bluuebunny/crossref_metadata_2025 huggingface dataset:
Upper thoracic sympathetic neuron responses to input from urinary bladder afferents
Authors: Schondorf R. , Laskey W. , Polosa C.
Published: December 2017

The aim of the present study was to evaluate the organization of neural circuitry responsible for the intersegmental transmission of input from urinary bladder afferents to sympathetic preganglionic neurons (SPNs). The electrical activity of SPNs was recorded from axons of the cervical sympathetic trunk in anesthetized central nervous system (CNS)-intact and in unanesthetized midcollicular-decerebrate or acute C1 spinal cats. In all three preparations, tonically active SPNs were excited or inhibited by 1) electrical stimulation of myelinated afferents of the pelvic or hypogastric nerve, both of which contain bladder afferents, and 2) spontaneous contraction or distension of the urinary bladder. The SPN responses to bladder distension were abolished by pelvic nerve section. A comparison of responses of SPNs in CNS-intact and acute spinal animals to electrical stimulation of pelvic nerve afferents suggests that both propriospinal and supraspinal circuits are involved in the intersegmental transmission of input from bladder afferents to SPNs.
Nascent and remnant lipoprotein turnover in rats: experimental design and simulation
Authors: Baker N. , Rostami H. J. , Elovson J.
Published: December 2017

We have attempted to predict the kinetic behavior of the complex very low-density lipoprotein (VLDL; d less than 1.006) fraction in blood plasma of rats in the steady state. Specifically we proposed a simple model with two different kinds of nascent VLDL particles derived from the liver, one containing apoprotein B (PI/II) [apoB(PI/II)], the high-molecular-weight apoB, and the other, apoprotein B (PIII) [apoB(PIII)], the low-molecular-weight apoB. Two other particles, the corresponding remnants derived from the nascent VLDL particles were also included. Then a number of feasible in vivo tracer experiments were considered in which VLDL labeled in the apoB and/or triglyceride (TG) moieties would be injected into recipient rats and the kinetic behavior of the various compartments predicted by simulation analysis. In addition the kinetic behavior of products such as free fatty acids formed during hydrolysis of labeled TG fatty acids and liver TG derived from labeled circulating remnants was considered. Both the relative sizes of nascent and remnant particles and the extent of average hydrolysis of nascent VLDL-TG (before formation of a remnant particle) were considered in our analysis. On the basis of these predictions we have suggested a number of experimental approaches that should be helpful in defining the relative pool sizes and the turnover rates of each kind of particle in vivo.
Spontaneous obesity and weight loss: insulin binding and lipogenesis in the dormouse
Authors: Melnyk R. B. , Mrosovsky N. , Martin J. M.
Published: December 2017

Obese dormice (Glis glis) become anorexic during the weight loss phase of the 2-mo (infradian) body weight cycle. We have shown previously that this phase is characterized by severe insulin resistance, manifested by impaired insulin-stimulated glucose utilization in isolated adipocytes. Contrary to other obesity models, the insulin resistance was not accompanied by hyperinsulinism. In the present study, impaired lipogenesis was associated with decreased maximal insulin-binding capacity (due to a reduction in receptor concentration) and a postreceptor defect, which were exacerbated rather than attenuated during weight loss.
Components of mucus of terrestrial slugs (Gastropoda)
Authors: Deyrup-Olsen I. , Luchtel D. L. , Martin A. W.
Published: December 2017

Mucous secretion by the body wall of the terrestrial slugs (Ariolimax columbianus, Arionidae; and other species) was found to involve at least three distinct stages--release of vesicles, formation of granules, and organization of strands. Mucus is stored intracellularly in membrane-bound vesicles, and these are shed intact from the mucous cells. Disruption of the vesicle membrane, with release of contents, can be effected by endogenous lytic agent(s), as well as by exogenous surfactants, lipid solvents, or hypotonic media. Thereupon 1-micron granules are released. These may be stable, or they may change to material that is finely granular or in the form of strands; the transition to strands is facilitated by shear stress exerted through the fluid containing the mucous components. Lectins organize, or are organized with, the strands, as evidenced by agglutination of erythrocytes on them. Mucous formation, as seen in the living slug, differs markedly from the one-step process of exocytosis of fluid mucus inferred from studies of mucous membranes fixed for ultrastructural investigation.
From intermittency to transitivity in neuropsychobiological flows
Authors: Mandell A. J.
Published: December 2017

Nonlinear dynamics offers a language for describing many aspects of brain function. Intermittency, alternating periods of periodic and chaotic behavior, and transitivity, the indecomposability of a flow, are discussed here in detail. Applications are suggested to neuropsychobiological phenomena, such as the effects of drugs and other agents.
Lipoprotein lipase activity and lipolysis after swim training in obese Zucker rats
Authors: Walberg J. L. , Greenwood M. R. , Stern J. S.
Published: December 2017

