bluuebunny/crossref_metadata_2025 huggingface dataset:
The structure and interactions of starch with food constituents
Authors: Biliaderis Costas G.
Published: April 2011

For most starch-containing foods, the physical and functional properties can be traced to characteristic molecular species being present, their interactions with each other, and modifications caused by environmental conditions (moisture, temperature, shear) during processing and storage. In the present paper, the chemistry and physical chemistry of starch are discussed with an emphasis on how structure (molecular and supermolecular) and composition influence the functionality of this polysaccharide. New experimental findings brought forward on structure indicate that this polymeric carbohydrate is found in various metastable states, depending on the thermomechanical history of the product. Even more important to processing and quality attributes of starch products is the recognition that the dynamics of the supermolecular structure and interactions between starch and other food constituents are governed by the mobility of the amorphous phase of each particular system. In this respect, water, acting as a plasticizer, depresses the glass transition temperature (Tg) and thereby alters the kinetics of state transformations (e.g., gelatinization, retrogradation) and reactivity of starch. The effects of water on phase transition behavior of starch as well as the underlying molecular mechanisms to the phenomena of gelatinization, gelation, retrogradation, and starch–lipid interactions are reviewed herein. Finally, consideration is given to factors affecting the digestibility of starch from the viewpoint of processing-related changes in the susceptibility of starch to α-amylase.Key words: starch, amylose, amylopectin, gelatinization, gelation, retrogradation, interactions, water, lipids, supermolecular structure, digestibility.
The clinical utility of the glycemic index and its application to mixed meals
Authors: Hollenbeck Clarie B. , Coulston Ann M.
Published: April 2011

A classification of carbohydrate-containing foods based on their glycemic response to 50-g carbohydrate portions has recently been developed. The relative glycemic potency of many of these carbohydrate-containing foods have been compared, and these data have been published in the form of a glycemic index. It has been suggested that meals containing low glycemic index foods will result in a lower postprandial glucose response than meals with a higher glycemic index. However, whether or not these data will lead to a clinically useful reduction in postprandial hyperglycemia in individuals with carbohydrate intolerance remains controversial. In this review, we will try to delineate why we believe that the glycemic index, as currently developed, may be a specious issue. In addition, we will briefly discuss a number of factors that may explain the apparent discrepancy in viewpoints on this issue.Key words: glycemic index, noninsulin-dependent diabetes mellitus, glycemic response, dietary carbohydrate.
Starch and dietary fibre: their physiological and epidemiological interrelationships
Authors: Stephen Alison M.
Published: April 2011

Until the 1980s, starch in the human diet was assumed to be totally degraded and absorbed in the small intestine. Several lines of evidence since then have indicated that this is not the case, including studies of factors controlling stool output, stool bulk on elemental diets, epidemiological studies of starch intakes in developed versus developing nations, and indications using breath hydrogen that fermentation takes place in the large intestine when starch is fed. Of the few direct estimations of starch escaping absorption in the small intestine that have been carried out, one has been conducted using intubation of healthy volunteers, where two different starch meals were fed and samples aspirated from the terminal ileum. This study demonstrated that 8–10% starch escaped absorption on average, with subjects varying from 2 to 20%. Hence a sizeable proportion of starch consumed daily may reach the large intestine, with important physiological consequences. Neither small intestinal transit time nor volume of flow were related to the extent of starch malabsorption in this study. However, many factors may play a role in the extent of malabsorption, and research is continuing to investigate physiological and food characteristics that may influence the digestion and absorption of starch.Key words: starch, dietary fibre, malabsorption, ileum, gastrointestinal function.
Passage of starch into the colon of humans: quantitation and implications
Authors: McBurney Michael I.
Published: April 2011

It has been suggested that a significant amount of starch may reach the colon undigested and stimulate microbial fermentation. Indirect estimates of the quantity of starch reaching the colon have been obtained from breath hydrogen (H2) measurements, but numerous variables, i.e., dietary fiber source and level of intake, oral hygiene, hyperventilation, and cigarette smoking, stimulate H2 production and may exaggerate estimates of starch malabsorption. With proper controls, however, the lactulose breath H2 test based on total excess volume seems to provide a reasonable measure of the average amount of starch metabolized in the colon. Direct estimates of starch metabolism from human ileostomy studies suggest that typically < 5% of the ingested starch escapes digestion in the small intestine. The general assumption that starch malabsorption stimulates normal colonic function, particularly with respect to colorectal carcinogenesis, is not entirely supported by the limited number of available epidemiologic studies. Further experimental studies are needed to elucidate the role of starch intake and malabsorption on colonic function and human health issues.Key words: starch, malabsorption, colonic fermentation, carcinogenesis, large bowel.
The mechanism of [3H]noradrenaline release by histamine and its analogs from the rat vas deferens
Authors: Boudreau N. J. , Vohra M. M.
Published: April 2011

