bluuebunny/crossref_metadata_2025 huggingface dataset:
The correlation of ethanol-induced depression of glucose and water transport with morphological changes in the hamster jejunum in vivo
Authors: Fox J. E. , McElligott T. F. , Beck I. T.
Published: April 2011

Glucose and water transport is depressed in the hamster jejunum in vivo by ethanol (4.8%) which also produced fluid-filled blebs at the tips of the villi. The epithelial cells over the blebs appeared stretched and cuboidal, the lateral intercellular spaces (LIS) were no longer recognizable, and the lacteals were closed. Forty-five minutes after discontinuation of the ethanol, water transport returned to normal while glucose transport remained depressed. At this time the villus structure had returned to normal. The blebs had disappeared, the LIS were again recognizable, and their appearance and number were similar to those in the control animals. Thus, the depression of water transport correlated with the obvious structural changes caused by ethanol; however, the depression of glucose absorption is associated with some effect of ethanol not evident by routine light microscopy.
The electrophysiological effects of disopyramide phosphate on canine ventricular muscle and Purkinfe fibers in normal and low potassium
Authors: Kus Teresa , Sasyniuk Betty I.
Published: April 2011

We studied the effect of lowering the extracellular potassium concentration ([K+]0) on the electrophysiological actions of disopyramide phosphate, a new antiarrhythmic drug. At low [K+]0, therapeutic concentrations of disopyramide phosphate caused significantly less depression of action potential amplitude and maximum upstroke velocity of both Purkinje fiber and ventricular muscle action potentials. The drug shifted the membrane responsiveness curve along the voltage axis to more negative membrane potentials regardless of [K+]0. However, a greater shift occurred when [K+]0 was normal. Disopyramide phosphate prolonged both action potential duration and effective refractory period in all fibers but there was consistently greater prolongation of these parameters at low [K+]0, More importantly, disopyramide phosphate altered repolarization time course of action potentials in such a way that action potentials with dissimilar durations throughout the ventricular conducting system became more equal. The drug was less effective in decreasing this disparity in action potential durations throughout the ventricles in the presence of low [K+]0. These modifications of the electrophysiological actions of disopyramide by low [K+]0 suggest that a therapeutic concentration of disopyramide might have less of an antiarrhythmic effect in the presence of hypokalemia.
Effect of prolonged intermittent thyrotropin-releasing hormone administration to fetal and neonatal rats
Authors: Walker P. , Dussault J. H.
Published: April 2011

Fetal and neonatal rats received daily subcutaneous injections of 10 μg thyrotropin-releasing hormone (TRH) until 7 or 14 days postnatally. At 70 days the pups were challenged with 1 μg TRH intravenously via an indwelling jugular cannula. Basal serum thyroxine, triiodothyronine, and thyroid-stimulating hormone (TSH) concentrations did not differ among the three groups. The mean TSH responses as determined by the mean peak TSH concentration and the total TSH response as determined by planimetry were not significantly different, and there was no significant difference in pituitary TSH content following the TRH challenge among the three groups. This study suggests that the integrity of the hypothalamo–pituitary axis in adult rats cannot be affected by the repeated administration of pharmacologic doses of TRH during the perinatal period.
Cardiovascular actions of kinins in the rabbit
Authors: Barabé J. , Marceau F. , Thériault B. , Drouin J.-N. , Regoli D.
Published: April 2011

The results obtained in this study indicate that the complex cardiovascular effect of BK in vivo may result from direct actions on vascular smooth muscles, presumably mediated by at least two types of receptors, as well as from the release of endogenous prostaglandins. BK and congeners exert a direct action on vascular smooth muscle by stimulating specific receptors both of the B1 type (in the aorta, the large arteries, and the mesenteric vein) and of the B2 type (in the jugular vein); and these vascular tissues provide useful preparations for pharmacological studies of bradykinins. Isolated organs perfused through their main arteries with physiological medium respond to BK by an increase of perfusion pressure (vasoconstriction in isolated ears and kidneys) or by a decrease (vasodilation in the rabbit heart). The vascular effects of BK in the heart and the kidney depend in part on the release of endogenous prostaglandins and on the activation of receptors that appear to be of the B2 type.Like other endogenous hypotensive agents, BK appears to reduce the tonus of the peripheral vessels, while contracting large arteries and veins. The results obtained in vitro are discussed with respect to the hypotensive effect in vivo and to the role of kinins in inflammation and oedema.
Properties of phrenic nerve activity during experimental periodic breathing in cats
Authors: Tamas Laszlo , Polosa Canio
Published: April 2011

Periodic breathing was evoked in Nembutal-anesthetized cats by graded hemorrhage and common carotid artery occlusion. The cats were vagotomized, paralyzed, and artificially ventilated, and the integrated phrenic neurogram (IPN) was recorded. In all cases, the periodic breathing was associated with sustained oscillation of blood pressure (Mayer waves). Twelve episodes of periodic breathing were analyzed. End-inspiratory IPN voltage (Vm) showed characteristic quasi-sinusoidal oscillations with a 30-s average period, accompanied in all 12 cases by a synchronous oscillation of IPN slope. Both oscillations persisted after abolishing the blood pressure waves with an α-adrenergic blocking agent, showing that they were not dependent on phasic baroreceptor input. In four cases there were oscillations of inspiratory and total respiratory cycle duration (and in three of these, expiratory duration also) in synchrony with the Vm and slope waves. In two further cases, expiratory duration oscillated 180° out of phase to Vm and slope, while inspiratory duration records showed only irregular variations. In the remaining six cases, inspiratory, expiratory, and total respiratory cycle duration remained relatively constant during the Vm and slope oscillation. The observed modulation of total respiratory cycle duration indicates that the mechanism generating periodic breathing was acting on the brainstem respiratory oscillator, where respiratory cycle duration is set. The slope modulation is also likely to result from an action at the brainstem oscillator level, although a spinal site of action cannot be entirely excluded.
Parathyroïdes et hypertension artérielle à l'acétate de désoxycorticostérone chez le rat
Authors: Berthelot A. , Schleiffer R. , Gairard A.
Published: April 2011

