bluuebunny/crossref_metadata_2025 huggingface dataset:
OXYGEN SUPPLY AND PERFORMANCE IN PEROMYSCUS: COMPARISON OF EXERCISE WITH COLD EXPOSURE
Authors: Segrem Neri P. , Hart J. S.
Published: April 2011

Oxygen consumption, heart rate, and body temperature were measured at temperatures ranging from 27 °C to −28 °C and at oxygen partial pressure [Formula: see text] levels from 60 to 196 mm Hg. Temperature regulation and O2 uptake were progressively limited by reduction of [Formula: see text]. Limitation of O2 consumption by O2 supply was similar to that seen during exercise. The highest oxygen uptake during exposure to cold was greater than during exercise at the higher levels of [Formula: see text].
EFFECT OF D-GLUCOSAMINE ON GLUCOSE METABOLISM AND INSULIN ACTION IN THE RAT INTACT DIAPHRAGM
Authors: Martin Julio M.
Published: April 2011

Previous studies in this laboratory demonstrated that insulin, when administered simultaneously with glucosamine, significantly lowered the hyperglycemic effect of the latter. This result conflicts with reports suggesting that glucosamine competes with glucose at the site of insulin action. To explore further this apparent contradiction, the effect of insulin and glucosamine on glucose metabolism by the intact rat diaphragm preparation was studied. The distribution ratio of glucose-1-14C and glucosamine-1-14C, the glycogen content, and the 14CO2 production were measured in the presence or absence of insulin after 90 and 120 min incubation. Insulin increased glucose and glucosamine penetration 7 and 4 times respectively. Glucosamine did not interfere with glucose entry into the cell either in the presence or absence of insulin. Glycogen synthesis was not impaired by glucosamine, although glucosamine itself did not contribute to glycogen formation. 14CO2 production from glucose-1-14C was markedly depressed by glucosamine, and glucosamine-1-14C did not contribute to 14CO2 production. These results indicate that in muscle tissue, glucosamine interferes neither with the glucose transport across the cell membrane, nor with the metabolic pathway of glucose to glycogen; but glucosamine, or a metabolic intermediate, does inhibit some metabolic step in the breakdown of glucose to CO2.
LATENCY OF THE GASTRIC SECRETORY RESPONSE TO SHAM FEEDING IN THE DOG
Authors: Preshaw R. M.
Published: April 2011

In conscious dogs with gastric fistulas the latency of both the gastric acid and pepsin responses to sham feeding was about 6 min. When a background secretion was induced with various closes of hog gastrin, the latency of the acid response to sham feeding was unchanged, but the latency of the pepsin response was shortened. The peak rates of acid and pepsin secretion after sham feeding were not altered by the infusion of gastrin.
INFLUENCE OF RESERPINE, HEART FAILURE, AND IMMUNOSYMPATHECTOMY ON THE CARDIAC EFFECTS OF OUABAIN
Authors: Wendlandt S. , Varma D. R.
Published: April 2011

A possible relationship between myocardial noradrenaline and the cardiac effects of ouabain has been investigated. Pretreatment with reserpine, with or without acute adrenalectomy, failed to reduce the positive inotropic effect of ouabain in cats. Similarly, reserpine did not reduce the positive inotropic effect of ouabain in cats which had developed congestive heart failure from chronic pulmonary artery stenosis and which had approximately 40% of the normal amount of myocardial noradrenaline. The positive inotropic effect of ouabain on isolated papillary muscles from reserpine-treated rabbits and on the isolated left atria from reserpine-treated rats or rats with immunosympathectomy was also normal. Depletion of myocardial noradrenaline did not influence the toxicity of ouabain except in cats with congestive heart failure. In these cats, pretreatment with reserpine increased the arrhythmic and the lethal dose of ouabain. Reserpine or immunosympathectomy produced a marked depletion of myocardial noradrenaline stores. It is concluded that the positive inotropic effect of ouabain is not due to a release of noradrenaline from the heart. The mechanism by which pretreatment with reserpine reduces the toxicity of ouabain in cats with congestive heart failure is not clear. It may or may not be due to a depletion of myocardial noradrenaline.
FRAGILITY AND TURNOVER OF LIVER MITOCHONDRIA OF COLD-ACCLIMATED RATS
Authors: Lusena C. V. , Depocas Florent
Published: April 2011

Cold acclimation did not change the amount of mitochondrial protein which could be isolated per unit weight of liver. When isolated liver mitochondria from cold-acclimated rats were tested for fragility by a freezing and thawing procedure, they released more glutamic and β-hydroxybutyric dehydrogenases than did mitochondria from warm-acclimated rats. Liver mitochondria from both groups could be separated into fractions showing different fragilities but all fractions from cold-acclimated rats were more fragile than the corresponding fractions from warm-acclimated animals; thus the greater fragility of liver mitochondria of cold-acclimated rats is a property shared by all fractions. Cold acclimation had little effect on renewal of liver mitochondria.
A COMPARISON OF THE EFFECTS OF HEXAFLUORODIETHYL ETHER AND PENTYLENETETRAZOL ON THE EXCITABILITY OF FROG SKELETAL MUSCLE FIBERS
Authors: Inoue F. , Pinsky C. , Sanders H. D.
Published: April 2011

