bluuebunny/crossref_metadata_2025 huggingface dataset:
Blockade of hyperbaric oxygen induced seizures by excitatory amino acid antagonists
Authors: Colton Carol A. , Colton Joel S.
Published: April 2011

The effectiveness of several excitatory amino acid antagonists to delay or block seizures induced by oxygen at high pressure was examined in mice. Of the antagonists tested, namely, L-proline, DL-α-aminoadipate, DL-2-amino-5-phosphonovalerate, and L-glutamic acid diethyl ester, DL-2-amino-5-phosphonovalerate was the most effective in delaying or preventing seizures. L-Glutamic acid diethylester was also effective but at significantly higher doses, which were also associated with marked sedation.
Role of diet fat in subcellular structure and function
Authors: Clandinin M. T. , Field C. J. , Hargreaves K. , Morson L. , Zsigmond E.
Published: April 2011

Current concepts of the biomembrane will be extrapolated to membranes of homeotherms to illustrate the influence of the nature of dietary lipid in nutritionally complete diets on membrane polar head group content and fatty acid composition. Utilizing animal models, the controlling influence of dietary long chain fatty acids on major lipid constituents of the mitochondrial membrane in cardiac tissue, the plasma membrane of liver, and the synaptosomal membrane in brain can be demonstrated. Diet-induced alterations in membrane composition arc associated with demonstrable changes in the function of specific membrane proteins. To illustrate this relationship, the effect of diet on mitochondrial ATPase activity and on a hormone receptor-stimulated function in the plasma membrane of the liver will be discussed. These observations suggest that the diet fat modulates enzyme functions in vivo by changing the surrounding lipid environment in the membrane.
Effect of 1,25(OH)2D3 on the relative contributions of skeletal 45Ca and intestinal 40Ca to blood calcium in normal and thyroparathyroidectomized dogs
Authors: Klein LeRoy , Wong Kam M.
Published: April 2011

The effects of gradually increasing doses of 1,25(QH)2D3 on plasma calcium and 45Ca radioactivity were studied in young dogs that had been extensively prelabelled with 45Ca. The effects of orally and intravenously administered 1,25(OH)2D3 were evaluated in normal and thyroparathyroidectomized dogs fed a normal diet. In normal dogs when 1,25(OH)2D3 increased the plasma calcium within the normal range (2.9–3.1 mmol/L) there was no significant increase in plasma 45Ca. In thyroparathyroidectomized dogs, oral or intravenous 1,25(QH)2D3 increased the low blood calcium to a normal level (1.8–2.9 mmol/L) without significantly increasing plasma 45Ca. In normal and thyroparathyroidectomized dogs, any 1,25(OH)2D3-induced increase in plasma calcium above the normal range was associated with a significant increase in 45Ca, indicating mobilization of bone calcium. Intravenous administration of 1,25(OH)2D3 in the normal or thyroparathyroidectomized dogs had a much larger effect than oral doses in mobilizing bone 45Ca when inducing a similar level of hypercalcemia. The major physiological effect of 1,25(OH)2D3 in the low or normal range of plasma calcium is on intestinal absorption of calcium without a significant effect on mobilizing bone calcium. The pharamacological effect of 1,25(OH)2D3in vivo is to mobilize bone calcium as well as dietary calcium into blood.
Activity of in situ middle cervical ganglion neurons in dogs, using extracellular recording techniques
Authors: Armour J. A.
Published: April 2011

Neuronal activity in the in situ middle cervical ganglion of dogs was investigated using extracellular recording techniques. The recorded action potentials were frequently active during specific phases of the cardiac cycle, particularly during systole, and this activity persisted following acute decentralization of the ganglion. The activity of these action potentials was modified when systemic arterial pressure was altered by isoproterenol, noradrenaline, adrenaline, or partial occlusion of the aorta, whether in the intact or acutely decentralized preparation. These neurons were active between systolic pressures of 70 and 180 mmHg (1 mmHg = 133.322 Pa). Action potentials were frequently modified by mechanical distortion of the superior vena cava, ventricular epicardium, or adventitia of the aorta, whether the preparation was acutely decentralized or not. Seventy percent of these action potentials were unaffected by stimulation (1 ms, 4 V, 0.5 Hz) of a cardiopulmonary nerve and 27% were suppressed by such stimulation. Five of the neurons were activated by such stimulation. It is presumed that the latter neurons had axons in a cardiopulmonary nerve and most likely were efferent sympathetic postganglionic neurons. Sixty-three percent of these spontaneously active phase-locked units were modified by stimulation of a ramus or an ansa. It is postulated that some of the neurons in the middle cervical ganglia can be modified by afferent axons arising from receptors in thoracic organs, in particular from the great vessels and heart, whether in an intact or acutely decentralized preparation. The majority of these neurons are presumed not to be afferent neurons or efferent postganglionic neurons, as they are not activated directly by electrical stimulation of axons in cardiopulmonary nerves. Rather they are presumed to be interneurons. These results lend support to the thesis that considerable integration of neuronal activity related to thoracic cardiovascular dynamics occurs within the middle cervical ganglia of dogs.
Quantitative determination of histamine metabolites by capillary gas chromatography
Authors: Navert H. , Bérubé R. , Wollin A.
Published: April 2011