We studied the importance of parathyroids in the development of mineralocorticoid hypertension in male Sprague–Dawley rats. Ablation of the parathyroids 1 week before deoxycorticosterone acetate (DOCA) + NaCl administration prevented development of hypertension (for 1 year). But ablation of parathyroids 2 weeks after the start of treatment has no effect on the development of arterial hypertension. Autotransplantation of parathyroids in thyroidectomized rats caused a recurrence of mineralocorticoid hypertension, which was completed after DL-thyroxine supplementation: blood pressure levels were nearly the same as in DOCA sham rats. We conclude that parathyroid glands favor the establishment of mineralocorticoid hypertension in the rat. These results raise the question of the mechanism of action of parathyroid hormone in the hypertensive process.
Catechol O-methyltransferase activity in the human placenta and liver
Authors: Burba John V.
Published: April 2011

Catechol O-methyltransferase (COMT) obtained from human liver (HL) and human placenta (HP) was found to be much less active than rat liver (RL) COMT when norepinephrine, epinephrine, dopamine, and isoproterenol are used as substrates. The Km values, which reflect the affinity of substrate and enzyme, show that RL COMT has the highest affinity toward the catecholamine substrates followed by HP COMT and then HL COMT. Both HP and RL COMT preparations O-methylate the catecholamines primarily in the meta position.
The effects of periarterial nerve activation on coronary vessel tone in an isolated and perfused slab of beef ventricle
Authors: Kalsner Stanley
Published: April 2011

The direct effects of extrinsic nerve stimulation on coronary artery tone are unclear because of the complications arising from alterations in myocardial dynamics which themselves alter flow. An isolated and perfused nonbeating slab of beef ventricle was utilized in the present experiments to eliminate secondary complications and the effects of periarterial nerve activation on coronary perfusion pressure were examined. It was found that stimulation induced vasoconstrictor responses which were enhanced by physostigmine, a cholinesterase inhibitor, and blocked by atropine. These responses were duplicated by exogenous acetylcholine both in the perfused preparation and in isolated strips of coronary artery. Although added noradrenaline gave vasodilatation, no response attributable to the release of noradrenaline from nerves was obtained. It is concluded that the coronary vasculature of the beef receives a cholinergic innervation and that its activation, especially under conditions of reduced transmitter degradation, may induce considerable coronary vessel constriction.
Study on the influence of tyrosine deprotonation on the myotropic action of angiotensin II
Authors: Escher E. , Guillemette G.
Published: April 2011

The influence of phenolic tyrosine ionization in angiotensin II on the myotropic action of this peptide has been investigated in vitro on rabbit aortic strips. [Sar1, Tyr4]angiotensin II and [Sar1, (4′-amino)Phe4]angiotensin II (as a reference which cannot undergo the same ionization) were tested over a pH range from 6.8 to 9.0 and their activities compared. The results clearly indicate that angiotensin II with a deprotonated phenolic hydroxyl group on Tyr in position 4 is not the most active or only active form of angiotensin II.
The effects of nitrilotriacetic acid on solubilities of zinc, copper, manganese, and iron in the stomach of sheep
Authors: Ivan M. , Jui P. , Hidiroglou M.
Published: April 2011

Four sheep, each prepared with a rumen fistula and reentrant cannula in the proximal duodenum, were used to study the effects of ruminal administration of nitrilotriacetic acid on solubilities of zinc, copper, manganese, and iron in rumen and duodenal digesta. The sheep received a pelleted diet and were dosed with 0, 300, 600, and 1200 μg of nitrilotriacetic acid per gram of diet via the rumen fistula.Higher concentrations of soluble zinc, manganese, and iron, but not copper, were found in the rumen of the sheep when they were dosed with nitrilotriacetic acid. The concentrations increased with increasing dose of the acid. However, only the solubility of iron was increased in the duodenal digesta. Concentrations of soluble zinc and manganese in the rumen increased, whereas copper decreased, during the first 2 h after feeding. The pattern was reversed thereafter. Changes in the concentrations of soluble iron during 6 h after feeding were comparatively small.It is concluded that the solubility of iron in the stomach of sheep is increased by ruminal administration of nitrilotriacetic acid.
Norepinephrine concentration in kidneys of normotensive Wistar–Kyoto and spontaneously hypertensive rats
Authors: Stuart P. J. , Kline R. L. , Mercer P. F.
Published: April 2011

Renal norepinephrine (NE) concentration was measured in normotensive Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHR) at 7, 9, 11, and 13 weeks of age. Although the weight of kidneys was similar in the two strains of rats, renal NE concentration was significantly lower in SHR at all ages (147 ± 9 to 175 ± 13 ng/g for SHR, and 216 ± 8 to 262 ± 17 ng/g for WKY rats). The difference in renal NE concentration during this time of rapidly-increasing arterial pressure in the SHR suggests that renal NE may in some way be related to the development of hypertension.
Effect of allyl isothiocyanate on plasma and urinary concentrations of some biochemical entities in the rat
Authors: Muztar A. Jabbar , Huque Taufiqul , Ahmad Parvez , Slinger S. J.
Published: April 2011