Hexafluorodiethyl ether (HFE) and pentylenetetrazol (PTZ) differ in their ability to reduce the excitability of the frog's sartorius muscle. HFE increases the threshold current and threshold depolarization necessary for the production of action potentials. At 7.8 mM this drug abolishes the overshoot phase of the action potential and at 23.2 mM it completely blocks the compound action potential response to extracellular stimulation. PTZ is a less potent depressant than is HFE on all the parameters measured. Treating the muscle with 1.5 times the usual concentration of sodium chloride was much more effective in restoring the overshoot potential after HFE depression than after PTZ depression. It is likely that the decrease in overall excitability which results from treatment of the muscle with HFE represents impairment of a sodium-dependent process, whereas depression induced by PTZ, even in very high concentrations, does not. It is suggested on the basis of these results that the very marked central nervous system stimulation which follows parenteral administration of either PTZ or HFE occurs through different mechanisms.
TETRAETHYLAMMONIUM-INDUCED CONTRACTIONS OF FROG'S SKELETAL MUSCLE: II. EFFECTS ON INTRAMUSCULAR NERVE ENDINGS
Authors: Beaulieu G. , Frank G. B. , Inoue F.
Published: April 2011

By recording simultaneously from muscle fibers and from the ventral root supplying the muscle, it was found that low concentrations of tetraethylammonium (TEA) caused the muscle fibers to fire without antidromic impulses being conducted to the ventral root. Exposing the muscles to higher TEA concentrations induced action potential firing in both the muscle and the ventral root. d-Tubocurarine prevented the muscle fiber activity but did not modify the ventral root firing. The application of a single supramaximal electrical stimulus to the sciatic nerve resulted in an afterdischarge of the muscle fibers either alone or simultaneous with an afterdischarge of fibers in the ventral root. By recording from fine intramuscular motor nerve fibers with extracellular glass capillary microelectrodes while simultaneously recording from the ventral root, it was demonstrated that TEA could cause these fine intramuscular motor nerve fibers to fire without the activity being conducted antidromically to the ventral root. A consideration of the patterns of TEA-induced electrical activity and afterdischarging led to the suggestion that TEA causes these effects by displacing calcium from binding sites on the motor nerve endings, making the latter hyperexcitable and unstable and thereby causing afterdischarging and 'spontaneous' activity.
AN EQUATION FOR CALCULATING "DERIVED" ACID–BASE PARAMETERS
Authors: Suero Jesus T. , Woolf C. R.
Published: April 2011

An equation to derive standard bicarbonate from any given pH and [Formula: see text] values was derived based on the observation of an empirical exponential relationship between hydrogen ion concentration and the slope of standard bicarbonate/[Formula: see text]. The equation was used in a computer program to give tables of calculated values of various derived parameters that are presently used in clinical acid–base assessment; namely, standard bicarbonate, buffer base, and base excess, from a given range of pH and [Formula: see text] values including variations imposed by hematocrit values. A new term, "non-respiratory acid excess", is introduced.
EFFECT OF MONOAMINE OXIDASE INHIBITORS ON THE CONCENTRATIONS OF DOPAMINE AND SEROTONIN IN THE STRIATUM OF THE CAT WITH AND WITHOUT UNILATERAL BRAINSTEM LESIONS
Authors: Singh P. , Poirier L. J. , Boucher R.
Published: April 2011

A comparison between the effects of tranylcypromine and harmaline on the concentrations of dopamine, and serotonin in the striatum of the brain of normal cats gave the following results. Harmaline produced an increase in serotonin but not in dopamine whereas tranylcypromine increased both biogenic amines. In addition, harmaline produced its maximal effect on serotonin concentration within 1 hour whereas tranylcypromine caused an increase in both dopamine and serotonin only after a much longer period of time. In cats with unilateral brainstem lesions that interrupted the striatopetal fibers from the brainstem nuclei concerned with the elaboration of dopamine and serotonin, the administration of harmaline resulted in different effects in the two striata of the brain. Under such circumstances the concentrations of dopamine and serotonin in the striatum of the intact side of the brain were similar to those found in normal cats treated with harmaline. In cats with a complete interruption of the fibers concerned with the elaboration of the two biogenic amines, there was a complete cell loss in the corresponding brainstem nuclei, associated with a complete depletion of dopamine and serotonin in the ipsilateral striatum. This depletion was apparently unaffected by treatment with harmaline.
STUDY OF THE INTERACTION OF BARBITURATES AND DICUMAROL AND THEIR EFFECT ON PROTHROMBIN ACTIVITY, HEMORRHAGE, AND SLEEPING TIME IN RATS
Authors: Lucas Oscar N.
Published: April 2011

In this study the influence of barbiturates (Nembutal and Barbitone) upon the pharmacological activity of Dicumarol and the converse interaction were evaluated. Prothrombin time, incidence of hemorrhage, and sleeping time were measured in relation to the pharmacological action of each drug when given simultaneously and separately. Groups of Sprague–Dawley, white, male rats weighing approximately 250–350 g were fed Dicumarol, barbiturates, or the combination of both mixed with powdered food during the 10 days of the experiment. Groups treated with Dicumarol plus barbiturates showed a significantly shorter mean prothrombin time and lower incidence of hemorrhage than the group treated with Dicumarol alone. When the combination of drugs or each drug alone was administered by stomach tube or intraperitoneally, similar findings were obtained. Barbiturates exerted a protective action against the hypoprothrombinemic and hemorrhagic effects of even a toxic dose of Dicumarol, regardless of the route of administration. The mean sleeping time of groups treated with Nembutal alone was not significantly different from that of groups treated with Nembutal–Dicumarol. No hemorrhage was observed in the control animals or those receiving barbiturates only, nor was there a difference in the mean prothrombin time of these groups.
EFFECT OF VARIOUS ABLATIONS IN THE HYPOTHALAMUS ON ESTABLISHED PREGNANCY IN THE RAT
Authors: Holloway S. A. , Stevenson J. A. F.
Published: April 2011

