bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration and regulation of cardiovascular function.
Authors: Hall J E
Published: December 2017

New methods in molecular biology and genetics have made possible many of the dramatic advances in physiological research that have occurred in recent years. For those of us who spend most of our time in the research laboratory, it si sometimes difficult to avoid a research-oriented, reductionist mind-set when discussing physiology with students. This article illustrates, with a few examples, the importance of conveying a "big picture" conceptual framework before discussing the details of cardiovascular physiology. Also, I have chosen examples from cardiac output and blood pressure regulation that show the importance of discussing cardiovascular physiology in terms of feedback control systems and integrating information from other areas, such as renal and endocrine physiology. Finally, I have highlighted the importance of two principles that I believe are often underemphasized in teaching physiology: mass balance and time dependence of physiological control systems.
Teaching the principles of hemodynamics.
Authors: Belloni F L
Published: December 2017

Knowledge of hemodynamic principles is crucial to an understanding of cardiovascular physiology. This topic can be effectively taught by discussing simple physical principles and basic algebraic equations. A variety of examples from everyday observations can be used to illustrate the physical principles underlying the flow of blood through the circulation, thereby giving the student an experiential feel for the topic in addition to an understanding of theory. Moreover, opportunities abound for showing how each hemodynamic principle can explain one or another functional feature of the cardiovascular system or a cardiovascular pathophysiological state. Thus hemodynamics can be used as an organizational thread to tie together other aspects of cardiovascular physiology.
Biomedical device design discovery team approach to teaching physiology to undergraduate bioengineering students.
Authors: Cudd T A , Wasser J S
Published: December 2017

Teaching effectiveness is enhanced by generating student enthusiasm, by using active learning techniques, and by convincing students of the value of acquiring knowledge in the area of study. We have employed a technique to teach physiology to bioengineering students that couples students' enthusiasm for their chosen field, bioengineering, with an active learning process in which students are asked to design a biomedical device to enhance, replace, or create a new cellular or organ system function. Each assignment is designed with specific constraints that serve to direct students' attention to specific areas of study and that require students to create original designs. Preventing students from using existing designs spurred student invention and enthusiasm for the projects. Students were divided into groups or "design discovery teams" as might be done in a biomedical device industry setting. Students then researched the physiological issues that would need to be addressed to produce an acceptable design. Groups met with faculty to brainstorm and to obtain approval for their general design concepts before proceeding. Students then presented their designs to the instructors in a structured, written outline form and to the class as a 10-minute oral presentation. Grades were based on the outline, oral presentation, and peer evaluations (group members anonymously rated contributions of other members of their team). We believe that this approach succeeded in generating enthusiasm for learning physiology by allowing the students to think creatively in their chosen field of study and that it has resulted in students developing a more thorough understanding of difficult physiological concepts than would have been achieved with a traditional didactic lecture approach.
Construction of a model demonstrating cardiovascular principles.
Authors: Rodenbaugh D W , Collins H L , Chen C Y , DiCarlo S E
Published: December 2017

We developed a laboratory exercise that involves the construction and subsequent manipulation of a model of the cardiovascular system. The laboratory was designed to engage students in interactive, inquiry-based learning and to stimulate interest for future science study. The model presents a concrete means by which cardiovascular mechanics can be understood as well as a focal point for student interaction and discussion of cardiovascular principles. The laboratory contains directions for the construction of an inexpensive, easy-to-build model as well as an experimental protocol. From this experience students may gain an appreciation fo science that cannot be obtained by reading a book or interacting with a computer. Students not only learn the significant physiological concepts but also appreciate the importance of laboratory experimentation for understanding complex concepts. Model construction provides a hands-on experience that may substantially improve performance in science processes. We believe that model construction is an appropriate method for teaching advanced concepts.
Amino acid metabolism of dog jejunum before and during absorption of keto analogues.
Authors: Weber F L , Maddrey W C , Walser M
Published: December 2017

In fasting dogs, significant uptake by the jejunal wall from arterial blood was found for glutamine and eight other amino acids. Significant release into the mesenteric vein of ammonium, alanine, citrulline, and proline occurred, equal in nitrogen content to glutamine nitrogen taken up. The keto analogues of leucine, valine, and isoleucine, infused for 1 h into the lumen at initial concentrations of 10mM, disappeared from the lumen at 20.2 +/- 1.6, 18.6 +/- 2.0, and 15.7 +/- 2.8 mumol/cm in 1h, respectively. Eight fifteen and seventeen percent, respectively, of these absorbed quantities were released into mesenteric blood as leucine, valine, and isoleucine plus alloisoleucine, indicating significant amination of the keto acids by the gut wall. No significant changes were detected in the arteriovenous differences of any other amino acids or ammonium. The remainder of the absorbed analogues of valine and isoleucine appeared as such in the blood. In the case of the keto analogue of leucine, there was apparent degradation by the gut wall of 34% of the absorbed compound.
[3H]inositol incorporation into phosphatidyl-inositol in work-induced growth of rat muscle.
Authors: Jablecki C , Dienstag J , Kaufman S
Published: December 2017