A method using capillary gas chromatography is described for the determination of histamine and eight of its basic and acid metabolites in a single biological sample of serum, urine, or gastric juice. Ion-exchange chromatography and extraction with organic solvents are used for isolation and purification, and gas chromatography for identification and quantitation. The heptafluorobutyryl derivatives of histamine and some basic metabolites are compatible with nitrogen–phosphorus and electron capture detection modes and offer an excellent sensitivity (detection limit 0.1 pmol with electron capture). The acid metabolites are quantitated after esterification. The linearity range, the sensitivity, a partial study of reproducibility and typical chromatograms show that the method is adaptable to a variety of applications.
Stereospecific opioid drug receptors on excitable cell membranes
Authors: Frank G. B.
Published: April 2011

In the past decade evidence has accumulated showing that there are stereospecific opioid drug receptors located on the surface membranes of neurones and skeletal muscle fibres which can block action potentials when opioid drugs are applied to the cells. The nature of this evidence and the difficulties involved in this area of investigation are discussed in detail. Two different mechanisms have been described for this depression of excitability; one, a direct blocking action on sodium channels (or the calcium channels in the case of cells with calcium action potentials) and the other, a stimulation of membrane potassium conductance which results in hyperpolarization and increased membrane conductance both of which decrease excitability. For the most part these different mechanisms seem to prevail in different cell types as will be discussed. Some other points discussed are as follows: first, in higher doses (or concentrations) opioids produce a local anestheticlike effect which cannot be antagonized by opioid antagonists; next, the opioid antagonists which are easily available and commonly employed change from antagonists to agonists as their concentration is increased; and finally, the evidence required for the demonstration of stereospecific opioid receptors is considered in some detail.
Temporal desensitization of rat uteri for the decidual cell reaction is abolished by cholera toxin acting by a mechanism apparently not involving adenosine 3′:5′-cyclic monophosphate
Authors: Johnston M. E. Anne , Kennedy T. G.
Published: April 2011

To determine if increased endometrial vascular permeability (a response which precedes decidualization) could be obtained in temporally nonsensitized uteri by treatments designed to increase endometrial adenosine 3′:5′-cyclic monophosphate (cAMP) concentrations, cholera toxin (an activator of adenylate cyclase) was injected into the uterine lumen of immature rats treated to be at the equivalent of day 4, 5, or 6 of pseudopregnancy. In all experiments, the rats were pretreated with indomethacin to inhibit endogenous prostaglandin (PG) synthesis. Endometrial vascular permeability, determined using 125I-labeled bovine serum albumin, was assessed 8 h later. Cholera toxin increased endometrial vascular permeability to the same level in all groups. As determined by uterine weights 5 days after the intrauterine administration of cholera toxin or its vehicle, the toxin produced the same extent of decidualization in all groups. Cholera toxin had no detectable effect on uterine cAMP concentrations in rats sacrificed 15 min after intrauterine treatment. In contrast, intrauterine administration of PGE2 increased uterine cAMP concentrations at 15 min in all groups. These data suggest that the effects of cholera toxin and of PGE2 on endometrial vascular permeability and decidualization are not mediated by cAMP.
Compliance characteristics of the hind-limb arterial system of normal and hypertensive rabbits
Authors: Langille B. Lowell , Osberg Catherine
Published: April 2011

Pressure transients resulting from square-wave changes in abdominal aortic blood flow rate were used to derive effective arterial compliance and peripheral resistance of the hind-limb circulation of anaesthetized rabbits. The model for deriving these parameters proved applicable if step changes in flow were kept less than 35% of mean flow. Under resting conditions, the effective hind-limb arterial compliance of normal rabbits averaged 3.46 × 10−3 mL/mmHg (1 mmHg = 133.322 Pa). Hind-limb arterial compliance decreased with increasing pressure at low arterial pressures, but unlike compliance of isolated arterial segments, compliance did not vary at and above normal resting pressures. Baroreflex destimulation (bilateral carotid artery occlusion) caused an increase in effective hind-limb vascular resistance at 48.4% and a decrease of arterial compliance of 50.7%, so that the constant for flow-induced arterial pressure changes (resistance times compliance) was largely unchanged. Similarly, the arterial time constant for rabbits with chronic hypertension was similar to that for controls because threefold increases in hind-limb vascular resistance were offset by decreases in compliance. Reflex-induced decreases in arterial compliance are probably mediated by sympathetic nerves, whereas decreases associated with hypertension are related to wall hypertrophy in conjunction with increased vasomotor tone. Arterial compliance decreased with increasing pressure in hypertensive animals, but this effect was less pronounced than in normotensive rabbits.
Evidence for a role of prostaglandin I2 and thromboxane A2 in the ductus venosus of the lamb
Authors: Adeagbo A. S. O. , Bishai I. , Lees J. , Olley P. M. , Coceani F.
Published: April 2011

The prostaglandin (PG) endoperoxide, PGH2, and the thromboxane (TX) A2 analog, 9,11-epithio-11,12-methano-TXA2, were tested in vitro on the ductus venosus sphincter from fetal (premature and mature) and neonatal (1-day-old) lambs. PGH2 relaxed the indomethacin-contracted fetal ductus in a dose-dependent manner and its action was reduced after treatment with 15-hydroperoxyarachidonic acid. In contrast, reduced glutathione did not affect the PGH2 relaxation in the indomethacin-treated ductus, nor did it modify the response of the untreated ductus to constrictor stimuli. Unlike PGH2, the stable 9α, 11α-epoxymethano-PGH2 analog contracted the vessel. Similarly, the TXA2 analog was a contractile agent, its action exceeding that of the PGH2 analog in potency and efficacy. The TXA2 analog was active on preparations from both premature (minimum 117 days gestation) and mature lambs, but a maximal effect was attained during the perinatal period. These results confirm the existence of a PG-mediated relaxing mechanism in the ductus venosus and suggest that the active compound is PGI2. This mechanism is likely responsible for keeping the ductus patent in the fetus. TXA2, formed within the liver parenchyma, is well suited for playing a role in postnatal closure of the vessel.
Effect of lanthanum on the inotropic response of isoproterenol: role of the superficially bound calcium
Authors: Fawzi Ahmad B. , McNeill John H.
Published: April 2011