To investigate the role of the hypothalamus in the maintenance of established pregnancy, bilateral electrolytic lesions were made in various regions of the hypothalamus in Wistar rats on day 10 of gestation. These lesioned rats were compared with pair-fed controls, and controls fed ad libitum. No significant differences were noted between lesioned and pair-fed control rats in litter and fetal weights, length of gestation, or stillbirth rates. Lesioned rats were able to complete their pregnancies to term. Fetal birth weight was normal or slightly subnormal in the face of significant decreases, and in one group an increase, in maternal food intake. After lesions in some regions of the hypothalamus, there were changes in maternal endocrine weights, suggesting a disturbance of hypothalamic control of the anterior pituitary. These results show that pregnancy can be maintained successfully in the presence of large symmetrical lesions in several regions of the hypothalamus and support the concept that the fetus is nourished at the expense of maternal resources.
Angiotensin in the analysis of the intrinsic nerve supply of isolated intestines
Authors: Goldenberg M. M.
Published: April 2011

Angiotensin-induced contraction of the isolated guinea pig and rabbit intestines is mediated through activation both of the intrinsic nerves and on the smooth muscle. An extension of such studies was carried out to include the effects of angiotensin on the isolated ilea of the Mongolian gerbil, the mouse, and the rat. These studies indicate further the diversity in the intrinsic motor nerves of intestine of the three species, as has been suggested in previous studies. Angiotensin (1 μg/ml) produced a biphasic effect on the ileum of the gerbil, mouse, or rat, i.e. an initial fast spike-like contraction followed by a slow, progressive contraction. The spike-like contraction was abolished by procaine, cocaine, and mecamylamine, but not by hexamethonium or pentolinium. In the mouse and gerbil, this initial response was blockaded by atropine, morphine, and epinephrine; and in the rat it was resistant to atropine and morphine but inhibited by epinephrine. The slow progressive contraction of the three ilea was inhibited by only papaverine and epinephrine. Motor nerve stimulation (cholinergic pathway in mouse and gerbil, non-cholinergic in rat) was responsible for the initial angiotensin effect and direct musculotropic stimulation for the secondary effect.
The effect of aminophylline and isoproterenol on venous distensibility
Authors: Zsotér Thomas
Published: April 2011

Venous distensibility, i.e. Δ volume/Δ pressure, was examined in vivo in humans and in vitro in canine veins. Saline and isoproterenol (1 and 3 μg) when injected directly into the venous segment examined had no effect on the distensibility of superficial forearm veins. Aminophylline on the other hand (48 and 100 mg) significantly increased distensibility, as did dihydroxypropyl-theophylline. Similar results were obtained when 480 mg aminophylline was injected into a distant vein. The venous distensibility of dogs in vitro was not significantly changed either by isoproterenol or aminophylline. Drugs may alter venous distensibility, and this should be considered in their pharmacological and therapeutic evaluation.
Effects of parathyroid hormone on bone acid hydrolases in tissue culture
Authors: Tolnai Susan
Published: April 2011

Experiments were carried out to assess the activity of acid hydrolases of bone cells under in vitro conditions. Rat and mouse skull bones were kept in vitro for 2 to 6 days in the presence and absence of added parathyroid hormone. The activities of acid protease (cathepsin D), acid phosphatase, and β-glucuronidase were measured in the culture media and in homogenates prepared from the cultured bones. All three enzymes showed increased activity in various degrees in the media when parathyroid hormone (PTE) was present, but increased enzyme synthesis in the homogenates could be detected only in the case of acid protease and acid phosphatase. The acid protease showed maximum activity at pH 3.0–3.2, and the PTE-stimulated increase was time-dependent. Lysozyme incorporated into the culture medium stimulated acid protease activity, while histone had an opposite effect. Cultures kept in incomplete media for a limited period of time also responded to PTE treatment with an increased release of acid hydrolases into the medium.
On the interaction of calcium, sodium, and water transport in the diuresing kidney
Authors: Schück O. , Cort J. H.
Published: April 2011

Diuresis was induced in cats by infusion of 3% glucose in 10% ethanol. When urine flow had stabilized at high levels a solution of the Ca salt of ethylenediaminetetraacetate (Na2CaEDTA) was infused as a control for the effect of the EDTA molecule on renal function. The infusion was then changed over to the same molar rate of Na2EDTA, which resulted in a 30% decrease in serum Ca levels. Ca was then repleted rapidly as CaCl2 given intravenously, and the infusion was shifted back to Na2CaEDTA. The decrease in extracellular Ca concentration was associated with a significant antidiuresis. In further experiments on anesthetized dogs, osmotic diuresis was induced either by (a) infusion of hyperosmotic mannitol solutions, which were then shifted over to hypertonic NaCl, or (b) the same solutions in reverse order. Ca excretion correlated in linear fashion with Na excretion, but not with total solute excretion or with filtration rate. When Ca was added to the mannitol infusion, Na excretion increased in linear relation to Ca. It is suggested that Ca (a) decreases tubular permeability for water reabsorption and (b) decreases Na reabsorption, while Na (c) decreases Ca reabsorption. Mechanisms a and b would appear to involve membrane transport directly in the proximal tubule.
The role of afferents from the low-pressure system in the release of antidiuretic hormone during non-hypotensive hemorrhage
Authors: Henry J. P. , Gupta P. D. , Meehan J. P. , Sinclair R. , Share L.
Published: April 2011

