maintain a Na steady state in artificial pondwater: JiNa = 1.2 +/- 0.1 mumol/g dry tissue per h. Na uptake is Cl independent. The affinity (KS) of the Na transport system is 0.15-0.23 mmol Na/1. Sodium influx is coupled to H and/or NH4 exchange. Salt depletion stimulates JiNa 300% relative to nondepleted animals with no change in Ks. Injected ammonium ion stimulates JiNa. Sodium transport is inhibited 84% by 0.5 mM amiloride but is not affected by 4 mM NH4 or 1 mM furosemide in the bathing solution or injection of acetazolamide (0.26 mumol/ml blood).
Redistribution of blood flow in acute hypometabolic behavior
Authors: Jevning R. , Wilson A. F. , Smith W. R. , Morton M. E.
Published: December 2017

Cardiac output, renal and hepatic blood flows, arterial lactate concentration, and minute volume were measured before, during, and after 40 min of rest induced either by the practice known as "transcendental meditation" (TM) or by an ordinary eyes-closed rest-relaxation period. Two groups of normal young adults were studied: one group consisted of regular practitioners of TM and the other of similar individuals studied prior to learning this technique. Marked declines of renal blood flow were noted in both groups. Decline of hepatic blood flow, increased cardiac output, decreased arterial lactate, and minute volume were also recorded in the TM-induced rest period. These changes imply a considerable increase of nonrenal, nonhepatic blood flow during TM (44%) and, to a lesser extent, during rest (12%). Increased cerebral and/or skin blood flow is hypothesized to account for part of the redistributed blood flow in the practitioner.
Cutaneous blood flow during heating and cooling in the American alligator
Authors: Smith E. N. , Robertson S. , Davies D. G.
Published: December 2017

Nine alligators, Alligator mississippiensis, were injected with 133Xe and the clearance half times measured in response to heating and cooling. Mean half times for thermostable, heating, and cooling conditions were 12.2, 8.6, and 28.3 min, respectively, indicating cutaneous vasodilation in response to local heating and reduced blood flow during cooling. Alterations of cutaneous blood flow occurred before changes in body temperature or heart rate. Warming portions of the animal while shading the injection site resulted in reduced blood flow when heat loss occurred. Skin thickness (S in cm) was related to body mass (M in kg) as S = 0.08 M0.38. Cutaneous blood flow per unit area was found to increase with increasing body mass from approximately 0.0025 to 0.025 ml blood-cm-2 of skin-min-1 during warming and from 0.0018 to 0.0045 during cooling for the 0.18--8.6 kg animals, respectively.
A model of potassium ion efflux during exercise of skeletal muscle
Authors: Hazeyama Y. , Sparks H. V.
Published: December 2017

Potassium (K+) is a vasoactive agent and is released from muscle cells during exercise. A simple diffusion model does not predict the time course of K+ efflux during exercise, which decreases as the exercise progresses. We constructed a mathematical model using the concept of an active Na+-K+ ion pump to account for the decreased efflux during and uptake after exercise. Passive fluxes are calculated by the Nernst equation. Active fluxes are constrained to balance these passive fluxes at rest. The pump activity increases as either extracellular K+ or intracellular Na+ concentration increases. To test the model, the venous K+ efflux profile was simulated for direct stimulation (4/s) of the anterior calf mus cles of dogs. The model simulated the K+ release during the stimulation period and [K+] undershoot after the stimulation. The active Na+-K+ ATPase transport concept used in the model was further tested by observing K+ efflux after administration of ouabain. Ouabain infusion decreased K+ uptake during exercise slightly and abolished [K+] undershoot after the stimulation. These experimental data were matched by the model only if a discontinuous effect of ouabain is assumed. This suggests that ouabain may more completely block the sensitivity of the pump to intracellular [Na+] than to extracellular [K+].
On model and data requirements for determining the bioavailability of oral therapeutic agents: application to gut absorption of thyroid hormones
Authors: DiStefano J. J. , Mak P. H.
Published: December 2017

