bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for the Mediatory Role of Brown Adipose Tissue During Nonshivering Thermogenesis in the Cold-Acclimated Mouse
Authors: Hayward J. S. , Davies P. F.
Published: April 2011

The increased rate of oxygen consumption by cold-acclimated, adult mice after subcutaneous injection of noradrenaline has been measured for intact individuals and for those with the arterial supply to their interscapular brown adipose tissue ligated. An immediate reduction of 40% of this calorigenic response was noted in mice thus operated. Dissection of the total brown fat of the body indicated that the interscapular deposits comprise 43% by weight of the total brown adipose tissue, which in turn forms only 1% of the body weight. Since a 40% reduction in calorigenic response to noradrenaline cannot be ascribed to the loss of an amount of brown fat constituting less than 0.5%) of the body weight, the results support the hypothesis that brown fat can mediate calorigenic responses of other tissues.
Slow Rhythms of Sympathetic Discharge Induced by Convulsant Drugs
Authors: Polosa Canio , Teare Jane Lake , Wyszogrodski Issie
Published: April 2011

We have previously reported (Can. J. Physiol. Pharmacol. 1969. 47, 815–826) that sustained oscillations of blood pressure, similar to Mayer waves, can be produced by the drug picrotoxin in anesthetized cats. We have investigated further the properties of these oscillations by recording the electrical activity of sympathetic preganglionic, somatic motor, and phrenic nerves. We found that the sympathetic preganglionic and somatic motor nerves show a periodic increase of electrical activity in synchrony with the oscillations of blood pressure. The phrenic nerve shows changes in repetition rate and duration of its bursting activity, which are synchronous with the blood pressure waves (i.e. phrenic bursts are more frequent and longer lasting on the ascending than on the descending limb of the blood pressure waves). The synchronous oscillation of these three output systems is not due to proprioceptive feedback because it is present when the animals are paralyzed, ventilated artificially, and even when the blood pressure is prevented from oscillating by ganglionic block. We conclude that the observed rhythmic pattern of neural activity is generated in the central nervous system.
Effects of a Sulfated Mucopolysaccharide (R01-8307) on Zona Glomerulosa Width and Steroid Production by the Rat Adrenal Cortex
Authors: Levine J. H. , Laidlaw J. C. , Ruse J. L.
Published: April 2011

Heparin and a semisynthetic mucopolysaccharide (R01-8307) cause a fall in aldosterone production by both the human and rat adrenal, and narrowing of zona glomerulosa width in the rat. We have shown in studies of R01-8307-treated rats that the fall in aldosterone production precedes histological changes in the zona glomerulosa. Corticosterone production was not altered, suggesting that pituitary adrenocorticotropin production and the function of the inner cortical zones were not affected. Direct addition of R01-8307 to incubating rat adrenal quarters did not alter either aldosterone or corticosterone production.
The Effects of Manganese on the Rabbit Anterior Mesenteric–Portal Vein
Authors: Collins G. A. , Sutter M. C. , Teiser J. C.
Published: April 2011

The effects of manganese and lanthanum were tested on the contractile responses of the rabbit anterior mesenteric–portal vein (A.M.V.). Since these ions have been shown to block calcium fluxes in other tissues, examining their effects may give information concerning the importance of calcium influx for contractions of the A.M.V. The effects of the two cations on the A.M.V. were found to be similar except that lanthanum was more potent and its inhibitory effects were not readily reversible. Spontaneous action potentials and their associated contractions were abolished by the addition of 0.5 mM Mn2+. This inhibition could be rapidly reversed by adding EDTA to chelate the manganese. Manganese inhibited the responses to all agonists tested (noradrenaline, histamine, serotonin, procaine, and KCl). The inhibition of responses to all agonists but procaine could be partially reversed by raising the external calcium concentration. The interaction between calcium and manganese follows competitive kinetics. Adding manganese during the tonic phase of a contraction evoked by 10−6 g/ml noradrenaline resulted in a relaxation to a decreased, but sustained, tension. The inhibitory effects of manganese add further evidence that an influx of calcium from the extracellular fluid is required for spontaneous activity and for both the initiation and maintenance of contractions to agonists in the rabbit A.M.V.
Comparison of the Elastic Properties of Human Intracranial Arteries and Aneurysms
Authors: Scott Susan , Ferguson Gary G. , Roach Margot R.
Published: April 2011

Static pressure–volume curves were done on seven intracranial saccular aneurysms and 16 major cerebral arteries from human autopsies. The aneurysms were much less distensible than the arteries. The major change was in the initial or elastin part of the curve (elastance of 6 ± 5 S.D. × 105 dynes/cm per 100% elongation in the artery compared to 13.5 ± 5 × 105 dynes/cm per 100% elongation for the aneurysm; p < 0.005). This agrees well with histological studies which show that elastin is decreased and fragmented in aneurysms.As the aneurysm enlarges, its wall must become thinner. This change, coupled with the loss of distensibility, makes it more prone to rupture. Obviously the larger the aneurysm, the thinner the wall (if the volume of tissue remains constant), and the greater the risk of rupture.The distensibility of major cerebral arteries could be dramatically decreased by two or three runs to pressures of 200 mm Hg. The elastance of the initial part of the curve changed from 2 ± 1 × 105 dynes/cm per 100%; elongation to 8 ± 1 × 105 dynes/cm per 100% elongation (different at p < 0.001). The final elastance was altered less significantly (42 ± 6 × 105 dynes/cm per 100% elongation to 82 ± 28 × 105 dynes/cm per 100% elongation; p < 0.01). This shift in distensibility was accompanied by a significant increase in diameter of the artery. High pressures appear able to break the single elastin layer of cerebral arteries.
Ventilation and Fibrinolytic Activity
Authors: Rossman A. , Goode R. C. , Monkhouse F. C. , Milojevic S. , McAlpine V. , Arnold D.
Published: April 2011