Allyl isothiocyanate (AITC) is a constituent of several plants of the family Cruciferae that are commonly used as food. This study investigated the effect of feeding AITC to male Sprague–Dawley rats on their plasma glucose and uric acid levels as well as on the urinary concentrations of glucose, 17-ketosteroids (17-KS), creatinine, and uric acid. Other test compounds included were thyroxine (T4) and thiouracil (TU). AITC caused a highly significant (P ≤ 0.01) depression in the plasma glucose and uric acid levels compared with the control. TU caused a significant depression only of the plasma glucose. T4, on the other hand, significantly increased the levels of both glucose and uric acid.The AITC-treated rats voided twice as much urine as the controls or those receiving TU or injected with T4. The 24-h excretion of glucose, uric acid, and creatinine was significantly (P ≤ 0.01) higher in animals fed AITC than in those consuming the control diet, while the excretion of 17-KS was significantly lower. Results on an equal urine volume basis showed that differences in the excretion of glucose and creatinine were related to differences in the urine volume. TU significantly depressed excretion of all the compounds but glucose. The effect of T4 on the excretion of 17-KS and uric acid resembled that of AITC and TU, thus showing that these compounds depressed the androgenic function of the animal.
Factors affecting the encapsulation of drugs within liposomes
Authors: Stamp D. , Juliano R. L.
Published: April 2011

The reported efficiencies of drug encapsulation into liposomes range from less than 0.1% to more than 10% per micromole phospholipid, depending on the nature of the drug and of the liposome employed. We have sought to investigate some of the factors which control the efficiency of drug encapsulation. We have found that most polar drugs are sequestered within the internal aqueous compartment of the liposomes, while nonpolar drugs can bind to the liposome membrane in addition to being sequestered, thus accounting for their higher efficiencies of encapsulation. The encapsulation of nonpolar drugs, but not of polar drugs, is very sensitive to the physical characteristics of the liposome membrane; in particular, a fluid membrane favors the efficient encapsulation of nonpolar compounds. The drug cytosine arabinoside is anomalous in that this highly polar compound seems to interact with the liposome membrane at physiological conditions of pH and ionic strength, thus allowing it to be encapsulated with high efficiency.
High-affinity choline uptake in regions of rat brain and the effect of antidepressants
Authors: Hrdina P. D. , Elson K.
Published: April 2011

The effect of tricyclic antidepressants, chlorpromazine, and some monoamine oxidase inhibitors on the accumulation of [14C]choline by crude synaptosomal (P2) fraction from different regions of rat brain (cortex, striatum, and hippocampus) was investigated. Analysis of choline uptake kinetics resulted in high- and low-affinity components with different Michaelis constants. All tricyclic antidepressants tested inhibited in a dose-dependent manner the high-affinity choline uptake in the three regions, amitriptyline being the most potent. The IC50 values correlated significantly with the relative potencies of imipramine congeners in binding to muscarinic receptors in the brain. Neither tranylcypromine nor pargyline in concentrations up to 0.1 mM had any effect on choline transport. Concentrations of tricyclic antidepressants effective in inhibiting the uptake of choline failed to influence significantly the activity of choline acetyltransferase in brain regions examined. The results suggest that the effect of imipramine congeners on high-affinity choline uptake may be reflected in the anticholinergic properties of these compounds.
The effect of propranolol and dimethylpropranolol on cardiac conduction
Authors: Dresel Peter E. , Potter Pamela
Published: April 2011

Isolated dog hearts perfused with blood from a donor dog and driven at two heart rates were used to compare the effects of propranolol with those of its quaternary ammonium derivative on atrial, atrioventricular (AV) nodal, and His-Purkinje conduction. Propranolol slowed only AV-nodal conduction, increasing the minimal conduction time and the effect of prematurity, without affecting fatigue. Practolol did not have this effect. Dimethylpropranolol had similar but not identical effects on the AV node, but also slowed atrial and ventricular conduction. In contrast with the quaternary derivative of lidocaine, dimethylpropranolol's effect on atrial and ventricular conduction was not dependent on the heart rate. The effect of dimethylpropranolol on ventricular conduction was observed at doses lower than those reported by others to be antiarrhythmic.
Effect of acute and chronic renal denervation on renal function after release of unilateral ureteral obstruction in the rat
Authors: Wilson D. R. , Honrath U. , Sole M.
Published: April 2011

The role of the renal nerves in determining renal function after relief of 24-h unilateral ureteral obstruction (UUO) was studied using clearance techniques in anaesthetized rats. Acute renal denervation during the first 1-2 h after relief of UUO resulted in a significant increase in glomerular filtration rate (GFR), renal plasma flow (RPF), urine flow, and sodium and potassium excretion, changes which were not seen in the sham-denervated postobstructive kidney. Acute denervation of sham-operated normal kidneys caused a similar natriuresis and diuresis but with no change in GFR or RPF. Chronic renal denervation 4-5 days before UUO resulted in no change in the function of the postobstructive kidney compared with sham-denervated postobstructive controls, while chronic denervation alone was associated with a significantly higher urine flow and sodium excretion rate from the denervated kidney. The effectiveness of renal denervation was confirmed by demonstrating marked depletion of tissue catecholamines in the denervated kidney.It was concluded that renal nerve activity plays a significant but not a major role in the functional changes present after relief of UUO. Chronic renal denervation did not protect against the functional effects of unilateral ureteral obstruction.
Acetylcholine does not stimulate the release of growth hormone from perifused rat adenohypophyses
Authors: Kraicer J.
Published: April 2011