Unilateral tenotomy of the gastrocnemius muscle in normal rats caused rapid hyptertrophy of the soleus and plantaris muscles. The phospholipid content of hypertrophied muscles increased; the increase was proportional to the extent of hypertrophy and was distributed proportionally among the major phospholipid components. During the growth process, the hypertrophying muscles incorporated [3H]inositol into phosphatidyl-inositol more rapidly than did the contralateral, control limb muscles. The increased incorporation was evident 2 h after the operation and cannot be explained solely by an increased uptake of [3H]inositol. After growth had ceased, the incorporation of [3H]inositol into phosphatidyl-inositol gradually returned toward control levels. The increase in incorporation after tenotomy was prevented by simultaneous spinal section to abolish activity in the tenotomized limb muscles. By contrast, in rats that had been forced to swim for prolonged periods of time, there was no increased incorporation of [3H]inositol into phosphatidyl-inositol. It is concluded that the increased incorporation of [3H]inositol into phosphatidyl-inositol is related to increased muscle activity sufficient to produce compensatory hypertrophy.
Intracellular pH in hypoxic smooth muscle.
Authors: Stephens N L , Kroeger E A , Loh W
Published: December 2017

Hypoxia impairs contractility in canine tracheal smooth muscle (TSM). This is attributed to intracellular lactacidosis. The present studies were undertaken to confirm this. Lactate was found to be significantly increased in hypoxic TSM (65.36 +/- 7.37 mg/100 g wet tissue), compared to normoxic (29.83 +/- 5.05). Intracellular pH (pHi) was, however, significantly increased in hypoxic active TSM to 7.71 +/- 0.05 as compared to 7.30 +/- 0.03 in normoxic active muscle. pHi of resting normoxic muscle (7.20 +/- 0.04) was statistically not different from that of resting hypoxic muscle. The pHi's of resting normoxic and active hypoxic muscles were significantly different. These results show that under in vitro, hypoxic conditions: 1) an increase in glycolysis in TSM is indicated by the increased lactate production, 2) there is a surprising, concomitant rise in pHi rather than a decrease as previously expected, and 3) it is mechanical activity of the muscle which leads to this paradoxical result, inasmuch as pHi is unaltered in the resting hypoxic muscle.
Kinetic analysis of iodide transport in dog thyroid slices: perchlorate-induced discharge.
Authors: Rocmans P A , Penel J C , Cantraine F R , Dumont J E
Published: December 2017

Dog thyroid slices were incubated with methimazole (2 mM) and radioiodide. The medium radioactivity was continuously recorded for 8 h. Multiple data were collected for individual glands to calculate simultaneously by compartmental analysis the influx and efflux rates of iodide from the slices. A two-compartment thyroid model was necessary and sufficient to simulate the transport of inorganic iodide. The two compartments could be defined as the cellular and the luminal spaces, but interferences due to slice thickness, nonuniform follicle sizes, and open follicles were not excluded. Sodium perchlorate (1 mM) inhibited the influx of iodide into the follicles and discharged the trapped radioiode into the medium with increased efflux rates. Our data suggest that perchlorate decreases the inward influx rates by competition and enhances the outward efflux rates by countertransport and support the hypothesis of mobile iodide carriers at the basal and apical membranes of the thyroid cells.
Pulmonary fatty acid synthesis. I. Mitochondrial acetyl transfer by rat lung in vitro.
Authors: Evans R M , Scholz R W
Published: December 2017

Incorporation of tritiated water into fatty acids by rat adipose tissue and lung tissue slices incubated with 5 mM glucose indicated a level of fatty acid synthesis in rat lung approximately 15% that observed in adipose tissue in vitro. (-)-Hydroxycitrate, and inhibitor of ATP citrate lyase, markedly reduced tritiated water incorporation into fatty acids by lung tissue slices. The effects of (-)-hydroxycitrate and n-butymalonate on the incorporation of 14C-labeled glucose, pyruvate, acetate, and citrate suggested that citrate is a major acetyl carrier for de novo fatty acid synthesis in lung tissue. Alternative mechanisms to citrate as an acetyl carrier were also considered. Lung mitochondrial preparations formed significant levels of acetylcarnitine in the presence of pyruvate and carnitine. However, the effect of carnitine on the incorporation of 14C-labeled glucose, pyruvate, acetate, and citrate into fatty acids by lung tissue slices indicated that acetylcarnitine may not be a significant acetyl carrier for fatty acid synthesis but may serve as an acetyl "buffer" in the control of mitochondrial acetyl-CoA levels. Additionally, it appears unlikely that either acetylaspartate or acetoacetate are of major importance in acetyl transfer in lung tissue.
Dependence of pulmonary prostaglandin metabolism on carrier-mediated transport processes
Authors: Bito L. Z. , Baroody R. A. , Reitz Mary E.
Published: December 2017

Inhibitors of prostaglandin (PG) transport (probenecid, indomethacin, or bromcresol green) were found to eliminate the difference between the pulmonary transit time of 3H and 14C when [3H]PGF2alpha and E114C]sucrose were injected as a single intra-arterial bolus into the isolated perfused rat lung. Similar results were obtained with PGE1. The transit time of [3H]PGA1 was not significantly different from that of [14C]sucrose even in the absence of an inhibitor. These inhibitors increased the amount of [3H]PGF2alpha or [3H]PGE1 and decreased the amount of [3H]PG metabolites found in the venous effluent: these agents also inhibited the pulmonary metabolism of continously infused, nonradioactive PGF2alpha. One of the three inhibitors, bromcresol green, was shown not to be an effective inhibitor of PG metabolism in cell-free preparations of rat lung homogenates. These results indicated that under normal conditions, PG's are rapidly transported into intracellular compartment(s) where they are metabolized. Inhibition of this transport process prevents rapid access of PG's to the cytoplasmic enzymes and therefore inhibits pulmonary PG metabolism. This implies that inhibitors of PG transport, including anti-inflammatory organic acids, and some PG antagonists, metabolites, and analogues, can be expected to inhibit the pulmonary metabolism of PG's and thus could potentiate the systemic effects endogenous or exogenous PG's.
Metabolic features of isolated rat lung cells. I. Factors controlling glucose utilization.
Authors: Pérez-Díaz J , Martín-Requero A , Ayuso-Parrila M S , Parrilla R
Published: December 2017