Previous studies have shown that increases in fibrinolytic activity are related to the intensity of exercise. To provide information as to the mechanism that might initiate this increase in activity the effects of breathing various gas mixtures for 10-min periods were investigated in 11 subjects. Hypercapnia ([Formula: see text], [Formula: see text], [Formula: see text]) and hypocapnia ([Formula: see text], [Formula: see text], [Formula: see text]) were associated with increases in fibrinolytic activity (P < 0.001) whereas no consistent change occurred with hypoxia ([Formula: see text], [Formula: see text], [Formula: see text]), hyperoxia ([Formula: see text],[Formula: see text], [Formula: see text]) and eucapnic hyperventilation ([Formula: see text],[Formula: see text],[Formula: see text]). The average times for lysis to occur with hypocapnia and hypercapnia as compared with the control values were 78 and 84%, respectively.
Fate of 14C-phytoI Administered Orally to Sheep
Authors: Hidiroglou M. , Jenkins K. J.
Published: April 2011

The metabolism of phytol was investigated in 12 sheep, each given a single oral dose of 14C-phytol. In the unsaponifiable material of abomasum liquor or liver tissue. 14C-phytol radioactivity was recovered unchanged as the administered compound or as an unidentified metabolite of phytol. Most of the radioactivity in the saponifiable material of tissues, after esterification. occurred in the methyl ester of phytanic acid. A portion of the phytol occurring in the rumen lumen was converted to phytanic acid.
Amino Acid Composition of Digesta Taken from Swine Receiving Diets Containing Soybean or Rapeseed Meals as Sole Source of Protein
Authors: Cho C. Y. , Bayley H. S.
Published: April 2011

The usefulness of amino acid digestibility measurements as indices of availability can be evaluated by comparing the amino acid composition of distal ileal digesta (where absorption is believed to be complete) with that in the rectum. Two semipurified diets containing either soybean or rapeseed oil meals were each fed to four castrated male pigs of 60 kg liveweight. The pigs were sacrified and samples of digesta were removed from the stomach, duodenum, jejunum, ileum, cecum, colon, and rectum. The concentrations of nitrogen and the proportions of 14 amino acids in the samples were studied. Digesta taken from the duodenum contained the greatest concentration of nitrogen; the nitrogen concentration decreased through the small intestine, and then remained constant through the large intestine. Comparing the ileal and rectal digesta, there were no significant differences in the proportions of valine, arginine, serine, tyrosine, threonine, phenylalanine, and aspartic acid for both diets. This was also true for lysine for the soybean meal diet and for methionine and alanine for the rapeseed meal diet, so that for these amino acids, digestibility should be a good estimate of availability. However, there were lower proportions of leucine plus glycine, proline, and glutamic acid in the rectal than in the ileal contents for both diets, and for lysine in the rapeseed meal diet, suggesting that digestibility values would overestimate availability. In contrast, there were higher proportions of isoleu-cine in the rectal than in the ileal contents for both diets, and of methionine and alanine for the soybean meal diet, suggesting that digestibilities would underestimate the availabilities of these amino acids.Partition of the digesta and the water-soluble digestion marker (polyethylene glycol) in the stomach precluded reliable quantitation of digesta flows through the ileum, but the experiment suggests that such quantitative measures would provide a basis for more valid estimates of amino acid availabilities than measurements of the amounts of amino acids voided in the feces.
The Effect of Phentolamine and Other Drugs on Rat Brain Phosphodiesterase
Authors: McNeill John H. , Lee Cheng-Yi , Muschek Lawrence D.
Published: April 2011

A number of derivatives of imidazole, and the imidazoline derivatives phentolamine and tolazoline, were tested for their effect on cyclic AMP phosphodiesterase obtained from rat brain. Phentolamine and tolazoline inhibited the enzyme with phentolamine being the most potent. Histamine and a derivative of triazole (3-β-aminoethyl-1,2,4-triazole) increased enzyme activity about 10%. It is suggested that enzyme inhibition by phentolamine in addition to an α-adrenergic blockade may explain the reported enhancement of certain catecholamine responses. The stimulation of the enzyme by histamine also may exlpain some of the pharmacological actions of histamine.
Relative Importance of Liver and Kidney in Synthesis of Uric Acid in Chickens
Authors: Chou S. T.
Published: April 2011

Broiler chickens of 1, 2, and 7 months of age were used for enzymatic spectrophotometric determination of uric acid and its precursors, xanthine, hypoxanthine, and inosinic acid, in the liver and kidney in an attempt to show the relative importance of the two organs in the synthesis of uric acid, the major nitrogenous compound excreted by birds.Uric acid concentration of the kidney was two to three times as high as the liver, probably attributable in part to preformed uric acid trapped in the urinary passages in the kidney. Significantly higher concentrations of xanthine, hypoxanthine, and inosinic acid were found in the kidney than in the liver. The calculations based on organ weight and the concentrations of uric acid precursors suggest that the kidney synthesizes 96, 60, and 73% as much uric acid as does the liver for the 1-, 2-, and 7-month-old chickens, respectively.
Effect of Catecholamines and Dibutyryl-cyclic-AMP on Glucose Turnover, Plasma Free Fatty Acids, and Insulin in Dogs Treated with Methylprednisolone
Authors: Issekutz Jr. Bela , Borkow Ingrid
Published: April 2011