Acetylcholine (1 μmol/L − 1 mmol/L) has been reported to stimulate growth hormone release from perifused bovine pituitary slices. We have carried out studies using the perifused pars distalis of the rat adenohypophysis to see whether a similar response is observed. Neither acetylcholine, acetylcholine with eserine, nor carbamylcholine, at concentrations of 10−9, 10−6, and 10−3 M, stimulated the release of growth hormone. Thus we could not demonstrate a similar response to acetylcholine in the pars distalis of the rat adenohypophysis as reported in the bovine gland.
Electropharmacological analysis of the actions of histamine in cardiac tissue
Authors: Inoue F. , McNeill J. H. , Puil E. , Tenner Jr. T. E.
Published: April 2011

The effects of histamine in cardiac muscle of the guinea pig were resolved into actions at H1 and H2 receptors and compared with the effects and interactions of adrenergic agonists and antagonists. Using intracellular recording techniques and drug administration by superperfusion, right atrial muscle fibres and papillary muscle fibres from both ventricles were studied in vitro in conditions where the fast Na+-current system was presumably inactivated by depolarization with high [K+] perfusion. Application of histamine or the H2 agonist, 4-methyl-histamine, and of isoproterenol permitted restoration of action potential activity in such fibres which were otherwise incapable of generating action potentials following intense (> 100 times threshold) electrical stimulation. The above effects of histamine and 4-methyl-histamine were antagonized by metiamide; propranolol antagonized only the effects of isoproterenol. Perfusion with high [Ca2+] increased, while application of D 600 (an inhibitor of Ca2+ movements) reduced, the restorative effect of 4-methyl-histamine, implicating the involvement of a Ca2+-current system in the ionic events following H2 receptor activation. Specific α or H1 receptor agonists (methoxamine and 2-(2-pyridyl)-ethylamine) did not exhibit any restorative action. Applications of methoxamine, in the presence of a β blocker, increased the duration of action potentials without affecting their amplitude; this effect could be blocked with phentolamine. On the other hand, the H1 receptor agonist reduced the duration of ventricular action potentials; this effect could be antagonized by concomitant perfusion of promethazine. Although the effects of the H1 receptor agonist were demonstrated to be different from those of the α receptor agonist, the data suggest that histamine may cause its positive inotropic and chronotropic effects in the heart by activating H2 receptors in a manner analogous to that of β-adrenergic agents.
Activation by adenosine-5′-triphosphate of glutamic decarboxylase from a subcellular fraction of mouse brain
Authors: Tunnicliff Godfrey , Ngo That T.
Published: April 2011

Glutamate decarboxylase from a mouse brain P2 fraction undergoes a twofold activation in the presence of 0.5 mM ATP. No such stimulation by ATP occurs if the enzyme is assayed in the presence of excess pyridoxal phosphate as cofactor. The ATP-induced stimulation is almost completely eliminated if the enzyme is dialysed before its assay. [γ-32P]ATP present during the enzyme measurement is converted to [32P]pyridoxal phosphate. These results demonstrate that the activation produced by ATP is the result of the generation of cofactor during the course of the assay. This phenomenon may be a reflection of a control mechanism of glutamate decarboxylase activity.
Effects of microiontophoretically applied flurazepam on responses of cerebral cortical neurones to putative neurotransmitters
Authors: Nestoros J. N. , Nistri A.
Published: April 2011

Utilizing standard microiontophoretic techniques and recording extracellularly in cats, we studied the effects of flurazepam, a water-soluble benzodiazepine, on the spike activity of single cerebral neurones and its interactions with several excitatory and inhibitory putative neurotransmitters. Large iontophoretic doses (5–30 nA, 0.1 M solution) of flurazepam induced a depression of spike amplitude. Smaller doses (less than 5 nA, 0.1 M solution or 20–50 nA, 20 m.M in 0.16 M NaCl) reduced the excitation produced by glutamate, aspartate, and homocysteate, but antagonism of acetylcholine-evoked excitations required large flurazepam doses (up to 30 nA, 0.1 M solution). Even lower doses of flurazepam (<10 nA, 20 mM in 0.16 M NaCl) enhanced the inhibitory effect of γ-aminobutyric acid (GABA) but antagonized that of 5-hydroxytryptamine, and had no effect on dopamine-induced inhibition of firing. Hence, only GABA-evoked inhibitions were significantly potentiated by flurazepam. These results demonstrate the multiple possible interactions between a benzodiazepine and different putative neurotransmitters in the mammalian cerebral cortex.
The characteristics of in vitro hormone release from rat adenohypophysis provoked by acute chilling
Authors: Milligan John V.
Published: April 2011