Obese and lean Zucker rats, 7 wk old, were swim trained or kept sedentary. Another group of obese rats was food restricted and exercised. Half the rats were killed after training for 8 wk, the remainder were retired and killed after an additional 8 wk. Neither treatment decreased adipocyte size in obese rats. Although basal lipolysis per cell was elevated in obese rats, their adipocytes were insensitive to epinephrine at 15 and 23 wk of age. Exercise training did not affect lipolysis. At all ages, adipose lipoprotein lipase (LPL) capacity was higher in obese relative to lean rats. In obese rats, swim training and exercise plus food restriction increased adipose and gastrocnemius LPL activity and depressed plasma insulin and triglyceride levels. All effects of exercise were transient. Thus, exercise training improved some of the metabolic disturbances in the Zucker obese rat but did not normalize adipocyte size, LPL activity, or lipolysis.
Are peptides truly satiety agents? A method of testing for neurohumoral satiety effects
Authors: Billington C. J. , Levine A. S. , Morley J. E.
Published: December 2017

Because controversy exists as to the interpretation of the known feeding-suppressive effects of various neuropeptides, we attempted to construct a model that could differentiate satiety from other nonspecific effects. Reasoning that a satiety factor should be less inhibiting of feeding in a hungrier animal, whereas aversive agents should be unaffected by hunger, we studied the neuropharmacologic dose responses of five substances administered peripherally to rats at two different degrees of starvation. Included were four neuropeptides with putative satiety effects: cholecystokinin, calcitonin, bombesin, and pancreatic polypeptide, as well as the known aversive agent lithium chloride. In the study, cholecystokinin behaved as we postulated a satiety factor would, showing significant effect of starvation at every dose and in the ANOVA. The aversive agent lithium showed overlapping among the starvation groups and no starvation effect by ANOVA. Calcitonin failed to show differences attributable to starvation. Bombesin produced some overlapping of starvation groups and a barely significant starvation effect by ANOVA. Pancreatic polypeptide produced no feeding suppression in the rat. We conclude that cholecystokinin is a short-term satiety signal and that calcitonin acts peripherally by some nonspecific nonsatiating means. Bombesin's effects are unclear but may be nonspecific.
A model eliciting transient responses
Authors: Ekblad E. B. , Licko V.
Published: December 2017

A simple parametrically controlled chemical transformation scheme is used to exemplify a model with transient response to sustained stimulation. More complicated schemes are also discussed. Analyses of three experimental examples are given: short-circuit current changes in toad bladder exposed to adenosine 3',5'-cyclic monophosphate (cAMP) stimulation; histamine secretion in acetylcholine-stimulated frog gastric mucosa; and cAMP dynamics, expressed in terms of adenylate cyclase dynamics, in histamine-stimulated frog gastric mucosa. The model responds primarily to the changes of the stimulator level, although it is not a model with derivative control.
Analysis of relative change and initial value in biological studies
Authors: Williams G. W. , Forsythe S. B. , Textor S. C. , Tarazi R. C.
Published: December 2017

In analyzing longitudinal data, the relationship between initial value (x1) and change in response to a maneuver or over time is often of interest. This relationship is often determined by the Pearson correlation between x1 and subsequent change (x2 - x1), but a correlation will often be obtained by mathematical necessity even when x1 and x2 are uncorrelated. It has been suggested that use of relative change, or (x2 - x1)/x1, avoids these mathematical artifacts. By reference to early work by Pearson (Proc. R. Soc. London 60: 489-498, 1897) on an approximation to the correlation between ratios and by computer simulations, this paper shows that this solution is frequently not valid. An alternative approach to the analysis of the relationship between x1 and relative change is presented and is illustrated by a study of renal blood flow.
Sodium handling by aging human parotid glands is inconsistent with a two-stage secretion model
Authors: Baum B. J. , Costa P. T. , Izutsu K. T.
Published: December 2017

Sodium handling by stimulated human parotid glands was evaluated in male and female subjects across the adult life-span. Young adults secreted more sodium in saliva than their middle-aged and older counterparts. To assess the extent of ductal sodium reabsorption on sodium levels calculated to be present in parotid primary secretory fluid, the relationship between sodium output and parotid saliva flow rate was analyzed. Results are inconsistent with a simple two-stage model of salivary secretion.
In vivo effect of volume expansion on rectal gland function. II. Hemodynamic changes
Authors: Solomon R. J. , Taylor M. , Rosa R. , Silva P. , Epstein F. H.
Published: December 2017

Intravascular volume expansion causes a 300% increase in the rate of fluid secretion from, and blood flow to, the in vivo rectal gland of the spiny dogfish Squalus acanthias. Similar increases are also observed in explanted rectal glands perfused through a catheter from the dorsal aorta of a volume-expanded dogfish. Stimulation of rectal gland secretion by volume expansion is not associated with a change in the ratio of chloride secreted to oxygen consumed by the rectal gland and the oxygen extraction ratio, suggesting that an increase in blood flow is necessary to support the increased rate of chloride secretion. Perfusion of the explanted gland with bumetanide (10(-4) M) completely inhibits the secretory response to volume expansion but does not prevent the increase in blood flow. Bumetanide also inhibits dibutyryl adenosine 3',5'-cyclic monophosphate- and theophylline-induced increases in chloride secretion but does not inhibit the hyperemic response. Somatostatin inhibits the secretory response of the explanted gland to volume expansion but does not prevent the increase in blood flow. Although an increase in blood flow is necessary to support the increased energy requirement of enhanced transport, the secretory response and the increase in blood flow appear to be independently regulated and mediated, at least in part, by humoral factors.
Properties and metabolism of the aqueous cytoplasm and its boundaries
Authors: Clegg J. S.
Published: December 2017