A two-pool model is proposed as a first approximation of the dynamics of thyroid hormone dissolution and absorption in the human gut. It is shown that this model, or any more complex one of the same process, must be imbedded in a larger whole-body model for the purpose of quantifying its parameters. Parameter identification experiments are designed with the aid of identifiability analysis and a complete quantification is obtained, for both triiodothyronine (T3) and thyroxine (T4) absorption, using kinetic data obtained from the literature. The average percent absorption of oral dosages calculated from the model for T3 (95.8%) and for T4 (49.3%) are exceptionally close to reported measured values. Other data not used in model development also serve to validate the results, for use in applications not demanding greater physiological detail, such as for determining the bioavailability of orally administered hormones, or for the "inverse problem," computing optimal dosage regimens for hormone therapy.
Plasma volume and electrolyte shifts with heavy exercise in sitting and supine positions
Authors: Greenleaf J. E. , Van Beaumont W. , Brock P. J. , Morse J. T. , Mangseth G. R.
Published: December 2017

Plasma volume (PV) and electrolyte shifts were measured before and for 60 min after a continuous peak oxygen uptake (VO2 peak) test in four men (26-45 yr) on a bicycle ergometer. Mean (+/-SE) sitting VO2peak (3.16 +/- 0.32 1/min) was the same as supine VO2peak (3.13 +/- 0.33 1/min). In recovery (R + 1.5 min), mean PV had decreased by 477 ml (-16.1%, P less than 0.05) in the sitting and by 548 ml (-17.6%, P less than 0.05) in the supine positions, whereas total osmolality increased progressively with its peak at R + 3.5 min. The percentage losses of protein, total Ca2+, and ionized Cai2+ were about half as great as the percentage loss in PV, indicating a selective retention of these constituents. Calculated osmolality (sigma Na+, K+, Cl-, Cai2+) returned to control levels within 1.5 min after sitting exercise but required about 15 min after supine exercise. These small increases in protein concentration were not likely to significantly aid restitution of plasma volume and the ions were probably in equilibrium across the capillary membrane. So a change in hydrostatic and/or systemic blood pressures most likely provided the force for restitution of plasma volume.
Abolition of hypoxic vagal bradycardia by lateral mesencephalic lesions in spinal cats
Authors: Hall R. E. , Rubinstein E. H. , Sonnenschein R. R.
Published: December 2017

To examine central sites that integrate the vagal bradycardia induced by hypoxia, heart rates were recorded continuously in spinal, precollicular, decerebrated cats during transient hypoxia induced by ventilation with 100% nitrogen. Bilateral lesions in the lateral mesencephalic reticular formation either decreased the extent of bradycardia or caused a reversal to tachycardia; anesthesia induced the same change. In contrast, bilateral lesions in the medial mesencephalic reticular formation failed to alter the bradycardia. Hence, the lateral mesencephalic reticular formation is essential for the appearance of hypoxia-induced vagal bradycardia.
Autonomic cardiovascular control during submergence and emergence in bullfrogs
Authors: Lillo R. S.
Published: December 2017

Unanesthetized bullfrogs were involuntarily submerged for 25 min in air-saturated water at 21 degrees C. Significant bradycardia was observed while systemic blood pressure was maintained or slightly elevated. Upon emergence, heart rates immediately returned to presubmergence levels or higher. Similar responses were observed in frogs allowed to make voluntary dives in an experimental tank. Heart rates of vagal-blocked (atropine) frogs did not change during submergence or emergence. beta-Adrenergic blockade (propranolol) had little effect on the magnitude of heart rate decrease during submergence or its increase upon emergence. After alpha-adrenergic blockade (phentolamine), frogs developed diving bradycardia while undergoing a fall in systemic blood pressure. It is concluded that, in bullfrogs, 1) bradycardia during submergence is entirely due to increased vagal activity, 2) the immediate cardiac rate increase upon emergence apparently results from a decrease in vagal tone; and 3) there appears to be no substantial reciprocal sympathetic influence on heart rate during alterations in vagal tone.
Look at physiological integration
Authors: Adolph E. F.
Published: December 2017

Physiological integration results from cooperating processes at work within an individual. Two chief types of study are a) empirical experiments and generalizations, and b) predictive relations derived from models. In this essay the empirical type is illustrated. For example, heart rates and other circulatory properties are modified in response to messages from specific muscles, viscera, glands. In those tissues, augmented blood flow increases the supplies of oxygen and other substances at active local sites. Because specialized actions are segregated among tissues and organs, each performer evidently informs cooperating tissues of its state. Messages are transmitted at various kinds of junctions and chemical receptors. In this essay the results or actions are emphasized: in what ways do the compounded processes promote survival and advantage? Messages are sorted as they travel, certain powers of decision residing at cellular junctions. Because selected processes are corrdinated, each compound action represents an accomplishment. Thermoregulation serves as an example of relations by which several parameters yield a complex result. The multiple correlations and the intricate timing and switching are recognized.
Probability of peripheral interaction between motor units and implications for motor control
Authors: Demieville H. N. , Partridge L. D.
Published: December 2017