The exposure of rat adenohypophysial tissue to iced media for brief periods of 2–7 min provokes a biphasic release of growth hormone (GH). An increased release of adrenocorticotropin (ACTH) and prolactin (PRL) is also detected in the "instantaneous" first phase which takes place while the tissue is still cold. No detectable movement of Ca2+ into or out of the cells occurs during this phase and the magnitude of release is unaffected when Ca-free media (<10 μM) are used. A "delayed" phase of GH and other hormone release begins some 20 min after the acute chill. It too occurs without changes in either 45Ca2+ uptake or Ca2+ content. This delayed release is unaffected by Ca-free media. The release of the cytoplasmic marker enzyme, lactic dehydrogenase (LDH), was also measured after a brief chill. LDH release was an order of magnitude less than the release of hormone measured in the same experiment indicating that exocytosis was reponsible for hormone release rather than nonspecific damage to the cells. I conclude that the hormone release following a brief chill does not employ a "stimulus–secretion coupling" mechanism. However, as the release is via exocytosis, some common aspect of the release mechanism beyond the "coupling" stage is activated to provoke the release of at least three adenohypophysial hormones, GH, ACTH, and PRL.
Biological activities of kinins and substance P octapeptides (4–11) in which phenylalanine residues have been replaced with L-carboranylalanine
Authors: Couture R. , Drouin J. -N. , Leukart O. , Regoli D.
Published: April 2011

The boron-containing amino acid carboranylalanine (Car) has been used for replacing the phenylalanine residues of bradykinin (BK), des-Arg9-BK and octa (4–11)-substance P (octa (4–11)-SP), in order to determine how the increased size and hydrophobicity of the aromatic residues will affect the biological activities of these peptides. Analogues of BK and of octa (4–11)-SP containing Car instead of Phe in positions 5 and 8 (BK) or 7 and 8 (octa (4–11)-SP) are practically inactive. A similar marked reduction of activity is observed with [Car8]-des-Arg9-BK, while [Car5]-des-Arg9-BK, although less potent than the natural BK fragment, shows a prolonged duration of action. Car has also been used to replace Phe5 in combination with the substitution of Phe8 by a Leu in the sequence des-Arg9-BK, in order to prolong the duration of action of antagonists for the B1 receptor of kinins. Moreover, a Lys has been added at the N-terminal of this sequence for further improving the affinity of the antagonism. The two chemical modifications have not produced the expected additive change of biological activity but a potent long-acting antagonist has been obtained with [Lys1,Car6,Leu9]-des-Arg10-BK.It is concluded that Car is unsuitable for replacing the phenyl residues of BK and octa (4–11)-SP, and also Phe8 of the fragment sequence des-Arg9-BK; Car appears, however, to be of some utility when used to replace Phe5 of the same sequence, as it prolongs the duration of action of agonists and of antagonists acting on the B1 receptor for kinins.
Interaction of clonidine with chronotropic agents on isolated right atria
Authors: Rodgers Robert L. , Tenner Jr. Thomas E. , Laher Ismail E. , McNeill John H.
Published: April 2011

Clonidine was administered to isolated guinea pig right atria in order to characterize its chronotropic activity and its interaction with other chronotropic agents at the postjunctional level. Clonidine either had no significant effect (10−7–10−4 M) or decreased (10−3 M) atrial rate. Pretreatment of the atria with clonidine noncompetitively antagonized (10−6–10−4 M) the positive chronotropic actions of isoproterenol, and competitively antagonized (10−4 M) the negative chronotropic actions of pilocarpine. At doses of 10−6 or 3 × 10−6 M, clonidine also noncompetitively antagonized the positive chronotropic effects of 4-methylhistamine and glucagon. The results show that clonidine antagonizes both adrenergic and cholinergic influences on atrial rate at the postjunctional level and suggest that the antagonism of adrenergic influences does not involve a direct interaction with β-adrenergic receptors.
Lack of effect of botulinum toxin on nonadrenergic, noncholinergic inhibitory responses of the guinea pig fundus in vitro
Authors: Paul M. L. , Cook M. A.
Published: April 2011

The nonadrenergic, noncholinergic inhibitory (NAI) response of guinea pig fundic strip to electrical field stimulation was examined in the presence of botulinum toxin and tetrodotoxin. Tetrodotoxin completely abolished the NAI response while botulinum toxin did not alter it. It is concluded that the mediator of NAI responses is unlikely to be released with acetylcholine from cholinergic nerves or that such release would have to occur by a mechanism resistant to botulinum toxin.
Cerebral monoamine and energy metabolism during recovery from hypoxia–oligemia
Authors: MacMillan V.
Published: April 2011

The effects of 30 min of exposure to arterial [Formula: see text] of 25–27 mmHg and right carotid artery occlusion upon the cerebral monoamine and energy metabolism were studied in lightly anesthetized rats following reoxygenation for 0, 30, and 60 min. At 0 min of recovery the clamped hemisphere showed decreases in ATP and increases in ADP, AMP, and lactate which indicated an advanced disturbance of the tissues' mitochondrial function. At 0 min of recovery the tryptophan hydroxylation rate was 40% of control, whereas tyrosine hydroxylation was unchanged. Removal of the clamp and reoxygenation for 60 min resulted in a normalization of oxidative metabolism and aromatic amino acid hydroxylase function and thus indicated no permanent detectable defect of these processes in the restituted hypoxemic-oligemic brain.
La S-adénosyl-L-homocystéine : 1. Inductrice de sommeil
Authors: Fonlupt Pierre , Roche Maurice , Cronenberger Lucien , Pacheco Henri
Published: April 2011