Mammalian myocardial contractility is believed to be related to the amount of calcium contained in a highly labile superficial calcium pool. The purpose of this study was to determine the role of such sites in the positive inotropic effect of isoproterenol. Lanthanum, an ion that is restricted to the extracellular space and that displaces the superficially bound calcium, was selected as a tool for this investigation. In Langendorff preparations of the guinea pig heart, lanthanum decreased the basal contractility index (+ dP/dtmax) in a concentration-dependent fashion (0.05–3μM) and blocked the inotropic response of isoproterenol in a noncompetitive manner (0.25–3 μM). Three-micromolar lanthanum (i) reduced basal contractility and the maximum response to isoproterenol by 97 and 95%, respectively, (ii) had no significant effect (p > 0.05) on basal and isoproterenol-induced cyclic AMP levels, and (iii) had no effect on the Kd of [3H]nitrendipine binding, but reduced the Bmax by 31%. While 1 μM lanthanum reduced basal contractility and the maximum response to isoproterenol by 90 and 70%, respectively, it had no effect on [3H]nitrendipine binding. These results suggest that the effects of such low concentrations of lanthanum (≤3 μM) are not related to a direct action on the calcium channels and are not mediated by an inhibition of isoproterenol stimulation of the enzyme adenylate cyclase. Therefore, one interpretation of these results suggests that superficially bound calcium is required for the inotropic response of isoproterenol.
Rebound cardiovascular responses following stimulation of canine vagosympathetic complexes or cardiopulmonary nerves
Authors: Armour J. A. , Randall W. C.
Published: April 2011

Electrical stimulation of a canine vagosympathetic complex or a cardiopulmonary nerve can elicit a variety of negative chronotropic and inotropic cardiac responses, with or without alterations in systemic arterial pressure. In the period immediately following cessation of such a stimulation "rebound" tachycardia, increased inotropism above control values in one or more regions of the heart, and (or) elevation in systemic arterial pressure can occur. These "rebound" phenomena are abolished by propranolol or ipsilateral chronic sympathectomy. It is proposed that "vagal" poststimulation "rebound" of the canine cardiovascular system is primarily the result of activation of sympathetic neural elements present in the vagosympathetic complexes or cardiopulmonary nerves.
Neonatal hyperthyroidism alters submandibular gland epidermal growth factor response to thyroxine in the adult mouse
Authors: Walker Peter
Published: April 2011

Neonatal hyperthyroidism (NH) in the rat is associated with permanent reductions in serum thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH) concentrations in the adult, changes suggestive of a hypothyroid state. In the adult NH rat, the thyrotroph appears to be more sensitive to the feedback effects of thyroid hormones. To determine whether thyroid hormone sensitive tissues retain their responsiveness to thyroid hormones, the long-term effects of NH on mouse submandibular gland (SMG) epidermal growth factor (EGF) content were examined. NH was induced in female mice by 20 daily subcultaneous injections of 0.4 μg of T4 per gram of body weight. Control female mice received daily injections of vehicle alone. At 21 days of age, NH and control mice were sacrificed and SMG EGF content was measured by specific radioimmunoassay. SMG EGF content and concentration in 21-day-old NH mice exceeded that of control mice by 2400- and 1500-fold, respectively (P < 0.001). SMG EGF content and concentration in adult (90-day-old) NH mice were slightly, but not significantly, lower than those of control mice. Mean SMG weight, however, was significantly decreased in adult NH mice (P < 0.01). Interestingly, SMG content and concentration of EGF in adult NH mice were lower than in 21-day-old NH mice. After 5 days T4 treatment (16 μg/d) of adult mice, SMG weight in NH mice increased significantly (P < 0.01) but was unchanged in control mice. SMG EGF content and concentration increased significantly in both adult NH and control mice (P < 0.01). However, the magnitude of the increase was markedly obtunded in adult NH mice. These observations indicate that thyroid hormones precociously and exponentially increase SMG EGF content and concentration in neonatal mice. The marked increases strongly suggest thyroid hormone mediated synthesis of EGF and acceleration of maturation of gene expression for EGF synthesis. In addition, NH appears to modify thyroid hormone regulation of gene expression for EGF synthesis in adult mice.
Time course of the total and radioactive carbon dioxide production by piglets receiving dietary [14C]phenylalanine
Authors: Ball R. O. , Bayley H. S.
Published: April 2011

The influence of experimental protocol (i.e., timing of feeding and of the collection of expired carbon dioxide) upon the sensitivity of using the oxidation of a labelled amino acid as an indicator of the adequacy of the dietary amino acid balance was investigated using 2.5-kg piglets confined in ventilated chambers. In the first experiment it was shown that consumption of two meals, each of 20 g and separated by 2 h, after an overnight fast resulted in a rapid rise in carbon dioxide concentration in the air withdrawn from the chamber. The concentration peaked 12 min after the second meal and remained elevated for 50 min. In the second experiment the piglets received two meals containing three levels of either lysine (8, 10, and 12 g/kg) or tryptophan (1.3, 1.8, and 2.0 g/kg) plus 10 μCi L-[alanine-1-14C]phenylalanine (1 Ci = 37 GBq) in each meal. Radioactivity released as 14CO2 peaked in the second hour following the last meal, but there was such great variation in the mean for the three diets that they were not statistically different. However, in the third hour following the second meal both the means and their variances had decreased with the differences between the diets being statistically significant for this time period. An experiment with varying levels of tryptophan showed a similar effect of meal consumption on 14CO2 release. The third experiment confirmed the effect of time of collection upon the statistical significance of the dietary amino acid balance measured by the release of radioactivity from [14C]phenylalanine.
Heterogeneous uptake of 9-β-D-arabinofuranosyladenine by mouse spleen lymphocytes
Authors: Almeida Anthony F.
Published: April 2011

