bluuebunny/crossref_metadata_2025 huggingface dataset:
The renal response to volume expansion
Authors: Pearce J. W.
Published: April 2011

The renal response to expansion of the extracellular fluid volume by infusion of a blood substitute is described as including increased glomerular filtration rate, increased renal plasma flow, natriuresis, and diuresis. The diuresis, initially accounted for by an increased tubular solute load, was often associated with a delayed decrease in tubular free-water reabsorption. These responses were not remarkably altered in a denervated kidney and they could be produced in a cross-perfused kidney following infusion to the donor animal. The proposed humoral effector mechanism may be a natriuretic hormone which has direct actions on both renal hemodynamics and tubular reabsorption. Consideration is given to the possibility that the natriuretic substance may interact with intrarenal autoregulatory mechanisms involving renin release.
Electron microscopy of the pancreatic islets stimulated by insulin antibody
Authors: Logothetopoulos John
Published: April 2011

Mice were maintained hyperglycemic by daily intraperitoneal injections of immunoglobulins from guinea pigs highly immunized with beef insulin. Hyperglycemic and control mice were killed throughout a period of 3 weeks. Inflammatory infiltrations around the islets were minimal The stimulated beta cells remained heavily degranulated throughout the period of injections. Insignificant changes were seen on the cytomembrane of the beta cell facing the capillary during the initial period of rapid degranulation and thereafter. The density of the rough endoplasmic reticulum increased progressively. The Golgi complexes expanded and became more elaborate. The mitochondria enlarged. Evidence for the continuous elaboration of secretory granules in the Golgi area and for the existence of an immature pregranule in the formation cycle of the secretory granule was obtained in both normal and hyperglycemic animals. Regressive changes in the cells of the islets were absent.
Hemopexin in newborn infants of diabetic mothers
Authors: Sirek O. V. , Sirek A. , Bucalossi A.
Published: April 2011

Serum proteins from cord blood of 27 infants of diabetic and 16 infants of normal women of comparable gestational age (38–39 weeks) were studied by immunoelectrophoresis. In accord with our previous finding of elevated serum glycoprotein levels in newborn infants of diabetic mothers, a well-defined precipitation arc in the beta-one globulin region, inside the concavity of the transferrin arc, was identified in these infants as hemopexin, because it (a) stained intensively for carbohydrate, (b) did not bind hemoglobin but did bind hemin, and (c) formed a single benzidine-positive line with anti-hemopexin serum.
Lipid metabolism: Effects of immunosympathectomy and acclimation to cold
Authors: Steiner G. , Schönbaum E. , Johnson G. E. , Sellers E. A.
Published: April 2011

The effects of immunosympathectomy and acclimation to cold on the incorporation of glucose-U-14C into lipids of the interscapular brown adipose tissue, epididymal fat pad, and liver of rats have been investigated. Acclimation to cold was associated with an increase in glucose recovered in the total lipids of brown adipose tissue. These changes in glucose recovery were the same in immunosympathectomized as in intact rats. The brown adipose tissue of the two groups of cold-acclimated rats differed, however, in that this tissue in the immunosympathectomized animals was larger and had more lipid. Suggestions are raised to explain these findings. Neither immunosympathectomy nor cold acclimation produced any changes in white adipose tissue. Immunosympathectomy did not alter the liver's handling of glucose. However, cold-acclimation was associated with an increase in the relative weight of the liver and a decrease in glucose recovery in liver lipids.
Effects of a single choline-deficient meal on the phospholipids of hepatic particulate lipid of the rat
Authors: Rosenfeld Bruno
Published: April 2011

In 3 h after ingestion of a choline-deficient meal, a profound decrease of the phospholipid content in the particulate lipid (floating fat) fraction of the liver was observed. This change of phospholipid preceded by 5–10 h the increase of triglyceride in the same fraction, thus pointing to phospholipid alterations as the initial metabolic defect in choline deficiency. A single choline-deficient meal also caused two significant changes in the phospholipid composition of the floating lipid fraction: (a) lecithin decreased, and (b) cephalin increased; the ratio lecithin/cephalin decreased, on an average, from 5 2 to 2.8. In short-term choline deficiency, betaine may replace choline in maintaining the phospholipid composition of floating lipid.
Impairment of plasma glycoprotein synthesis in choline deficiency compared with effects of carbon tetrachloride intoxication
Authors: Mookerjea Sailen
Published: April 2011

The incorporation of glucosamine-1-14C into plasma proteins is impaired in rats within 2 days when they are fed a choline-deficient diet. Separation of plasma proteins by starch-gel electrophoresis, and autoradiography of the dried gels, showed four labelled areas (glycoproteins). In choline deficiency there was visual evidence of depletion of radioactivity in the fast α-globulin area, a finding confirmed by the specific radioactivity of proteins eluted from electrophoretic zones of the starch gel. Within 4 h after ingestion of carbon tetrachloride, the synthesis of plasma glycoprotein was reduced by 90% and labelling of all four glycoprotein areas on dried starch gel autoradiograms virtually ceased. The results suggest that the defect in glycoprotein synthesis in carbon tetrachloride intoxication is nonspecific, whereas in choline deficiency the impairment is specific and localized in the fast α-globulin fraction. The results suggest a limiting role of a glycoprotein in the pathway of plasma lipoprotein synthesis.
Molecular species of lecithins of some functionally distinct rat tissues
Authors: Kuksis A. , Marai L. , Breckenridge W. C. , Gornall D. A. , Stachnyk O.
Published: April 2011