Potential and importance of mechanical interactions between motor units are examined. Studies were conducted on simple physical models of systems of motor units assembled from separate muscles and driven with electrical stimulus. Two separate muscles were connected to move a common load to represent mechanically coupled motor units while avoiding other interactions present between natural units. Force, velocity, length, power, and work outputs of one unit were measured with and without stimulus to the other unit. Excitation of one unit modified all response measures in the other. The basis for these interactions appears equally applicable to real motor units. Consequently, unqualified use of such terms, which imply independence, as quantal, summation, and average unit response is not acceptable without qualification when referring to activity of motor units. It is argued that the effects of force-velicty and length-tension relationships will cause appreciable mechanical interaction between motor units. Therefore, central nervous system strategies for organization of motor control cannot depend on unchanging response of individual units, and the principle of superposition should not be assumed in analyses of motor activities. The nature of the interactions suggests that the total effect of a unit response may include a "negative force" phase, and also energy exchanges can be expected between motor units in some configurations.
On the anatomic relation of choroid plexus to brain: a comparative study
Authors: Cserr H. F. , Bundgaard M. , Ashby J. K. , Murray M.
Published: December 2017

The size of choroid plexuses and cerebral ventricles relative to brain varies widely among vertebrates. The functional significance of this variability has attracted little attention since Herrick's original proposal that large choroid plexuses might enhance oxygen delivery to the brain and therefore be of adaptive value in the transition of vertebrates from water to air breathing. We compared choroid plexus and brain weight or ventricular and brain volume in 40 species from nine vertebrate groups. Both choroid plexus weight and ventricular volume were unrelated to brain size. Plexus weight ranged from 0 to 5.2% of brain weight and ventricular volume from 0.9 to 132% of brain volume. Amid this diversity the dipnoans, chondrosteans, holosteans, amphibians, and crossopterygian examined in this study are exceptional in uniformly having large plexuses. The adaptive significance of large choroid plexuses may lie in the presence of specific homeostatic mechanisms and their role in the response to the increases in PCO2 that accompany the transition to air breathing.
Gill arch of the mullet, Mugil cephalus III. Rate of response to salinity change
Authors: Hossler F. E.
Published: December 2017

The rate of response of gill filament epithelium to salinity changes was determined by scanning electron microscopy and biochemical techniques. An increase in Na-K-ATPase content, as measured by [3H]ouabain binding, was detected at 3 h and continued to about 24 h after mullet were transferred from a salinity of 1-4.5%. In contrast, filaments from mullet transferred to freshwater exhibited a decrease in ouabain-binding sites. Similarly, scanning electron microscopy revealed that ultrastructural modifications occurred in epithelial pores of the filament surface in response to salinity changes. These modifications, which included changes in pore diameter and depth and in the number of cellular extensions in the pore's interior, were evident as early as 6 h and were mostly completed by 24 h after the salinity change. Because epithelial pores likely represent apical pits of chloride cells and because the Na-K-ATPase is localized within chloride cells, the present observations likely represent different manifestations of the very rapid response of chloride cells to osmotic stress, and indicate the close association of structure with function.
Effect of food or water restriction on erythropoiesis in mice: relevance to "anemia" of space flight
Authors: Dunn C. D.
Published: December 2017

Dehydrated mice showed a negative energy balance and hemoconcentration similar to that thought to occur in men during space flight, although the mechanism producing these changes may be completely different. The relative importance of dehydration and a negative energy balance in producing erythroid suppression has been investigated. The initial suppression appeared to be due to a reduced food intake. Thereafter, this negative energy balance produced about 40% of the erythroid suppression, the severity of which was augmented by dehydration. The decreased food consumption appeared to suppress erythropoiesis by reducing the sensitivity of the target cells in the spleen to erythropoietin (Ep), the erythropoietic hormone. Hemoconcentration decreased titers of Ep thus also suppressing erythropoiesis. Attempts to alleviate the effects of water deprivation and reduced food consumption by effects of water deprivation and reduced food consumption by water injections and the feeding of supplemented diets were only marginally effective at ameliorating the erythroid suppression. These studies indicate the importance of maintaining an adequate energy and fluid balance in the regulation of erythropoiesis.
Calcitonin stimulation of urine flow and sodium excretion in the starling
Authors: Clark N. B. , Wideman R. F.
Published: December 2017