The turnover rate of glucose was measured in dogs with indwelling arterial and venous catheters, according to the primed constant rate infusion techniques, using 2-3H-glucose as tracer. The effects of adrenalin (A), noradrenalin (NA), and dibutyryl-cAMP (DBcAMP) infusions were tested on normal dogs and on dogs treated for 3 days with methylprednisolone (MP, 3–3.5 mg/kg day). MP potentiated the hyperglycemic effect of A (0.5 μg/kg min) six- to sevenfold, and the increase of hepatic glucose output (Ra) 11-fold. In addition, the free fatty acid (FFA) increasing and lactacidemic effects of A were significantly potentiated by MP. A prevented the rise of immunoreactive insulin even though plasma glucose reached values of 400–450 mg%. The metabolic clearance rate was significantly decreased by A. NA (0.5 μg/kg min) had no hyperglycemic effect in the controls, but it increased the blood sugar by 120 mg% in the treated group. This was caused by a more than twofold increase in the hepatic glucose output. MP treatment did not alter the NA induced rise of FFA and no effect was seen on plasma lactate levels. NA caused a transient rise of insulin in the controls and a greater and more sustained one in treated dogs. Following MP treatment, DBcAMP (0.1 or 0.2 mg/kg min) also caused a much greater hepatic glucose output and hyperglycemia than what had been obtained on the same animals prior to treatment. DBcAMP increased plasma insulin and decreased FFA. It is concluded that the cyclic-AMP sensitivity of hepatic enzyme systems involved in glucose output was greatly increased by MP treatment.
Acceleration of Renal Hypertension Accompanied by Increase in Plasma Volume as a Result of Prior Thoracic Sympathectomy
Authors: Chessar John R. , Ferrario Carlos M. , McCubbin James W.
Published: April 2011

The renal pressor system exerts a dramatic effect on body fluid volumes when the thoracic sympathetic chains are removed in dogs. This effect was demonstrated in experiments designed originally to determine the influence of cardiac sympathectomy on the increase in cardiac output that precedes development of renal hypertension. While removal of the cardiac sympathetic nerve supply did not prevent the increase in cardiac output after wrapping one kidney in cellophane, a modest rise in blood pressure was accompanied by a remarkable 46 ± 8 (S.E.) % (p < 0.005) increase in plasma volume at the expense of interstitial fluid space. Removal of the contralateral kidney caused the appearance of malignant hypertension within 6 to 56 days while the plasma volume decreased somewhat though it remained well above control values. Unwrapping the kidney restored the blood pressure and fluid volumes to normal. Infusion of small dosage of angiotensin for 5 days into two other dogs after removal of the thoracic sympathetic chains had a similar effect on plasma volume; infusions were without effect prior to sympathectomy. The findings uncover an as yet unexplained interaction between the renal pressor and sympathetic nervous systems.
I. Pharmacology of Angiotensin Antagonists
Authors: Rioux F. , Park W. K. , Regoli D.
Published: April 2011

Several analogues of angiotensin II (ATII) have been characterized as antagonists against ATII and ATI, and compared with lidoflazine and guancydine, on the rat isolated stomach strip.The pA2 and pA10 values have been determined according to Schild (1947, Br. J. Pharmacol. 2, 189–206) after 5 and 15 min of contact of the antagonist with the tissue.The results show that (8-Gly)-ATII, (8-n-But)-ATII, (8-Val)-ATII, (8-Ile)-ATII, and (8-Leu)-ATII are specific and competitive antagonists of ATII and ATI, because the differences pA2 – pA10 are near to 0.95, the theoretical value for competitive antagonists. The same compounds do not influence the myotropic effect of 5-hydroxytryptamine (5-HT) or bradykinin on the same tissue. (8-Leu)-ATII and (8-Ile)-ATII are 12 times more active than (8-Gly)-ATII and the similarity of pA2 values for (8-Leu)-ATII and(8-Ile)-ATII to the pD2 value for ATII strongly suggests that one molecule of agonist is blocked by one molecule of antagonist. (1-Sar-8-Leu)-ATII is specific for ATII, but the antagonistic action of this compound is not of the competitive type (pA2 – pA10 = 0.65).PA2 – pA10 for guancydine and lidoflazine correspond approximately to 0.75. Myotropic action of 5-HT and bradykinin are antagonized by concentrations of guancydine and lidoflazine similar to those used to inhibit ATII and ATI. This suggests that guancydine and lidoflazine are noncompetitive and nonspecific antagonists of angiotensin.
Effect of Adrenocorticotropin (ACTH) upon the Drug Response of Intact and Adrenalectomized Rats
Authors: Szabo S. , Kourounakis P. , Selye H.
Published: April 2011

In intact female rats, pretreatment with crystalline ACTH for at least 4 days reduces zoxazolamine paralysis and diminishes the toxicity of aniline, N-methylaniline, and acetanilide. The corticotropic hormone increases the aggravation of drug toxicity by adrenalectomy. Corticosterone also reduces zoxazolamine paralysis; its action (when given alone or in combination with ACTH) is evident both in intact and in adrenalectomized animals. The prophylactic effect of ACTH against zoxazolamine is not associated with decreased plasma levels of the drug. Hence, ACTH and corticosterone act syntoxically in that rats pretreated with these hormones tolerate high blood levels of drugs without exhibiting signs of poisoning.
Mechanism of Potentiation of Vascular Responses by Tetraethylammonium: A Novel Form of Sensitization
Authors: Kalsner Stanley
Published: April 2011