The nucleoplasm, the interiors of cytoplasmic membrane-bound organelles, and the aqueous cytoplasm make up the aqueous compartments of animal cells. The extent to which these compartments are concentrated solutions of macromolecules, metabolites, ions, and other solutes is a matter of some importance to current thinking about cell structure and function. This paper will focus on the aqueous cytoplasm. It will show that the composition and metabolic activities of the cytosol, obtained by methods of cell disruption and fractionation, bear almost no resemblance to those of the aqueous cytoplasm in intact cells. The consequences of this to contemporary views on cell structure and function are considered. A closely related topic concerns the physical properties of the dominant component of these compartments, water: Are these properties the same as those of water in aqueous solutions, or are they altered as a result of interaction with cell architecture? Available evidence strongly suggests that at least a large fraction of the total cell water exhibits properties that markedly differ from those of pure water. Selected examples of these studies will be reviewed, and the roles of cell water will be discussed, notably as they relate to metabolism and cell ultrastructure. Although dimly perceived at present, it appears that living cells exhibit an organization far greater than the current teachings of cell biology reveal.
Effects of glucagon, insulin, propionate, acetate, and HCO3 on K excretion in sheep
Authors: Rabinowitz L. , Sarason R. L. , Tanasovich C. , Mendel V. E. , Brockman R. P.
Published: December 2017

The effects on renal K excretion of 1 h intravenous infusion of glucagon, insulin, Na propionate, Na acetate, or NaHCO3 were studied in mature, conscious fasted ewes. These treatments were compared with the fasted state without treatment (control) and with feeding a single daily meal. Renal K excretion was increased by feeding and by Na propionate and Na acetate treatments but not by infusion of glucagon, insulin, and NaHCO3. Since hormone levels were elevated more by specific hormone infusions than by feeding or Na propionate infusions, these results do not support a role for glucagon and insulin in mediating the increases in renal K excretion that occurred after meals or during acetate and propionate infusions. The mechanisms responsible for the acetate- and propionate-induced kaliuresis are not clear but do not appear to include changes in plasma K (PK), glucagon, and insulin (Pinsulin) or in urine flow and urine Na excretion. However, a relation between insulin and K was observed during infusion of KCl in fasting sheep. Above a PK threshold of 4 meq/l, Pinsulin (ng/ml) = 1.52 PK (meq/l) - 5.89. In other experiments, K excretion increased after an intravenous bolus injection of 1 mg of glucagon, indicating that sheep, like humans and dogs, respond to pharmacologic doses of glucagon with kaliuresis.
Role of ion transfer processes in acid-base regulation with temperature changes in fish
Authors: Heisler N.
Published: December 2017

The contributions of transmembrane and transepithelial ion transfer processes and of nonbicarbonate buffering to the in vivo acid-base regulation have been evaluated. Model calculations were performed utilizing experimental data on transepithelial transfer of ions relevant for the acid-base regulation, the intracellular buffering properties of fish tissues, and the behavior of intracellular and extracellular pH and bicarbonate concentration with changes of temperature. The results of these studies indicate that the changes in the pK values of physiological nonbicarbonate buffers with changes in temperature support the adjustment of pH to lower values with rising temperature; however, transmembrane and transepithelial ion transfer mechanisms determine the acid-base regulation of intracellular and extracellular compartments.
Airway receptor activity in the developing opossum
Authors: Farber J. P. , Fisher J. T. , Sant'Ambrogio G.
Published: December 2017

Characteristics of airway receptor discharge were evaluated in pentobarbital-anesthetized, gallamine-paralyzed, artificially ventilated, open-chest suckling and weanling opossums (Didelphis marsupialis). Animals were tested with single-unit vagal recordings at 20, 30, 55, and 90 days of age; results were compared with previous data from adults. Rapidly adapting airway receptors ( RARs ) comprised a smaller percentage of the sampled population at 20 and 30 days of age than in older groups. The static firing properties of slowly adapting airway receptors (SARs) were examined at 0-20 cmH2O transpulmonary pressure (Ptp). At the higher Ptp levels, average receptor discharge rates increased with increasing age; these results are similar to findings in placental mammals. At 5 cmH2O, however, only the 20-day-old animals exhibited reduced rates of SAR discharge. The dynamic response of SARs in 20- and 30-day-old animals was reduced compared with adult values, as measured by the adaptation of their discharge frequencies; however, the reduction was proportional to the lower receptor firing rates. About 80% of tested SARs were inhibited by CO2 at 20 and 55 days; similar results were obtained in adults. Other results have shown that morphologic development of the vagi in opossums at 50 days of age compares with placental mammals similarly studied at birth. In contrast, the static SAR discharge in the 50-day-old opossum at low Ptp (i.e., 5 cmH2O) is similar to that observed in adults, whereas the newborn placental mammal has a greatly reduced SAR firing rate. This suggests that early utilization of the lungs can contribute to functional maturation of airway receptors.
Stimulatory and inhibitory reflexes from somatic receptors: effect on renin release
Authors: Holdaas H. , DiBona G. F.
Published: December 2017