The lecithins of the liver, lung, intestine, plasma, and red blood cells of rats were isolated and the major individual molecular species identified and estimated quantitatively by combined thin-layer and gas chromatographic analyses and specific enzymic hydrolyses. The lecithins prepared from different tissues of the same animal varied significantly in the composition, positional distribution, and molecular association of the fatty acids. The most complex were the highly unsaturated lecithins of the liver and plasma, while the more saturated lecithins of the red blood cells and lung showed somewhat simpler patterns. In most cases the fatty acid distributions differed markedly from random. The results are interpreted to reflect the existence of both common structural and specific or functionally distinct lecithins in these rat tissues.
Microdetermination of alcohol in blood by gas–liquid chromatography
Authors: LeBlanc A. E.
Published: April 2011

A combination of deproteinization by ZnSO4 and BaOH, and use of a butanol internal standard, permits gas–liquid chromatographic analysis of ethanol in blood, with high precision, in samples as small as 20–50 μl. Deproteinized samples gave stable values for up to 2 weeks if properly stored.
Increase in palmar sweat gland activity by heat
Authors: Schubert Daniel S. P.
Published: April 2011

Palmar sweating of 14 men at 80–90 °F as indicated by palmar skin conductance was found to be significantly greater statistically (p < 0.05) than that of 30 men at 70–75 °F. These data support Wilcott's (J. Comp. Physiol. Psychol. 56, 778 (1963)) finding that palmar perspiration increases with heat, and cast further doubt on earlier conclusions that palmar perspiration does not increase at all at high ambient temperatures.
The effect of a single injection of estradiol benzoate on thyroid function in intact male rats
Authors: Brown-Grant K.
Published: April 2011

The changes observed in the metabolism of radioiodide and radiophosphorus by the thyroid gland of intact adult male rats following a single injection of estradiol benzoate (4 μg/100 g body weight) are consistent with the suggestion (F. Labrie, G. Pelletier, and C. Fortier. Federation Proc. 26, 484 (1967). Abstr.) that at this dose level estrogen causes a hypersecretion of TSH in such animals.
Interscapular Location of Brown Adipose Tissue: Role in Noradrenaline-Induced Calorigenesis in Cold-Acclimated Rats
Authors: Himms-Hagen Jean
Published: April 2011

Tying Sulzer's vein does not alter the enhanced metabolic response to noradrenaline of cold-acclimated rats, neither immediately after the operation nor 1, 2, or 5 days later. In contrast, removal of the interscapular brown adipose tissue, while having no marked immediate effect upon the enhanced metabolic response to noradrenaline, causes a delayed loss of the enhancement during the subsequent 2 days. These findings argue against the hypothesis that the local direction of heat from the interscapular brown adipose tissue via Sulzer's vein to the spinal cord has importance in determining the capacity of the rat to respond to noradrenaline or to use nonshivering thermogenesis. The difference between the effect of complete removal of the interscapular brown adipose tissue and the effect of tying Sulzer's vein would suggest that the reduced circulation through the interscapular brown adipose tissue when Sulzer's vein is tied is still sufficient for it to exert its influence upon other tissues. The results are compatible with the endocrine hypothesis for the function of the interscapular brown adipose tissue during acclimation to cold.
Factors Related to the Dive Reflex in Harbor Seals: Sensory Contributions from the Trigeminal Region
Authors: Dykes Robert W.
Published: April 2011

Three harbor seals were immersed in five different water temperatures ranging from 7 to 37 °C. Unlike the response in men, the bradycardia observed during immersion was not influenced by water temperature. When the faces of four seals were rendered insensible by neurotomy and local anesthetic, the bradycardia during immersion followed the same time course as that observed during periods of forced apnea while the seals were in air. In two seals with insensible faces, which were forcefully respired during immersion, the heart rate did not drop from the rate observed before immersion. The data presented are consistent with the hypothesis that the two principal sensory contributions to the bradycardia of immersion are: (1) a cessation of the movements of the lungs and rib cage; (2) a change in neural activity in receptors located in the face.
Effect of Acute and Chronic Pretreatment with Δ1-Tetrahydrocannabinol on Motor Impairment by Ethanol in the Rat
Authors: Kalant H. , LeBlanc A. E.
Published: April 2011

Pretreatment with Δ1-tetrahydrocannabinol (THC) in doses of 3–15 mg/kg produced a biphasic effect on the degree of impairment caused by ethanol (1.4 g/kg) in the performance of a motor task by the rat. Small doses of THC increased the impairment, but larger doses reversed the trend. The point of inflection occurred at a lower dose, and therefore a lower impairment, when THC was given 15 min rather than 45 min before the alcohol. None of the doses of THC had any effect on test performance in the absence of ethanol. Daily treatment with 12 mg/kg THC for 17 days caused a reversible development of tolerance to the THC augmentation of ethanol impairment, without any apparent cross-tolerance to ethanol alone.
The Action of Cholecystokinin and Related Peptides on Guinea Pig Small Intestine
Authors: Yau W. M. , Makhlouf G. M. , Edwards L. E. , Farrar J. T.
Published: April 2011