Evidence was obtained for a previously unidentified form of sensitization in vascular smooth muscle related to calcium utilization. The quaternary ammonium compound tetraethylammonium potentiated the amplitude of contractions elicited by a variety of agonists in rabbit aortic strips. The potentiating effect was not reduced in strips from rabbits pretreated with reserpine to deplete endogenous catecholamine. An analysis of the mechanism of enhancement indicated that tetraethylammonium increased the utilization of extracellular and/or loosely bound calcium for contraction. It was found that potentiation was much reduced and usually blocked in a low-calcium solution. In addition, SKF-525A, a substance that inhibits selectively the influx of extracellular calcium to the contractile elements, generally abolished enhancement. Effects on calcium utilization should be considered as a possible mechanism in other currently undefined potentiations.
Stimulation of Glucose Production by Hypoxia in Newborn Dogs
Authors: Varma S. , Rakušan K. , Cowan J. S. , Hetenyi Jr. G
Published: April 2011

The aim of the experiments was to examine the role of hypoxia as a possible regulator of hepatic glucose production in newborn dogs. In pups 1–30 days of age the rate of endogenous (hepatic) glucose production increased when the animals were ventilated with a gas mixture containing 10% or 5% O2. During a single 45 min exposure to hypoxia the increase in glucose production was significantly correlated with the O2 saturation in arterial blood. A second exposure to the more severe hypoxia (5% O2) following the first (10% O2) led to a second increase in the concentration of glucose in plasma and in glucose production. In pups less than 10 days of age, the increases during the second hypoxic period were only transient. During a 60 min rest following exposure to the more severe hypoxia (5% O2) basal glucose production rates and plasma concentrations were not reestablished. The metabolic clearance rate of glucose was not changed by hypoxia. There was a significant drop in plasma free fatty acid level. The increase in endogenous glucose production to hypoxia in pups indicates that the liver in the newborn animal is capable of increasing the rate of glucose production and that the known lack of a response to hypoglycemia is due to the absence of the feedback between glucose production and extracellular glucose concentration.
Function–Structure Correlation Studies on Excised Hamster Lungs in Papain-induced Emphysema
Authors: Martorana P. A. , McKeel N. W. , Richard J. W. , Share N. N.
Published: April 2011

Emphysematous lesions induced by a single exposure of hamsters to papain aerosol were evaluated both physiologically (lung elastic recoil) and histologically (mean linear intercept). The extent of the developed lesions was directly related to the concentration of papain employed, and progressed with time following exposure. Histological evaluation was most sensitive for quantitation of minimal lesions; an approximate 20% increase of the mean linear intercept being required for significant functional changes. Maximal mean increase of the mean linear intercept compatible with survival was approximately 75%. Using raw data values, all functional tests exhibited high correlation coefficients (r) with histological evaluation, but prediction efficiencies (r2) were below a practically acceptable value of 75%. However, using group mean values, thereby reducing individual biological variations, higher correlation coefficients as well as high prediction efficiencies were obtained for all functional tests with histological evaluation. In this regard, best prediction efficiencies were obtained for the functional specific static compliance and specific volume at full inflation versus the morphological mean linear intercept.
Erythrocyte Sedimentation Rates in Inclined Vessels
Authors: O'Brien R. N. , Hocking M. B. , McOrmond P. , Thornton K. R.
Published: April 2011

The rates of erythrocyte settling have been investigated in round and square cross-section tubes, vertically; and at nine different angles; and with the square tubes flat and on edge, to a minimum of 15° from the horizontal. Apparent settling rates increased as the angle from the horizontal decreased. Real settling rates (vertical settling rates) increased sharply on decreasing the angle from the horizontal, to a maximum at about 60°, and then decreased less abruptly for the shallower angles. The cross-sectional shape of the tube did not significantly affect the settling rates of erythrocytes. Settling in inclined tubes proceeds fast enough to permit clinical erythrocyte settling rate (E.S.R.) tests to be carried out in 10 min in place of the usual 60 min. If the standard E.S.R. test rack deviates as little as 5° from the vertical it can cause the observed settling rates to double relative to readings obtained on a vertical rack.
Evidence for the Existence of a Corticotropin-Releasing Factor in the Pigeon Hypothalamus
Authors: Sato Takenori , George John C.
Published: April 2011

Evidence is presented for the existence of a corticotropin-releasing factor in the pigeon hypothalamus employing an intrapituitary microinjection method. A crude acetic acid saline extract of pigeon median eminence was shown to increase significantly plasma corticosterone levels in the dexamethasone–chlorpromazine–Nembutal blocked assay rats. On the other hand, the crude extract of brain cortex of the bird failed to elevate plasma steroid levels in the assay animals. A dose–response relationship was obtained between the dose of the median eminence extract and plasma corticosterone increments. Arginine vasotocin, oxytocin, epinephrine, and norepinephrine were ineffective in eliciting adrenocorticotropic hormone (ACTH) release when injected directly into the adenohypophysis of the assay rats.It was concluded that the ACTH releasing effect of the hypothalamic extracts was not due to the neurohypophysial hormones or to catecholamines, but due to a corticotropin-releasing factor (CRF). These observations are discussed with special reference to the specificity of CRF activity.
Sialic Acid Content of Red Blood Cells from Protein-Calorie Malnourished Children and During Recovery, and from Normal Children and Adults
Authors: Contreras C. , Viteri F. E.
Published: April 2011