Moderate hemorrhage insufficient to reduce seriously the pulse pressure, had no effect on the total flow of afferent impulses per unit time from stretch receptors of the high-pressure system (systemic circulation). However, it sharply reduced the flow from the atrial receptors of the low-pressure system (lesser circulation). Thus acute non-hypotensive blood volume loss permits a differentiation between the effects of the stretch receptors in the two divisions of the cardiovascular system. Eleven conscious animals were trained to lie quietly with catheters in the femoral vessels. The loss of no more than 10–20% of the estimated blood volume led to a sharp drop in atrial stretch receptor firing. Measurements of blood ADH showed variable increases which in most cases were to significant levels. Other aspects of cardiovascular and fluid volume regulation were affected by changes in firing of stretch receptors in the low-pressure system. They include the tachycardia of non-hypotensive hemorrhage and changes in kidney function with atrial distension.
Elevation in serum insulin, albumin, and FFA, with gains in liver lipid and protein, induced by glucocorticoid treatment in dogs
Authors: Campbell James , Rastogi Krishna Sudha
Published: April 2011

Administration of methylprednisolone to dogs (4 mg/kg per day, intramuscularly for 17 days) had the following effects. Immunoreactive insulin (IRI) in serum (postabsorptive) rose threefold to a peak in 4 days and later returned to normal. Serum glucose was little altered. The rise in the IRI/glucose ratio suggests that the sensitivity of the insulin release mechanism of the pancreatic beta cells to glucose was increased. Serum albumin rose, concomitantly with IRI, then returned to normal at a slower rate than did IRI. Globulins were not appreciably altered. Free fatty acids (FFA) rose later, during days 7–14. Liver weight increased, owing to gains in total lipid and fat-free solids. The plasma volume percent increased, and polyuria occurred. In response to a glucose load (1 g/kg, intravenously) methylprednisolone caused an augmented rise in serum IRI on days 1 and 4, with a later return to or below normal, and an increase in the rate of disappearance and the apparent volume of distribution of glucose. Cortisone (5 mg/kg per day intramuscularly, for 6 days) exerted similar effects in the dog. The results suggest that an increased insulin secretion was induced by glucocorticoids, and that this effect was involved in enhanced synthesis of liver protein and albumin and in increased rate of uptake of glucose.
Experimental parathyroid hormone deficiency produced by injection of antibodies to bovine parathyroid hormone
Authors: Kooh Sang Whay , Fraser Donald
Published: April 2011

Antiserum to bovine parathyroid hormone (Anti-PTH) was produced in guinea pigs by repeated subcutaneous injections of purified bovine PTH with Freund's adjuvant. Specific binding of PTH with Anti-PTH was demonstrated in vitro by a two-antibody system. Anti-PTH was administered intravenously to three species of animals. Within 8 h, rats had developed a decrease in plasma calcium and an increase in plasma phosphorus concentrations, physiological changes characteristic of the PTH deficiency state. A similar degree of hypocalcemia occurred in rabbits. Some of the animals injected with Anti-PTH died within 24 h; in survivors, the hypoparathyroid state was transient and recovery occurred within 24 h. Equivalent amounts of Anti-PTH had no effect on the levels of plasma calcium in normal guinea pigs. Injections of parathyroid extract to rats, rabbits, and guinea pigs caused a hypercalcemic response. Since antibodies produced in the guinea pig to bovine PTH neutralized the physiological action of rat and rabbit PTH, but did not neutralize that of guinea pig PTH, it is concluded that bovine, rat, and rabbit PTH are immunologically similar, but that guinea pig PTH is dissimilar. However, the hormones of all four species have a common attribute that determines biological activity.
Effect of growth hormone, an anabolic steroid, and cortisone upon various fractions of skin and bone hydroxyproline in mice
Authors: Kowalewski K. , Yong S.
Published: April 2011

Various fractions of hydroxyproline were determined in skin, femora, and humeri of DBA/2 mice treated for 2 weeks with one of three hormones: bovine growth hormone, anabolic steroid (17-β-hydroxy-17-α-methylandrostano[3,2-c]pyrazole), and cortisone acetate. The following fractions were studied: 0.15 M NaCl, 0.50 M NaCl, 0.50 M citrate, and total hydroxyproline. Since collagen is the only protein in the body containing hydroxyproline in significant amounts, this fractionation method allows an appraisal of the rates of synthesis, maturation, and breakdown of collagen. Growth hormone produced a significant increase in all extractable fractions and in the total hydroxyproline content of tissues studied. The action of anabolic steroid on hydroxyproline was generally comparable to that of growth hormone, but was less marked. Both total hydroxyproline and saline-extractable fractions were significantly reduced in skin and bone of cortisone-treated mice.
A possible dual role of noradrenaline in cardiovascular responses mediated by the central nervous system
Authors: Gagnon D. J. , Melville K. I.
Published: April 2011

The cardiovascular responses induced by intraventricular noradrenaline after intraventricular pretreatment with reserpine, imipramine, and chlorpromazine were studied in cats anesthetized with chloralose and under artificial respiration. Pretreatment with all three agents produced various degrees of "reversal" of the usual cardiovascular depressant responses to noradrenaline (50 μg intraventricularly), leading to significant pressor responses and tachycardia. These sympathetic excitatory cardiovascular responses were significantly reduced by spinal C-2 section. It is suggested that this reversal phenomenon is not due entirely to brain noradrenaline depletion, but that all three agents (reserpine, imipramine, and chlorpromazine) act by blocking neuronal uptake of noradrenaline, thereby preventing the usual central cardiovascular inhibitory effects of the amine. These findings also suggest a possible dual role of noradrenaline in cardiovascular changes mediated by the central nervous system.
The effect of noradrenaline infusions and adrenergic blocking agents on serum glutamic–oxalacetic transaminase in dogs
Authors: Loegering Daniel J. , Critz Jerry B.
Published: April 2011