The mode of action of cholecystokinin (CCK), an octapeptide fragment of CCK, caerulein, and pentagastrin on isolated guinea pig ileal muscle was investigated and their relative potencies determined. On a molar basis, octapeptide-CCK and caerulein were about twice as potent as CCK, whereas pentagastrin and Urecholine were respectively 23 and 46 times less potent. Scopolamine (6.84 × 10−4 M) inhibited the response to all four peptides relatively less than the response to Urecholine. Tetrodotoxin (0.1 μg/ml) inhibited the response to all peptides by 91%. It was concluded that the effect of these peptides on ileal muscle was largely mediated by cholinergic mechanisms. It could not be ascertained, however, whether the effect resulted solely from release of acetylcholine by nerve endings or from the participation of acetylcholine mainly as a synergist of the peptides' action on smooth muscle fibers.
The Effect of Prostaglandin E1 on Lipid Metabolism and Hormone Secretion in Sheep
Authors: Carruthers T. C. , Manns J. G. , Quesnel S. J.
Published: April 2011

Intravenous infusion of prostaglandin E1 at 1 μg/kg min caused a significant decline in plasma free fatty acid concentration in sheep fasted for 72 h. There was a simultaneous increase in plasma pancreatic glucagon concentration although plasma insulin and gut glucagon-like immunoreactivity did not change.
Central Release of Acetylcholine Following Administration of Morphine to Unanesthetized Rabbits
Authors: Mullin W. J.
Published: April 2011

Intravenous administration of 5 mg/kg of morphine sulfate to unanesthetized rabbits was without effect on the output of acetylcholine (ACh) into the effluent collected by push–pull perfusion from the cerebral lateral ventricles or the sensorimotor cortex. Alterations in the rate of ACh release (enhancement of cortical release and depression of ventricular release) were noted with a variable delay following the injection of 10 mg/kg of morphine. These effects of morphine on cortical and ventricular ACh release were observed while behavioral sedation, analgesia, and respiratory depression were manifest in the animals. These results suggest a lack of correlation between behavior and ACh release from these areas of the brain in response to administration of morphine to the rabbit.
Hemodynamic Effects and Hypertrophy-Inducing Potential of D- and L-Thyroxine
Authors: Axelrod Glenn B. , Whitbeck April A. , Cohen Jules
Published: April 2011

The capacities of D- and L-thyroxine to induce cardiac hypertrophy have been studied in rats as a function of the extent of the circulatory changes produced by the two isomers. D-Thyroxine had no effect on blood pressure, heart rate, or cardiac output, but significantly increased heart mass. L-Thyroxine had a small effect on mean blood pressure, a larger effect on heart rate, and caused a large increase in cardiac output. The closest parallels were between effects on heart rate and on heart growth. In companion experiments, D- and L-thyroxine were shown to be equipotent in stimulating atrial protein synthesis in vitro. The growth-promoting effects of both D- and L-thyroxine, therefore, seem largely direct and independent of the large increase in flow work produced by administration of the L-isomer in vivo.
Effect of Carbachol on Amino Acid Incorporation into Protein of Rat Pancreas In Vitro
Authors: Irwin C. , Tenenhouse A.
Published: April 2011

The effect of various cholinergic drugs on incorporation of 3H-leucine into protein of rat pancreas in vitro was studied. It was found that carbachol and bethanechol, but not pilocarpine, inhibited incorporation 70–80%. Even in the continued presence of carbachol, the rate of incorporation is depressed only 40–60 min. It recovers and eventually exceeds that seen in untreated tissue. After 4 h incubation the amount of 3H-leucine incorporated into protein is the same in carbachol-treated and untreated tissue. The alteration of amino acid incorporation can be dissociated from the effect of the drug on secretion in several ways: (1) calcium deprivation abolishes carbachol-stimulated secretion but not the inhibition of amino acid incorporation; (2) atropine, 10−8 M, totally abolishes the effect of carbachol on amino acid incorporation without affecting secretion (10−5 M atropine is needed to abolish carbachol stimulated secretion); (3) pilocarpine stimulates secretion but has no effect on amino acid incorporation. The inhibition of amino acid incorporation is not due to inhibition of amino acid transport nor to a decrease in tissue ATP concentration. It is concluded that there is no clear relationship between protein secretion and synthesis. Muscarinic agents, which stimulate secretion of protein, may also cause changes in the rate of amino acid incorporation into protein; however, the change one measures will depend on when, after administration of the secretagogue, protein synthesis is measured.
Anti-inflammatory Properties of Furobufen
Authors: Martel R. R. , Rochefort J. G. , Klicius J. , Dobson T. A.
Published: April 2011

Furobufen (γ-oxo-2-dibenzofuranbutyric acid) produced anti-inflammatory, antiarthritic, and antipyretic effects. It also reduced the pain resulting from an acute inflammatory reaction. The potency of furobufen to inhibit carrageenin-induced paw edema was comparable to that of phenylbutazone. The activity profile of furobufen was similar to that of the non-steroidal anti-inflammatory drugs.
The Effect of Physical Conditioning on Cardiac Response to Acute Exertion
Authors: Kôrge P. , Masso R. , Roosson S.
Published: April 2011

The effect of chronic exercise (training) and acute exertion on myocardial water and electrolyte metabolism, Na–K-ATPase activity, and morphology was studied in the male rat. Training increased the potassium content in myocardial cells, the effect depending on the duration of the training period. Potassium accumulation in the heart cells was not associated with the cardiac hypertrophy that developed relatively quickly and depended primarily on the intensity of work, rather than on the duration of the training period. The most regular effect of acute exertion on myocardial electrolyte content was potassium uptake by the heart. Chronic physical overload, depending on its severity, reduced or abolished the heart's ability to accumulate potassium during physical exertion. An attempt was made to evaluate the possible role of Na–K-ATPase in the mechanism of depression of potassium transport against its electrochemical gradient after chronic physical overload. In comparison with normal response of the heart, both morphological and biochemical changes were diminished in both the trained and, to a smaller extent, the overtrained heart during acute extreme exertion. It is concluded that potassium accumulation in myocardial cells is an essential adaptive reaction to physical exertion and the extent of potassium uptake depends on the functional state of the heart.
Evidence against a Mediatory Role of Brown Adipose Tissue in the Calorigenic Response of Cold-Acclimated Rats to Noradrenaline
Authors: Foster David O.
Published: April 2011