Sialic acids were measured in the red cells of two groups of subjects. One group consisted of 12 children with severe protein-calorie malnutrition (P.C.M.); six of them were followed longitudinally throughout the recovery period. The control group included 28 normal children and 11 normal adults. All subjects were studied hematologically and the sialic acid content of the red cells was determined in three layers of erythrocytes, separated according to their density by ultracentrifugation. The results indicate that there are no alterations in the content of sialic acids in the red cells of children with severe P.C.M. Furthermore, they show that the sialic acid content of the red cell is not influenced by various levels of red cell folates nor by differences in the concentration of serum proteins, serum iron, percentage saturation of transferrin, serum folates, or serum vitamin B12.
The Anticonvulsant Properties of Isonicotinic Acid Hydrazide and Associated Changes in γ-Aminobutyric Acid Metabolism
Authors: Wood J. D. , Peesker S. J.
Published: April 2011

The administration of isonicotinic acid hydrazide and pyridoxine to chicks prior to their being exposed to oxygen at high pressure brought about a delay in the onset of the hyperbaric-oxygen-induced seizures in the birds. The hydrazide was the active anticonvulsant component of the drug mixture but pyridoxine was necessary to prevent seizures induced by the hydrazide itself shortly after its administration. The anticonvulsant action of the drug mixture developed relatively slowly but lasted for several hours and correlated well with concomitant changes in the concentration of γ-aminobutyric acid (GABA) in the brain. No similar correlation was observed between the anticonvulsant action and the activity of either glutamic acid decarboxylase or GABA-α-oxoglutarate aminotransferase.
Effect of EGTA on Protein Release and Cyclic AMP Accumulation in Rat Parotid Gland
Authors: Harfield B. , Tenenhouse A.
Published: April 2011

An attempt was made to determine whether accumulation of cyclic AMP (cAMP) was essential for epinepnrine-stimuiated secretion of protein from the rat parotid gland in vitro. EGTA (10−2 M) did not inhibit secretion but did reduce cAMP accumulation by 80% suggesting that this nucleotide may not be an essential intermediate in the epinephrine-stimuiated secretion process.
Constancy and Linearity of the Metabolic Clearance of Adrenocorticotropin in Dogs
Authors: Cowan John S. , Davis Allan E. , Layberry Ross A.
Published: April 2011

The study of the turnover characteristics of adrenocorticotropin (ACTH) has been facilitated by (1) a sensitive bioassay for ACTH in plasma based upon the response of suspended adrenal cells to ACTH and (2) a technique for preserving the ACTH in small plasma samples. The metabolic clearance rate (MCR) of ACTH was determined by intravenous step infusions of ACTH into dogs lightly anesthetized with Nembutal, without blockade of ACTH secretion; in these dogs the endogenous plasma ACTH level was negligible. The infusion rates ranged from 0.25 to 3.0 mU/kg∙min, yielding plasma ACTH plateau concentrations of 1.8 to 37 mU/100 ml. In no dog did the MCR correlate significantly with plasma concentration, nor did the MCR differ significantly from dog to dog. The 34 successful plateaux yielded a mean MCR of 9.54 ± 0.24 ml/kg∙min. Linear regression of MCR versus concentration yielded a correlation coefficient of −0.00026. The findings showed that the disappearance of ACTH from blood is not dose-dependent and varies negligibly with time or among animals. Hence the measured MCR may be used to convert concentrations of ACTH in plasma into turnover rates.
Regulation of Pancreatic Acinar Function: Effects of Cyclic AMP, Dibutyryl Cyclic AMP, and Theophylline in Vitro
Authors: Haig T. H. Brian
Published: April 2011

The role of cyclic AMP in the regulation of pancreatic acinar function has been assessed by measuring the effects of exogenous cyclic AMP, dibutyryl cyclic AMP, and theophylline on protein synthesis and amylase secretion. The rate at which slices of rat pancreas incorporated leucine into protein did not change as a consequence of treatment with either cyclic AMP or dibutyryl cyclic AMP, nor did the slices alter their rate of amylase secretion. Moreover, theophylline did not enhance the ability of submaximal doses of pancreozymin to stimulate amylase secretion or to suppress protein synthesis. These results fail to demonstrate that cyclic AMP regulates either the synthesis or secretion of pancreatic digestive enzymes but they do not rule out the possibility.
Extracellular Accumulation of K+ Evoked by Activity of Primary Afferent Fibers in the Cuneate Nucleus and Dorsal Horn of Cats
Authors: Krnjević K. , Morris M. E.
Published: April 2011

K+-selective microelectrodes were used to measure extracellular K+ activity (aK) in the neuraxis of cats under Dial. In resting conditions, aK is stable (in range 2.0–3.0 mM) but may vary systematically with electrode position. Anoxia causes a progressive rise in aK, but only after a delay of 2–3 min and a maximum is not reached even after 15 min. Movements of the electrode are associated with transient increases in aK, presumably caused by tissue trauma. In areas rich in afferent terminals, direct stimulation through a microelectrode causes a sharp increase in aK, whose time course is consistent with diffusion from an instantaneous spherical source. Smaller increases in aK are produced by stimulating afferent fibers more peripherally, but definite changes can be recorded even with single pulses, and there is a cumulative, maintained rise in aK during repetitive stimulation at rates > 0.5 s−1. Although the observed changes in aK fit reasonably a simple diffusion model at low frequencies (< 5 s−1), a reuptake term (proportional to the change in aK) is necessary to obtain a satisfactory fit over a wide range of frequencies (1–200 s−1). The maximum aK reached during repetitive stimulation does not increase linearly with frequency, owing to a corresponding falling-off in K+ release per impulse.
Hypoxia and Extracellular Potassium Activity in the Guinea-Pig Cortex
Authors: Morris Mary E.
Published: April 2011