Spleens of mice treated with 9-β-D-[2,8-3H]arabinofuranosyladenine (araA), 0.5–30.0 mg/kg showed rapid dose-dependent accumulation of 3H, which peaked at 2.5 mg/kg. Lymphocytes from spleens showed linear uptake when incubated with 0.68, 1.36, and 5.03 μM araA over 120 s. With 1.0 mM araA, uptake was reduced in rate but was not saturated. Tritiated metabolites identified from these lymphocytes were araA which predominated after brief incubations, its deaminated form (araH), and some phosphorylated product in small amount. Inhibition of deaminase increased intracellular araA. Although potent inhibitors of nucleoside transport inhibited araA uptake marginally, adenosine competed with araA for about 50% of the uptake capacity. The data suggest that the uptake of araA by mouse lymphocytes, which is not simple diffusion, occurs by a mechanism distinct from typical nucleoside transport.
N-Glucosidation of amobarbital in the cat
Authors: Carro-Ciampi Giovanna , Jurima Mallé , Kadar Dezso , Tang Bing K. , Kalow Werner
Published: April 2011

N-Glucosidation is a novel pathway of barbiturate metabolism, so far known to occur only in man. A search for an animal model, conducted through in vitro screening, revealed that amobarbital-N-glucoside was formed in liver preparations from the cat. The presence of amobarbital-N-glucoside was demonstrated in cat urine, following i.p. administration of amobarbital.
The elastic properties of canine abdominal aorta at its branches
Authors: Touw Deborah M. , Sherebrin M. H. , Roach Margot R.
Published: April 2011

The elastic properties of the abdominal aorta at regions of junctions were studied using strips from 17 dogs. Strips of tissue cut longitudinally and circumferentially at the celiac, mesenteric, and renal branches were used to compare the properties of the proximal and distal junctions, as well as the aorta and artery regions adjoining. The tissues were stored for at least 24 h to ensure that no active component of the smooth muscle remained. The elastic properties measured here are due to elastin and collagen, with a small contribution from dead smooth muscle cells. The tissue strips were tested at 20 °C while immersed in saline using an Instron tensile testing machine. Elongation of the three regions was measured from photographs taken as the tissue was stretched. Stress values went to 200 kN/m2 as the strain increased to approximately 0.8. (The physiological range for the dog was calculated as 40–85 kN/m2.) The distal junctional region was found to be the most extensible for both longitudinally and circumferentially oriented strips. These results have important implications for flow models as they imply that the shape of the junctional region probably changes between diastole and systole.
Calcium-translocating and cardiotonic properties of oxidation products of linoleic acid
Authors: Kim Ryungsoon Song , Bihler Ivan , LaBella Frank S.
Published: April 2011

Calcium-translocating activity of linoleic acid and its lipoxygenase (linoleate: oxygen oxidoreductase; EC 1.13.11.12) metabolites or autoxidation products was determined in vitro by estimation of 45Ca transport from a bulk aqueous to a bulk organic phase. Fresh commercial linoleic acid, tested immediately after removal from a sealed vial, stimulated calcium translocation only at concentrations greater than 1 mM. In contrast, 45Ca translocation by linoleic acid exposed to air was detectable at 10 μM. Oxidation products of linoleic acid obtained either by incubation with lipoxygenase or by autoxidation were much less potent than the calcium ionophore A23187. The products obtained by enzymic oxidation of linoleic acid enhanced contractility in the Langendorff-perfused guinea pig heart up to 45% over control (at 3 × 10−8 M). The inotropic response was transient with rapid onset and not affected by the beta-adrenergic antagonist, propranolol. The autoxidation products of linoleic acid increased cardiac contractility up to 43% at 10−6 M. In contrast, fresh linoleic acid caused only a negative inotropic effect at 10−8 to 3 × 10−7 M, progressing to contracture at 10−6 M. These findings suggest that conflicting reports on the cardiostimulant effect of linoleic acid may be due to varying levels of the autoxidation products. Linoleic acid metabolites in vivo may have a physiological role in myocardial function related to their Ca2+-ionophoric activity.
Modulation of positive inotropy and metabolic coronary dilatation by myocardial α-adrenoceptors
Authors: Youngson Bruce J. , Talesnik Jaime
Published: April 2011

Cardiac hyperactivity and its consequent metabolically induced coronary vasodilatation (MCD) were studied in isolated, perfused, electrically paced rat hearts. The α-adrenoceptor agonists, phenylephrine and methoxamine, produced a concentration-dependent inhibition of the inotropic responses to noradrenaline, dobutamine, isoprenaline, tyramine, and glucagon, while relatively potentiating their MCD reactions. This inhibition was unrelated to the α-agonists' known inotropic action and was not affected by catecholamine depletion of the heart. Withdrawal of the α-agonists or administration of the α-adrenoceptor antagonists phentolamine, phenoxybenzamine, or prazosin returned the inotropic and MCD reactions to normal. Neither the MCD response to electrically induced tachycardia nor the inotropic reactions produced by calcium chloride were affected by α-adrenoceptor agonists or antagonists. Alone, α-adrenoceptor antagonists were shown to potentiate the inotropic responses to noradrenaline and isoprenaline while the MCD was relatively diminished. The responses to glucagon were unaltered by α-antagonists. We postulate that myocardial reactivity to sympathetic stimulation can be modulated through α-adrenoceptors by the inhibition of processes that mediate cardiostimulation at post-β-adrenoceptor sites, together with facilitation of those leading up to MCD. Accordingly, this modulation would act to prevent ischaemic damage to the heart by acting to limit the inotropic responses to increasing sympathetic stimulation while maximizing the blood supply to the myocardium.
The distension stimulus to gastric acid secretion in the isolated mouse stomach
Authors: Davison J. S. , Najafi-Farashah A.
Published: April 2011