S-Adenosylhomocysteine, 0.1–20 mg/kg, influences the sleep patterns of rat, cat and rabbit by increasing the slow-wave and fast-wave sleep for 6 h. The SAH effects are increased by p-chlorophenylalanine and iproniazid and unchanged by reserpine. SAH effects are correlated with modification of norepinephrine and serotonin metabolism.
Intraneuronal effects of inhibitory amino acids
Authors: Constanti A. , Krnjević K. , Nistri A.
Published: April 2011

Injections of γ-aminobutyric acid (GABA) into spinal motoneurons (in cats under Dial) induce a small but relatively prolonged hyperpolarization (mean −1.7 mV, SD 2. 1; n = 25), which is associated with a rise in input resistance (mean 44%, SD 122; n = 34), is not reversed by hyperpolarization, and is not potentiated by intracellular release of benzodiazepines. Muscimol sometimes has a comparable effect, but α-aminoisobutyric acid and glycine do not. These observations are consistent with the possibility that motoneurons have a Na+-coupled GABA transport mechanism that is electrogenic and can be reversed by an excess of intracellular GABA.
Diazepam receptors on mouse astrocytes in primary cultures: displacement by pharmacologically active concentrations of benzodiazepines or barbiturates
Authors: Hertz Leif , Mukerji Srimathie
Published: April 2011

Astrocytes in primary cultures were found to bind large amounts of [3H]diazepam. More than 90% of the total binding is specific, i.e., displaceable by an excess of nonlabeled diazepam. At saturation the specific binding amounts to about 20 pmol/mg protein and the Kd value is 30 nM. Clonazepam and flurazepam displace [3H]diazepam from its specific binding sites; 20–30% displacement is brought about by 0.1–0.3 μM clonazepam, which is similar to the plasma concentrations encountered in epileptic patients treated with this drug. Barbiturates have a similar effect, but considerably higher concentrations are required.
Effects of oxytocin and methacholine on cyclic nucleotide levels of rabbit myometrium
Authors: Schlageter N. , Janis R. A. , Gualtieri R. T. , Hechter O.
Published: April 2011

The effects of oxytocin and methacholine on cyclic nucleotide levels in estrogen-primed rabbit myometrium were studied in the presence and absence of 1-methyl-3-isobutyl xanthine (MIX), a phosphodiesterase inhibitor. In the absence of MIX, methacholine increased guanosine 3′,5′-cyclic monophosphate (cGMP) levels at a time when contraction was decreasing, but had no influence on adenosine 3′,5′-cyclic monophosphate (cAMP) levels. In contrast, oxytocin did not elevate cGMP, but rapidly increased cAMP levels. MIX (1 mM) increased both cAMP and cGMP levels. Oxytocin or methacholine further increased cGMP, indicating activation of guanylate cyclase. Oxytocin- but not methacholine-induced stimulation of guanylate cyclase was abolished in Ca2+-free solution. Oxytocin increased cAMP over the levels produced by MIX alone, whereas methacholine decreased cAMP below the MIX control values; these effects were insensitive to indomethacin. Tissue levels of cGMP and cAMP did not directly correlate with isometric tension. The results also indicate that both oxytocin and methacholine stimulate guanylate cyclase but have opposing effects on adenylate cyclase of rabbit myometrium.
Influence of thromboxane inhibition on the severity of myocardial ischemia in cats
Authors: Smith III Edward F. , Lefer Allan M. , Smith J. Bryan
Published: April 2011

The effects of thromboxane (Tx) inhibition or arachidonic acid (AA) infusion were studied in anesthetized cats during acute myocardial ischemia (MI). AA (7.2 mg kg−1 h−1) or imidazole (25 mg kg−1 h−1) infusions were initiated 30 min after occlusion of the left anterior descending coronary artery. Assessment of the degree of protection of the ischemic myocardium was made by measurement of S-T segment elevation, plasma and myocardial creatine phosphokinase (CPK) activities, and myocardial amino-nitrogen content. Assessment of Tx inhibition was performed by radioimmunoassay. Administration of imidazole inhibited the sevenfold increase in plasma thromboxane B2 (TxB2) levels occurring in MI (p < 0.001 at 2–5 h), markedly decreased S-T segment elevations at 2–5 h (p < 0.025), significantly prevented the elevation in plasma CPK (p < 0.05, at 4 and 5 h), and significantly reduced the loss in myocardial CPK activity and myocardial amino-nitrogen content. AA infusion also reduced the increase in TxB2 post-MI, significantly decreased (p < 0.025) S-T segment elevations at 2 5 h, caused a decrease in plasma CPK levels (p < 0.05 at 5 h), but did not prevent loss of myocardial CPK or amino-nitrogen. In summary, the administration of imidazole resulted in significant protection of the myocardium in all indices of ischemic damage measured, while AA infusion resulted in only a partial protection. The mechanism of the imidazole protection of ischemic myocardial tissue appears to be via inhibition of Tx synthesis although we cannot exclude a hemodynamic or cytoprotective mechanism. These results suggest that specific inhibition of Tx formation is beneficial during acute MI.
Effect of cold water immersion and its combination with alcohol intoxication on urine flow rate of man
Authors: Cupples W. A. , Fox G. R. , Hayward J. S.
Published: April 2011