During brief periods of hypoxia caused by the inhalation of pure nitrogen, reversible increases in extracellular potassium activity (aK) were detected in the guinea-pig cortex with K+-selective microelectrodes. The increases in aK produced by varying intensities of hypoxia were inversely related to the availability of O2 measured simultaneously in brain tissue with a [Formula: see text] electrode. They were associated with an increased negativity of the potential recorded between the reference electrode and ground, which is presumed to reflect depolarization of cortical elements such as glia and presynaptic terminals. When the inspired O2 concentration was raised from 21 to 100% small decreases in extracellular aK were sometimes observed.
Induction of Rhythmic Activity by Harmaline
Authors: Lamarre Y. , Puil E.
Published: April 2011

Microiontophoretic application of harmaline evoked rhythmic multiunit activity in the inferior olive of decerebrate cats. Harmaline caused strong excitation of individual olivary neurones but did not seem to cause them to discharge in high frequency bursts. These effects suggest that the tremorgenic action of harmaline may be due to an exaggeration of the normal tendency of olivary neurones to fire rhythmically in multiunit bursts.
Hemodynamic Effects of Strontium Chloride in Acute Experimental Myocardial Infarction
Authors: Côté Pierre , Harrison Donald C.
Published: April 2011

The hemodynamic effects of strontium chloride infused intravenously were compared with the effects of calcium chloride in dogs with infarction produced by coronary artery ligation. Strontium improved the circulatory depression resulting from the experimental myocardial infarction. These effects were manifested by a 49% peak increase in the first derivative of left ventricular pressure (dp/dt), 74% in cardiac output, a significant although transient decrease in left atrial pressure of 13%, and a marked drop of 40% in systemic vascular resistance. Mean aortic pressure increased by 18% during the first half of the infusion, and thereafter returned toward the control value. The 31% decrease in heart rate is probably secondary to the overall improvement in cardiac function. Calcium in approximately one-half the amount of strontium was infused during the same length of time to a different group of animals with depression of venticular function by coronary artery ligation. Similar hemodynamic responses occurred during calcium infusion, but were of greater magnitude in left ventricular dp/dt and left atrial pressure, these changes being respectively +117 and −32%. However, the effects on heart rate and systemic vascular resistances were similar, −22% and −42%, respectively. Mean aortic pressure increased less in the calcium group. Strontium has beneficial circulatory effects in depressed ventricular function produced by infarction in dogs.
Effects of Guanethidine and Imidazole on Histamine Metabolism
Authors: Doré F. , LeBlanc J. , Côté J.
Published: April 2011

Chronic treatment with guanethidine increased histamine excretion, as shown in a previous paper (Can. J. Physiol. Pharmacol. 50, 539–544 (1972)). This increase was due to a partial inhibition of a degradation enzyme, imidazole N-methyltransferase, rather than to histamine liberation. Testosterone and noradrenaline diminished the high histaminuria caused by guanethidine. Imidazole, which was also shown to increase histamine excretion, was not affected by testosterone or noradrenaline. The mode of action of imidazole is still unknown, but its molecular configuration suggests competitive effects with histamine at many sites.
Cardiovascular Response to Glucagon in Hypovolemic Dogs
Authors: Pinardi G. , Santiago E. , Vasquez J. V.
Published: April 2011

Glucagon in a dose of 50 μg/kg body weight was studied for its cardiovascular effects in hypovolemic dogs in which coronary blood flow was reduced to an average of 40% of its control value and cardiac depression was evident. Myocardial contractility, as judged mainly by dP/dt and acceleration of aortic blood flow, was brought to a normal level for a short time. Systemic and coronary vascular resistances were markedly reduced. These effects were similar in normovolemic dogs. The inotropic, chronotropic, and peripheral vascular effects of glucagon can be evoked also in hypovolemic dogs in which coronary blood flow is less than normal and myocardial metabolism is impaired.
The Insulinotropic Action of Gastric Inhibitory Polypeptide
Authors: Pederson Raymond A. , Schubert Harold E. , Brown John C.
Published: April 2011

The effect of highly purified gastric inhibitory polypeptide (GIP) on immunoreactive insulin (IRI) secretion in the conscious fasted dog was investigated. Significant increases in IRI release were observed with intravenous administration of three different doses of GIP. These were accompanied by depression in fasting serum-glucose levels. Preliminary studies were undertaken to determine whether this insulinotropic action of GIP could be attributed to a particular segment of the GIP molecule. GIP fragments produced by cleavage with cyanogen bromide and trypsin showed no significant stimulation of IRI release. The possibility that GIP might itself enhance glucose uptake or potentiate insulin-induced glucose uptake was studied with the rat hemi-diaphragm preparation. No such effect was observed. In the light of this and other recent work, it is concluded that GIP is a strong candidate for an active principle in the enteroinsular axis.
Presynaptic Effect of the Aziridinium Ion of Acetylcholine Mustard (Methyl-2-acetoxyethyl-2′-chloroethylamine) on the Phrenic Nerve – Rat Diaphragm Preparation
Authors: Clement John G. , Colhoun E. Howard
Published: April 2011