Distension of the isolated mouse stomach stimulated gastric acid secretion. Atropine, cimetidine, or proglumide antagonized the actions of cholinomimetics, histamine, and gastrin, respectively. However, these antagonists and the nerve blocking agent, tetrodotoxin, were without effect on basal secretion or distension-stimulated secretion. It is concluded that in the isolated mouse stomach neither basal secretion nor secretion evoked by distension involve the release of any of the established "physiological" secretagogues or the activation of intramural nerves.
Evidence for a secretory component in the handling of unconjugated bilirubin by the isolated perfused rat kidney
Authors: Elías María M. , Comin Elbio J. , Ochoa Elena J. , Garay Emilio A. Rodríguez
Published: April 2011

Previous studies in rats have suggested that the urinary excretion of unconjugated bilirubin (UB) comprises only a small fraction of the pigment that reaches the tubular lumen by glomerular filtration and escapes from tubular cell reabsorption. However, additional data also indicated that UB interacts with renal peritubular cell membranes impairing the secretion of p-aminohippurate (PAH). In this study we examined the possibility of a secretory step which could also be involved in the renal excretory mechanism for UB. An isolated rat kidney preparation was used, and the uptake of UB by renal tissue, the UB appearance in the urine, and the secretion of PAH were analyzed throughout the perfusion. The results indicated that the UB urinary excretion rate changed independently of UB filtered load. The latter remained almost unchanged during the perfusion, whereas the excretion rate of UB and the UB-to-creatinine (Cr) clearance ratio increased significantly. Furthermore, a relationship between the uptake of UB by the kidney, the UB-to-Cr clearance ratio, and the decrease in PAH secretion rate, was proved. In addition, when probenecid was added to the perfusate solution the cumulative uptake of UB by the kidney and the rate of excretion of UB in the urine were diminished. We conclude that the mechanism of UB excretion by the kidney may be considered as the result of a process involving glomerular filtration plus tubular secretion followed by a back diffusion step from the lumen in a similar way to other endogenous compounds, thus explaining the virtual absence of UB from the normal urine.
Pathogenesis of hyperphosphatemia in lactic acidosis: disparate effects of racemic (DL-) and levo (L-) lactic acid on plasma phosphorus concentration
Authors: Oster James R. , Alpert Helen C. , Vaamonde Carlos A.
Published: April 2011

The mechanism(s) for the hyperphosphatemia associated with lactic acidosis is unknown. Experimental lactate-induced hyperphosphatemia appears to require acidemia because we have shown that prevention of acidemia with NaHCO3 obviates increases in plasma phosphorus concentration ([P]). Since the rate of lactate metabolism (by utilizing NAD or other mechanisms) might modulate transcellular movement of phosphorus, we assessed the plasma [P] response to 3-h infusions of DL-lactic acid versus L-lactic acid. The dog metabolizes primarily the L- moiety of DL-lactic acid (thereby consuming H+), so more L-lactic acid is needed to produce the degree of acidemia attained with DL-lactic acid. Group 1 (n = 6) mongrel dogs received 12 mequiv./kg DL-lactic acid; group 2 (n = 6) 12 mequiv./kg L-lactic acid, and group 3 (n = 7) 16–19 mequiv./kg L-lactic acid. Prior to acid loading, the plasma [P] and acid–base status of the three groups were similar. After 3 h, blood pH and [HCO3] and change from base line in plasma [P], in both milligrams per decilitre and percent, were as follows: group 1: 7.05 ± 0.02, 9 ± 2 mM, 1.9 ± 0.4 mg/dL, 38 ± 10%; group 2: 7.28 ± 0.02, 18 ± 1, 0.9 ± 0.3, 17 ± 6; group 3: 7.06 ± 0.04, 12 ± 1, 1.1 ± 0.3, 26 ± 10, respectively. Thus, there was a tendency for both infusion rates of L-lactic acid to increase [P] less than DL-lactic acid, suggesting the importance of other factors in addition to pH. Also, since presumably more lactate was metabolized in group 3 than in group 2 (but the change in [P] was approximately the same in both), the findings do not support the hypothesis that the rate of lactate utilization is a major modulator of plasma [P] in acute lactic acidosis.
The neurotoxic actions of quinolinic acid in the central nervous system
Authors: El-Defrawy S. R. , Boegman R. J. , Jhamandas K. , Beninger R. J.
Published: April 2011