Urine flow rate was determined for man before and after immersion in either thermoneutral (33 °C) or cold (10 °C) water. The effect of alcohol intoxication of a level of approximately 80 mg dL−1 was also evaluated for the cold water immersion. Immersion and cold were additive in their effect, resulting in a mean urine flow rate of 4.25 mL min−1, approximately 3.5 times the preimmersion level. Alcohol intoxication in conjunction with cold water immersion caused a further large increase in urine flow to 8.03 mL min−1. These results permit better evaluation of the importance of volume diuresis as it relates to the reduction of insulative performance of dry-type immersion suits for cold water survival, and to the possible enhancement of "rewarming shock" during therapy for hypothermia victims. The increased urine production observed when alcohol treatment was added to cold immersion provides information for speculation on mechanisms of volume diuresis.
The actions of motilin, luteinizing hormone releasing hormone, cholecystokinin, somatostatin, vasoactive intestinal peptide, and other peptides on rat cerebral cortical neurons
Authors: Phillis J. W. , Kirkpatrick J. R.
Published: April 2011

The effects of a number of neuronally localized peptides have been ascertained on corticospinal and other unidentified neurons in the rat cerebral cortex. Motilin, somatostatin, and luteinizing hormone releasing hormone excited most of the corticospinal neurons on which they were tested. Cholecystokinin, Met-enkephalin, vasoactive intestinal peptide, and neurotensin also excited some corticospinal neurons. Many nonidentified neurons were excited by all of these peptides. Met-enkephalin had a depressant action on some (14%) corticospinal neurons. Leu-enkephalin depressed many identified and nonidentified neurons and had an excitatory action on a few neurons. Both excitatory and inhibitory actions of the enkephalins were antagonized by naloxone. Thyrotropin-releasing hormone had predominantly depressant actions on the spontaneous firing of corticospinal and nonidentified neurons but did excite some unidentified cortical neurons. Secretin had no effect on the firing of most of the neurons tested.
Unilaterally ovariectomized pregnant mice: dieldrin induction of the hepatic monooxygenases and plasma progesterone levels
Authors: Virgo Bruce B.
Published: April 2011

Plasma progesterone, pregnancy maintenance, gestation period, and litter size were measured in mice unilaterally ovariectomized on day 6 of pregnancy (plug day = day 0) and then treated daily with dieldrin (2 mg kg−1, p.o.). By days 15–16, dieldrin had reduced the pentobarbital sleep time by 54% (P < 0.05), increased the liver mass by 8% (P < 0.05), and increased hepatic microsomal cytochrome P-450 by 66% (P < 0.05). However, the levels of plasma progesterone in the hemiovariectomized, dieldrin-treated mice were not different from those in the hemiovariectomized controls. Other experiments showed that hemiovariectomy decreased plasma progesterone by about 25%. Moreover, hemiovariectomy increased the frequency of premature delivery but it did not affect litter size; dieldrin treatment did not alter these effects. The failure of the induction to reduce plasma progesterone could result from (1) increased progesterone synthesis compensating for its elevated metabolism or (2) no (net) increase in progesterone metabolism.
The effects of coal tar and ultraviolet radiation upon the incorporation of thymidine into DNA by Ehrlich ascites carcinoma cells in vitro
Authors: Menon I. A. , Haberman H. F.
Published: April 2011

The effects of coal tar with and without radiation from three types of sources upon the incorporation of thymidine into DNA by Ehrlich ascites carcinoma cells were investigated. It was found that addition of varying concentrations of coal tar inhibited the thymidine incorporation by progressively greater amounts. Irradiation by mercury vapor lamp or fluorescent tubes, both emitting predominantly UVA (320–400 nm) and visible radiations, inhibited the DNA synthesis to a small extent. However irradiation with either of these sources in the presence of tar gave a synergistic effect on the DNA synthesis. Irradiation with a predominantly UVB (260–320 nm) source inhibited the DNA synthesis to a large extent. Irradiation with this source in the presence of coal tar did not give a synergistic effect but gave a summation effect. These findings have relevance in helping to choose the approporate radiation source for tar phototherapy of psoriasis. This in vitro system could also be used for other applications such as determining potencies of various tars or tar fractions.
The effects of methylprednisolone and diabetes on the turnover of alanine and on the transfer of carbon atoms from alanine to pyruvate and glucose in dogs
Authors: Hetenyi Jr. G. , Pagurek B. , Dittmar Elizabeth A. , Ferrarotto Catherine
Published: April 2011

The turnover rate of glucose, the irreversible disposal rate of alanine, and the transfer of carbon atoms from alanine to glucose were studied with the help of tracer methods in normal, methylprednisolone (MP) treated and pancreatectomized dogs. The incorporation of carbon from alanine into pyruvate was also followed. In comparison with normal dogs, in MP-treated dogs the plasma level of alanine and pyruvate were elevated by a factor of about 3 whereas the level of plasma glucose was increased by 10%. Both the turnover rate of glucose and the irreversible disposal rate of alanine were significantly higher. In pancreatectomized dogs plasma alanine and pyruvate levels were not different from normal. There was no increase in the irreversible disposal rate of alanine. Glucose turnover was about twice as much as in normals. The transfer of C atoms from alanine to glucose was increased in both MP-treated and pancreatectomized dogs. The increase was in direct proportion to the increase in the irreversible disposal rate of alanine in MP-treated dogs whereas in pancreatectomized dogs it was due to an increased fraction of the irreversible disposal rate of alanine being converted to circulating glucose. Thus two different mechanisms are responsible for the increased carbon transfer and hence presumably gluconeogenesis in MP-treated and in pancreatectomized animals. The role of insulin as the determinant of the preferred route to increase gluconeogenesis is discussed.
Similarities between cold- and diet-induced thermogenesis in the rat
Authors: Rothwell Nancy J. , Stock Michael J.
Published: April 2011