Isolated rat lung cell suspensions were prepared by collagenase digestion of the lung stroma. These cells were functionally competent as judged, among other criteria, by their constant rates of oxygen uptake and glucose utilization. An important metabolic feature of these cells is that they display very high glycolytic rates. At least 60% of the glucose utilized was converted to lactate, regardless of the glucose concentration in the medium. The state of reduction of the nicotinamide system, as indicated by the lactate-to-pyruvate ratio, was normal, thus indicating that the high glycolytic fluxes are not related to poor oxygenation of the preparation. Utilization of glucose displayed Michaelis-Menten saturation type kinetics with a Vmax of 331 nmol/10(6) cells per h and an apparent Km of 2.4 mM. These values were not affected by the presence of ouabain (0.1 mM), mannoheptulose (5 mM), or insulin (1 mU/ml), whereas phloridzin produced a drastic inhibition of glucose utilzation showing an apparent Ki of 0.4 mM. The substitution of sodium by K+ or Li+ as the predominant cations in the incubation medium does not alter rates of glucose utilization. Optimal pH for glucose utilization was within the physiological range with a more pronounced inhibitory effect at alkaline pH's. The intracellular concentration glucose was found to be low. This finding, in conjunction with a Q10 (27-37 degrees C) for glucose utilization above 2.0 and the differential effects of D- and L-glucose on production, seems to indicate that a stereospecific glucose transport system exists in lung cells. Several findings point to glucose transport into the lung cells as a probable rate-limiting step for its metabolism:1) the activity of the glycolytic enzymes largely exceeded the observed rate of glucose utilization;2) the decrease in enzyme activity during starvation was not accompanied by a decreased glycolytic flux, suggesting that factors other than enzyme activity, perhaps the supply of fuel, are rate limiting in the overall process of glucose breakdown;3) fructose was able to increase lactate production in the presence of saturating concentrations of glucose. These additive effects of glucose and fructose seem to support the point of view that it is not the glycolytic machinery but the supply of fuel which is rate limiting for glucose utilization by isolated rat lung cells.
Oxidative response to aldosterone of pyridine nucleotide in rat kidney in situ.
Authors: Ogata E , Nishiki K , Kugai N , Kishikawa T
Published: December 2017

In an attempt to elucidate early biochemical events in the action of aldosterone on rat kidney in situ, the response of the pyridine nucleotide oxidation-reduction state of surface cells was directly and continuously recorded with an organ-fluorometer. Intravenous administration of aldosterone induced a rapid (maximum response in 10 min) and dose-related (2.5-25 microng/100 g rat) oxidative response that was specific to aldosterone and to the kidney. The oxidative response was 1) detectable with minute dise (approximately 0.2 microng/100 g rat) of hormone: 2) reproduced by other mineralocorticoids; 3) enhanced by a maneuver for expanding the extracellular fluid compartment or by adrenalectomy; and 4) prevented by spironolactone, progesterone, actinomycin D, and cycloheximide. All of these data argue that the redox response is related to the subsequent changes in aldosteronemediated ion transport. Experiments with an uncoupler and with redox substrates showed that mitochondrial NADH was the major nucleotide pool responding to hormone. The oxidation was not accompanied by changes in the adenylate energy charge level of the whole organ. These observations support the view that aldosterone acts on energy metabolism of tubular cells before developing apparent cation transport effects.
Calcium transport across avian uterus. III. Comparison of laying and nonlaying birds.
Authors: Pearson T W , Pryor T J , Goldner A M
Published: December 2017

Transepithelial calcium fluxes were measured across isolated uterus of laying, nonlaying, and molting quail under conditions where no electrochemical difference existed across the tissue. Net uterine transfer of calcium in molting and nonlaying birds occurs in the secretory direction and is approximately one-fifth the value obtained for laying birds. The carbonic anhydrase enzyme activity of uteri from laying birds is twice that of uteri from molting birds and five times greater than that of uteri from nonlaying birds. When measured in the presence and absence of 2-mercaptoethanol or dithiothreitol, no statistical difference exists in uterine carbonic anhydrase activities of laying birds or the inhibitory effect of acetazolamide. These results indicate that nonlaying and molting quail secrete calcium at a rate much lower than that of laying quail and that net uterine transfer of calcium exhibits varing degrees of dependence on bicarbonate ion in laying, nonlaying, and molting birds. Carbonic anhydrase data sugges that the activtiy of this enzyme in the quail uterus may be related to uterine calcium secretion.
Evidence for interference of 25 (OH) vitamin D3 with phosphaturic action of calcitonin.
Authors: Popovtzer M M , Blum M S , Flis R S
Published: December 2017