Excitotoxins such as kainic acid, ibotenic acid, and quinolinic acid are a group of molecules structurally related to glutamate or aspartate. They are capable of exciting neurons and producing axon sparing neuronal degeneration. Quinolinic acid (QUIN), an endogenous metabolite of the amino acid, tryptophan, has been detected in brain and its concentration increases with age. The content of QUIN in the brain and the activity of the enzymes involved in its synthesis and metabolism show a regional distribution. The neuroexcitatory action of QUIN is antagonized by magnesium (Mg2+) and the aminophosphonates, proposed N-methyl-D-aspartate (NMDA) receptor antagonists, suggesting that QUIN acts at the Mg2+-sensitive NMDA receptor. Like its excitatory effects, QUIN's neurotoxic actions in the striatum are antagonized by the aminophosphonates. This suggests that QUIN neurotoxicity involves the NMDA receptor and (or) another receptor sensitive to the aminophosphonates. The neuroexcitatory and neurotoxic effects of QUIN are antagonized by kynurenic acid (KYN), another metabolite of tryptophan. QUIN toxicity is dependent on excitatory amino acid afferents and shows a regional variation in the brain. Local injection of QUIN into the nucleus basalis magnocellularis (NBM) results in a dose-dependent reduction in cortical cholinergic markers including the evoked release of acetylcholine. A significant reduction in cortical cholinergic function is maintained over a 3-month period. Coinjection of an equimolar ratio of QUIN and KYN into the NBM results in complete protection against QUIN-induced neurodegeneration and decreases in cortical cholinergic markers. In contrast, focal injections of QUIN into the frontoparietal cortex do not alter cortical cholinergic function. Animals showing central cholinergic hypofunction induced by QUIN could serve as experimental models for testing pharmacological agents aimed at improving the function of damaged cholinergic neurons.
The effects of dihydropyridine calcium antagonists on heme biosynthesis in chick embryo liver cell culture
Authors: Marks G. S. , Goldman D. R. , McCluskey S. A. , Sutherland E. P. , Lyon M. E.
Published: April 2011

A variety of 1,4-dihydropyridine calcium antagonists were tested for porphyrinogenic activity in chick embryo liver cell culture. 3,5-Dimethoxycarbonyl-1,4-dihydro-2,6-dimethyl-4-(ortho-nitrophenyl)pyridine (nifedipine) was shown to be a potent porphyrinogenic agent. This activity was shared by a number of related analogues, viz., the 4-phenyl, 4-(meta-nitrophenyl), 4-(para-nitrophenyl), 4-(ortho-methoxyphenyl), 4-(meta-trifluoromethylphenyl), and 4-(para-trifluoromethylphenyl) analogues and nitrendipine; nicardipine exhibited very weak activity. The porphyrinogenic potency of the 1,4-dihydropyridines did not parallel their calcium antagonist activity. Nifedipine did not exhibit ferrochelatase-lowering activity in chick embryo liver cell culture and uroporphyrin and heptacarboxylic acid porphyrin were the major porphyrins to accumulate. Nifedipine did not cause suicidal destruction of cytochrome P-450 in chick embryo hepatic microsomes. Because nifedipine possesses comparable porphyrinogenic activity to sodium secobarbital in chick embryo liver cell culture, caution is required if nifedipine or related drugs are administered to patients with hereditary hepatic porphyria.
Direct measurement of the influx of sodium in frog skeletal muscle
Authors: Menard M. R.
Published: April 2011

When a frog's sartorius is immersed in sodium-free lithium-substituted solution at 0 °C, the tissue sodium content declines in two distinct phases. The rate of the slow phase has a temperature dependence expected for a process dependent on metabolism (Q10, ca. 3), and sodium content (51.5 mmol/kg dry weight) equal to that measured by others using electron microprobe microanalysis. The rate of the rapid phase has a temperature dependence (Q10, 0.3–1) expected for a passive process, and a sodium content equal to that in the sorbitol space. It was concluded that incubation of a muscle at 0 °C for 45 min in sodium-free solution will wash out almost all of the sodium in the extracellular space but will leave almost all the sodium in the intracellular space. The unidirectional sodium influx was measured by incubating a muscle in 22Na-containing Ringer's solution for a timed interval at 23 °C, then in sodium-free lithium-substituted solution at 0 °C for 45 min, before analysis for ion content and radioactivity. The ratio of the specific activity of sodium in the muscle to that in the radioactive bathing solution was calculated, and the time course of its rise was used to calculate an influx rate coefficient. The use of the specific activity minimizes the error due to the loss of intracellular sodium and radiosodium which occurs during the wash in cold solution. It was found that the rate of the radiosodium uptake varied as the uptake proceeded, in a manner similar to that previously shown for the rate of the radiosodium efflux and attributed to the existence of a diversity of cell size in this muscle.
In vivo bupivacaine reduces the in vitro sensitivity of the human vas deferens to phenylephrine
Authors: Kawamoto J. H. , Owen J. A. , Morales A. , Nakatsu K.
Published: April 2011

The isolated human vas deferens (HVD) has been the subject of a limited number of pharmacological studies. Furthermore, it has not been established whether the local or general anesthetics used in obtaining the HVD affect the responses of this isolated tissue. Therefore, the aim of this study was to determine if the local anesthetic, bupivacaine (BPV), alters the sensitivity of the HVD to agonists. It was shown that BPV, injected into subjects undergoing vasectomy, was present in the excised HVD and in sufficient concentration to attenuate the phenylephrine (PE)-induced contraction. Bupivacaine assays were done by gas chromatography – mass spectrometry. Following 3 h of equilibration with repetitive washing, 95.0 ± 2.1% (SD) of the BPV could be eliminated from the tissue, which correlated well with an observed increase in sensitivity of the HVD to PE. The sensitivity to PE of HVD isolated from subjects under general anesthesia was less than the sensitivity of tissues obtained with bupivacaine and in this case the depressant effect was not reversed by washing. These results indicate that it is important to consider the anesthetic procedure used to acquire the HVD and also the equilibration procedure prior to pharmacological studies.
Disopyramide phosphate effects on slow and depressed fast responses
Authors: Schanne Otto F. , Bkaily G. , Dumais B. , Boutin L.
Published: April 2011