The calorigenic response to infused noradrenaline (NA) of barbital-anesthetized, cold-acclimated, adult, gnotobiotic, albino rats tested 1 h after removal of interscapular brown adipose tissue (I.B.A.T.) was 14% lower than before surgery and 15% lower than the response of either sham-operated or non-operated rats; but 4 days later, the response of rats without I.B.A.T. was not significantly different from that of the controls. In unanesthetized rats, response to NA was also unaffected by interruption of blood flow to I.B.A.T. 1–3 days before the measurements. Since these results do not conform with previous findings of 30–60% reductions in response to NA following removal of I.B.A.T. or interference with the tissue's vascular connections, they contradict the current hypothesis that the B.A.T. of cold-acclimated rodents has a unique role as a mediator of calorigenesis in other tissues.A supplementary feature of the study was the discovery of apparent thermolability in the process by which cold-acclimated rats respond calorigenically to NA. If, during infusion of NA, colonic temperature exceeded about 41.5 °C, an apparently critical degree of hyperthermia response to the hormone during a subsequent infusion was reduced. This reduction was linearly related to the previous maximum colonic temperature over the range 41.6–42.4 °C and amounted to approximately 70% at 42.4 °C. These results indicate the necessity for monitoring the body temperatures of animals during infusion of NA, particularly in experiments in which two or more tests of response to NA are done on the same animal. Since such temperature measurements were not reported in those studies that have suggested a mediatory role of B.A.T. in calorigenesis in rodents, it is not possible to resolve the discrepancies on this basis.
Inhibition by Δ1-Tetrahydrocannabinol of a Na+–K+ Transport ATPase from Rat Ileum. Preliminary Report
Authors: Laurent B. , Roy P. E. , Gailis L.
Published: April 2011

The effect of Δ1-trans-tetrahydrocannabinol (THC) on ATPase activities of a microsomal fraction from rat ileum was measured. A concentration of 10−5 M completely abolished the stimulation due to sodium and potassium, whereas the activity of the Mg-ATPase was about 60% of the control. Even at concentrations found in blood after smoking one marihuana cigarette there was a slight inhibition of the Na+–K+-ATPase. The inhibition may be due to a specific binding or, more likely, to a general action of the THC on membranes.
Pharmacological Studies on Active Bronchial Anaphylaxis in the Rat
Authors: Stotland L. M. , Share N. N.
Published: April 2011

Pharmacologic studies upon the active bronchial anaphylactic response considered to be mediated primarily by reagin-type antibodies were carried out in rats. Inhibition of the response by pharmacologic-mediator antagonists at maximally active doses were methysergide > mepyramine = atropine, but burimamide, indomethacin, mecamylamine, and bilateral vagotomy were ineffective. This suggests that 5-hydroxytryptamine is the major pharmacologic mediator involved in the response, histamine acting upon H1 receptors is contributory, involvement of prostaglandins and vagal reflexes are minor, and atropine probably exerts a moderate direct bronchial smooth-muscle relaxant effect. Activation of β-adrenergic receptors with isoproterenol is also inhibitory whereas sub-maximal bronchoconstrictor responses are enhanced by β-adrenergic blockade with propranolol. A dose-related bell-shaped inhibition was observed after disodium cromoglycate and dexamethasone was active only with pretreatment over a 3-day period. However, ineffective doses of either disodium cromoglycate or dexamethasone given alone become markedly effective when combined, indicating marked synergistic drug action. The data suggest that the active bronchial anaphylactic rat used in the present study provides an animal model similar to that of the immediate (type I) reagin-mediated asthmatic reactions in man. This model could therefore provide a greater index of predictability for clinical drug utility in human asthma than exists at present.
Effects of Modifiers on the Optical Properties of Oxidized Cholesterol Model Membranes
Authors: Szekely J. G. , Morash B. D.
Published: April 2011

Brewster angle reflections from oxidized cholesterol membranes are described in terms of uniaxial crystal model. The refractive indices perpendicular and parallel to the membrane are 1.515 and 1.555, respectively. A multilayer model was also considered; however, under the approximations used, both models are equivalent and cannot be distinguished. Egg albumin and hexadecyltrimethylammonium bromide altered the refractive indices while 2,4-dinitrophenol and valinomycin addition did not produce a detectable change.
The Influx of Uric Acid and other Purines into Everted Jejunal Sacs of the Rat and Hamster
Authors: Khan A. H. , Wilson S. , Crawhall J. C.
Published: April 2011