In this study the mechanism by which histamine and H1 and H2 agonists evoked an overflow of radioactivity from rat vasa deferentia preloaded with [3H]noradrenaline was investigated. The overflow evoked by the various agonists was unaffected by the presence of such receptor antagonists as propranolol, phentolamine, cimetidine, or scopolamine. On the other hand, the overflow evoked by all agonists except dimaprit was inhibited by mepyramine and by two well-known neuronal uptake inhibitors, cocaine and desipramine. The inhibition by mepyramine has been attributed to its effect on the neuronal uptake process. Metabolic profile studies showed that 3,4-dihydroxyphenylglycol (DOPEG) was the major constituent in the evoked overflow caused by histamine, 2-methylhistamine, 4-methylhistamine, and dimaprit and that the overflow evoked by 2-pyridylethylamine and 2-thiazolylethylamine consisted predominantly of unchanged noradrenaline. Based on these findings, it is concluded that all of the agonists tested evoke noradrenaline release intraneuronally by entering the adrenergic nerve terminals. While dimaprit might enter by passively diffusing into the adrenergic nerves, other agonists seem to use the neuronal uptake process. Noradrenaline released intraneuronally is subsequently degraded by neuronal monoamine oxidase to form DOPEG. However, there are qualitative and quantitative differences in the metabolic profile of the overflow evoked by various agonists. It is suggested that these differences could arise from their additional properties, such as their effect on the neuronal uptake process and (or) their ability to act as substrate for neuronal monoamine oxidase.Key words: noradrenaline, vas deferens, histamine, histamine H1 and H2 agonists.
Peripheral vasodilator and cardiac properties of the 1,5-benzothiazepine calcium antagonist analog, TA-3090, in dogs
Authors: Dumont L. , Derouin M. , Chartrand C. , Archambeault P. , Garceau D. , Caillé G.
Published: April 2011

Diltiazem, a 1,5-benzothiazepine, has demonstrated efficacy in the treatment of numerous cardiovascular diseases. TA-3090, a newly synthetized 1,5-benzothiazepine compound was studied in open-chest anesthetized dogs to characterize its hemodynamic properties, to compare it with diltiazem, and finally to correlate hemodynamic properties and plasma level concentrations. Anesthetized open-chest dogs were instrumented with electronic devices and fluid-filled catheters to monitor cardiac, coronary, and peripheral hemodynamic changes. A cumulative intravenous bolus administration of TA-3090 (n = 16) or diltiazem (n = 15) (15, 50, 200, and 400 μg/kg) was carried out, and blood samples were taken before and 5 min following each dose administration. Hemodynamic changes were followed for 30 min after each administration, at which time most hemodynamic parameters were back to baseline levels. The results indicate that both TA-3090 and diltiazem elicit slight peripheral and coronary vasodilator properties at low doses (15 and 50 μg/kg). With higher dosage, hemodynamic effects were maximal: coronary blood flow increased by 75%, arterial pressure decreased by 25%, and reflex positive inotropic effects were also observed. Heart rate was significantly reduced (10%). Comparison between TA-3090 and diltiazem indicates that both drugs elicit coronary vasodilator selectivity and TA-3090 has a prolonged duration of action compared with that of diltiazem. A straightforward relationship is demonstrated between vasodilator properties and plasma levels of either TA-3090 or diltiazem. Our data suggest that with plasma levels between 40 and 80 ng/mL, significant hemodynamic changes were observed with TA-3090. Changes of heart rate were not correlated with plasma levels. TA-3090 appears to be an effective coronary and peripheral vasodilator with demonstrated coronary selectivity, and to possess a prolonged duration of action compared with diltiazem.Key words: TA-3090, diltiazem, vasodilation, coronary, plasma levels.
Effects of sympathetic stimulation on use dependence of lidocaine, mexiletine, and quinidine in an intact canine model
Authors: Newman David , Herre John M. , Chin Michael , Scheinman Melvin M. , Franz Michael , Katzung Bertram
Published: April 2011

The use- or rate-dependent effects of a continuous infusion of lidocaine (n = 6, serum level 3.1 ± 0.34 μg/mL), mexiletine (n = 8, serum level 7.08 ± 0.90 μg/mL), and quinidine (n = 6, serum level 6.8 ± 1.22 μg/mL) were studied in an open chest canine preparation. A use-dependent effect on conduction was assessed by measuring the change in the His to surface ventricular activation (HV) time at differing atrial paced rates during drug infusion. Global sympathetic activation was achieved by nondecentralized left stellate ganglion stimulation (4–10 Hz, 6–12 V, 2 ms) and use dependence at the same cycle lengths was compared. Repolarization times were measured from epicardial monophasic action potentials recorded from the anterior left ventricle throughout the study. There was no significant change in the HV time during control studies with or without left stellate stimulation. Use-dependent slowing of conduction was seen in all studies during drug infusion. This was evident at cycle lengths of 300−190 ms for quinidine and at cycle lengths less than 250 ms for lidocaine and mexiletine. Stellate stimulation attenuated use dependence in all studies. This effect was significant from cycle lengths of 300−190 ms for lidocaine and quinidine and at cycle lengths shorter than 230 ms for mexiletine (p <0.05). Stellate stimulation significantly reduced use-dependent prolongation of the HV interval by an average of 60%. During stellate stimulation there was a nonsignificant trend towards cycle length independent shortening of action potential duration both at baseline and in the presence of drugs. These results suggest that enhanced sympathetic tone can antagonize the effects of sodium channel blocking agents on conduction. Clinical benefit from β-adrenoreceptor blockade added to sodium channel blocking agents may be mediated by such a mechanism in addition to effects on heart rate or ischemia.Key words: rate dependence, modulated receptor hypothesis, sodium channel blockers, sympathetic stimulation.
Problems associated with the measurement of mean circulatory filling pressure by the atrial balloon technique in anaesthetized rats
Authors: Cheng Linong , Rankin Andrew J.
Published: April 2011