Rats were maintained at 24 and 4 °C (WA, CA) and fed either a pelleted stock diet (WAS, CAS) or a varied and palatable cafeteria diet (WAC, CAC). Resting oxygen consumption ([Formula: see text], 29 °C) was significantly elevated by 15, 14, and 24% in WAC, CAS, and CAC rats, respectively, compared with WAS controls and these differences were completely abolished by injection of propranolol in all but CAC rats, where [Formula: see text] remained only slightly elevated. Experimental groups showed an increased capacity to respond to the thermogenic effects of norepinephrine (percentage increase in [Formula: see text]: WAS, 43 ± 5; WAC, 88 ± 6; CAS, 75 ± 6; CAC, 128 ± 5) and greather deposits of interscapular brown adipose tissue (IBAT) (WAC, 542 ± 27; CAS, 469 ± 27; CAC, 1111 ± 85 mg) compared with WAS controls (339 ± 22 mg).When exposed to 5 °C, WAS rats shivered continuously whereas in the WAC animals shivering had ceased by 5 h. Rectal temperature was maintained at a higher level in the WAC rats than in the WAS group (WAS, 34.7 ± 0.9 °C; WAC, 36.2 ± 0.5 °C; p < 0.01). Injection of propranolol lowered the core temperature of WAC rats and caused shivering to recommence but had no effect on WAS rats.The similarities between diet- and cold-induced thermogenesis suggest that both have a common metabolic origin residing in BAT and that dietary-induced thermogenesis may be important in the maintenance of body temperature as well as in energy balance regulation.
The role of hypoxemia, vasoactive compounds, and acidemia in the pathogenesis of pulmonary edema in the dog with experimental left ventricular overload
Authors: Baumber John S.
Published: April 2011

The pathogenesis of pulmonary edema (PE) in left heart failure involves a consideration of the hydrostatic, osmotic, and permeability changes in the pulmonary circulation. In 14 dogs with isolated left ventricular overload induced by suturing a Teflon graft between the aorta and left atrium, left ventricular end-diastolic pressure (LVEDP) was 36 mmHg (1 mmHg = 133.322 Pa) 3 weeks following surgery. There was no clinical evidence of PE. Seven of these animals developed PE when allowed to breathe 10% O2 in N2 for 15 min. There was no further increase in LVEDP or right ventricular systolic pressure (RVSP). It was postulated that a change in permeability superimposed on increased capillary hydrostatic pressure could result in the overwhelming accumulation of fluid in the alveoli. The release of vasoactive substances from pulmonary mast cells or from the adrenal medulla might alter capillary permeability. However, the infusion of histamine or epinephrine in seven dogs with elevated LVEDP and RVSP failed to precipitate fulminating PE. We have previously observed an increase in plasma renin activity in dogs associated with PE. Nonpressor infusions of angiotensin failed to produce PE. The infusion of lactic acid to decrease the arterial pH to 7.00 (the level observed as a result of hypoxia-induced PE) resulted in fulminating PE. It is concluded that acidemia can be an important factor in the development of severe intra-alveolar pulmonary edema.
Angiotensin II inhibits both heat production and heat loss mechanisms in the rat
Authors: Lin M. T. , Chandra A. , Jou J. J.
Published: April 2011

The effects of intracerebroventricular injections of angiotensin II on thermoregulatory responses of conscious rats to ambient temperatures (Ta) of 8, 22, and 30 °C were assessed. Administration of angiotensin II produced dose-dependent hypothermia in rats at both Ta 8 and 22 °C. The hypothermia in response to angiotensin II was due to decreased metabolic heat production. In addition, angiotensin II produced cutaneous vasoconstriction at Ta 8–22 °C. However, at Ta 30 °C angiotensin II produced no change in rectal temperature or other thermoregulatory responses. Furthermore, the hypothermia induced by angiotensin II was antagonized by pretreatment with 6-hydroxydopamine (a selective catecholamine neurotoxin) and propranolol (a selective β-adrenergic antagonist) but not by either 5,6-dihydroxytryptamine (a selective serotonin neurotoxin), atropine (a cholinergic antagonist), or phentolamine (a selective α-adrenergic antagonist). The data indicate that angiotensin II inhibits both heat production and heat loss mechanisms which lead to an alteration in body temperature, probably via the activation of central adrenergic receptors.
Sensory–motor processing in the caudate nucleus and globus pallidas: a single-unit study in behaving primates
Authors: Aldridge J. W. , Anderson R. J. , Murphy J. T.
Published: April 2011

Monkeys were prepared for chronic recording of single neurons in the caudate nucleus (Cd) or globus pallidus (GP) during learned wrist flexion–extension movements triggered by visual and somatic sensory inputs. Almost two-thirds of GP cells and more than one-third of Cd cells modified their discharge during these tasks. Three categories of response types were observed. The first was movement related. The second type was event related, in which the cells responded to either the onset or offset of the sensory inputs regardless of the correcting movement direction. A third type combined elements of the first two categories and was termed complex. These cells responded to complex abstractions of the sensory–motor event. A latency analysis indicated that the majority of cells was not involved in initiating movements but may have participated in movement execution. The results of this experiment suggest that during voluntary movement the basal ganglia activity is correlated with motor outputs, sensory inputs, and perceptual abstractions of these sensory–motor events. As such the results are compatible with an influence by diverse regions of cerebral cortex on basal ganglia neurons during the movement control process.