The in vitro transport of [2-14C]uric acid, [8-14C]hypoxanthine, and [8-14C]xanthine, each dissolved in Krebs–Ringer bicarbonate buffer, was studied with everted jejunal sacs from rat and hamster. No evidence could be obtained for the development of a concentration gradient between the intracellular fluid and the incubation medium or between the sac contents and the incubation medium, for any of the three oxypurines. Inhibitors of active transport, such as anaerobiosis or dinitrophenol, had no significant effect on the rate of transport. A large percentage of hypoxanthine and xanthine was oxidized to uric acid in the sac-wall homogenate, sac contents, and incubation medium during the course of the incubation. This oxidation could be prevented by addition of allopurinol (3 mM) to the incubation medium, but concentration gradients were still not obtained. No active transport mechanism could be demonstrated for uric acid, hypoxanthine, or xanthine in rat or hamster jejunum.
Action of Acetazolamide on the Chick Embryo During Late Development
Authors: Narbaitz Roberto , Bélanger Leonard F.
Published: April 2011

Acetazolamide was injected into chick embryos on the 14th or 15th day of incubation. Doses ranging between 5 and 10 mg per egg produced a retardation in the growth of long bones. The affected bones contained a normal proportion of mineral as determined by ashing and presented a normal histological picture. On the basis of these findings, it is suggested that the alterations were not due to a specific direct effect of the drug on bones.The incorporation of 131I by the thyroid glands of acetazolamide-injected embryos was analyzed radioautographically and quantitated on the same 6 μm-paraffin sections, with a thin window Geiger counter. The incorporation appeared notably reduced 3 h after the injection of acetazolamide and the reduction persisted for at least 24 h. The electron microscopical observation of thyroid follicular cells from similarly treated embryos showed that the cytological characteristics indicating an active protein synthesis were unmodified with respect to those found in control embryos. These results may indicate that acetazolamide inhibits the iodination of the thyroid hormone without interfering with the synthesis of the globulin. It is suggested that the growth retardation observed in the embryos treated with acetazolamide may be secondary to the action of the drug on the thyroid gland, although this action appears to be a transitory one.
The Effect of Caesium on Adrenergic Transmission in Rabbit Vas Deferens
Authors: Johns A. , Paton D. M.
Published: April 2011

The effect of caesium on the responses of rabbit vas deferens to transmural stimulation was investigated. The tissue responded to transmural stimulation with a phasic spike contraction followed by a sustained contractile response. The sustained response was inhibited by phentolamine and guanethidine and thus apparently results from noradrenaline release from adrenergic nerves. Addition of 2–5 mM Cs+ greatly potentiated this secondary response without altering the sensitivity of the tissue to added (−)-noradrenaline. This potentiation was not due to Cs+ decreasing the neuronal uptake of noradrenaline, or by Cs+ altering prostaglandin synthesis. Addition of 2 mM Cs+ significantly increased the amount of (±)-[3H]metaraminol released from tissues in response to transmural stimulation (5 Hz). It is suggested that caesium potentiated responses of rabbit vas deferens to transmural stimulation by increasing the amount of transmitter released per nerve impulse, possibly as a result of prolongation of the action potential.
Catecholamine Binding to Plasma Membrane Enriched Fractions of Heart and Skeletal Muscle
Authors: Vallières Julien , Drummond Maureen , Drummond George I.
Published: April 2011

Binding of [3H]epinephrine to plasma membrane enriched fractions from guinea pig heart and rabbit skeletal muscle was investigated using the micropore filtration technique. [3H]Epinephrine and [3H]norepinephrine were found to be degraded rapidly in aqueous buffer at pH 7.6 and 37 °C. Deterioration of the compounds could be prevented by low concentrations of dithiothreitol. Binding of [3H]epinephrine to both membrane preparations was a slow process requiring 60 min to approach equilibrium in the case of cardiac membranes at 37 °C, and 20 min for skeletal muscle membranes at 0 °C. Binding was antagonized by the unlabeled beta-agonists, isopropyl-norepinephrine, epinephrine, and norepinephrine but all were equipotent. A variety of catechol compounds were as effective antagonists of binding as the catecholamines. The beta-adrenergic antagonists propranolol, pronethalol, and dichloroisoproterenol were not effective in inhibiting binding to either membrane preparation. D-Norepinephrine and L-norepinephrine were equieffective in antagonizing binding of [3H]norepinephrine to skeletal muscle membranes. It was concluded that binding of labeled catecholamine to isolated tissue membranes using the micropore filtration technique does not represent interaction with the specific beta-adrenergic receptor, but more likely reflects a less specific binding of compounds having one or more hydroxyl groups on a ring.
Different Sites of Membrane Action for Tetrodotoxin and Lipid-Soluble Anesthetics
Authors: Staiman A. L. , Seeman P.
Published: April 2011

1. To examine whether different local anesthetics act on different or similar sites in the nerve membrane, the effects of combinations of lipid-soluble anesthetics and tetrodotoxin (TTX) were studied on the compound action potential of the frog sciatic nerve.2. The nerve-blocking potency of TTX was potentiated 5-fold by benzyl alcohol and 10-fold by lidocaine, at concentrations of these latter two drugs which were just barely anesthetic; no such synergism occurred between saxitoxin (STX) and TTX, their combined effect being merely additive.3. Simple additive effects also occurred between benzyl alcohol and phenol, benzyl alcohol and urethane, as well as lidocaine with a spirosuccinimide, RAC 109 II.4. Synergism occurred between STX and 2-aminobenzimidazole.5. A small but consistent synergism occurred between lidocaine and benzyl alcohol.6. It is concluded that uncharged anesthetics, tertiary amines, and TTX act via different membrane binding sites which are all closely associated with the Na+ conductance channels.
Early Effects of Aminonucleoside on Enzymes in the Golgi Apparatus of Rat Liver
Authors: Katona E. , Moscarello M. A.
Published: April 2011