The effect of stimulation of skeletal muscle somatic receptor afferents on renal function and renin release was examined in anesthetized dogs (bilateral carotid occlusion and vagotomy) with controlled renal arterial pressure. Afferent sciatic nerve stimulation (20–40 V, 1 ms) at 0.6–1.5 Hz elicited cardiovascular pressor responses, renal vasoconstriction, and stimulation of renin release, whereas at 0.3–0.8 Hz cardiovascular depressor responses and inhibition of renin release without changes in renal blood flow were found. Renal denervation abolished the inhibition of renin release but not the cardiovascular depressor response to afferent sciatic nerve stimulation at 20–40 V, 1 ms, and 0.3–0.8 Hz. Peripheral somatic afferent nerves contain fibers which, when appropriately stimulated, produce either pressor or depressor cardiovascular responses. At constant renal arterial pressure, increases in renin release occur with pressor responses, whereas decreases in renin release, mediated by the renal nerves, occur with depressor responses.
Intrinsic characteristics of activity: a comment on Kent's psychobiology
Authors: Smith M. R.
Published: December 2017

Kent has made seven statements that should inspire responses from linguists, kinesiologists, and developmentalists, among others. His goal of reforming our current theoretical perspective on the development of speech will be accomplished, in part, by their corrections, elaborations, and further speculations. Not all of his statements have the same status or consequence for an evolving theory of development. Those on the anatomic and neurological differences between infants and adults are much less controversial than those on the initial separateness of the perception and production systems or those on the relation of rhythmic behavior to phonology. Across all the statements, two major topics merit discussion: 1) the relevant descriptive terms of the vocal behavior of infants and 2) the relation of vocal activity to other behavior.
Common origin of linguistic and movement abilities
Authors: Bellman K. L. , Goldberg L. J.
Published: December 2017

We start with the view that the development of systems of symbols is rooted in the regulation of cellular processes and the behavior of unicellular animals. Animals would thereafter start to externalize these internal symbol systems, to coordinate movements with each other. We propose that the brains of multicellular animals can be understood as a continuing elaboration of the early chemical symbol systems of unicellular animals: the labile symbols of the unicellular animal are replaced by hormones, more stable chemical compounds, and nerves that are seen as more stable and more specific routes of activation; and brains developed layers of symbols such that the domain of a symbol is not a set of bodily processes but rather a set of brain processes. Human language is very much in the “style” of the rule-governed symbol manipulation required by all behaving animals, although unique in its complexity. We suggest that the essential question is not how humans have evolved symbolic and linguistic abilities from a primitive sensorimotor brain but rather how do symbols come to exist in biological systems and what is useful and necessary about a system of symbols for the coordination of action within animals and among animals.
A linguist's view of the Bellman-Goldberg thesis
Authors: Smith M. R.
Published: December 2017

From a linguistic perspective, the Bellman-Goldberg thesis of a necessary relationship between the abilities of organisms to move and communicate is very interesting. Since several concepts and terms are represented in both the thesis and contemporary linguistic literature, these items are discussed in further detail. Questions of the implicit assumptions of the homology of the motor and linguistic systems are also raised here. Finally, there are requests for further clarification on issues of evolution in this test of the strength of the thesis.
Intrinsic emptying pattern of the human stomach
Authors: Smith J. L. , Jiang C. L. , Hunt J. N.
Published: December 2017

Twenty-three subjects were given a total of 336 meals of 750 ml saline that was recovered at 5, 10, and 20 min to determine the intrinsic gastric emptying pattern. Minimal slowing of gastric emptying by duodenal receptors resulted from 120 mM NaCl. Analysis of the residuals from the within-subject regressions for every subject's remaining volume vs. time showed that the exponential model of gastric emptying most appropriately described the data when the volume instilled at time 0 was included.
Adipocyte blood flow: influence of age, anatomic location, and dietary manipulation
Authors: Crandall D. L. , Goldstein B. M. , Huggins F. , Cervoni P.
Published: December 2017

Adipocyte blood flow in four distinct adipose tissue depots has been measured in conscious, unrestrained, male Sprague-Dawley rats by using the microsphere technique together with cellularity determinations. Blood flow was determined in young rats (90 days old, 387 g mean body wt), spontaneously obese rats (450 days old, 713 g mean body wt), and long-term calorically restricted rats (450 days old, 390 g mean body wt), therefore allowing the comparison of the relative effects of age and fat mass on adipose tissue blood flow. Results of these experiments indicate that while cardiac index remained constant, cardiac output increased in only the obese group, concomitant with increased body fat mass. Spontaneously obese rats exhibited increased adipose tissue depot weight, fat cell lipid, and fat cell size compared with young and restricted groups. Despite significant differences in cell volume, blood flow per cell was remarkably similar between young and obese rats. Long-term caloric restriction, however, was associated with decreased flow per cell. Interdepot comparisons of flow per unit surface area (mm2) or per unit volume (pl) indicate that mesenteric cells receive significantly more blood than cells of the other depots. Our results suggest that adipocyte blood flow is dependent in part on anatomic location, may be further influenced by age or dietary manipulation, and is not a limiting factor in the enlargement of adipocytes during the development of spontaneous obesity.
Hemodynamic effects of weight reduction in the obese rat
Authors: Crandall D. L. , Goldstein B. M. , Gabel R. A. , Cervoni P.
Published: December 2017