Renal effects of synthetic salmon calcitonin (CT) were examined in normal and parathyroidectomized (PTX) starlings, Sturnus vulgaris. Standard clearance studies were performed. Anesthetized birds were infused with [14C]-inulin in 2.5% mannitol containing either 0.25% gelatin alone as a control, or gelatin plus CT (2 IU CT/h; Armour). In intact starlings, CT significantly increased urine flow and relative clearance of sodium (CNa/CIn). CCa/CIn was significantly elevated only 40 min after start of hormone infusion. No significant change occurred in CK/CIn, CPO4/CIn or in serum levels of Na, K, Ca, or PO4. In PTX starlings, CT induced significantly higher CNa/CIn. Urine flow was significantly higher at 40 and 60 min, whereas CK/CIn increased significantly only 20 min following start of CT infusion. Serum calcium decreased significantly 1 h after hormone administration and was accompanied by increased incidence of tetany. Serum phosphate levels were significantly lower than those of corresponding PTX controls 1 h post-CT, indicating that CT prevented the expected hyperphosphatemia. Higher CT dose (20 IU/h) in PTX birds substantially enhanced urine flow, CNa/CIn, CK/CIn, and occurrence of tetany.
Vagal mediation of hypothalamic obesity but not of supermarket dietary obesity
Authors: Gold R. M. , Sawchenko P. E. , DeLuca C. , Alexander J. , Eng R.
Published: December 2017

In two independent experiments, complete subdiaphragmatic vagotomy did not prevent the development of the obesity that results from the addition of highly palatable foods to the diet of rats. The vagotomized animals exhibited only a 1-day delay in the onset of overeating, and this only when first exposed to the tasty diet. In independent tests of the functional completeness of the vagotomies, the vagotomized animals failed to overeat or gain excessive weight on a standard laboratory diet following bilaterally parasagittal hypothalamic knife cuts. Thus, hypothalamic knife-cut obesity requires the integrity of the vagus for its full expression, whereas dietary obesity does not.
Effect of 5-hydroxytryptamine and acetylcholine on the energy budget of chickens
Authors: Hillman P. E. , Scott N. R. , van Tienhoven A.
Published: December 2017

Intraventricular injections of 5-hydroxytryptamine-HCl (258 nmol) or acetylcholine-HCl (550 nmol) in the chicken caused body temperature to rise at 35 degrees C ambient, a result of decreased evaporative heat loss due to bradypnea. At 10 and 20 degrees C ambient, neither drug affected body temperature. Although these drugs decreased physical activity or shivering or both at 10 and 20 degrees C, metabolic heat production was not depressed enough to alter body temperature significantly. Heart rate decreased simultaneously with decreased activity at 20 degrees C. This study is the first to inject 5-hydroxytryptamine as a salt of HCl, instead of creatinine sulfate, as is commonly used. It is suggested that some of the differences reported herein, compared to other studies, are due to the type of salt used. It is postulated that either 5-hydroxytryptamine or acetylcholine, rather than norepinephrine, may be an important neurotransmitter in the neural pathways for thermoregulation in chickens, even though their action on thermoregulation is minor compared with norepinephrine.
A predictive model study of the visual contribution to canine postural control
Authors: Talbott R. E. , Brookhart J. M.
Published: December 2017

Dogs were trained to stand on a movable table and their quiet stance was perturbed by osccillation of the table during normal sighted condition and during blindfolded condition. The data formed the frequency response characteristic (describing function) for postural control with and without visual input. A feedback model was tested to assess the effect of visual input during the perturbation of quiet stance. The results of the tests of the model indicate that the effect of a visual input depends on the context of the multiple sensory factors influencing postural control. The effectiveness of the visual input increases if there is a conflict between the visually derived body position cues and the other cues that indicate the orientation of the body.
Subfornical organ: forebrain site of pressor and dipsogenic action of angiotensin II
Authors: Mangiapane M. L. , Simpson J. B.
Published: December 2017