The present study evaluated the effect of 25(OH)vitamin D3[25(OH)vit D3] on the phosphaturic action of calcitonin in anesthetized parathyroidectomized rats. In group 1, calcitonin was given intravenously over six clearance periods. In group 2, after three periods of calcitonin given intravenously, 25(OH)vit D3 was added and given together with calcitonin for three additional periods. During calcitonin infusion, Cp/CIn 0.18 +/- 0.02 (mean +/- SE) in group 1 was not different from the corresponding Cp/CIn 0.18 +/- 0.03 in group 2; but when 25(OH)vit D3 was added, Cp/CIn 0.12 +/- 0.01 in group 2 was lower (P less than 0.001) than the corresponding Cp/CIn 0.26 +/- 0.02 in group 1. With intravenous calcitonin the urinary excretion of cycle AMP (UcAMP) 97 +/- 29 in group 1 did not differ from the corresponding UcAMP 86 +/- 27 pmol/min in group 2, but when 25(OH)vit D3 was added UcAMP 41 +/- 12 in group 2 was lower (P less than 0.001) than the corresponding UcAMP 131 +/- 14 pmol/min in group 1. This study demonstrated that 25(OH)vit D3 blocks the phosphaturic action of calcitonin. The associated fall in Uctamp suggests that25 (OV)vit D3 acts possibly by inhibiting the calcitonin-induced activation of adenylate cyclase in the kidney. However, other alternative mechanisms of action have not been excluded.
Dependence of tonin activity in rat submaxillary gland on growth hormone and testosterone.
Authors: Lis M , Boucher R , Chrétien M , Genest J
Published: December 2017

Tonin, an enzyme present in rat submaxillary gland, converts angiotensin I to angiotensin II and is able to form angiotensin II directly from renin substrates. This enzyme was previously shown to be different from renin, tissue isorenins, and angiotensin I converting enzyme. The specific activity of tonin in rat submaxillary gland increases with the age of the animal and is much higher in male than in female rats; this sex difference is apparent from 60 to 70 days of age. There is a sharp drop of tonin activity in hypophysectomized animals, whereas adrenalectomy, thyroidectomy, and gonadectomy have have little effect. The marked increase in tonin activity was observed in animals bearing MtT-F4 transplantable tumors known to produce ACTH, prolactin, and growth hormone. Tonin specific activity in hypophysectomized male rats is restored to control levels by combined treatment with growth hormone and testosterone. Prolactin alone or in combination with testosterone, as well as transplanted pituitaries, has no effect in hypophysectomized animals. There is a significant specific binding of 125I-labeled growth hormone to isolated membranes of rat submaxillary gland.
Hexose monophosphate shunt in isolated cardiac myocytes from normal rats.
Authors: Burns A H , Reddy W J
Published: December 2017

The activity of the hexose monophosphate shunt was studied in myocytes obtained from the ventricles of normal, adult, male rats. When myocytes were incubated in buffer containing either 1-14C- or 6-14C-labeled glucose the ratio of C-1/C-6 14CO2 evolved was essentially unity. The addition of plasma levels of amino acids did not alter this finding. If, however, a competitive substrate (pyruvate, octanoate, acetate, or lactate) was present, in sufficient quantity to lower the oxidation of glucose to approximately 20% of the control, the C-1/C-6 14CO2 ratio rose to values between 1.3 and 2.1. This ratio was dependent on the concentration of the competitive substrate, which was dependent on the buffer system. The data indicates that the hexose monophosphate shunt is active in the heart because it can be demonstrated when a substrate, which competes with glucose for oxidation, is present. The presence of competing substrates parallels the situation occuring in vivo.
Active alkalinization by amphibian gastric fundic mucosa in vitro.
Authors: Flemström G
Published: December 2017

Gastric fundic mucosae in vitro from four species of frog and Necturus secrete HCO-3 at a steady-state rate of 0.25-0.55 microneq-cm-2-h-1 which corresponds to 5-10% of maximal H+ secretion. Net alkalinization was quantitated in mucosae with spontaneously resting H+ secretion or in mucosae inhibited by histamine H2-receptor antagonists or SNC-. HCO-3 secretion was inhibited by DNP (10(-4) M), CN- (10(-2) M), or anoxia. Acetazolamide inhibited alkalinization at 10(-2) M when added to the nutrient side and at 10(-4) M on the luminal side. Carbachol (10(-4) M) and DBcGMP (10(-4) M) stimulated alkalinization and caused a transient rise in the transmucosal PD; DBcAMP (10(-3) M) was without effect. An almost identical secretion occurred spontaneously in antral mucosae and was insensitive to histamine (10(-5) M). Occurrence in both antral and fundic mucosa suggests that active alkalinization is a property of gastric surface epithelial cells. Gastric alkalinization may protect the luminal surface of the mucosa from the damaging effects of acid and contribute to the continuous removal of H+ ions from gastric contents.
Pancreatic bicarbonate, serum gastrin, and secretin responses to meals varying in pH.
Authors: Llanos O L , Konturek S J , Rayford P L , Thompson J C
Published: December 2017