Rats were injected with a single intravenous dose of aminonucleoside (AMN) and sacrificed 1–48 h later. The activity of several enzymes was assayed in the Golgi apparatus isolated from the liver. Galactosyltransferase activity showed little changes after the AMN, but both acid (EC 3.1.3.2) and alkaline phosphatase (EC 3.1.3.1) activities increased within the first hour and reached control levels only 5–24 h later. Thiamine pyrophosphatase and arylsulfatase A (EC 3.1.6.1) activities also increased and stayed at higher levels for the duration of the experiment. Arylsulfatase B (EC 3.1.6.1) activity decreased shortly after the AMN but later increased to above control levels. These findings support earlier results in which liver ultrastructural and biochemical changes were observed early before renal lesions and proteinuria.
Organ Distribution of 3-Hydroxy-3-methylglutaric Acid, a Potential Anticholesterolemic Agent
Authors: Savoie Laurent L. , Lupien Paul-J.
Published: April 2011

The distribution of radioactivity after oral administration of 3-hydroxy-3-[3-14C]methylglutaric acid has been studied by whole-body autoradiography in the mouse. The compound (a potential anticholesterolemic agent) was promptly and almost completely absorbed. Relatively high and persistent levels of radioactivity were seen in organs responsible for cholesterol synthesis, mainly liver and intestinal wall. Rapid and pronounced uptake of radioactivity was seen in the kidney and the time course of the level of radioactivity indicated that the kidney is not only the main excretory route of 3-hydroxy-3-methylglutaric acid but also represents an important site of distribution of the compound. Detectable uptake of radioactivity, mainly in the first phase, occurred also in the lungs, the salivary glands, the lacrimal glands, the skin, and the brown fat. Results obtained by autoradiography have been checked in part by direct measurement of radioactivity in individual organs and data obtained with the two techniques are in agreement.
The Effect of Glucagon on Glomerular Filtration Rate in Dogs During Reduction of Renal Blood Flow
Authors: Levy Mortimer
Published: April 2011

Glucagon in small intravenous (i.v.) doses markedly increases glomerular filtration rate (GFR) in normal anesthetized dogs. In this study, the effects of glucagon 5 μg/min (i.v.) on renal hemodynamics was tested in four canine models of acute pre-renal failure (hemorrhage, barbiturate overdose; renal arterial clamping and renal arterial infusions of noradrenaline) and in a model of unilateral acute tubular necrosis at 4 h and 6–7 days following completion of the ischemic insult. Following hemorrhage and barbiturate excess, with arterial blood pressure maintained at 65–70 mm Hg, whole-kidney GFR and clearance rate of p-aminohippurate decreased by 50–70%. During this reduction of perfusion pressure, the subsequent infusion of glucagon increased GFR by 90–130%. In models where arterial pressure was normal during the period of ischemia (clamping and noradrenaline infusion), not only did glucagon significantly increase renal perfusion, but the ischemic kidney proved to be far more sensitive to the hemodynamic effects of glucagon (ΔGFR = 120–160%) than the contralateral control (ΔGFR = 30–40%). In three dogs completely anuric following renal arterial clamping, glucagon was able to improve blood flow and restart urine formation. Glucagon, but not dopamine, was able to simulate the beneficial effects of hypertonic mannitol on renal function in dogs with hemorrhagic hypotension. Glucagon was without effect in established acute tubular necrosis. This study, therefore, indicates that, during renal ischemia, glucagon may be quite effective in preserving urine output and perfusion of the kidneys.
The Mode of Spontaneous Transmitter Release at the Insect Neuromuscular Junction
Authors: Washio H. M. , Inouye S. T.
Published: April 2011

The time intervals between miniature excitatory postsynaptic potentials and the counts of them in the cockroach, Periplaneta americana, were analyzed, using a computer program to test for properties of a Poisson process. The miniature potentials occurred basically in random manner at this neuromuscular junction. Although the distribution of the potentials did not fit the criteria for a Poisson process when the muscle fiber exhibited the short burst of high-frequency discharges, it was suggested that the primary process of such a distribution is Poisson, which is occasionally contaminated by the burst phase of the release rates.
Bile Acid Metabolism in Mammals. VIII. Biliary Secretion of Cholylarginine by the Isolated Perfused Rat Liver
Authors: Yousef I. M. , Fisher M. M.
Published: April 2011

In studies of cholic acid metabolism using the isolated perfused rat liver system, an unknown conjugate of cholic acid was observed. This conjugate comprised 15–27% of the biliary bile acids in these experiments, was less polar than cholylglycine on thin-layer chromatography using butanol, acetic acid, and water, and had an apparent molecular weight greater than that of cholyltaurine on gas–liquid chromatography. Amino acid analysis of the hydrolyzed conjugate demonstrated the presence of arginine. Perfusion studies with radioactive arginine, and mass spectrometric analysis proved that the conjugate was cholylarginine. Secretion of this conjugate does not represent a deficiency of available glycine and taurine.
Quantitative Aspects of Cyclic AMP and Relaxation in the Rabbit Anterior Mesenteric-Portal Vein
Authors: Collins G. A. , Sutter M. C.
Published: April 2011