We studied the effects of disopyramide phosphate on explanted neonatal rat ventricle cells exhibiting depressed fast responses or naturally occurring slow response action potentials together with automatic activity. Disopyramide suppressed the spontaneous activity at a concentration of 2.5 μg/mL with a half-maximal value of 10 μg/mL. Before spontaneous activity was lost, there was an increase in beating rate possibly related to membrane depolarization. In depressed fast and slow response action potentials there was an increase in action potential duration (APD) which was consistently found both at the level of the plateau and at 90% repolarization. Comparison of the APD increase observed after disopyramide treatment and that after exposure to 20 mM tetraethylammonium suggested a block of a potassium conductance as a possible cause underlying the change in APD. The [Formula: see text] values of the depressed fast response decreased at constant membrane potential and this was attributed to the local anesthetic effect of the drug. In addition, we report two novel findings: (i) a decrease of [Formula: see text] of the slow response action potentials which may be secondary to membrane depolarization, and (ii) an increase in the duration of slow action potentials, possibly caused by inhibition of a potassium conductance.
Symposium Changing perspectives on the functional organization of the segmental motor system
Authors: Binder Marc D.
Published: April 2011

Results from a wide variety of recent studies on the architecture and innervation of skeletal muscles, the neuromechanical characteristics of motor units, and the properties and spinal reflex actions of muscle proprioceptors present a number of challenges to conventional views of the functional organization of the segmental motor system. To illustrate the nature of these challenges, studies directed toward several specific issues are reviewed. These include the functional subdivision of single muscles into two or more neuromuscular compartments; the patterns of synaptic input from peripheral afferent fibers to motoneurons innervating muscle units of different "type;" and the convergence in the segmental reflex pathways from muscle spindles and tendon organs to motoneurons.
Uptake of glucose and release of fatty acids and glycerol by rat brown adipose tissue in vivo
Authors: Ma Stephanie W. Y. , Foster David O.
Published: April 2011

The net in vivo uptake or release of free fatty acids glycerol, glucose, lactate, and pyruvate by the interscapular brown adipose tissue (IBAT) of barbital-anesthetized, cold-acclimated rats was determined from measurements of plasma arteriovenous concentration differences across IBAT and tissue blood flow. Measurements were made without stimulation of the tissue and also during submaximal and maximal stimulation by infused noradrenaline (NA), the physiological activator of BAT thermogenesis. There was no appreciable uptake of glucose or release of fatty acids and glycerol by the nonstimulated tissue. At both levels of stimulation there was significant uptake of glucose (1.7 and 2.0 μmol/min) and release of glycerol (0.9 and 1.2 μmol/min), but only at maximal stimulation was there significant release of fatty acids (1.9 μmol/min). Release of lactate and pyruvate accounted for 33% of the glucose taken up at submaximal stimulation and 88% at maximal stimulation. By calculation, the remainder of the glucose taken up was sufficient to have fueled about 12% of the thermogenesis at submaximal stimulation, but only about 2% at maximal stimulation. As estimated from the rate of glycerol release, the rate of triglyceride hydrolysis was sufficient at submaximal stimulation to fuel IBAT thermogenesis entirely with the resulting fatty acids, but it was not sufficient to do so at maximal stimulation when some of the fatty acid was exported. It is suggested that at maximal NA-induced thermogenesis a portion of lipolysis proceeded only to the level of mono- and di-glycerides with the result that glycerol release did not fully reflect the rate of fatty acid formation. Both in absolute terms and in relation to the export of glycerol the in vivo export of fatty acids from the adipocytes of IBAT was much less than is observed with brown adipocytes in vitro.
Effects of dieldrin on hepatic carbohydrate metabolism in the suckling and adult rat
Authors: Fox Glyn R. , Virgo Bruce B.
Published: April 2011

Hepatic carbohydrate metabolism was studied in adult and suckling rats given age-specific LD50 doses of dieldrin po. These doses in 5-, 10-, and 60-day-old Wistar rats were 38, 28, and 63 mg/kg, respectively. Plasma glucose and free fatty acids (FFA), and hepatic glycogen, phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-diphosphatase (FDP), and glucose-6-phosphatase (G6P) were measured 1 and 3 h after administration of the insecticide. Plasma glucose concentrations were elevated (17%) in some 5-day-old rats after 1 h and in all adults after 1 and 3 h (45 and 30%, respectively). Plasma FFA concentrations were decreased (9%) in the 5-day-old rat 1 h after dieldrin. Hepatic glycogen content was reduced in both 5- and 10-day-old pups at 1 hour (22 and 17%, respectively). Hepatic FDP activity was elevated in the 5-day-old rat at 1 h (17%) and was decreased (10%) in the 10-day-old rat at 3 h. Hepatic PEPCK activity was increased in adult animals by 30% 1 h after dieldrin. Furthermore, PEPCK activity was increased at 3 h in rats of all ages (76%, 5-day-old pup; 115%, 10-day-old pup; 56%, 60-day-old adult). Hepatic G6P activity was unaltered by dieldrin. Thus only the activity of hepatic PEPCK is consistently elevated by dieldrin exposure. However, this enhanced PEPCK activity is associated with dieldrin-induced hyperglycemia only in the adult rat.
Gastric and duodenal motility in the cat: the role of central innervation assessed by transient vagal blockade
Authors: Bendeck M. P. , Reynolds R. P. E.
Published: April 2011