To examine the existence of pressure equilibrium between tributary veins and the central vena cava during the mean circulatory filling pressure manoeuvre, pressures in the hepatic portal vein, renal vein, and inferior vena cava were determined at 4-s intervals over a 20-s period of circulatory arrest induced by inflating a right atrial balloon in normal blood volume, 10% volume depletion, and 10% volume expansion states in urethane-anaesthetized rats. Portal vein pressure determined 8 s after arrest during volume depletion and expansion was significantly higher than vena caval pressure (6.2 ± 0.8 vs. 3.4 ± 0.2 and 7.7 ± 0.5 vs. 6.2 ± 0.4 mmHg (1 mmHg = 133.32 Pa), respectively; p < 0.01): this pressure disequilibrium continued for 16 s during volume expansion and for the entire 20 s during volume depletion. Renal vein pressure was equal to vena caval pressure during this manoeuvre. Portal vein pressure at normal blood volume was not significantly different from vena caval pressure following circulatory arrest (4.6 ± 0.3 vs. 3.8 ± 0.4 mmHg, respectively). Following ganglionic blockade, portal vein pressure was still significantly higher than vena caval pressure for 12 s during volume alterations. At the 8th s of the arrest the portal pressure determined in volume depletion was 3.6 ± 0.3 mmHg and the inferior vena caval pressure was 2.6 ± 0.4 mmHg (p < 0.05). Under the volume expansion condition, the respective values were 6.5 ± 0.3 and 5.3 ± 0.4 mmHg (p < 0.05). We conclude that, under conditions of blood volume alterations, there is no pressure equilibrium between the portal vein and the inferior vena cava when mean circulatory filling pressure is measured by this technique; a transhepatic barrier independent of reflex control during the measurement of mean circulatory filling pressure appears to play a role in obstructing the establishment of pressure equilibrium within the venous system.Key words: mean circulatory filling pressure, vascular capacitance, hepatic portal vein pressure, unstressed volume.
Glibenclamide depresses the slowly inactivating outward current (ID) in hippocampal neurons
Authors: Crépel Valérie , Krnjević Kresimir , Ben-Ari Yehezkel
Published: April 2011

Sulphonylurea drugs, such as glibenclamide and tolbutamide, are widely used as selective blockers of adenosine triphosphate-sensitive K channels. In experiments on hippocampal slices (from Wistar rats) glibenclamide (and possibly gliquidone and tolbutamide) significantly reduced the highly voltage-dependent, 4-aminopyridine-sensitive D-type outward current of CA3 neurons. Judging by these observations, the sulphonylureas may not be as selective as generally believed.Key words: glibenclamide, gliquidone, tolbutamide, K currents, rat hippocampal slices.
The effects of dopamine on prolactin mRNA levels in rat pituitary cells in culture
Authors: Shin Seon H. , Elce John S.
Published: April 2011

Dopamine is known to be the prolactin-release inhibiting factor, but the effects of dopamine itself on regulation of prolactin messenger RNA have been little studied because of the instability of dopamine. We have compared the effects of dopamine and bromocriptine on the levels of prolactin mRNA and on the rates of synthesis, storage, and release of prolactin in primary cultured rat pituitary cells. The cells were incubated for 72 h with no secretagogue (control group) or in the presence of either dopamine (10 μmol/L) plus ascorbic acid (100 μmol/L) or bromocriptine (0.1 μmol/L). Prolactin mRNA was measured in cell extracts by means of slot blots, and newly synthesized prolactin was measured in similar incubations by the addition of [3H]leucine, followed by gel electrophoresis. The levels of total prolactin were measured by radioimmunoassay. Prolactin mRNA was reduced to 78 ± 9% (mean ± SEM) of control levels in bromocriptine-treated cells and to 59 ± 7% in dopamine-treated cells, demonstrating that dopamine stabilized by ascorbic acid was able to reduce the levels of prolactin mRNA in rat pituitary cells in culture. Dopamine may act at sites in addition to the dopaminergic D2 receptor, since the level of prolactin mRNA was reduced more by a supramaximal dose of dopamine than by a supramaximal dose of bromocriptine. The results of the [3H]prolactin and prolactin measurements suggested that availability of mRNA was not a major factor in controlling the rate of prolactin synthesis.Key words: prolactin, dopamine, bromocriptine, prolactin mRNA, prolactin biosynthesis, cell culture.
Inhibition of chick embryo hepatic uroporphyrinogen decarboxylase by components of xenobiotic-treated chick embryo hepatocytes in culture. II.
Authors: Green-Thompson R. P. , Kimmett S. M. , Marks G. S.
Published: April 2011

A variety of xenobiotics, viz., 3,3′,4,4′-tetrachlorobiphenyl (TCBP), sodium phenobarbital (PB), 3,5-diethoxycarbonyl-2,4,6-trimethylpyridine (OX-DDC), and nifedipine, cause a decrease in uroporphyrinogen decarboxylase (UROG-D) activity, accompanied by uroporphyrin accumulation, in chick embryo hepatocytes in culture. In this study the activity of 17-day-old chick embryo hepatic UROG-D was determined by measuring the conversion of pentacarboxylporphyrinogen I to coproporphyrinogen I, and it was shown that a UROG-D inhibitor, previously reported to accumulate in TCBP-treated and PB-treated chick embryo hepatocytes in culture, also accumulates in OX-DDC-treated and nifedipine-treated chick embryo hepatocytes in culture. It was concluded that the accumulation of a UROG-D inhibitor provides an explanation for the UROG-D inhibition observed in this culture system with xenobiotics that cause uroporphyrin accumulation. Studies of the UROG-D inhibitory fraction isolated from the 10 000 × g, 40 000 × g, and 100 000 × g supernatant fractions of cultured chick embryo hepatocyte homogenate led to the conclusion that the UROG-D inhibitor is derived from a soluble component of the homogenate.Key words: uroporphyrinogen decarboxylase, chick embryo hepatocyte culture, nifedipine, 3,5-diethoxycarbonyl-2,4,6-trimethylpyridine, enzyme inhibition.
85Sr uptake by the chick embryonic heart: Effect of high doses of isoproterenol
Authors: Oštádalová I. , Oštádal B.
Published: April 2011