The rat diaphragm has been used to investigate the neuromuscular blocking action of acetylcholine mustard which yields a potent nicotinic agonist, an aziridinium ion, in aqueous medium. Evidence was obtained that the acetylcholine mustard aziridinium ion impaired neuromuscular activity when the phrenic nerve was stimulated and that the ion did not directly inhibit muscle contraction. Impairment of neuromuscular activity was characterized by a latent period and depended both on the concentration of aziridinium ion and the frequency of stimulation of the phrenic nerve. Elevated concentrations of Ca2+ and choline changed the response of the rat diaphragm to the aziridinium ion, the former increasing the rate of development of neuromuscular block and the latter protecting against neuromuscular block. These results indicated that the aziridinium ion may act either at the site of choline uptake or have an effect on acetylcholine synthesis in the nerve ending and that impairment of neuromuscular transmission in the rat diaphragm involved the availability of acetylcholine. Similar results were obtained with acetylcholine mustard aziridinium ion subjected to alkaline hydrolysis. This substance is thought to be choline mustard aziridinium ion. Although difficult to prove with the rat diaphragm it is possible that acetylcholinesterase of this preparation could hydrolyze acetylcholine mustard aziridinium ion at the neurotransmitter site and the resultant choline mustard aziridinium ion would interfere with the uptake of choline and eventually prevent neuromuscular transmission. This hemicholinium-like hypothesis for the mechanism of action of choline mustard aziridinium ion is compatible with reported data for toxicity of acetylcholine mustard aziridinium ion in the mouse.
The development of dermal lesions and alopecia in male rats fed rapeseed oil
Authors: Hulan H. W. , Hunsaker W. G. , Kramer J. K. G. , Mahadevan S.
Published: April 2011

For 8 weeks 10 male weanling Sprague–Dawley rats were fed a semisynthetic diet containing by weight either 20% corn oil or rapeseed oils containing different amounts of erucic acid (Brassica napus var. Zephyr, 0.6%; B. napus var. Oro, 1.8%; B. campestris var. Span, 4.8%; or B. campestris var. Echo and Arlo, i.e., regular rapeseed oil, 23.6%). At 4–5 weeks after the experiment began, rats receiving the diets containing rapeseed oil showed evidence of alopecia and developed scaly, hemorrhagic, and necrotic tails, as well as scaliness of the feet, similar to the lesions described in essential fatty acid (EFA) deficiency. This condition became most severe between 5 and 8 weeks and had disappeared by 14 weeks. Fatty acid analysis of the diets and tissues of the animals did not reveal any evidence of EFA deficiency. It is suggested that these symptoms observed might be related to a possible inhibition of prostaglandin biosynthesis in rats fed rapeseed oils.
Effects of a series of alcohols on the binding of a fluorescent dye to erythrocyte membranes
Authors: Roth S. H. , Spero L.
Published: April 2011

1. The effects of a series of aliphatic alcohols (methanol to octanol) on membrane proteins of erythrocytes were studied by monitoring the fluorescence of a dye (1-anilino-8-naphthalenesulfonic acid (ANS)) that adsorbs to erythrocyte ghost membranes. Low concentrations of all the alcohols reduced the ANS fluorescence of the membrane–ANS suspensions; lent to those which protect against hypotonic hemolysis on intact erythrocytes; higher concentrations markedly increased the fluorescence. Ethanol and methanol decreased ANS fluorescence at all concentrations.2. Lytic concentrations of saponin did not increase ANS fluorescence and did not modify the membrane action of the alcohols.3. None of these effects were observed in liposomes prepared from lipid extracts of the erythrocyte membrane.4. Since the apparent dissociation constant for the ANS–membrane interaction was unchanged in the presence of the alcohols, it was assumed that the fluorescence changes reflected alterations in the number of ANS binding sites. One conclusion is that low anesthetic concentration of the alcohols alter the conformation of membrane proteins, as indicated by the decreased number of ANS binding sites.
Prostaglandin E2 and cyclic AMP in the coronary vasodilatation due to cardiac hyperactivity
Authors: Sen A. K. , Sunahara F. A. , Talesnik J.
Published: April 2011

In the isolated perfused rat heart, the dose-related cardiostimulation produced by norepinephrine (NE) or calcium chloride (Ca2+) was followed by a corresponding increase in coronary flow (CF) and in the cardiac level of adenosine 3′,5′-cyclic phosphate (cAMP). Prolonged prostaglandin E2 (PGE2) infusion did not change the basic force of contraction, CF, or cAMP level but when NE or Ca2+were administered, only the responses of the CF and the cAMP were diminished. A phosphodiesterase inhibitor, diazoxide (Dx), caused insignificant increase in the basal cAMP, without affecting the force of contraction or CF. With NE or Ca2+, during Dx both the changes in CF and cAMP were augmented compared to the nontreated hearts. The inhibitory effects of PGE2 were also observed in Dx-treated hearts, even though the cardiostimulating effects of NE or Ca2+ remained unchanged. Propranolol abolished the NE but not the Ca2+ effects. It is suggested that PGE2 modulates the cardiac cAMP level and that the latter plays an important role in the adaptive regulation of the CF. It is also postulated that changes in cAMP levels may be brought about by the hyperactivity per se produced by a variety of cardiostimulating agents.
Quantitative aspects of secretion and hepatic removal of glucagon in sheep
Authors: Brockman Ronald P. , Manns J. G. , Bergman E. N.
Published: April 2011

The secretion of immunoreactive glucagon (IRG) into the portal blood and its removal by the liver were determined in conscious-fed sheep by simultaneous measurement of venoarterial plasma concentration differences and portal and hepatic plasma flows. IRG was determined using Manns' antiserum and Unger's 30K antiserum, the latter being highly specific for pancreatic glucagon. In 21 experiments in which Manns' antiserum was used the IRG secretory rate was 7.1 ± 0.4 μg/h. The value using 30K antiserum was lower (5.5 ± 1.3, n = 6), but not significantly different. Although the hepatic extraction ratio (hepatic removal – total IRG presented to the liver) was only 7%, the hepatic removal of 2.4 ± 0.5 μg/h was equivalent to 31–35% of the portal IRG secretory rate. Since during steady-state conditions, glucagon secretion equals glucagon removal, the liver must account for approximately one-third of the glucagon degraded by the entire body.
The effect of SKF-525A and of altered hepatic blood flow on lidocaine clearance in the cat
Authors: Lautt W. Wayne , Skelton F. Steve
Published: April 2011