The effect of defined increments of weight loss on hemodynamics has been investigated in conscious, unrestrained, spontaneously obese rats. Obese rats were subjected to a calorically restricted diet and were used for experimentation on achieving a 10, 20, or 30% reduction in body weight. After monitoring resting blood pressure and heart rate, radioactive microspheres were infused for determination of blood flow distribution. Of 10 organs sample, only heart, liver, kidneys, and 2 adipose tissue depots exhibited significant decreases in weight associated with body weight reduction. Mean arterial blood pressure remained unchanged, while stroke volume, left ventricular work, and cardiac output decreased significantly. Blood flow decreased to kidneys, testes, and adipose tissue through a 30% reduction in body weight, but the fractional distribution of cardiac output decreased only to adipose tissue. Therefore the large decreases in renal and adipose tissue blood flow during weight reduction may contribute to the associated decrease in cardiac output. Of those vascular beds examined, however, both absolute and relative blood flow decreased only to adipose tissue, thus denoting the influence of fat mass on hemodynamics during obesity.
Suppression of food intake by intravenous nutrients and insulin in the baboon
Authors: Woods S. C. , Stein L. J. , McKay L. D. , Porte D.
Published: December 2017

Intravenous nutrients were infused at 25 and 50% of total base-line daily caloric intake to determine the role of circulating factors on spontaneous food ingestion in young adult male baboons (Papio cynocephalus). Glucose infusion suppressed food intake (15.1%) when 25% of total calories was infused (P less than 0.05) and 41.8% when 50% of total calories was infused (P less than 0.05) for 14-21 days. Both infusions produced basal hyperglycemia (82-172 mg/dl during 25% glucose and 120-239 mg/dl during 50% glucose). Both infusions also caused an increase in circulating insulin (48.1-63.1 microU/ml during 25% glucose and 68.5-77.2 microU/ml during 50% glucose). The simultaneous infusion of exogenous insulin (0.33 mU X kg-1 X min-1) prevented hyperglycemia (85.8-87.9 mg/dl during 25% glucose) but maintained raised basal peripheral insulin levels (52.4-84.4 microU/ml). The 13% suppression of food intake (P less than 0.05) was similar to glucose infusion alone. Comparable infusions of Intralipid as 25 and 50% of total daily calories also suppressed spontaneous food intake but did not produce hyperglycemia or elevated insulin levels. The magnitude of suppression was similar to that of glucose: 16% when 25% of basal calories was infused (P less than 0.05) and 31.3% when 50% of basal calories was infused (P less than 0.05). However, the pattern was different with a more rapid effect, which tended to diminish in time, rather than the slow effect found with glucose, which was maintained for 14 days. We conclude that circulating nutrients can regulate food intake independent of gastrointestinal absorption in primates.(ABSTRACT TRUNCATED AT 250 WORDS)
Castration prolongs tolerance of young male rats to pulmonary O2 toxicity
Authors: Neriishi K. , Frank L.
Published: December 2017

We tested the hypothesis that the normal loss of tolerance of neonatal rats to prolonged hyperoxic exposure at around 1 mo of age might be related to the marked increase in sex hormones occurring around this period. Male rats castrated at 20 days of age demonstrated significantly increased survival in greater than 95% O2 compared with sham-operated rats when exposed to high O2 at various ages greater than 45 days [castrated, 115 of 166 (69%) vs. sham, 59 of 156 (38%) (P less than 0.001)]. Testosterone replacement led to survival rates comparable with sham-operated rats [30 of 87 (34%)]. No such protective effect was observed in female rats [survival: ovariectomy, 16 of 33 (48%) vs. sham, 14 of 28 (50%)]. The improved survival in the older castrated males was not associated with an increase in lung antioxidant enzymes, which is normally seen in O2-tolerant neonatal rats. Castration did result in marked morphological lung changes, including significantly enlarged lung volumes (4.54 +/- 0.72 vs. 3.76 +/- 0.29 ml/100 g) and terminal air spaces [mean linear intercept (LM) = 51.6 +/- 5.0 vs. 46.3 +/- 4.1 micron (P less than 0.001)]. Testosterone replacement also prevented these morphological changes. The altered lung growth 1) may be related to the influence of other endocrine imbalances after castration and 2) may be an important factor in the relative O2 tolerance of the castrated male rats beyond the neonatal period.
Computer modeling identifies glucokinase as glucose sensor of pancreatic beta-cells
Authors: Garfinkel D. , Garfinkel L. , Meglasson M. D. , Matschinsky F. M.
Published: December 2017

Previous work from this laboratory indicates that glucokinase serves as the glucose sensor of pancreatic islets. Here we show by nonlinear computer optimization that the kinetic properties of glucokinase (together with hexokinase, known to be present in islets) account for the observed glycolytic rates in islets as a function of glucose level. Alternative enzymes that have been suggested to perform the same function as glucokinase, N-acetyl-D-glucosamine kinase and glucose-6-phosphatase, are shown to have incompatible properties, including a poor fit, different curve shapes, and unreasonable parameter values resulting from optimization. Their activities in islets are shown to be too low to account for observed glucose usage rates. This work endorses our previous proposal that glucokinase acts as the glucose sensor in pancreatic islet cells.
Relationship between type L hormone-sensitive lipase and endogenous triacylglycerol in rat heart
Authors: Miller W. C. , Oscai L. B.
Published: December 2017