Mongrel dogs were infused with 6, 96, or 384 μg/kg of noradrenaline at a constant rate for 1 h. Serum glutamic–oxalacetic transaminase (SGOT), blood pressure, and heart rate were recorded during and for 10 h after the infusion. There was no change in SGOT levels at the lowest dose of noradrenaline. The SGOT activity was increased at the end of the infusion of the 96 μg/kg dose. The 384 μg/kg dose caused the SGOT activity to more than double by the end of the infusion and to more than triple 10 h later. Blood pressure increased with only the two larger doses of noradrenaline. Animals infused with 384 μg/kg of noradrenaline and pretreated with either phenoxybenzamine or propranolol showed a delayed rise in SGOT activity. Neither of these drugs alone blocked increases in SGOT activity but a group pretreated with both blocking agents showed no increase in enzyme levels. The hypertension due to the vasoconstriction produced by noradrenaline may be accompanied by hypoxic conditions in the tissues, and this hypoxia may cause changes in membrane permeability of sufficient magnitude to allow release of the GOT enzyme. The adrenergic blocking agents may reduce or eliminate the pressor response to noradrenaline and thus reduce the hypoxia.
Hypotensive action of bretylium after central administration
Authors: Jaju B. P. , Tangri K. K. , Bhargava K. P.
Published: April 2011

Bretylium has been found to have a central hypotensive effect independent of its peripheral adrenergic neuron blocking action. It decreases the excitability of the medullary vasoactive neurons, as shown by inhibition of vasopressor responses evoked by stereotaxic stimulation of the medulla oblongata or reflex responses mediated at the medullary level. A possible role of catecholamines in the central hypotensive action of bretylium is suggested.
Age as a determinant of the effect of testosterone upon disuse osteoporosis of paralyzed limbs of rats
Authors: Bullard T. Robert , Lindsay Hugh A.
Published: April 2011

The effect of testosterone on atrophy of disuse in bone was investigated in animals of various known ages. Rats ranging from 3 weeks to 3 months of age were randomly assigned to control and experimental groups; the latter were injected with testosterone propionate to determine whether its influence was the same at all ages. In all animals atrophy of disuse was induced by neurectomy in one hind limb. In control animals the effect of neurectomy on femur weight and load at failure varied inversely with age. In experimental animals testosterone accentuated the effect of neurectomy in the youngest animals and reduced the effect in the oldest.
The influence of norethindrone and mestranol on pituitary–adrenal function
Authors: Usher David R.
Published: April 2011

Female Wistar rats were force-fed either Ortho-Novum (66 μg norethindrone and 1 μg mestranol), norethindrone (66 μg), mestranol (1 μg), or water daily for 1 month. After decapitation, organs were weighed, plasma was analyzed for corticosterone concentration, and the adenohypophyseal ACTH content was assayed. Animals treated with Ortho-Novum and mestranol showed a significant ovarian, adrenal, and pituitary weight loss; this was more marked after mestranol. Mestranol also produced a significant uterine atrophy. Norethindrone lowered adrenal weight but had little effect on the other organ weights. Adenohypophyseal ACTH content was significantly decreased after norethindrone but not after mestranol. On the basis that the effects of norethindrone may have been due to estrogenic contaminants, rigorously purified norethindrone was used in a further study. No effects were seen on organ weights although some decrease in pituitary ACTH was still observed. Thymus weight and plasma corticosterone levels were unaltered by any of the treatments. It would appear that increasing estrogenicity (pure norethindrone < crude norethindrone < Ortho-Novum < mestranol) resulted in a decrease in the weight of both the pituitary and the adrenals, and an increased ACTH storage in the adenohypophysis.
The Origin of Glycosaminoglycans in Baboon Urine During the Menstrual Cycle
Authors: Naidoo S. S. , Qureshi A. M.
Published: April 2011

Deturgescence of the baboon sex skin is frequently accompanied by the appearance in urine of relatively large amounts of nonsulfated glycosaminoglycans (GAG). In order to identify their tissue origin, sequential biopsies of the sex skin were analyzed for the type and amounts of GAG present. During the normal menstrual cycle turgescence is accompanied by a considerable net increase in hyaluronic acid, which disappears almost completely during deturgescence. Sulfated GAG showed relatively little change. Interstitial fluid obtained from the sex skin during deturgescence contained hyaluronic acid but not sulfated GAG. The disappearance of hyaluronic acid from the sex skin coincides with the appearance in urine of increased amounts of nonsulfated GAG, indicating that the latter originate in the perineum. GAG, excreted in urine during perineal deturgescence, constitutes a small fraction of that mobilized from the sex skin, suggesting considerable in vivo degradation. The results emphasize the potential value of the sex skin as a connective tissue model.
Aryldiazonium Salts as Antagonists at Cholinergic Muscarinic Receptors
Authors: Ross D. H. , Triggle D. J.
Published: April 2011