Intracranial injection of angiotensin II (AII) at three brain sites elicited near simultaneous dipsogenic and pressor effects in rats. Both effects were maximal, occurred with the shortest latencies, and at the lowest doses of AII when the cannula terminated precisely within the parenchyma of the subfornical organ (SFO). Pressor effects were produced by SFO injection of a dose of AII (0.1 pg) which approximates plasma AII concentrations at the high end of the physiological range. Both the drinking and pressor effects were blocked by saralasin. Injections of AII at sites immediately adjacent to SFO produced smaller effects with longer latencies. These results ruled out the possibility that SFO injections were effective via leakage to alternative sites. The pressor effect of AII at the SFO remained in animals under chloralose anesthesia, demonstrating that it is not an artifact of drinking behavior. These results indicate that the SFO is a site of AII pressor action, and confirm previous demonstrations that the structure is a site of AII drinking action.
Sensitivity to change in electrical environment: a new bioelectric effect
Authors: Marino A. A. , Cullen J. M. , Reichmanis M. , Becker R. O. , Hart F. X.
Published: December 2017

The action of a 60-Hz, 5 kV/m electric field on erythrocyte parameters in mice was determined. No effects attributable to the magnitude of the field were found, but a transition either from or to an environment containing the field caused decreased red blood cell concentrations and decreased hematocrits. The failure of others to observe effects on erythrocyte parameters following exposure to low-frequency electric fields may have been due to an inappropriate choice of duration of exposure.
Portal vascular route from hypophysial stalk/neural lobe to adenohypophysis
Authors: Baertschi A. J.
Published: December 2017

Adenohypophysis, neural lobe, stalk, and median eminence are interconnected by capillary networks and portal vessels, but the directions of blood flow are not clearly understood. To test the hypothesis that peptides released from the hypothalamohypophysial tract (HHT) may reach the adenohypophysis, the HHT of anesthetized rats were stimulated electrically with 5-s trains of constant current (400 microA) biphasic impulses (0.2-1 ms) at 30 Hz, and extracellular potassium activity was recorded in various parts of the hypothalamohypophysial complex with microelectrodes (2- to 4-micrometer tip). Within HHT and neural lobe, K+ increased without delay (within 30 ms) from 2.20 +/- 0.25 (meq/l, mean +/- SE) and 2.65 +/- 0.40 to 4.50 +/- 0.60 and 7.60 +/- 0.85, respectively. Within the anterior dorsal regions of the adenohypophysis (AAH), K+ increased from 3.00 +/- 0.25 to 5.05 +/- 0.35, but with a delay of 1-4 s. Within the posterior regions of the dorsal adenohypophysis, the increase was barely significant (P < 0.1) and was delayed by 4-10 s. K+ responses in AAH to nicotine and HHT stimulation were abolished by circulatory arrest; thus K+ responses were not due to current spread or passive diffusion. Coagulation of long portal vessels did not diminish K+ responses in AHH. Results suggest that peptides released from HHT are not only secreted into the general circulation, but may reach the adenohypophysis through a portal vascular route.
Comparison of transcutaneous permeability in skins of larval and adult salamanders (Ambystoma tigrinum)
Authors: Bentley P. J. , Baldwin G. F.
Published: December 2017

The electrical properties and transcutaneous movements of Na, Cl, and water were compared (in vitro) in skins of larval and adult forms of Ambystoma trigrinum. Larval skin had a mean transcutaneous potential difference of 6 mV (inside positive) in adults it was 50 mV. Short-circuit current (Isc) was, respectively, about 2 microA x cm-2 and 20 microA x cm-2. Electrical resistances were similar. Passive effluxes of Na and Cl were similar in both forms but Na influx (active direction) was much greater in the adult. Diffusional permeability to water was less in the larval salamander skin. Influx of Na and Isc were increased by vasotocin in the adult but not larval skin. Water permeability was unaffected by vasotocin in either form. The properties of the premetamorphic skin are compared to those of two other urodele amphibians.
Comparison of the "mammal machine" and the "reptile machine": energy production
Authors: Else P. L. , Hulbert A. J.
Published: December 2017

Standard metabolism and body composition were measured in Amphibolurus nuchalis and Mus musculus (a reptile and mammal with the same weight and body temperature). The metabolic capacity for energy production was assessed in liver, heart, brain, and kidney in the lizard and mouse by two methods: measurement of mitochondrial enzyme activity (cytochrome oxidase) and measurement of both mitochondrial volume density and membrane surface area. Both methods gave a three- to sixfold greater capacity for energy production in the mammal compared to the lizard which is less than the eightfold difference in their standard metabolisms. The difference in energy production capacity was not due to any single parameter but was a summation of several smaller differences. The mammal had relatively larger internal organs than the reptile, their organs had a greater proportion of mitochondria, and their mitochondria had a greater relative membrane surface area. These differences, it is suggested, may be due in part to different thyroid function in reptiles and mammals.
Water intake elicited by injections of angiotensin II into preoptic area of rats
Authors: Richardson D. B. , Mogenson G. J.
Published: December 2017