The role of secretin in the postprandial bicarbonate response by the pancreas is not clear. This study reports secretin and bicarbonate secretion after exogenous and endogenous acidification of meal. In dogs with gastric and pancreatic fistulas, a liver extract meal at various pH levels was introduced into the stomach and kept at the preselected pH by intragastric titration. Gastric acid, pancreatic bicarbonate, serum gastrin, and plasma secretin were measured. The meal at pH 7 produced an increase of gastrin levels of 230% above basal and a gastric acid output from a basal of 0.8-16.9 meq/30 min. Acidification of the meal evoked a pH-dependent reduction of gastrin and gastric acid secretion, a pH-dependent elevation of pancreatic bicarbonate, and significant elevation of secretin at pH 3 (43% above basal) and at pH 2 (80% above basal). Postprandial endogenous acidification of a meal, without intragastric titration, also provoked significant release of secretin. Maximal pancreatic bicarbonate secretion in response to exogenous secretin was augmented 30% by the addition of a liver extract meal at pH7. It is concluded that in dogs with pancreatic fistulas, a meal exogenously or endogenously (postprandial) acidified is capable of the release of secretin in immunoassayable amounts. The normal pancreatic bicarbonate response to food may depend partially upon potentiation of the secretin effect by other neurohumoral stimuli.
Influence of aldosterone on renal ammonia production.
Authors: Welbourne T C , Francoeur D
Published: December 2017

Administering D-aldosterone, 7 microgram 100 g-1, to rats results in a marked rise in ammonium excretion and metabolic alkalosis. Increased ammonium excretion is not related to either a significant elevation in potassium excretion nor to hypokalemia. Consequently, potassium depletion does not appear to be the causative factor in the aldosterone-stimulated ammonium excretion. Isolated kidneys from aldosterone-treated rats, perfused with 1 mM L-glutamine, produced twice as much ammonia from glutamine as did controls. Ammonia production per glutamine extracted increased from 1.33 +/- 0.07 in control to 1.79 +/- 0.08 in kidneys from hormone-treated rats, suggesting stimulation of the mitochondrial glutaminase I-glutamate dehydrogenase pathway; this was supported by a proportional rise in production of glucose and CO2, end products of glutamine's carbon skeleton. Consequently, aldosterone-stimulated renal ammonia production, by specifically activating the mitochondrial pathway, leads to the elimination of hydrogen ions in the form of urinary ammonium excretion and an ensuing metabolic alkalosis.
Vitamin K2 colonic and ileal in vivo absorption: bile, fatty acids, and pH effects on transport.
Authors: Hollander D , Rim E , Ruble P E
Published: December 2017

Colonic and ileal absorption of vitamin K2 ([2-methyl-3H]menaquinone-9) was investigated in the conscious rat. When the absorption rate was plotted against the perfusate concentration, a linear relationship was found between these two parameters in the ileum and colon. The absorption rate of menaquinone by the ileum was increased as the bile salt concentration, degree of unsaturation of the added long-chain fatty acids, hydrogen ion concentration, and perfusate flow rates were increased. Colonic menaquinone absorption decreased as the bile salt concentration was increased. Menaquinone colonic absoprtion increased as the pH decreased, but no change was noted as the perfusion rate was increased. The present experimental observations in vivo, coupled with prior observations in vitro, indicate that absorption of menaquinone by the ileum and colon occurs by a passive diffusion process that is modified by variations in the perfusate bile salt concentration, the presence of unsaturated fatty acids, and the perfusate pH. The present observations indicate that the mammalian colon and terminal ileum can provide a constant source of vitamin K to aid hemostasis despite episodic lack of dietary vitamin K.
Effect of burn trauma on glucose turnover, oxidation, and recycling in guinea pigs.
Authors: Wolfe R R , Burke J F
Published: December 2017

The simultaneous primed-constant infusion of [6-3H]- and [U-14C]glucose was used to determine the effect of burn injury on glucose turnover, oxidation, and recycling in guinea pigs. Eleven burned animals survived more than 72 h (survivors), whereas five died between 60 and 72 h postburn. All of the controls (n = 9) survived more than 72 h. At 48 h postburn, glucose turnover in the burned survivors was elevated 40% above that in control animals. A greater portion of the burned survivors' turnover was due to recycling and less was directed towards oxidation. The nonsurvivors had both a significantly depressed rate of appearance of glucose and an increased glucose clearance rate. Consequently, they were profoundly hypoglycemic and had a low rate of glucose oxidation. The alterations in glucose kinetics and oxidation apparent after burn did not reflect an inability of burned animals to oxidize exogenously infused glucose, however, because of 2-h infusion of 55 mumol/kg-min of unlabeled glucose doubled glucose oxidation in the burned survivors and tripled it in the nonsurvivors.
Sheep lactate entry-rate measurements: error due to sampling jugular blood.
Authors: Reilly P E , Chandrasena L G
Published: December 2017

Carotid arterial and jugular venous blood samples were taken simultaneously during primed continuous infusions of L-[U-14C]lactate in four sheep. The mean rate (n = 4) of total net formation of lactate (0.394 +/- 0.047 mg C/min per kg) calculated from the results obtained by analyzing the jugular blood samples for lactate concentration and specific radioactivity was significantly higher (0.01 greater than P greater than 0.005) than the mean rate (n = 4) calculated from the results of analysis of the arterial samples (0.302 +/- 0.036 mg C/min per kg). The error in the estimation of the rate of total net formation of lactate due to jugular sampling resulted from the negative arteriovenous difference found for lactate across the tissues of the head. These results illustrate the general need for examination of the suitability of venous sampling in experiments that make use of the continuous infusion isotope-dilution method.
Magnesium-fluoride interrelationships in man. I. Effect of fluoride on magnesium metabolism.
Authors: Spencer H , Kramer L , Wiatrowski E , Osis D
Published: December 2017