A series of aryldiazonium salts were synthesized and tested for inhibitory activity on the longitudinal muscle of the guinea pig ileum. The most potent member of the series, benzenediazonium fluoborate (BDF) (at 10−4 M with incubation for 5 min), produced a dose ratio of 600 for acetylcholine (Ach), 58 for cis-2-methyl-4-trimethylammonium methyl-1,3-dioxolane (CD), and 30 for carbamylcholine (Cch). BDF was significantly less effective against histamine-induced responses and was without effect on K+-induced responses. BDF produced a differential effect on muscarinic responses, producing right-ward shifts of dose–response curves of polar ligands but only depressing maximal responses of nonpolar ligands. An exception to this was amyl-trimethylammonium, for which the curves were shifted and the maximal responses depressed. Protection experiments showed that polar ligands (Cch, CD) offered protection against BDF antagonism of nonpolar ligand (alkyl-trimethylammonium) responses that decreased with alkyl chain length, but that nonpolar ligands afforded strong protection for both polar and nonpolar activity that was indpendent of chain length. A discussion of these findings is offered in terms of both the receptor reserve concept and of allosteric mechanisms of antagonist action.
Effect of Angiotensin II on Blood Volume and Water Intake in the Rat
Authors: Abdelaal A. E. , Mercer P. F. , Mogenson G. J.
Published: April 2011

Experiments were performed to investigate whether the copious drinking of rats infused with angiotensin II results from a reduction in plasma volume. Angiotensin II (Hypertensin, CIBA) dissolved in 0.9% NaCl was infused through a jugular cannula into conscious, unrestrained rats at a rate of 0.72 ± 0.015 μg kg−1 min−1 for a 30 min period. The amount of angiotensin II required to induce the first drinking response was 6.43 ± 0.667 μg/kg body weight and the latency to drink following the initiation of the infusion was 9.1 ± 0.97 min. The average intake of water during the first drinking bout was 6.3 ± 0.43 ml/kg. The total intake of water during the 30 min infusion period was 13.0 ± 1.37 ml/kg. Plasma volume and hematocrit were determined before and during the angiotensin II infusion. Blood samples were obtained from the jugular cannula before the infusion began and again either 1, 2, 3, 4, 5, 10, 15, or 30 min after the infusion began. The same determinations were also made either when angiotensin II initiated drinking, 2 min or 8 min thereafter. There were no significant changes in either plasma volume or hematocrit. It is concluded that angiotensin-induced drinking does not occur because of hypovolemia produced by angiotensin II.
Effect of Calcitonin on P Uptake in Epiphyseal Cartilages of P-Deficient Rats
Authors: Denis G. , Kuczerpa A.
Published: April 2011

Proximal epiphysial cartilages from rats fed a P- and Ca-deficient diet for 2 weeks contained approximately one-half of the concentration of P and Ca found in normal cartilage. Calcitonin caused a highly significant increase in the P concentration in the cartilages of thyroparathyroidectomized rats fed the diet for 1 week and then a diet containing 0.5% P and 0.4% Ca for 16 h, but not in rats maintained only on the P-deficient diet.
Variations in the Relative Potencies of Bronchodilators in the Presence and Absence of Carbachol-Induced Tone
Authors: Jones Thomas R. , Hamilton John T. , Lefcoe Neville M.
Published: April 2011

Responses to dl-isoprenaline, aminophylline, and the bacteriostatic preservative methyl paraben were obtained on the isolated guinea pig trachea in the absence and presence of the spasmogen carbachol. The results demonstrate that the presence of carbachol significantly reduced the relaxant activity of dl-isoprenaline (one-quarter as potent) whereas the activity of aminophylline and methyl paraben were only reduced by one-half. It is concluded that the use of a "pharmacological tool" such as carbachol can alter the interpretation of results obtained in such studies since the beta sympathomimetic dl-isoprenaline appears to interact with carbachol in a manner different from that of the non-beta adrenoreceptor agonists aminophylline and methyl paraben.
Serum Alpha-Tocopherol in Pregnancies with Normal or Pathological Outcomes
Authors: Vobecky J. S. , Vobecky J. , Shapcott D. , Blanchard R. , Lafond R. , Cloutier D. , Munan L.
Published: April 2011

Results indicate that, in comparison with normal pregnancies, in pregnancies leading to abortions, stillbirths, and congenitally malformed infants, maternal alpha-tocopherol differs both as to serum levels and as to rates of increase during gestation. In women aborting or giving birth to malformed infants, decreases in serum alpha-tocopherol levels were noted in the second trimester. In pregnancies ending in stillbirths, the increases in alpha-tocopherol levels were slower and significantly lower than in normal pregnancies. Because of the limited number of observations no causal relationships were proposed but the hypothesis of a vitamin basis for congenital deformities appears worth testing.
Studies on 14C-imipramine Metabolism in the Isolated Perfused Rat Liver
Authors: Moldowan Mervin , Bellward G. D.
Published: April 2011

An analytical procedure for the measurement of 14C-imipramine and its metabolites in liver, bile, and perfusion fluid has been studied using the isolated perfused rat liver technique. The extraction efficiency and specificity have been found to be high (efficiency with liver perfusion, 90–100%; specificities: imipramine, 96.6%; desmethylimipramine, 96.7%; imipramine-N-oxide, 90%). The hydroxylation of imipramine was close to the maximal rate at a substrate concentration of 0.5 × 10−4 M (15 min perfusion). The demethylation reaction reached a maximal rate at an estimated substrate concentration of 1.25 × 10−4 M. The formation of the N-oxide metabolite remained linear at 2 × 10−4 M imipramine. It was found that the half-life of imipramine in the perfusion fluid was not an accurate method of estimating imipramine metabolism as a result of a change in distribution. Exogenous desmethylimipramine inhibited the hydroxylation reaction; inhibition of demethylation required higher concentrations.
The Role of the Intramural Cholinergic Innervation in the Acid Response of the Parietal Cell to Gastrin Derivatives
Authors: Davison J. S. , Fahrner P. C. , Schofield B. , Tepperman B. L.
Published: April 2011