Hepatic blood flow and hepatic uptake of lidocaine were determined in cats during constant intravenous infusion of lidocaine. Lidocaine clearance is directly linked to hepatic blood flow with reductions in flow being reflected in equal reductions in hepatic clearance. Altered blood flow did not result in altered rates of lidocaine extraction. Lidocaine extraction ratio was 28%.Hepatic blood flow and lidocaine metabolism were measured before and 60 min after an intramuscular injection of SKF-525A (50 mg/kg). SKF-525A produced a reduction in hepatic clearance of lidocaine to 60% of control values, entirely as a result of a reduction in hepatic extraction ratios. Hepatic blood flow and vascular conductance were not affected by SKF-525A.
Inhibition of the immune response by rapamycin, a new antifungal antibiotic
Authors: Martel R. R. , Klicius J. , Galet S.
Published: April 2011

Rapamycin, a new antifungal antibiotic, was found to inhibit the immune response in rats. It totally prevented the development of two experimental immunopathies (experimental allergic encephalomyelitis (EAE) and adjuvant arthritis (AA)) and the formation of humoral (IgE-like) antibody. It was about half as potent as cyclophosphamide in inhibiting EAE. In AA and on antibody formation, rapamycin and cyclophosphamide were about equipotent, whereas methotrexate was more potent. The immunosuppressant activity of rapamycin appears to be related to inhibition of the lymphatic system.
Effect of acute stress and ouabain administration on adrenal catecholamine content and cardiac function of rats pretreated with diazepam
Authors: Gascon André L.
Published: April 2011

The experiments described were carried out in an attempt to determine the participation of adrenal catecholamines in the higher incidence of cardiac arrhythmias produced by acute stress or ouabain injections in diazepam-treated animals. The pretreatments of rats with diazepam (150 mg kg−1 d−1) increase significantly the adrenal catecholamine content. Consequently, the application of electrical and immobilization stress releases more catecholamines from the adrenal glands of the diazepam-treated rats and also produces higher incidence of ventricular extrasystoles. Furthermore, various pretreatments of rats with diazepam (5–150 mg kg−1 d−1) also lead to an increase in the catecholamine content of the adrenal gland. In diazepam-treated rats, the intravenous administration of ouabain produces a greater release of adrenal catecholamines as well as a greater incidence of cardiac arrhythmias.Several hypotheses are proposed to explain the elevation of adrenal catecholamines and also the higher incidence of ventricular arrhythmias.
Compensatory renal hypertrophy in dogs: single nephron glomerular filtration rate
Authors: Carrière Serge , Gagnan-Brunette Michèle
Published: April 2011

Sodium ferrocyanide was used to measure the intrarenal distribution of single nephron glomerular filtration rate (SNGFR) in remaining kidneys of dogs, 10 d after contralateral nephrectomy. It was first demonstrated that the renal function of both kidneys in situ was comparable. Following right nephrectomy, the urine volume, p-aminohippuric acid clearance, creatine clearance, osmolar clearance, fractional excretion of potassium, and sodium excretion of the left kidney increased. Fractional excretion of sodium, free water clearance, and filtration fraction remained unchanged. Following that 10-d period, left kidney weight exceeded that of the previously removed contralateral kidney by 50%, indicating that most of the compensatory hypertrophy had already occurred. No significant difference in the length of the proximal tubule nor in the diameter of the glomeruli of superficial (SUP) and juxtamedullary (JM) nephrons of either kidney could be demonstrated. Most importantly, the ratio of radioactivity in the SUP/JM nephrons of the residual kidney was comparable with that previously observed in normal dog kidneys. Thus, the increase in total kidney GFR is explained through a proportional increase in the SNGFR of the SUP and JM nephrons.
Potentiation of the epileptogenic effect of penicillin G by marihuana smoking
Authors: Labrecque G. , Hallé S. , Berthiaume A. , Morin G. , Morin P. J.
Published: April 2011

Marihuana smoking is known to produce many subtle neurological modifications in animal and man. We investigated the effects of subconvulsive doses of penicillin after acute or chronic marihuana smoking. Twenty-four mongrel dogs weighing from 15 to 25 kg received 4 mg morphine per kilogram, intramuscularly, and 750 000 IU sodium penicillin G per kilogram, intravenously. In acute experiments, the animals smoked eight cigarettes containing approximately 6 mg of Δ9-tetrahydrocannabinol. In chronic experiments, they smoked four cigarettes per day for 10 weeks before being studied. Ten animals (five controls and five acute smokers) were observed visually while the electrocorticogram (ECoG) was recorded in the 14 others (five controls, five acute, four chronic). This last group received 20–30 mg succinylcholine chloride as muscle relaxant. Penicillin had no effect either on the behaviour or on the ECoG in 9 of the 10 controls. On the other hand, 9 out of the 10 acute smokers showed modifications (coarse tremors of the limbs and epileptiform waves). Two of the four chronic smokers had typical epileptiform episodes. The results suggest that marihuana smoking produces a blood–brain barrier permeability change towards sodium penicillin G. Another explanation could be that Cannabis modifies the excitability threshold of the brain.