Metabolic balances of fluoride and magnesium were determined in man in control studies and during fluoride supplementation. The studies were carried out during three intake levels of calcium (200, 1,400, and 2,200 mg/day) and during two intake levels of phosphorus (800 mg and 1,400 mg/day). The intake of about 10 mg fluoride per day, given as NaF, resulted in a two- to threefold increase of the urinary and fecal fluoride excretion. However, during the high fluoride intake, the urinary magnesium remained about the same, the fecal magnesium increased slightly, and the magnesium balances did not differ significantly. This was the case whether fluoride was given during a low or high calcium intake in the absence or presence of added phosphorus. Similar results were obtained with large doses of fluoride (40-45 mg/day) given to patients with osteoporosis. The studies have shown that supplemental fluoride ranging from 10 to 45 mg/day did not affect the magnesium balance during calcium intakes that ranged from 200 to 2,200 mg/day and during phosphorus intakes that ranged from 800 to 1,400 mg/day.
Effect of insulin, glucose, and controlled diabetes mellitus on human jejunal function.
Authors: Costrini N V , Ganeshappa K P , Wu W , Whalen G E , Soergel K H
Published: December 2017

The effects of serum insulin concentration, serum glucose concentration, and of insulin-dependent diabetes mellitus on human jejunal glucose, Na, and H2O absorption were assessed. Triple-lumen perfusion studies were carried out in 20 nondiabetic and 9 insulin-requiring diabetic male volunteers. In seven normal subjects, sequential elevation of serum insulin concentrations from 20 muU/ml to 50 and 100 muU/ml for 2 h each, with maintenance of constant serum glucose levels, failed to significantly alter glucose, Na, and H2O absorption. Absorption of glucose, Na, and H2O was similar when the serum glucose concentration was maintained at 125 and at 250 mg/100 ml. Glucose absorption results during 26 perfusion studies in 20 control subjects were compared with results obtained during 20 perfusion studies in 9 diabetic subjects. Glucose concentrations in isotonic perfusates were 25, 40, or 75 mM. Na and H2O absorption rates were similar in both groups. Regression lines relating glucose load or geometric mean study segment glucose concentration to glucose absorption were also comparable. These results indicate that insulin-requiring diabetics absorb glucose, Na, and H2O normally.
Stimulation of renal phospholipid formation during potassium depletion.
Authors: Toback F G , Havener L J , Spargo B H
Published: December 2017

Potassium depletion induces increased membrane phospholipid formation and renal growth in rats. To determine the mechanism by which potassium depletion augments phospholipid formation, the metabolism of radioactive choline, a precursor of choline-containing phospholipids, was studied in renal slices. Cortical and medullary tissue from potassium-depleted and control animals accumulated extracellular choline and sequentially converted it to phosphorylcholine, cytidine diphosphocholine (CDP-choline), and choline phosphoglyceride, thereby demonstrating that renal cells can utilize the Kennedy pathway for phospholipid synthesis. [14C]Choline uptake into intracellular fluid was increased in cortical slices from potassium-depleted animals. The apparent Km and Vmax of the kinase reaction which converts entering [14C]choline to [14C]phosphorylcholine were unchanged during potassium depletion. The rate of [14C]phosphorylcholine conversion to [14C]CDP-choline was also unchanged. In contrast, the Vmax of [14C]choline phosphoglyceride formation from [14C]CDP-choline was increased, whereas the apparent Km for this reaction was unchanged. These results indicate that increased renal choline phosphoglyceride formation during potassium depletion can occur via the Kennedy pathway and appears to be mediated by increases in choline uptake and the rate of CDP-choline incorporation into phospholipid, the first and last steps of the pathway.
Sensitizing effect of treatment with estrogens on TSH response to TRH in male rats.
Authors: De Lean A , Labrie F
Published: December 2017

Daily administration of estradiol benzoate (10 microgram/100 g body wt) to intact male rats led to a twofold increase of the plasma TSH (thyroid-stimulating hormone) response to thyrotropin-releasing hormone (TRH) after 4 and 7 days of treatment whereas the basal plasma TSH level was not affected. The basal plasma PRL concentration and the PRL response to TRH were both markedly increased by estrogen treatment. The TSH pituitary content remained unchanged, whereas the PRL pituitary content increased in parallel with the effect on PRL secretion. Treatment with estrogens for 1 wk sensitized the TSH secretory response to low doses of TRH (10 ng), whereas no significant effect on the response was found at high doses of the neurohormone. The present data show that the stimulatory effect of estrogens on the TSH response to TRH is due to true sensitization of the thyrotrophs to the action of the neurohormone, whereas that on prolactin secretion can result partly from increased pituitary prolactin content.
Effect of leukocytic endogenous mediators on endocrine pancreas secretory responses.
Authors: George D T , Abeles F B , Mapes C A , Sobocinski P Z , Zenser T V , Powanda M C
Published: December 2017

Crude mediators from stimulated rabbit peritoneal leukocytes (LEM) engender numerous physiologic alterations in rats, which are similar to those observed during infection. One hour after the intraperitoneal injection of crude LEM, plasma insulin and glucagon concentrations are elevated; at 2 h the hormonal alterations are manifested by a 30% increase in hepatic cyclic adenosine 3',5'-monophosphate (cAMP), glycogen depression, and uptake of 14C-labeled nonmetabolizable amino acid analogues (AA). Plasma hormone concentrations reach maximum levels by 5 h and decline by 24 h. The hepatic concentrations of AA parallel the insulin and glucagon responses and correlate with the inverse of insulin/glucagon molar ratio. In spite of mobilization of hepatic glycogen evident at 5 h, plasma glucose concentrations were transiently depressed. Plasma insulin, glucagon, and hepatic AA concentrations were dose dependent. Plasma insulin and glucagon responses to crude LEM may explain increases in hepatic cAMP, uptake of AA, and glycogenolysis as well as hypoglycemia. These data partially characterize the role of crude LEM, provide an explanation for the stimuli-inducing hyperglucagonemia and hyperinsulinemia during infection. They implicate the endocrine pancreas as a factor regulating the host's metabolic response to infection.
Static and dynamic characteristics of fluid-filled esophageal manometry systems.
Authors: Ask P , Oberg A , Tibbling L
Published: December 2017