The action of a number of nerve-blocking agents on gastric secretion in fundic pouches in dogs has been investigated. Histamine has been used as a direct acid stimulant, and was compared with gastrin and derivatives whose action may involve local nerves. In most cases, the inhibitor agent has been applied to an established plateau of secretion but in some series the local anesthetic lidocaine (xylocaine) benzyl chloride (LBC) has been allowed to act for [Formula: see text] h before stimulation was commenced.In Heidenhain pouches, atropine (5–20 μg/kg intravenously (i.v.)) produced a mean inhibition of submaximal pentagastrin and gastrin plateaus of –88%. Histamine plateaus were inhibited only –21%. Hexamethonium (1 mg/kg i.v.) was without effect on the pentagastrin response. This means that only the terminal element of the cholinergic pathway can be involved in gastrin stimulation of the parietal cell.Blockage of this terminal link was demonstrated in Pavlov pouches under insulin stimulation by pretreatment with LBC, the mean inhibition being –95%. Pepsin secretion was also abolished. LBC was without effect on established histamine plateaus in Heidenhain pouches and the same result was observed with stimulation by gastrin and its derivatives. This last result, implying no nervous involvement in the gastrin effect, led to recognition of a difference in design in the insulin experiments where LBC was applied before acid secretion.Experiments with LBC on established insulin responses gave an inhibition of only –44%. Thus a series of pentagastrin experiments with pretreatment were carried out but the mean inhibition was only –15%, which is not significant. This is directly comparable with the mean inhibition in the LBC pretreatment insulin series of –95%.To exclude nonspecific effects of LBC, sodium net flux studies have been carried out. There was a small increase in positive Na+ net flux in the vagal stimulation in which the acid response is virtually abolished. However, in the pentagastrin experiments with LBC pretreatment, larger positive net sodium fluxes occurred though acid secretion was not significantly reduced. It is therefore considered that the powerful inhibition in the vagal stimulation experiments is not related to nonspecific effects.It is concluded that the acid secretory response of the parietal cell to gastrin derivatives does not involve excitation of intramural cholinergic nerve elements as now seems likely for their motor effects. However, the response of the parietal cell to gastrin acting directly may be potentiated by quantal acetylcholine release from resting fibers, and until this possibility is excluded the blocking effects of atropine cannot be regarded as nonspecific.
The Metabolic Response to Exercise and Exhaustion in Normal and Growth-Hormone-Deficient Children
Authors: Winter Jeremy S. D.
Published: April 2011

The effects of exhausting bicycle exercise at close to maximal work capacity upon circulating levels of hormones and energy substrates in 4 fasting growth-hormone-deficient and 15 fasting healthy subjects (aged 13–18 years) have been studied. As expected, only the healthy subjects showed a rise in plasma growth hormone (GH) levels. In both groups plasma insulin tended to fall, but the decline was more prolonged in the GH-de-ficient group. Plasma Cortisol levels rose in both groups with the exception of one adrenocorticotropin (ACTH)-deficient subject. Blood sugar levels were well-maintained in all but this ACTH-deficient subject, whereas both groups showed marked lactate accumulation. Both groups demonstrated an initial fall and then a secondary rise in serum free fatty acid concentrations; however, fatty acid levels were lower in the GH-deficient group and there was no post-exercise overshoot, suggesting a possible reduction in the effectiveness of lipid mobilization.
Cocaine-Induced Supersensitivity in the Human Umbilical Artery
Authors: Reiffenstein R. J. , Triggle C. R.
Published: April 2011

Cocaine (3.3 × 10−7 – 3.3 × 10−5 M) has no effect on the uptake of noradrenaline by the smooth muscle cells of the human umbilical artery but was found to potentiate the mean effective dose (ED50) responses of isolated helical strips of human umbilical artery to noradrenaline (3 × 10−5 M), and, to a lesser degree, 5-hydroxytryptamine (3.65 × 10−4 M), but had no effect on the response to KCl (40 mM) or histamine (1.8 × 10−6 M). Concentrations of cocaine above 1.7 × 10−4 M were found to antagonize ED50 responses to all the agonists tested. Because the preparation used in these studies does not receive sympathetic innervation, the effect of cocaine is likely to be mediated by an action at the level of the muscle. This selective increase in the response mediated by noradrenaline may be explained by an allosteric alteration of the α-adrenergic receptor system and/or a semiselective increase in smooth muscle sensitivity.
Inhibition of Papain-Induced Emphysema in the Hamster by Human Alpha1-antitrypsin
Authors: Martorana P. A. , Richard J. W. , McKeel N. W. , Share N. N.
Published: April 2011

Human alpha1-antitrypsin administered intratracheally in the hamster prevented the development of emphysematous changes induced by papain aerosol exposure. Inhibition appeared dose-related and detectable by both physiologic and histologic methods.
Increased Diamine Oxidase Activity in the Intestinal Lymph of Rats on Fat Ingestion
Authors: Wollin A. , Jaques L. B.
Published: April 2011

When diamine oxidase activity was measured in the intestinal lymph of rats, a marked increase in the enzyme activity was observed shortly after oral administration of olive oil. The response was similar to that seen after intraperitoneal injection of heparin. Substitution of glucose solution for olive oil did not produce this response. Administration of olive oil on successive days resulted in a successively greater increase in diamine oxidase activity. Combined administration of olive oil and intraperitoneal injection of heparin gave diamine oxidase activity levels whch were greater than the sum of the increases resulting from the separate treatments.
Changes in Spleen Weight, Cyclic-AMP Content, and Serum-Corticosterone Levels of Rats in Response to CO2
Authors: Lehotay D. C. , Murphy B. E. Pearson
Published: April 2011