The aim of the present study was to establish whether intraamnial administration of toxic doses of isoproterenol to chick embryos increases cardiac accumulation of strontium, the homologue element of calcium. It has been shown that the ability of embryonic tissues (blood, heart, and liver) to accumulate 85Sr decreases significantly during ontogeny. Administration of isoproterenol to chick embryos did not elevate the concentration of 85Sr in the heart. It seems, therefore, that isoproterenol-induced developmental changes in the chick embryonic myocardium are not necessarily due to intracellular calcium (as measured by 85Sr) overload.Key words: heart, isoproterenol, radiostrontium, chick embryo.
Differential effects of intracellular calcium elevating agents on adrenergic-stimulated cyclic nucleotide and melatonin synthesis in rat pinealocytes
Authors: Ho Anthony K. , Cheng Joshua , Girard Marc
Published: April 2011

In this study, the role of elevation of intracellular Ca2+ and activation of protein kinase C on adrenergic-stimulated cyclic nucleotide accumulation and melatonin synthesis in rat pinealocytes was investigated. It was found that whereas KCl, ionomycin, and ouabain, three Ca2+-elevating agents, had a potentiating effect on adrenergic-stimulated cylic AMP response, their effects on melatonin synthesis were inhibitory. Similar inhibition was also observed when dibutyryl cyclic AMP was used to stimulate melatonin synthesis. By determining intracellular Ca2+ directly, it was found that the enhancing effects of these agents on the cyclic AMP response but not their inhibitory effects on melatonin synthesis paralleled their abilities to elevate intracellular Ca2+. In comparison, activation of protein kinase C significantly enhanced the adrenergic-stimulated cyclic AMP response and, to a lesser degree, the adrenergic-stimulated N-acetyltransferase and melatonin levels. These results indicate that (i) Ca2+-elevating agents have opposite effects on adrenergic-stimulated cyclic AMP and melatonin production; (ii) a post cyclic AMP event of importance to melatonin synthesis is inhibited by these agents; and (iii) the mechanism of inhibition may not be directly related to their effect on intracellular Ca2+.Key words: intracellular calcium, protein kinase C, melatonin, pineal gland.
Plasma atrial natriuretic factor and atrial wall stress in hypertensive and normotensive rabbits after pacing and volume expansion
Authors: King K. A. , Ledsome J. R. , Courneya C. A.
Published: April 2011

Atrial natriuretic factor (ANF) is present in high concentration in atria but in very low concentration in the ventricles. Under conditions of haemodynamic overload ventricular gene expression may become activated, but it is not clear if ventricular ANF can be released through a regulated or constitutive pathway. The purpose of this study was to determine whether basal and stimulated release of ANF are increased in perinephritic rabbits with mild hypertension. Six rabbits were rendered hypertensive by wrapping both kidneys in cellophane, and six sham-operated rabbits were used as controls. Eight weeks after renal wrapping, mean arterial pressure was approximately 20 mmHg higher in the experimental group. After anaesthesia, the renal-wrapped group had a higher vascular resistance. Right and left atrial wall stress was measured using sonomicrometry. Volume expansion by 30% of blood volume, using donor blood, caused a small increase in right and left atrial diastolic and systolic wall stress but did not significantly increase plasma ANF. Pacing the heart at 6 Hz caused increases in systolic but not diastolic wall stress and caused a significant increase in plasma ANF; the increase was larger after volume expansion. There were no significant differences between the responses of the experimental and control groups. It is concluded that mild hypertension, in the rabbit, does not lead to changes in atrial wall stress or either basal or stimulated release of ANF.Key words: atrial natriuretic peptide, atrial pressure, atrial stretch, hypertension, anaesthetized rabbits.
Calcitonin gene related peptide relaxes cholecystokinin-induced contraction in guinea pig gallbladder strips in vitro
Authors: Kline L. W. , Pang P. K. T.
Published: April 2011

Calcitonin gene related peptide has been shown to relax vascular and intestinal smooth muscle. This study examines the effects of calcitonin gene related peptide on cholecystokinin-induced contraction of guinea pig gallbladder strips in vitro. Calcitonin gene related peptide was found to cause a dose-dependent relaxation of cholecystokinin-induced tension, which was blocked by the calcitonin gene related peptide receptor antagonist human calcitonin gene related peptide8–37. Previous studies demonstrated that calcitonin gene related peptide acted directly on guinea pig gallbladder smooth muscle to inhibit acetylcholine- or KCl-induced contraction. The present results further confirm that calcitonin gene related peptide acts directly on the smooth muscle. In addition, the use of L-NG-nitroarginine methyl ester, glibenclamide, and other agents strongly suggests that calcitonin gene related peptide also acts by way of the nonadrenergic noncholinergic nervous system, to induce the relaxation of cholecystokinin-induced contraction observed in the guinea pig gallbladder strips.Key words: calcitonin gene related peptide, gallbladder, cholecystokinin.
The pituitary gonadotropin-releasing hormone (GnRH) receptor of the female rabbit: characterization and developmental aspects
Authors: Younglai E. V. , Todoroff E. C.
Published: April 2011