Esophageal manometric systems with water-filled catheters have been characterized by the use of model experiments. The examined parameters have been: catheter dimension, catheter compliance, catheter resistance, pump type, pump compliance, and perfusion flow. Accurate static pressure measurements have been obtained for perfused systems independently of the investigated parameters. The dynamic characteristics vary with catheter diameter and perfusion flow. For catheters with low diameter, a narrow bandwidth is obtained for the investigated perfusion flows. The results have been expressed in terms of an electric model of the measurement system. Perfusion pumps with low compliance are recommended to improve the dynamic properties of the measurement system.
Fetomaternal transfer of glucose analogues by sheep placenta.
Authors: Stacey T E , Weedon A P , Haworth C , Ward R H , Boyd R D
Published: December 2017

The steady-state permeability of the placenta to radiolabeled 3-O-methyl--D-glucopyranose (3MeG), alpha-methyl-D-glucopyranoside (AMG), and D-xylose was measured in chronically catheterized conscious sheep near term. Fetomaternal flux was calculated by application of Fick's principle to the uterine circulation after injection to the fetus. At a fetal glucose concentration of 10.2 +/- 1.25 mM, the permeability of 3MeG was half the maximal value of 59.5 +/- 11.2 ml/min found by extrapolation to zero glucose concentration. The permeability to 3MeG is considerably greater than is compatible with restricted diffusion, which together with the competitive effect of D-glucose suggests a carrier-mediated transfer mechanism. The permeability to AMG was less than 0.1 ml/min. The specificity pattern of sugar transport from the fetal side of the sheep placenta is different from that reported for gut lumen or kidney tubule in other species. D-Xylose is not metabolically inert after its injection into the fetal lamb.
Efffect of vasoactive intestinal polypeptide on gallbladder smooth muscle in vitro.
Authors: Ryan J P , Ryave S
Published: December 2017

The effect of vasoactive intestinal polypeptide (VIP) on basal and octapeptide of cholecystokinin (OP-CCK) induced tension was examined with guinea pig gallbladder smooth muscle strips in vitro. VIP alone produced dose-related decreases in resting tension and antagonized spontaneous contractile activity where present. In combination with OP-CCK, VIP decreased the expected contractile respone. The degree of antagonism depended upon the concentrations of OP-CCK and VIP. VIP had no effect on acetylcholine-induced contractions. From these observations, we propose that VIP can affect gallbladder motor activity by decreaseing smooth muscle tone and by antagonizing cholecystokinin. These findings lend further support to our proposal that gallbladder motor function may depend upon the action and interaction of the gastrointestinal hormones.
Effects of some gastrointestinal hormones on two muscle layers of duodenum.
Authors: Anuras S , Cooke A R
Published: December 2017

The duodenums of opossums and cats were cut into strips 2 mm wide and 2-2.5 cm long. Strips cut in the oral-caudal axis were called longitudinal strips; those cut at 90 degrees to that axis were called circular strips. Cholecystokinin (CCK) and cerulein stimulated phasic contractions of circular muscle of opossum duodenum, but had no effect on the longitudinal muscle. The effect of CCK was not blocked by tetrodotoxin (10(-7)M), indicating a direct muscle stimulation. CCK had no effect of both muscle layers of the cat duodenum. Vasoactive intestinal peptide raised tension in longitudinal muscle, but reduced tension in circular muscle of opossum duodenum. Glucagon slightly reduced tension in both longitudinal and circular muscle of opossum duodenum. It also inhibited contractions of circular muscle caused by acetylcholine. Pentagastrin and secretin had no effect on either muscle layer in either species. These findings suggest that the circular and longitudinal muscle layers of the duodenum respond differently to at least some gastrointestinal hormones. Also, there is species variation in response to gastrointestinal hormones.
Effect of insulin on kinetics of sugar transport in heart muscle.
Authors: Cheung J Y , Conover C , Regen D M , Whitfield C F , Morgan H E
Published: December 2017

Insulin increased the maximal rate of sugar transport in the perfused rat heart, but had essentially no effect on the Michaelis constant of sugar entry or half-maximal constant for equilibrium exchange. In control hearts, the following kinetic parameters of 3-O-methylglucose transport were measured: Michaelis constant for entry, 7-10 mM; equilibrium exchange constant, 7 mM; and activity constant (Vmax/Km) from 0.02 to 0.1 ml/g.min. In insulin-treated hearts, these values were 6 mM, 3 MM, and 2.2 ml/g.min, respectively. These changes in transport constants were consistent with a model in which 1) sequestered carrier was released by the hormone or 2) carrier movement, in all forms and directions, was accelerated. Measurements of glucose transport in control hearts indicated that the Michaelis constant for entry was 4 mM and the activity constant, 0.5 ml/g.min. In insulin-treated hearts, quantitation of transport parameters was prevented by accumulation of intracellular glucose.
Salivary gland K+ transport: in vivo studies with K+-specific microelectrodes.
Authors: Poulsen J H , Bledsoe S W
Published: December 2017