CO2 administration to rats anesthetized with sodium pentobarbitone caused contraction of the spleen and elevation of its cAMP content, but no rise in serum corticosterone. Studies with adrenoreceptor blockers showed that the contraction is caused by stimulation of α-receptors, whereas cAMP elevation is a β effect. The contraction was shown to be due to circulating catecholamines released from the adrenal glands, whereas cAMP elevation was due both to circulating and to locally released catecholamines in the spleen. Theophylline prevented the CO2-induced contraction. Dibutyryl cyclic GMP caused a fall in the cAMP content of the spleen but no contraction. The use of CO2 for the sacrifice of experimental animals is recommended where low levels of corticosteroids in blood are desirable.
The Immunological Release of Slow-Reacting Substance of Anaphylaxis from Bovine Lung
Authors: Burka J. F. , Eyre P.
Published: April 2011

Slow-reacting substance of anaphylaxis (SRS-A) was released immunologically from bovine lung in vitro. Polyphloretin phosphate inhibited release of SRS-A. Pretreatment of calves with aspirin potentiated SRS-A release on challenge. The partially purified SRS-A extract contracted the guinea-pig ileum and bovine pulmonary vein.
Effects of Morphine and Naloxone on Dorsal Horn Neurones in the Cat
Authors: Calvillo O. , Henry J. L. , Neuman R. S.
Published: April 2011

Morphine, applied by microiontophoresis to functionally identified dorsal horn neurones in segments L5–L7 of cats (chloralose anaesthetized, decerebrated or high spinal), produced primarily a depression of the discharge of neurones responding to noxious radiant heat applied to the skin. It depressed on-going activity (12 out of 20 neurones), glutamate-evoked excitation (8/8) and the response to the noxious stimulus (13/21). The response of two additional neurones to heat was potentiated. The effects began 10–30 s from the onset of application, reached a maximum in up to 8 min and outlasted application by up to 10 min. Morphine had relatively little effect on on-going activity and glutamate-evoked excitation of neurones responding to non-noxious stimuli (n = 18). Naloxone (intravenously and iontophoretic) reversed these depressions (4/11). It is suggested that morphine may produce analgesia, at least in part, by a direct action on a specific morphine receptor in the spinal cord.
Depression of Corticospinal Cells by Various Purines and Pyrimidines
Authors: Phillis J. W. , Kostopoulos G. K. , Limacher J. J.
Published: April 2011

Microiontophoretically applied adenine nucleotides depressed the firing of corticospinal and other unidentified cerebral cortical neurones. Adenosine 3′,5′-cyclic monophosphate was less potent than the other adenine nucleotides. Guanine nucleotides shared this depressant activity, although they were less potent. Pyrimidine nucleotides and xanthine derivatives were largely devoid of depressant activity. Adenosine triphosphate had an additional excitant action on some neurones, but this effect was not observed with corticospinal cells.
Effective Vascular Compliance of Dogs in Acute Heart Failure
Authors: Larochelle Pierre , Ogilvie Richard I.
Published: April 2011

Effective vascular compliance was measured repeatedly in dogs without circulatory arrest utilizing a closed-circuit venous bypass system and constant cardiac output. Compliance, determined by the ΔV/ΔP relationship at the end of a 1-min infusion of 5% of the circulating volume into the inferior vena cava, was independent of the initial venous pressure, total circulating volume and systemic arterial pressure. It remained constant over a 3 h experimental period at 1.55 ± 0.05 ml (mm Hg)−1 kg−1 body weight. Elevation of mean left atrial pressure and mean pulmonary arterial pressure by gradual aortic constriction was associated with a large and significant reduction in vascular compliance to a value of 1.14 ± 0.06 ml (mm Hg)−1 kg−1 after 2 h. This reduction was independent of the initial venous pressure and total circulating volume but was associated with the changes in left atrial and pulmonary artery pressures and an increase in plasma catecholamine concentrations. The mechanism responsible for the reduction in effective compliance is not clear from the present experiments. Increased circulating catecholamines and sympathetic nerve traffic resulting from baro- and volume receptor stimulation in the vascular tree may be the causative mechanism.
Catecholamine–Ouabain Interaction on the Isolated Perfused Rat Heart
Authors: Tremblay G. , Porlier G. , Elharrar V. , Nadeau R. , Champlain J. de , Biron P.
Published: April 2011

The effect of catecholamine-depleting pretreatments, reserpine, and 6-hydroxydopamine (6-OH-DA) on left ventricular pressure (LVP) and the inotropic response to graded doses of ouabain (up to 300 μg/0.05 ml) was studied in isolated perfused rat and guinea-pig hearts. In rats, reserpine and 6-OH-DA depleted myocardial catecholamine content (p <0.001), increased initial LVP (p < 0.05), and virtually abolished the inotropic response to ouabain (p < 0.01). The individual maximal inotropic response to ouabain was negatively correlated with the initial LVP (r = −0.47), and this relationship was significant. In guinea pigs, reserpine and 6-OH-DA significantly depleted the cardiac content of catecholamine, but did not increase initial LVP and did not reduce the inotropic response to the highest dose of ouabain. It is concluded that in isolated rat hearts, these catecholamine-depleting pretreatments nearly abolish the inotropic response to ouabain, and this effect appears to be mediated mainly through an increase in initial LVP. The reason why catecholamine depletion failed to increase initial LVP in guinea pigs remains unexplained.