The aim of the present study was to characterize the pituitary gonadotropin-releasing hormone (GnRH) binding site in the rabbit and investigate its possible role in sexual maturation of the female rabbit. A radioligand binding assay was established, and the presence of specific 125I-labelled D-Ala6-des-Gly10-GnRH ethylamide (125I-DAla6EA) binding sites in the anterior pituitary gland of the rabbit was demonstrated. 125I-DAla6EA binding was saturable, specific, displaceable, reversible, correlated with increasing tissue concentrations, and susceptible to physiological manipulation. 125I-DAla6EA binding indicated the presence of two binding sites in the female adult rabbit pituitary: a high affinity, low capacity site (KD = 0.3–0.4 nM; Bmax = 100–200 fmol/mg protein) and a lower affinity, high capacity site (KD = 30 nM; Bmax = 5–8000 fmol/mg protein). Ontogeny of 125I-DAla6EA binding in the female rabbit (40–120 days of age) did not show a correlation between binding site number and serum luteinizing hormone (LH). In addition, the net serum LH response in female rabbits to a subcutaneous injection of DAla6EA (10 ng, 100 ng, and 1 μg per kilogram body weight) was not significantly different between animals 40, 75, and 120 days of age. This suggests that a decrease in pituitary responsiveness to GnRH is not associated with sexual maturation in the female rabbit. Results indicate that factors other than and (or) in addition to GnRH binding site number, such as postreceptor events, play a role in gonadotropin secretion in the female rabbit.Key words: gonadotropin-releasing hormone, receptors, luteinizing hormone, female rabbit.
Maximal short-term exercise performance and ion regulation in cystic fibrosis
Authors: Lands L. C. , Heigenhauser G. J. F. , Jones N. L.
Published: April 2011

Controversy exists over whether defects in electrolyte transport exist in erythrocytes from cystic fibrosis (CF) patients. We hypothesized that differences in ion regulation in CF would affect skeletal muscle performance during intense exercise. Seven well-nourished CF patients were compared with seven healthy age-matched control subjects. Skeletal muscle performance was assessed during a 30-s sprint on an isokinetic cycle ergometer. Ion regulation was evaluated from arterialized venous blood sampled at rest, at peak exercise, and after 5 min of recovery. There was no difference in sprint performance between the CF (total work, 93.7 ± 30.02% predicted; endurance, 30.6 ± 9.93% decline) and control (109.7 ± 19.48%; 35.6 ± 14.76%) groups. The changes in plasma and erythrocyte ions and blood gases did not differ between the groups. There was a suggestion that the CF group may have had an inadequate ventilatory response to the metabolic challenge of short-term maximal exercise. The contribution of decreases in the strong ion difference to increases in plasma hydrogen ion concentrations was less in the CF group. This may be due to alterations in ionic regulation in CF, but the influence of inadequate arterialization of the blood samples could not be ruled out.Key words: isokinetic cycle ergometer, ion movement, hydrogen ion, cystic fibrosis.
Evidence for defective glucose sensing by islets of fa/fa obese Zucker rats
Authors: Chan Catherine B. , MacPhail Ruth M. , Mitton Katherine
Published: April 2011

The hypothesis that a defect in glucose sensing by islets of fa/fa Zucker rats contributes to hyperinsulinemia in these animals was tested. Islets from lean and fa/fa rats were isolated by collagenase digestion and step-density gradient purification and then cultured overnight in Dulbecco's modified Eagle's medium containing 12.5 mM glucose. Obese rat islets were more sensitive to hypoglycemic glucose levels with half-maximal effective concentration (EC50) of 5.6 mM compared with an EC50 of 8.2 mM for lean rat islets. In contrast, responsiveness of both phenotypes to α-ketoisocaproate and quinine was similar. Mannoheptulose did not inhibit insulin secretion from fa/fa islets, although inhibitors of later events in the stimulus–secretion coupling pathway were normally inhibited by iodoacetate and diazoxide. Finally, starvation in vivo and culture of islets in low glucose concentrations (5 mM) in vitro both decreased glucose-stimulated insulin secretion from lean but not fa/fa rat islets. We conclude that fa/fa rat islets have an exaggerated insulin response to hypoglycemic stimuli, possibly as a result of a defect in B-cell glucokinase function.Key words: insulin secretion, obesity, glucose metabolism, starvation.
Gastrointestinal inflammation: focus on the vascular endothelium
Authors: MacCannell Keith
Published: April 2011

Ischemia of the intestine predominantly affects the small bowel and colon, and may ensue from a variety of causes, ranging from radiation enteritis to the use of drugs that affect the intestinal vasculature. Gut ischemia has historically been thought of as "large-vessel" disease, but microcirculatory pathology and ischemia–reperfusion injury is increasingly being implicated in gut infections and even in chronic idiopathic inflammatory processes involving the gut, such as ulcerative colitis and Crohn's disease.Key words: intestinal ischemia, ischemia–reperfusion, gastrointestinal inflammation, microcirculation, Crohn's disease.
Polymorphonuclear leukocyte – endothelium interactions: a role for pro-inflammatory and anti-inflammatory molecules
Authors: Kubes Paul
Published: April 2011