Rabbit anterior mesenteric-portal vein was shown to exhibit a positive correlation between relaxation and cyclic AMP levels using different concentrations of isoproterenol for varying exposure times. No consistent relationship was found between cyclic AMP and relaxation using a series of phosphodiesterase inhibitors (papaverine, SC2964, or RA233). In sodium-free (Tris-substituted) Krebs' solution, the addition of isoproterenol still increased, cyclic AMP levels, but there was no relaxation. Dibutyryl cyclic AMP was also ineffective in sodium-free solution. Under identical conditions, both relaxation and increases in cyclic AMP produced by papaverine and SC2964 were found to be independent of extracellular sodium. We conclude, therefore, that increased cyclic AMP may be involved in isoproterenol-induced relaxation possibly acting via increased Na+–Ca2+ exchange, but plays only a small role, if any, in smooth muscle relaxation produced by papaverine, RA233, or SC2964.
The Effect of Atropine Upon Acetylcholine Release from Cat Superior Cervical Ganglia and Rat Cortical Slices: Measurement by a Radio-Enzymic Method
Authors: Kato A. C. , Collier B. , Ilson D. , Wright J. M.
Published: April 2011

Atropine is known to increase the release of acetylcholine (ACh) from cerebral cortex, and the present experiments tested the effect of this drug upon ACh release in the superior cervical ganglion of the cat. The release of ACh was measured by a radio-enzymic method, which was shown to provide an estimate of the ACh content of samples collected from perfused ganglia that was similar (102%) to that obtained by the method of bioassay more usually used. Atropine (3 × 10−6 M) increased (3.5- to 4-fold) the amount of ACh released by rat's sliced cerebral cortex incubated in a high (23 mM) potassium medium. However atropine (3 × 10−6–3 × 10−5 M) did not change the amount of ACh released by ganglia during preganglionic nerve stimulation (5–10 Hz). It is concluded that cholinergic nerve terminals in different tissues appear to have different pharmacological properties.
The Influence of Phenobarbitone on Maternal and Perinatal Hepatic Drug-metabolizing Enzymes in the Rat
Authors: Bell J. U. , Hansell M. M. , Ecobichon D. J.
Published: April 2011

Phenobarbitone (PB) (75 mg/kg) was administered orally for three consecutive days to pregnant or lactating rats at different pre- and postnatal stages in order that the perinatal animals would receive the agent either by transplacental passage or via the milk. Control animals received equivalent volumes of saline. The dams, fetuses, and pups were killed 24 h after the last dose. Hepatic p-nitroanisole O-demethylase (OD), carboxylesterase (CE), and bromosulfophthalein–glutathione (BSP–GSH) conjugating enzyme activities in a 12 100 g – 20 min supernatant of a 20% w/v homogenate were measured. The morphology of the developing rat liver in the absence and presence of PB was examined by electron microscopy.The results demonstrated that the transplacental passage of PB to rat fetuses at term or 3 days prepartum had no effect on either the hepatic drug-metabolizing enzyme activities or on the ultrastructural appearance of the liver. Increased hepatic OD activity was observed in the pregnant animal but no effect was observed in the lactating dam. Phenobarbitone received by the suckling rat had two distinct effects. Compared to control activities, twofold increases in hepatic OD activity were observed in rat pups as early as 4 days after birth, associated with a marked proliferation in hepatic smooth endoplasmic reticulum. In contrast, PB-related significant increases in neonatal hepatic CE and BSP–GSH conjugating enzyme activities were not observed until 21 days of age. In the 4-day-old treated pups, characteristic morphological changes included numerous small membrane whorls in addition to increased smooth endoplasmic reticulum and microbodies in the liver.
On the Mechanism of Coupling in Adrenaline-induced Bigeminy in Sensitized Hearts
Authors: Reynolds A. K. , Chiz J. F. , Tanikella T. K.
Published: April 2011

The mechanism of coupling in adrenaline-induced ventricular bigeminy in sensitized hearts has been investigated in intact animals, isolated preparations, and single cardiac fibers. The electrophysiological and cardiovascular dynamic changes during the development of fixed interval coupling strongly indicate that the coupled beats result from stretch of subsidiary pacemaker fibers in the specialized ventricular conduction system, induced by the mechanical response to the normally conducted sinus impulse. The resulting intraventricular pressure elicits an extrasystole, when a certain critical end systolic pressure for a particular animal is reached. The interval between the normal and premature ventricular beat decreases progressively as the intraventricular pressure rises, as a result of the combined action of adrenaline and postextrasystolic potentiation. The onset of ventricular bigeminy is preceded by a shift in the pacemaker site to the A–V junctional area, due to a differential effect of the anesthetic–adrenaline combination on fibers of the S–A node and those in the junctional area. The degree of prematurity of the coupled beat shows an inverse linear relationship to the intraventricular pressure of the initiating beat at the end of systole. The premature QRS complex occurs after a period of mechano–electrical latency, the duration of which is directly related to this pressure.
Studies of Glucose Production in Sheep Using [6-3H]Glucose and [U-14C] Glucose
Authors: Brockman R. P. , Bergman E. N. , Pollak W. L. , Brondum J.
Published: April 2011

Simultaneous primed-continuous intravenous infusions of [6-3H]glucose and [U-14C]glucose were performed on 13 fed, 4 fasted, and 4 dexamethasone-treated sheep. In 10 of the experiments on fed sheep, glucagon or insulin was infused intraportally for 2 h after control values were obtained. The 3H-labeled glucose gave glucose production values that were only 4.4 ± 0.5, 5.4 ± 1.0, and 5.8 ± 0.8% higher than 14C-labeled glucose in the normal fed, fasted, and dexamethasone-treated sheep, respectively. Glucagon or insulin infusions did not significantly alter this recycling. It is concluded that a recycling of glucose carbon through metabolic intermediates is minimal in the sheep as compared with other species and also that it is not significantly altered by fasting or by hormones that affect glucose production.
Effect of hypothyroidism on responsiveness to β-adrenergic stimulation
Authors: Fregly M. J. , Resch G. E. , Nelson Jr. E. L. , Field F. P. , Tyler P. E.
Published: April 2011