Stimulation-induced transport of K+ in the submandibular salivary gland of cats and dogs anesthetized with pentobarbital was studied with an extracellular K+-specific microelectrode. Electrical stimulation of the para-sympathetic chorda-lingual nerve caused a rapid transient increase in extracellular K+ concentration from 2.2 to 18.7 meq/liter in the cat and from 2.3 to 15.2 meq/liter in the dog. Eventually the K+ concentration fell below the prestimulatory level, indicating uptake of K+ by the gland cells. In case of prolonged stimulation (2-10 min), the uptake began during stimulation. However, a further reduction in extracellular K+ concentration occurred upon cessation of stimulation, a result that demonstrated that the cells did not fully recover their K+ ,content during stimulation. The latency of the release of K+, defined as the time from the beginning of stimulation to the point at which, the K+-specific microelectrode signal had increased by 2 mV, was 0.6 s in the cat and 0.8 s in the dog. Because these are overestimates of the "true" latencies, we conclude that the K+ release begins simultaneously with the hyperpolarization of the acinar cell membrane.
Experimental validation of measurements of glucose turnover in nonsteady state.
Authors: Radziuk J , Norwich K H , Vranic M
Published: December 2017

The aim of the present experiments is to validate, in conscious dogs, the tracer infusion methods of measuring nonsteady turnover rates. This was done in nine experiments performed in four normal dogs by infusing isotopically labeled glucose (2-3H, 6-3H, 1-14C) and monitoring the concentrations of both the labeled and unlabeled substances. The validation is based on the observation that a high exogenous infusion of glucose will suppress endogenous glucose production and become the sole source of glucose in the body. By infusing glucose at a high, time-varying rate, calculating its rate of appearance, (Ra) and comparing it to the infused rate, the method can be verified. The calculations were based on: a) a single-compartment model with a modified volume of distribution; b) a two-compartment model; and c) a generalized dispersion model. The absolute values of the areas of the deviations of the calculated from the infused curves were found to be, respectively, 9.5, 8.4, and 7.8 percent of the total area under the infused curve. It was concluded that the tracer infusion method can reliably measure Ra of glucose when it is changing rapidly, and the system is out of steady state.
Adrenergic modulation of insulin secretion in vivo dependent on thyroid states.
Authors: Okajima F , Ui M
Published: December 2017

Insulin secretory responses via adrenergic mechanisms were studied in vivo with hyperthyroid rats prepared by daily injections with thyroxine and with rats rendered hypothyroid by the addition of methylthiouracil in the drinking water. Isoproterenol, a beta-adrenergic agent, caused hyperinsulinemia in hyperthyroid rats more markedly than in euthyroid rats, but failed to induce hyperinsulinemia in hypothyroid rats. The isoproterenol-induced hyperinsulinemia was abolished by a beta-adrenergic receptor blocker in hyperthyroid as well as in euthyroid rats. The glucose-induced hyperinsulinemia was enhanced in hyperthyroid, was not essentially affected in euthyroid, and was inhibited in hypothyroid rats, by an alpha- and beta-adrenergic agent such as epinephrine. It is concluded that the relative function of alpha- to beta-adrenergic receptors responsible for the pancreatic secretion of insulin is dependent on the thyroid state; beta-adrenergic actions are predominant over alpha-actions in hyperthyroidism and vice versa in hypothyroidism.
Effect of fatty acids on isolated ovine pancreatic islets.
Authors: Jordan H N , Phillips R W
Published: December 2017

A procedure was developed for the isolation of intact islets of Langerhans from sheep pancreas. The pancreas was disrupted by syringe injection of Hanks solution followed by collagenase incubation and islet separation by sedimentation. The islets were incubated in varying concentrations of glucose and butyrate. The rate of insulin release was approximately linear while the glucose and butyrate concentrations were increased. In additional studies at 2.5 and 5.0 mM levels of substrate concentration, the stimulation of insulin had the following pattern: octanoate greater than hexanoate greater than butyrate, whereas beta-hydroxybutyrate, lactate, acetate, and propionate had only slight stimulatory effects that were not statistically significant. Decanoate did not alter insulin release from isolated islets. These data confirm earlier in vivo reports that fatty acids stimulate pancreatic hormone release in sheep and that the stimulus is related to chain length of the fatty acid through C-8 but that C-10 has no effect. A hypothesis was suggested to explain these results based on chain length, solubility, and plasma membrane alterations.
Effects of endogenous prostaglandin E on intestinal motility.
Authors: Sanders K M , Ross G
Published: December 2017

The role of endogenous prostaglandin E (PGE) in the regulation of intestinal motility in situ was studied in cats anesthetized with pentobarbital. The basal concentration of PGE in the ileum was found by radioimmunoassay to be 3.3 +/- 0.6 ng PGE per g wet wt (chi +/- SE, n = 12). Intramesenteric arterial infusion of acetylcholine (ACh) (100 microgram/min) increased intestinal motility, and PGE concentration rose to 6.7 +/- 0.8 ng/g. Intravenous infusion of indomethacin (4 mg/kg) enhanced spontaneous and ACh-induced motility and abolished the ACh-induced rise in ileal PGE concentration. We conclude that basal PGE synthesis limits the motility of the resting and ACh-stimulated cat ileum.