The movement of polymorphonuclear leukocytes (PMNs) from the mainstream of blood to the extravascular space is a characteristic feature of the inflammatory response. This process requires that the PMN initially contacts the endothelium, then adheres firmly to the vessel wall, and finely migrates out of the microvasculature. Each of these events requires signals or pro-inflammatory molecules that direct the PMN to the potential site of inflammation. These molecules include histamine, which appears to be of importance in the initial recruitment of PMNs, leukotriene B4, which promotes PMN adhesion, and platelet-activating factor, which may contribute to both the adhesion process as well as the migration through the endothelial barrier. Although many other pro-inflammatory molecules have been identified, including the cytokines and complement, the three aforementioned molecules are used in this review as paradigms of the varying functions that pro-inflammatory molecules have in the inflammatory process. There is a growing body of evidence that in addition to the many pro-inflammatory agents found in the body there are a number of important anti-inflammatory molecules, including nitric oxide, prostacyclin, and adenosine. Each of these molecules possess important properties that serve to interrupt or protect against the ongoing inflammatory process. The anti-inflammatory potential of these endogenous molecules is discussed.Key words: nitric oxide, histamine, platelet-activating factor, prostacyclin, leukotriene B4, adenosine.
Spinal modulation of duodenal and colonic motility and arterial pressure by neuropeptide Y, neuropeptide Y fragment 13–36, peptide YY, and pancreatic polypeptide in rats: involvement of the cholinergic nervous system
Authors: Wager-Pagé S. A. , Raizada E. , Veale W. L. , Davison J. S.
Published: April 2011

The pancreatic polypeptide-fold (PP-fold) peptides, peptide YY (PYY) and pancreatic polypeptide (PP) (200 pmol), increased duodenal intraluminal pressure following intrathecal (IT) administration into the thoracic (T8–T10) spinal cord of urethane-anesthetized rats. Neuropeptide Y (NPY), PPY, and PP (IT) increased colonic intraluminal pressure of rats. The excitatory effects of the PP-fold peptides, NPY and PYY, were accompanied by increases in mean arterial pressure (MAP) during the same time period followed by a decrease to hypotensive levels. There were no further alterations of duodenal or colonic pressure in rats during the hypotensive period. The effect of PP (IT) on MAP was characterized by a pattern of hypotension frequently followed by a hypertensive period. The modulation of duodenal and colonic pressure does not differ between the members of the PP-fold family of peptides; however, the effects of the different members of the PP-fold family of peptides on MAP were varied. The Y2 receptor ligand, NPY (13–36) (200 pmol) (IT), did not alter duodenal and colonic pressure or MAP in rats. Therefore, the effects of PYY and NPY in the thoracic spinal cord on duodenal and colonic motility may be mediated via Y1 (postjunctional) receptors. Atropine, a muscarinic antagonist, attenuated NPY's (IT) excitatory effect on colonic pressure but did not alter the MAP response to this peptide. Atropine did not modify PYY's (IT) regulation of duodenal and colonic intraluminal pressure. However, atropine did attenuate PPY's inhibitory effect on MAP. The modulatory effects of PP (IT) on colonic pressure and MAP were attenuated by atropine, suggesting that the cholinergic system may be mediating the effects of this peptide. These observations provide further evidence that the modulation of gastrointestinal motility by PYY, PP, and NPY in the thoracic spinal cord is through different mechanisms.Key words: PP-fold peptides, duodenum, colon, atropine.
Assessment of atrial natriuretic peptide resistance in cirrhosis with head-out water immersion and atrial natriuretic peptide infusion
Authors: Legault Louis , Warner Leonard C. , Leung Wai Ming , Logan Alexander G. , Blendis Laurence M. , Skorecki Karl L.
Published: April 2011

The nature of sodium retention in cirrhosis complicated by ascites has been studied for the last 30 years. Resistance to the natriuretic action of atrial natriuretic peptide (ANP) may play a potential role in this sodium retention. To further evaluate this possibility, we studied 12 patients with biopsy-proven cirrhosis and ascites on 2 consecutive days after a 7-day period off diuretics while receiving a 20 mmol/day sodium restricted diet. Following a crossover design, patients underwent head-out water immersion (HWI) for 3 h and were infused with a α-human ANP for 2 h on 2 consecutive days. Blood and urine samples were collected hourly. Five patients displayed a natriuretic response to HWI, sufficient to achieve negative sodium balance, and these patients were termed responders. Each of these five patients also displayed a natriuretic response to ANP infusion. In contrast, the other seven patients (nonresponders) consistently failed to develop a natriuretic response to either maneuver. The two groups had similar elevations in plasma ANP concentrations, but at baseline differed in terms of plasma sodium, plasma renin activity, and serum aldosterone. Despite higher serum aldosterone concentrations, nonresponders excreted less potassium than responders during the peak effect of the interventions, suggesting greater sodium delivery to the aldosterone-sensitive nephron segment in responders. We conclude that the inability to mount an adequate sodium excretory response to HWI in patients with cirrhosis may be conveyed through increased antinatriuretic factors that decrease the sodium delivery to the medullary collecting duct and inhibit the natriuretic effect of ANP at that site.Key words: atrial natriuretic peptide, cirrhosis, ascites, sodium.
Rhythmic delta-frequency activities in the nucleus accumbens of anesthetized and freely moving rats
Authors: Leung L. Stan , Yim C. Y. Conrad
Published: April 2011