Chronic administration of aminotriazole (0.5 g/kg food) to rats was accompanied by a reduced responsiveness to acute administration of the β-adrenergic agonist, l-isoproterenol (50–100 μg/kg, sc). The responses tested included water intake, change in heart rate in the anesthetized and unanesthetized rat, change in mean blood pressure, and change in blood glucose concentration. In addition, the increase in tail skin temperature accompanying administration of epinephrine (1 mg/kg, sc) was significantly reduced in the hypothyroid group. Administration of l-thyroxine (25 μg/kg per day, ip) to aminotriazole-treated rats prevented the reduction in responsiveness to β-adrenergic stimulation. Thus, an interaction appears to exist between the level of thyroid activity and responsiveness to β-adrenergic agonists in rats.
Further evidence that protein synthesis can be decreased in vivo following hormonal stimulation in the rat pancreas
Authors: Mongeau R. , Dagorn J. C. , Morisset J.
Published: April 2011

The present study has been undertaken to determine in the rat the influence of exocrine secretory stimulation on pancreatic protein synthesis. This stimulant consisted of a single injection of cholecystokinin–pancreozymin (8 Ivy units/kg) plus secretin (5 clinical units/kg). The rate of [14C]phenylalanine incorporation into total proteins was measured 5, 11, 17, 30, 45 and 60 min later. Incorporation was significantly decreased after 5 min, then significantly increased at 17 min, and finally returned to control values at 45 min. This biphasic evolution was shown not to be caused by variations in the precursor pool specific radioactivity. We concluded that secretory stimulation of the pancreas can induce a decrease in the rate of protein biosynthesis. This decrease is nevertheless a transient phenomenon, since the rate of biosynthesis was increased at 17 min. These results, obtained from a totally in vivo system, confirm previous data obtained from an in vivo – in vitro system.
A method for the study of the inhibition of DNA synthesis by rabbit tissue extracts
Authors: Sassier Pierre , Bergeron Michel
Published: April 2011

This paper describes a method to measure DNA synthesis in the jejunum. Everted rings of rat jejunum were incubated in the presence of [3H]thymidine. The specific activity of jejunal DNA was assayed at the end of incubation. This method was found to be valid when (1) incubation time was 30 min, (2) [3H]thymidine concentration was 90 ng/ml, and (3) paired flasks containing four, respectively, contiguous rings were compared.This method was used to investigate the existence of an intestinal chalone. An aqueous extract (S-105) of rabbit small intestine mucosa was prepared and tested for DNA synthesis inhibition in jejunum. A significant inhibition was noted, which was an hyperbolic function of the quantity of extract present in the media. The study of S-105 inhibition on other organs (kidney, liver, colon) failed to demonstrate organ specificity. However, aqueous extracts from intestinal organs were found to exert a greater inhibition than aqueous extracts from other organs. It is suggested that S-105 contains other nonspecific inhibitory fractions; our data prove the necessity of an extensive purification to demonstrate the existence of a specific chalone that regulates intestinal cell proliferation.
Postjunctional supersensitivity of the rat vas deferens and gap junctions
Authors: Paton D. M. , Buckland-Nicks J. , Johns A.
Published: April 2011

Tissues from the duodenum and vas deferens of Sprague–Dawley rats were examined of the rat vas deferens and gap junctions. Can. J. Physiol. Pharmacol. 54, 412–416. by electron microscopy after glutaraldehyde fixation and postosmication. Gap junctions (nexuses) were readily demonstrated in the duodenum in both control and reserpine treated animals (1.0 mg/kg per day for 7 days). However, gap junctions could not be demonstrated in vas deferens. It is concluded that the postjunctional supersensitivity and spontaneous activity induced by reserpine in vas deferens, does not result from the formation of gap junctions.
The effect of taurine on calcium exchange of sarcoplasmic reticulum of guinea pig heart studied by means of dialysis kinetics
Authors: Dolara P. , Agresti A. , Giotti A. , Sorace E.
Published: April 2011

Calcium binding and release by sarcoplasmic reticulum vesicles of guinea pig heart were studied by means of a dialysis apparatus and analyzed with a model of three closed compartments. The rate constants of calcium binding were increased by taurine, and this effect was dose-related, whereas calcium efflux rate constants were very near to 0 in control experiments and were not effected by taurine.Taurine therefore increased the calcium content of sarcoplasmic vesicles and decreased the calcium concentration of the medium. β-Alanine had no action on calcium fluxes.
Toxicity testing in vitro. II. Use of a microsome – cultured human fibroblast system to study the cytotoxicity of cyclophosphamide
Authors: Cooper James T. , Goldstein Samuel
Published: April 2011

The toxicity of cyclophosphamide (CP), has been studied using a human fibroblast cell culture system. A method is described in which CP is incubated with liver microsomes and appropriate co-factors before addition to the cells. This permits activation of the CP to its cytotoxic metabolite but avoids the necessity of adding microsomes directly to the cell culture. It was demonstrated that under these conditions CP was irreversibly toxic to the cells within hours at dose levels ≥ 0.3 mg/ml. In the absence of microsomal activation it was toxic at similar dose levels but the toxic effects required several days to develop.