The purpose of this study was to determine whether, under physiological conditions, intracellular lipoprotein lipase [type L hormone-sensitive lipase (HSL)] activity varied inversely with triacylglycerol (TG) content of the heart. The results show that fasting from 7:30 A.M. to 7:30 P.M. increased type L HSL activity from 72 +/- 1 to 96 +/- 1 U/g wet wt tissue (P less than 0.001) in the myocardium. At the same time, cardiac TG stores decreased from 1.83 +/- 0.03 to 1.37 +/- 0.01 mumol/g tissue (P less than 0.001). In a separate experiment, one night of eating a fat-rich diet (60% of calories from fat) caused a 42% increase in type L HSL activity, which was accompanied by a 42% reduction in the TG content of the heart. Likewise cold exposure (overnight) activated type L HSL (73%) and, at the same time, decreased cardiac TG stores (44%). When data from the fasting, fat-feeding, and cold-exposure experiments were combined, a significant correlation coefficient of -0.81 was obtained between type L HSL activity and TG content of the heart (P less than 0.001). These data provide evidence for a physiological relationship between intracellular lipoprotein lipase activity and cardiac TG content.
Quantitation of reticuloendothelial iron kinetics in humans
Authors: Stefanelli M. , Bentley D. P. , Cavill I. , Roeser H. P.
Published: December 2017

Reticuloendothelial iron kinetics were investigated in a simultaneous dual-isotope study in 10 healthy adult subjects in whom 55Fe-ferric hydroxide phosphate colloid was used to label the reticuloendothelial iron pools, and 59Fe-transferrin was used to define plasma iron kinetics. The simultaneous clearance of 55Fe and 59Fe from plasma and the uptake of each into red blood cells were measured over 14 days. The 55Fe-colloid was cleared almost immediately, and its iron was rapidly released to bind to plasma transferrin. Red cell incorporation of 55Fe was, however, much slower than that of 59Fe bound to transferrin in vitro. The data were analyzed by a new model of reticuloendothelial iron metabolism that contained two reticuloendothelial iron pools; one had a rapid turnover and donated iron to transferrin, and the other, a storage pool, had a slower turnover. The transit pool contained a mean of 164 mumol iron with little variation between subjects, whereas the storage pool was somewhat larger (mean 873 mumol iron) and showed more marked variation between subjects. In general an equal proportion of the iron leaving the transit pool went to transferrin and to the storage pool. The distribution between the two routes did not appear to be related either to plasma iron concentration, latent iron-binding capacity, or transferrin saturation.
Effect of inflammatory agents and interleukin 1 on iron and zinc metabolism
Authors: Klasing K. C.
Published: December 2017

Injection of either sheep red blood cells (SRBC), Escherichia coli, endotoxin, starch, or Sephadex into chicks significantly decreased plasma iron and zinc concentrations. After injection of E. coli or SRBC, plasma zinc was decreased maximally by 52% at 12 h and 15.7% at 48 h, respectively. A second exposure to SRBC or E. coli did not further decrease plasma iron or zinc. Injection of a crude preparation of interleukin 1 isolated from endotoxin-stimulated peritoneal monocytes induced hypozincemia, hypoferremia, increased the concentration of liver metallothionein, and increased liver-zinc concentrations. It is proposed that interleukin 1 mediates the changes in trace mineral metabolism that occur during inflammation and that loss of zinc from plasma is due in part to a sequestration of zinc by liver.
Scapular brown fat removal enhances development of adiposity in cold-exposed obese Zucker rats
Authors: Stern J. S. , Inokuchi T. , Castonguay T. W. , Wickler S. J. , Horwitz B. A.
Published: December 2017

To investigate the contribution of brown fat (BAT) to the development of obesity in genetically obese Zucker rats (fa/fa), scapular brown fat (SBAT) was removed from obese and lean 4-wk-old females. Eight weeks after surgery there was no regrowth of SBAT. Lipectomy had no effect on body weight gain, food intake, and body composition when rats were housed at 25 degrees C. Lean rats completely compensated for the lipectomy by increasing BAT mass, protein, cellularity, and activity of citrate synthase (CS) in axillary, perirenal, and thoracic depots. beta-Hydroxyacyl-coenzyme A dehydrogenase (HOAD) activity was increased, but compensation was incomplete. In lipectomized obese rats, only BAT protein and cell number were increased sufficiently for complete compensation. In a second experiment SBAT was removed from obese and lean rats, but rats were housed in the cold (10 degrees C) for 8 wk. In lean rats, although compensation was incomplete, it was sufficient to maintain a weight gain and body composition comparable with sham-operated lean rats. In obese rats, where there was little or no compensation for lipectomy, weight gain and fat deposition were greater than observed in sham-operated obese controls. These data support the hypothesis that reducing the amount of functional BAT contributes to the development of increased adiposity.
Homeostatic capability of rate-sensitive feedback system: mathematical model
Authors: Okamoto M. , Hayashi K.
Published: December 2017

We have predicted the mathematical model of rate-sensitive feedback control system and have investigated its homeostatic capability by using computer simulations. The results are summarized as follows. By installing a cyclic enzyme system as feedback control element, we could assume the rate-sensitive feedback system at molecular level. This type of feedback had realistic constant-value control capability for external perturbations. This feedback system was more effective for the exclusion of perturbation than was the concentration-sensitive feedback. A large-loop feedback was more stable for perturbation than was short-loop feedback. In sequential feedback system, every key enzyme sensitive to feedback control had to vary the activity at same time for the system to keep homeostasis.
Exogenous vasopressin reverses hyperactivity in the hypothalamus of Brattleboro rats
Authors: Krukoff T. L. , Calaresu F. R.
Published: December 2017