In urethane-anesthetized rats, a membrane potential oscillation (MPO) of up to 30 mV and 0.5–2 Hz (delta frequency range) was found in neurons of the nucleus accumbens. The membrane potential oscillations were of similar frequency and reversed in phase to the extracellular EEG of about 0.5 mV. In freely moving rats, a rhythmic delta EEG of 0.5–3 Hz was found in the nucleus accumbens, and it was of highest amplitude and regularity during awake immobility and face washing, less regular during slow wave sleep, and of the lowest amplitude during body and head movements and rapid eye movement sleep. The behavioural relation of the accumbens EEG was not critically affected after amphetamine, haloperidol, and parachlorophenylalanine, which depleted serotonin, although the accumbens EEG during awake immobility was less regular after blocking muscarinic cholinergic receptors by atropine sulfate. However, stimulation of the ventral tegmental area suppressed the accumbens delta membrane potential oscillations and EEG, and this effect was antagonized by haloperidol, suggesting that endogenous dopamine release may suppress the accumbens delta rhythm. It was concluded that the delta rhythm in the nucleus accumbens may represent a state of bilateral synchrony among accumbens neurons that is perhaps characteristic of an idling system, while desynchronization of the delta rhythm may occur closely with motor action.Key words: delta rhythm, nucleus accumbens, behaviour, membrane potential oscillations, dopamine.
A dual approach to self-stimulation and locomotor trace affected by chronic methamphetamine treatment for an animal model of schizophrenia
Authors: Takigawa Morikuni , Maeda Hiroshi , Ueyama Kenichi , Tominaga Hidefumi , Matsumoto Kei
Published: April 2011

The effect of long-term methamphetamine (MAP) treatment on intracranial self-stimulation of the lateral hypotholamus and locomotor traces was assessed. An attempt was made to provide a useful animal model for understanding anhedonia, stereotypy, and reoccurrence of liability, which are analogous to symptoms of schizophrenia. The frequency of intracranial self-stimulation (ICSS) as used as a measure of the animals' "hedonic–anhedonic" state. Following long-term MAP treatment (3 mg/kg), rats gradually showed stereotyped behavior, and became inactive and unresponsive to ICSS. These behavioral changes and decreased ICSS lasted several weeks after cessation of chronic MAP treatment and seemed to suggest post-MAP chronic psychosis and (or) anhedonia, two of the negative symptoms of schizophrenia. The traces of rat behavior affected by chronic MAP treatment were classified into three types, peripheral, mixed, and fixed, occurring in a dose-dependent manner. Reverse tolerance, similar to the reoccurrence of schizophrenic symptoms, was observed as a fixed stereotypy associated with loss of ICSS. These abnormal phenomena were suppressed by pretreatment with haloperidol. In the present study, the combination of ICSS and locomotor trace affected by chronic MAP treatment was proposed as an animal model of schizophrenia and as a useful technique for gauging the effect of neuroleptics.Key words: self-stimulation, anhedonia, stereotypy, reverse tolerance, animal disease model, schizophrenia, methamphetamine.
Lack of norepinephrine – neuropeptide Y interactions in the hypothalamic control of cardiovascular regulation in urethane-anesthetized rats
Authors: Petrie Jean Paul , Jones Douglas L.
Published: April 2011

Noradrenergic input to the hypothalamus is implicated in cardiovascular and behavioral regulation. The hypothalamus also contains high concentrations of neuropeptide Y (NPY), which often is colocalized in noradrenergic neurons. Systemically, NPY has been demonstrated to act synergistically with norepinephrine. Injections of concentrated solutions of NPY into the cerebral ventricles or hypothalamus have been found to alter ingestive behaviours, but the role of NPY in cardiovascular regulation is unknown. The objectives of this study were to determine if NPY injected directly into the hypothalamus elicits cardiovascular responses and (or) if the simultaneous administration of NPY with norepinephrine alters the cardiovascular responses elicited by norepinephrine alone. The hypothalamus of the urethane-anesthetized rat was mapped for heart rate and blood pressure responses to injections of one of the following: saline; NPY (1.9 or 0.6 pmol per injection site); norepinephrine (24, 81, or 243 nmol per injection site); or the combination of norepinephrine plus NPY. Site and drug selection were randomized. Injections of 0.25 μL were at 1.0 μL/min, bilaterally for bilateral structures and unilaterally for midline structures. Norepinephrine routinely elicited dose-dependant increases in blood pressure with latencies of approximately 1 min, which peaked by 3–5 min, accompanied or followed by tachycardia. Saline and NPY injections alone elicited no significant responses in any site. When NPY was injected together with norepinephrine, there were no significant alterations in cardiovascular variables except for attenuation of pressor responses when NPY was injected into the preoptic region and attenuation of tachycardia when NPY was injected into the caudal hypothalamus. These data suggest that, unlike the interactions between NPY and norepinephrine systemically or in the hypothalamic control of ingestive behaviour, there is little interaction with regard to hypothalamic control of cardiovascular function. However, as the animals were anesthetized with urethane, these negative responses need to be confirmed in the unanesthetized animal.Key words: neuropeptide Y, noradrenaline, cardiovascular regulation, hypothalamus, blood pressure.
Response characteristics of amygdaloid neurons provoked by emotionally significant environmental stimuli in cats, with special reference to response durations
Authors: Maeda Hisao , Morimoto Hiroshi , Yanagimoto Kazuyuki
Published: April 2011

Extracellular single or multiple neuronal activities were recorded from the basolateral portion of the amygdala of wild adult cats under an unanesthetized, freely moving condition, and neuronal responsiveness to neutral, aversive, and appetitive stimuli was studied. Of 71 units, 47 (66%) responded to some of the stimuli. The patterns of neuronal responses were classified into three types on the basis of response duration. Of the responses sampled, 9% rapidly attenuated and disappeared before termination of stimulus presentation (pattern A), 58% of responses were maintained during the period of the stimulus presentation but disappeared abruptly after termination (pattern B), and 33% of responses markedly outlasted the stimulus presentation period (pattern C). Pattern A responses habituated readily and were most prominent when neutral stimuli were presented, so this type of response was considered to underlie alterting or orienting responses. Pattern B responses were observed equally for the three kinds of stimuli, and were suggested to be predominantly involved in perception of the environmental stimuli. Pattern C responses habituated least and tended to be elicited more frequently by aversive stimuli. This type of response was interpreted to reflect emotional arousal. These findings were considered to be compatible with the hypothesis that the amygdala plays an important role in converting environmental stimuli into emotions such as rage or fear.Key words: emotions, aversiveness, appetitiveness, amygdala, extracellular neuronal activity.
Functional interaction of dopamine and glutamate in the nucleus accumbens in the regulation of locomotion
Authors: Wu Michael , Brudzynski Stefan M. , Mogenson Gordon J.
Published: April 2011