Experiments were performed on four cats to characterize fasting gastric and small bowel motility and to assess the role of extrinsic vagal innervation in the control of that motor activity. A multilumen manometry tube was positioned to record pressure changes from the proximal small bowel and stomach. Transient vagal nerve blockade was accomplished by cooling the cervical vagosympathetic nerve trunks, previously isolated in skin loops on each side of the neck. Two characteristic patterns of basal activity were documented in the stomach: (i) regular phasic contractions of variable amplitude in the body of the stomach; and (ii) infrequent, irregular contractions of high amplitude in the distal antrum. In the duodenum, two predominant activity patterns were noted: (i) periods of continuous irregular activity; and (ii) irregular clusters of contractions separated by quiescent intervals. No typical migrating motor complex activity was seen in the basal gastric or small bowel recordings. Bilateral vagal blockade did not consistently change the general pattern of gastric or small bowel activity, but did appear to reduce gastric contractile activity, as measured by motility indices. We conclude that extrinsic vagal innervation does not play a major role in the control of fasting feline gastric and duodenal motility.
The effect of prolonged infusion and withdrawal of angiotensin II in the spontaneously hypertensive rat
Authors: Chiu Edward K. Y. , McNeill J. Robert
Published: April 2011

In spontaneously hypertensive rats (SHR) and their normotensive Wistar–Kyoto controls (WKY), prolonged intravenous administration of angiotensin II (AII, 0.2 μg∙kg−1∙min−1 for 3 h) resulted in similar increases in arterial blood pressure. Heart rate decreased in WKY and increased in SHR. At the end of the infusion, blood pressure dropped substantially in SHR, but not in WKY: at 5 h after AII withdrawal, blood pressure in SHR had fallen from a control value of 172 ± 3.3 to 146 ± 3.9 mmHg (p < 0.01), whereas pressure in WKY had fallen from 116 ± 3.0 to 107 ± 4.2 mmHg (statistically non significant). Thus, pressure at 5 h after AII withdrawal was still substantially higher (p < 0.01) in the SHR than in the WKY. The results demonstrate that the fall in blood pressure following withdrawal of a prolonged infusion of AII in SHR is much less than that reported to occur following withdrawal of a prolonged infusion of vasopressin (AVP) in SHR.
Plasma lipids and other factors in the LA/N corpulent rat in the presence of chronic exercise and food restriction
Authors: Russell J. C. , Amy R. M.
Published: April 2011

The effects of regular exercise and food restriction were studied in the LA/N corpulent rat up to age 9 months. This congenic strain of the Lister and Albany rat is normotensive, corpulent, and hyperlipidemic when homozygous for the corpulent (cp) gene derived from the Koletsky strain. Food restriction of corpulent animals to the intake of matched lean rats caused body weight to be significantly lower, although not as low as that of the lean animals. Plasma total cholesterol in freely eating sedentary corpulent animals was significantly higher (210 mg/100 mL) than in food-restricted rats (165 mg/100 mL), in which plasma cholesterol was considerably elevated compared with lean rats (80 mg/100 mL). Exercise caused a modest but significant increase in both total and high density lipoprotein cholesterol in both corpulent and lean rats. The rise was greater in corpulent rats and, in food-restricted exercising corpulent rats, the cholesterol concentrations were equivalent to those of freely eating corpulent animals. Systolic blood pressure in lean rats fell slowly from 146 mmHg at 8 weeks to 132 mmHg at 36 weeks and was not affected by exercise. Sedentary corpulent rats showed a rapid rise in systolic pressure from 107 mmHg at 7 weeks to 128 mmHg at 11 weeks. This rise was reduced by food restriction and completely prevented by the combination of food restriction and exercise. Thus, in this strain of rats exercise was associated with higher plasma cholesterol concentrations, while food restriction had limited effects.
Stabilization of intracellular recordings in the cat spinal cord using high-frequency ventilation
Authors: Duffin J. , Lipski J.
Published: April 2011

Stabilization of intracellular recordings by a substantial reduction of respiratory motion may be accomplished by the use of high-frequency ventilation (600–800 breaths/min). The technique is a simple one and enables maintenance of relatively constant blood gas tensions. Although the improved stability was demonstrated in experiments performed on alpha motoneurones in the thoracic spinal cord, it is anticipated that a reduced respiratory movement should benefit recordings in other spinal and supraspinal sites.
Is the change in intracellular pH during fatigue large enough to be the main cause of fatigue?
Authors: Renaud J. M. , Allard Y. , Mainwood G. W.
Published: April 2011

The intracellular pH of frog sartorius muscles exposed to an extracellular pH 8.0 (25 mM HCO3−, 1% CO2) was 6.9–7.1. Following a fatiguing stimulation period (one tetanic contraction per second for 3 min), the intracellular pH was 6.5–6.7. When similar experiments were repeated with frog sartorius muscles exposed to pH 6.4 (2 mM HCO3−, 1% CO2), the intracellular pH was 6.8–6.9 at rest and 6.3–6.4 following fatigue. So, in both experiments the intracellular pH decreased by 0.4–0.5 pH unit during fatigue. When the CO2 concentration of the bathing solution was increased from 1 to 30%, the intracellular pH of resting muscles decreased from 7.0 to 6.2–6.3. Although the effect of CO2 on the intracellular pH was greater than the fatigue effect, the decrease in tetanic force with CO2 was less than 40%, while during fatigue the tetanic force decreased by at least 70%. Therefore in frog sartorius muscle the decrease in tetanic force during fatigue exceeds the decrease that is expected from just a change in intracellular pH.