We have previously described an increase of cytochrome oxidase (COX) activity in discrete hypothalamic nuclei of the Brattleboro rat (BR). The present experiments were done to investigate whether this increase in COX activity could be eliminated by administration of exogenous arginine vasopressin (AVP). Continuous infusion of AVP to BR for 7 days corrected the polyuria and the urine hypoosmolality, as expected, and it also eliminated the COX hyperactivity in the paraventricular nucleus and nucleus circularis of the BR hypothalamus. These results suggest that the hyperactivity of these nuclei in the BR is directly related to their inability to produce AVP.
Central indomethacin enhances volume-dependent vasopressin release
Authors: Brooks D. P. , Share L. , Crofton J. T. , Nasjletti A.
Published: December 2017

The effect of centrally administered indomethacin on hemorrhage-induced vasopressin release was studied in the morphine-sedated, urethan/chloralose-anesthetized dog. Ventriculocisternal perfusion of indomethacin 1) significantly reduced the amount of prostaglandin E2 in the effluent from the cisterna magna, 2) significantly enhanced the vasopressin response to volume depletion, and led to a greater fall in mean arterial blood pressure during severe hemorrhage. The results suggest that central prostaglandins may have an inhibitory effect on vasopressin secretion during volume depletion.
Contribution of activation-inactivation dynamics to the impairment of relaxation in hypoxic cat papillary muscle
Authors: Pasipoularides A. , Palacios I. , Frist W. , Rosenthal S. , Newell J. B. , Powell W. J.
Published: December 2017

Previous investigation of conventional isometric twitches of normothermic cat papillary muscle has shown that hypoxia prolongs relaxation, and this prolongation is actually accentuated during early reoxygenation. Our aim was to identify how hypoxia and reoxygenation affect the coupled processes of activation and inactivation that govern the time course of internally generated contractile tension (Ti). Activation and inactivation are modeled as first-order processes with rate constants ka and ki, respectively, and the overall isometric muscle as an underdamped second-order lag system driven by Ti. The analytical expression (To) for the externally recorded tension is dominated by two exponential terms incorporating ka and ki. Accurate least-squares fits of digitized twitches to To yielded estimates of ka and ki at 1- to 3-min intervals during control oxygenation, hypoxia, and early and late reoxygenation. Results follow. Compared with control, normothermic hypoxia prolonged activation [at 15 min ka decreased 61% from control, 35.5 +/- 6 (SE) s-1, P less than 0.05] and accelerated inactivation (at 15 min, ki increased 69% from control, 6.0 +/- 0.5 s-1, P less than 0.05). In early reoxygenation (1-3 min) activation remained impaired and inactivation returned to control levels (ki decreased 16% from control, NS). In late reoxygenation (15 min) both processes reverted to control. Thus inactivation kinetics can be dissociated from activation kinetics. Impaired relaxation in normothermic hypoxia is due to prolonged activation, whereas inactivation is actually accelerated. The further impairment of relaxation in early reoxygenation is due to rapid return of inactivation to control at a time when activation is still prolonged.
Insulin hypoglycemia, cerebral metabolism, and neural function in fetal lambs
Authors: Richardson B. S. , Hohimer A. R. , Bissonnette J. M. , Machida C. M.
Published: December 2017

The effect of insulin-induced hypoglycemia on cerebral oxidative metabolism (CMRO2) was studied in nine late gestational fetal lambs using the radiolabeled microsphere technique for cerebral blood flow and brachiocephalic to sagittal sinus blood O2 content differences. After 4 h insulin infusion to the fetus, arterial glucose fell from control levels of 0.96 +/- 0.11 (SE) to 0.69 +/- 0.09 mmol X l-1. CMRO2 was reduced from 199 +/- 23 to 155 +/- 22 mumol X 100 g-1 X min-1 (P less than 0.05), and cerebral glucose uptake fell from 31 +/- 4 to 25 +/- 4 mumol X 100 g-1 X min-1 (P less than 0.02). During both euglycemia and hypoglycemia, 6 mumol glucose were taken up for each micromole of O2, indicating that glucose was the sole metabolic substrate for oxidative metabolism. Although there was no change in fetal electrocortical activity during the hypoglycemia, fetal breathing movements were present only 19.4 +/- 3.4% of the hypoglycemic hours compared with 36.8 +/- 2.6% of the control period (P less than or equal to 0.01). These results suggest that during rapidly induced fetal hypoglycemia, blood-brain barrier transport of glucose can limit cerebral glucose and O2 uptake, and this decrease in cerebral metabolism is associated with a lowered incidence of fetal breathing movements.
alpha-Aminoisobutyric acid transport in rat soleus muscle during endotoxic shock
Authors: Karlstad M. D. , Sayeed M. M.
Published: December 2017