The interaction of dopamine and glutamate in the nucleus accumbens in the regulation of locomotion was investigated. Microinjection of N-methyl-D-aspartic acid (NMDA, a glutamatergic NMDA receptor agonist) or α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA, a quisqualic receptor agonist which is a glutamatergic non-NMDA receptor agonist) into the nucleus accumbens caused a substantial increase in locomotor activity. This increase in locomotor activity was significantly reduced by prior administration of the dopamine D2 agonist quinpirole, but not the D1 agonist, SKF 38393, into the same brain sites. The reduction in locomotion produced by quinpirole was dose dependent. Eight days after the ventral tegmental area was lesioned with 6-hydroxydopamine to destroy the dopamine projection and the axon terminals of the mesolimbic dopamine neurons in nucleus accumbens, the hyperkinetic effects produced by injections of NMDA and AMPA into the nucleus accumbens were substantially reduced. These results suggested that the glutamate agonist induced locomotion is mediated by dopamine. Thus, it appears that NMDA- or AMPA-induced locomotion is due to the activation of glutamate receptors on the mesolimbic dopamine terminals in the nucleus accumbens which release dopamine and subsequently increase locomotion.Key words: nucleus accumbens, dopamine, glutamate, quinpirole, locomotion, N-methyl-D-aspartic acid, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid.
Hypoxia and β-hydroxybutyrate acutely reduce glucose extraction by the brain in anesthetized dogs
Authors: Chang Albert S. Y. , D'Alecy Louis G.
Published: April 2011

Induced ketosis may acutely prolong hypoxic tolerance by altering glucose and (or) β-hydroxybutyrate extraction by the brain. Anesthetized dogs were ventilated and instrumented for arterial and cerebral venous blood sampling, taken during baseline, infusion, test, and recovery periods. Each dog received one of four different β-hydroxybutyrate doses and 25 min of either a normoxic or hypoxic (8% oxygen) test period. Arterial glucose and β-hydroxybutyrate were stable in the saline and 3 mg∙kg−1∙min−1 β-hydroxybutyrate infusion groups, but glucose declined and β-hydroxybutyrate increased in the 10 and 20 mg∙kg−1∙min−1 β-hydroxybutyrate infusion groups. During normoxia glucose arteriovenous differences across the brain decreased significantly only in the 20 mg∙kg−1∙min−1 β-hydroxybutyrate infusion groups, and during hypoxia the differences decreased for all groups. β-Hydroxybutyrate arteriovenous differences tended to increase with a 100-fold increase in β-hydroxybutyrate concentrations, but the trend was not statistically significant. Hypoxia further decreased glucose extraction, but did not change β-hydroxybutyrate extraction. We conclude that β-hydroxybutyrate may protect during hypoxia by depressing glucose uptake and consumption rather than by acting as an alternative cerebral energy substrate.Key words: ketosis, anoxia, high altitude, cerebral metabolism, brain damage.
Active calcium absorption in primary cultures of cortical collecting duct cells
Authors: Rochelle Lori G. , Deveshwar Sangita , Náray-Fejes-Tóth Anikó , Fejes-Tóth Géza
Published: April 2011

Primary cultures of rabbit cortical collecting duct (CCD) cells demonstrated accumulation of Ca at the basolateral (BL) side when cultured on either impermeable or permeable supports. Cell monolayers cultured on impermeable plastic surfaces absorbed Ca with such avidity that hydroxyapatite crystals formed. When cultured on a permeable matrix, the cells demonstrated significant net apical (A) to BL Ca transport against a lumen negative transepithelial potential difference. A steady-state BL/A [Ca] ratio of 120 developed across monolayers in 24 h on days 6 through 8 postseeding. Initial rates of unidirectional 45Ca fluxes on days 6 through 8 indicated a negligible BL to A flux (5.4 ± 2.6 nmol∙h−1∙cm−2) compared with A to BL 45Ca flux (99.4 ± 19.4 nmol∙h−1∙cm−2). Parathyroid hormone applied to the BL side had no significant effect on either unidirectional 45Ca flux, but the second messenger analog, 8-bromoadenosine cyclic monophosphate, increased the A to BL flux by 65%. Inhibiting the Na+–K+ ATPase with ouabain (10−4 M) reduced the A to BL flux by 77%; however, a significant net A to BL flux still remained. Apical addition of amiloride (2 × 10−5 M) did not affect either unidirectional 45Ca flux. In addition, the inorganic Ca channel blockers Ni2+ (100 μM and 1 mM), La3+ (100 μM and 1 mM), and Cd2+ (20 and 50 μM) did not significantly inhibit either unidirectional 45Ca flux. These results demonstrate that CCD monolayers actively absorb Ca and this can be stimulated by cyclic AMP, raising the possibility that apical Ca entry does not involve amiloride-sensitive channels, or typical Ca channels.Key words: calcium transport, cortical collecting duct, cultured cells.