Drinking in response to unilateral injections of angiotensin II (AII) into the preoptic area is relatively weak and a relatively high dose of AII is required. A comparison was made of the drinking elicited by bilateral and unilateral injections of AII. Reliable drinking was observed when 5 X 10(-12) mol of AII in 0.2 microliter was injected bilaterally into the preoptic area, and in some animals when the dose of AII was 0.5 X 10(-12) mol in 0.2 microliter. The volumes of water intake were significantly larger with bilateral injections compared to unilateral injections. By injection of tritiated AII to elicit drinking and subsequent autoradiographic analysis of brain sections, it was shown that the injections were confined to the preoptic region and did not reach the cerebral ventricles. The results suggest that 1) bilateral injections may be more appropriate for comparing the preoptic region with other putative angiotensin receptive sites, 2) there is a greater responsiveness of the preoptic region to bilateral as compared with unilateral injections, and 3) the AII receptive area is diffusely represented in the region of the medial preoptic nucleus.
Plasma angiotensin II concentrations and experimentally induced thirst
Authors: Johnson A. K. , Mann J. F. , Rascher W. , Johnson J. K. , Ganten D.
Published: December 2017

The systemic administration of angiotensin II or its precursors will result in increased water intake. Several manipulations that result in hypovolemia and/or hypotension (extracellular thirst challenges) are known to activate the peripheral renin-angiotensin system and also produce drinking. Although there are without question multiple mediators of thirst associated with extracellular thirst challenges, one of the major factors responsible for water intake has been hypothesized to be the action of angiotensin II. In the experimental analysis of thirst, several types of hypovolemic-hypotensive manipulations have been employed. However, there is a paucity of data available that characterize the systematic changes of angiotensin II levels following such challenges. The present studies determined plasma angiotensin II levels and drinking responses after isoproterenol administration, caval ligation, and subcutaneous polyethylene glycol treatment. The experimental protocols for treatment of the animals closely approximated conditions commonly employed in the experimental analysis of thirst. The results indicated that endogenous levels of angiotensin II increase after these treatments to levels that in all likelihood are sufficient to make a substantial contribution to the drinking response.
Seasonal changes in enzymes of aerobic heat production in the white-footed mouse
Authors: Wickler S. J.
Published: December 2017

During seasonal acclimatization in white-footed mice (Peromyscus leucopus), there is a substantial increase in the capacity for aerobic heat production under cold stress (Mmax) in winter animals. The possibility that increases in levels of enzymes involved in aerobic heat production could be responsible for the increase in Mmax was investigated in mice captured in summer and winter. Activities of citrate synthase (CS) and beta-hydroxyacyl-CoA dehydrogenase (HOAD) and concentrations of cytochrome c (cyt c) were measured in the two primary thermogenic tissues of small mammals, skeletal muscle and brown adipose tissue (BAT). Additionally, cyt c was measured in heart, liver, and whole-body samples. CS and cyt c were used as indicators of aerobic capacity, and HOAD was used to indicate the capacity for beta-oxidation. In winter CS, cyt c, and HOAD increased (expressed per g wet mass) in skeletal muscle and BAT. There was an increase in cyt c of whole-body samples, liver, and skeletal muscle of between 55 and 78%, but no change was observed in cardiac tissue. There was an approximately 80% increase in CS and HOAD in skeletal muscle. The highly aerobic nature of BAT and its primary role in heat production are supported by the high activities in summer animals and the increase observed in winter (200, 1,570, and 220% increase in CS, HOAD, and cyt c, respectively).
Regulations of intakes: clearances
Authors: Adolph E. F.
Published: December 2017

1) Intakes of substances (oxygen, food) are related to availability or concentration of the substance that is being taken from the environment. This removal accords with dimensions of clearance. 2) Intakes from limited sources, as gut or pocket, also vary with the concentrations there. 3) Reabsorptions of selected substances during excretion are intakes into body. 4) Intakes respond to bodily deficits of materials (water, sodium, heat). Wherever plasma or other concentrations are measured, intake clearances may be computed. These four relations allow quantitative comparisons of the mechanisms and regulations for transport of various substances into body or cells. Kinetic “constants” can be estimated.