We studied alpha-aminoisobutyric acid (AIB) transport by skeletal muscle and the effect of insulin and Na+ on the transport process during endotoxic shock. Rats (140–160 g) were injected with Salmonella enteritidis endotoxin (20 mg/kg iv) or saline and killed 5 h later. At that time an elevation of blood lactate and hypoglycemia marked the onset of shock in rats given endotoxin. AIB uptake was measured in isolated soleus muscles in vitro. Total cellular AIB uptake in the endotoxic muscles was 25, 28, and 47% lower than control muscles at 1-, 2-, or 3-h incubations, respectively. Insulin stimulated AIB uptake to a lesser extent in endotoxic muscles (from a basal value of 11.62 +/- 0.29 nmol X g dry wt-1 X 3 h-1 to 15.88 +/- 0.64, 19.10 +/- 1.06, and 18.78 +/- 0.52 at 1, 10, and 100 mU/ml insulin, respectively) than in controls (from 17.07 +/- 0.51 to 27.13 +/- 1.16, 27.25 +/- 0.93, and 29.01 +/- 1.09). Na+-dependent AIB uptake, calculated as the difference between AIB uptake in the presence and absence of Na+, was decreased in the endotoxic muscles to 36% of the control value. Na+-independent AIB uptake (measured in Na+-free media) was the same in control and endotoxic muscles. These results suggest that the decrease in both basal and insulin-stimulated AIB transport was due to the decrease in Na+-dependent AIB transport by skeletal muscle during endotoxic shock.
Effects of intragastric hyperalimentation on pair-fed rats with ventromedial hypothalamic lesions
Authors: Walgren M. C. , Powley T. L.
Published: December 2017

The present study was undertaken to determine the relative contributions of altered metabolic responses and excess food intake to the obesity and hyperinsulinemia of the ventromedial hypothalamic (VMH) syndrome. This experiment, employing an intragastric hyperalimentation protocol, was also designed to address the related issue of whether altered energy utilization serves as a compensatory strategy for reducing energy retention in the face of excess intake. Separate groups of VMH-lesioned and sham-lesioned female rats were fed, either orally or intragastrically, up to 200% of the calories ingested by a normally feeding intact rat. Both VMH-lesioned and intact rats became obese and hyperinsulinemic when hyperalimented for 30 days, but rats with lesions deposited 25% more fat than intact animals receiving an identical number of calories. Estimates of total carcass energy indicated that rats with lesions required 11% less calories than intact rats to retain identical levels of energy. Furthermore, intact hyperalimented rats failed to evidence the caloric wastage that has been reported to occur in orally fed rats that overeat cafeteria diets.
Neural projections from paraventricular nucleus that subserve vasomotor functions
Authors: Porter J. P. , Brody M. J.
Published: December 2017

Descending projections from the paraventricular nucleus of the hypothalamus (PVN) either terminate in the dorsal medulla or pass through the ventrolateral medulla to terminate in the intermediolateral column of the spinal cord. We sought to determine whether a cardiovascular function is subserved by these pathways. Electrical stimulation of the PVN in urethan-anesthetized rats produced increases in blood pressure and mesenteric and renal vascular resistances while hindquarter resistance decreased. This integrated cardiovascular response appeared to be neurogenically mediated because it was virtually abolished by ganglionic blockade and unaffected by blockade of peripheral vascular vasopressin receptors. Adrenal catecholamines appeared to contribute since adrenalectomy reduced the response, especially the hindquarter vasodilation. Interruption with a knife cut of the PVN-dorsal medullary pathway did not affect the response to PVN stimulation except for hindquarter vasodilation, which was reduced significantly. Interruption of the PVN-ventrolateral medullary pathway by local microinjection of lidocaine blocked the pressor and vasoconstrictor responses to PVN stimulation but enhanced the hindquarter vasodilation. These data suggest that fibers descending from the PVN responsible for skeletal muscle vasodilation pass to or through the dorsal medulla, whereas efferent vasoconstrictor pathways from the PVN appear to course through, or synapse in, the ventrolateral medulla.
Mammals: an allometric study of metabolism at tissue and mitochondrial level
Authors: Else P. L. , Hulbert A. J.
Published: December 2017

Body composition, mitochondrial volume density, and mitochondrial membrane surface area were measured in six species of mammals representing a 100-fold weight range (18-2,067 g). The mammals examined included three eutherian species, two marsupial, and one monotreme species. The tissues examined were liver, kidney, brain, lung, heart, and skeletal muscle (gastrocnemius). Allometric equations were derived for tissue weight, and the allometric exponents ranged from 0.69 (brain) to 1.01 (skeletal muscle). Allometric relationships for mitochondrial membrane surface area were also determined both per milliliter tissue and per total tissue. Small mammals had a higher mitochondrial membrane surface area per milliliter tissue than large mammals in all tissues examined. These differences were significant in liver, kidney, brain, and heart. Total mitochondrial membrane surface area per tissue had allometric exponents ranging from 0.55 (kidney) to 0.78 (skeletal muscle). When total mitochondrial membrane surface area was summated for the major internal organs examined (liver, kidney, heart, and brain), the allometric equation was mitochondrial membrane surface area (m2) = 3.04 body wt0.59 (g). This was similar to the exponent of standard metabolic rate against body weight in the species examined (i.e., 0.62). The inclusion of skeletal muscle and lung into the summated mitochondrial membrane surface area increased the exponent to 0.76. This is compared with the relationship between maximal O2 consumption and body size in mammals.