bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of hyperbaric oxygen on the GABA shunt pathway in brain homogenates
Authors: Myles W. S. , Wood J. D.
Published: April 2011

The effect of oxygen at high pressure (OHP) on the γ-aminobutyric acid (GABA) shunt pathway in rat brain homogenates was studied by measuring the formation of labelled succinate from GABA-4-14C in the presence of malonate. Under in vitro conditions, OHP inhibited the GABA shunt by 28% and 22%, with and without the addition of supplementary amounts of GABA and α-ketoglutarate to the incubation media respectively. A small inhibition (10%) was also observed with oxygen at ambient pressure. In further studies, rats were exposed to OHP, and the activity of the GABA shunt in the brains was subsequently measured by the in vitro method. Preexposure of the intact animals, with or without accompanying convulsions, did not affect the metabolism of GABA to succinate.
Compartments of sodium in a small artery
Authors: Friedman Sydney M. , Gustafson Brigid , Hamilton Dorothy , Friedman Constance L.
Published: April 2011

Viable tail artery samples, in a modified Krebs medium, gain Na in exchange for K during cooling and reverse the process during rewarming. The process, within the margin of experimental error, is usually in a 1:1 ratio and has a long time constant, about 8 to 9 meq/100 g dry weight being exchanged within 3 h of cooling, and up to 15 meq/100 g within 24 h. Three hours of rewarming of tissues prepared by overnight (18 h) cooling is sufficient for an exchange of at least 10 meq/100 g. A second component of Na, equal to approximately 10 meq/100 g in tissue incubated in a Tris-buffered medium [Formula: see text], is apparently paracellular, for it is fully mobilized within 30 min of exposure to a sodium-free environment, even at 2°. Since even 3 h of exposure to such a medium at 2° fails to mobilize metabolism-dependent cellular Na it is possible to differentiate these two components. Evidence is also presented to show that Na transport, ordinarily associated with K accumulation, can occur without it.
Characteristics of temperature-dependent sodium exchanges in a small artery
Authors: Friedman Sydney M. , Gustafson Brigid , Friedman Constance L.
Published: April 2011

The distribution of Na, K, and water in the rat tail artery was studied with a view to further characterizing the distribution of Na within the inulin-inaccessible phase of a typical small artery. Two components of Na can be demonstrated by rewarming precooled, Na-loaded arteries. One component is liberated within minutes of rewarming, unassociated with any K exchange and unaffected by iodoacetate blockade. The larger component is liberated slowly over hours, usually associated 1:1 with the converse movement of K and metabolically driven. The metabolic extrusion of Na can proceed, however, even if K influx is blocked.
Is the Peripheral Utilization of Glucose a Regulator of Hepatic Glucose Production and of Glycemia?
Authors: Achou C. J. , Hetenyi Jr. G.
Published: April 2011

The aim of the study was to examine the effect of an increase in peripheral uptake of glucose on its release by the liver in rats. If cross circulation is established between a normal and eviscerated rat, the turnover of glucose is elevated above that observed in single normal rat, indicating that the increase of glucose consumption from the system into which the liver releases glucose leads to an increase of the rate of glucose production. The duration of this compensation however is limited to about 90 min. Cross circulation established between diabetic and normal, non-eviscerated and eviscerated rats in different combinations demonstrated that the overall rate of glucose turnover is nearly identical in all such preparations although the level of glucose in the plasma is in inverse relationship to the metabolic clearance of glucose and is directly related to the amount of previously insulin-deprived tissues in the preparation. It appears that at least in such preparations the overall utilization rather than the plasma level of glucose is being regulated primarily.
Biochemical Reactions Involved in Pancreatic Enzyme Secretion. I. Activation of the Adenylate Cyclase Complex
Authors: Beaudoin A. R. , Marois C. , Dunnigan J. , Morisset J.
Published: April 2011

Pancreatic amylase secretion was studied using an in vitro system. Secretion was increased by urecholine and cholecystokinin–pancreozymin (CCK–PZ). Addition of tetracaine and dibucaine to the medium abolished secretion stimulated by urecholine and decreased by 75% that stimulated by CCK–PZ. In contrast, an increase in enzyme secretion was observed after dibutyryl cyclic AMP; this was potentiated by tetracaine added to the medium. Oxygen uptake by pieces of pancreatic tissue was not affected by tetracaine. Adenylate cyclase activity, increased in vitro when CCK–PZ was added to a pancreas homogenate, was inhibited by 15% by tetracaine at 2 mM and by 67.5% at the 10 mM concentration.From data known on biochemical reactions associated with the process of secretion and the results described in the present paper, we propose a model for the activation of the pancreatic adenylate cyclase complex. Associated to the depolarization of the acinar cell plasma membrane by urecholine and CCK–PZ and an inward movement of sodium and calcium, there is an immediate rise in adenylate cyclase activity within 10 s which is timed with the initiation of amylase secretion.
Estimation of Hepatic Glucose Output in Non-Steady State. The Simultaneous Use of 2-3H-glucose and 14C-glucose in the Dog
Authors: Issekutz Thomas B. , Issekutz Jr. Bela , Elahi Dariush
Published: April 2011

The rate of appearance of glucose (Ra) was estimated in a non-steady state caused by the infusion of glucose (exogenous increase of Ra) or glucagon (increase of hepatic glucose output) in unanesthetized dogs with indwelling arterial and venous catheters. First, Ra was measured with 2-3H-glucose according to the primed constant rate infusion technique in steady state, then with the onset of the perturbation the infusion of a second tracer, (U) 14C-glucose, was started. Exponential functions were fitted to the two specific activity curves. The second tracer made it possible to calculate Ra during the non-steady state without the need to assume a definite value for the "miscible" glucose space (V). The latter could also be calculated and it proved to be a single exponential function of time elapsed from the start of the perturbation. In the first few minutes the glucose load (10 or 15 mg/kg min for 120 min) caused a sharp fall of hepatic glucose output. This was followed by a rise of various degrees before the endogenous glucose output reached the steady state at about 50 or 70% below the base-line values. During the glucose load, in steady state (U) 14C-glucose as a tracer gave about 10% lower values for Ra than tritiated glucose.
Iproveratril: A Nonspecific Antagonist of Peripheral Vascular Reactivity
Authors: Greenberg Stanley , Wilson William R.
Published: April 2011

The effect of iproveratril (α-isopropyl- α-[(N-methyl-N-homoveratryl)-γ-aminopropyl]-3,4-dimethoxyphenolacetonitrile hydrochloride) on peripheral vascular responses to isoproterenol (ISO), norepinephrine (NE), angiotensin II (A), and nitroglycerin (GTN) was evaluated in the canine hindlimb and hindpaw preparations perfused with autologous blood at constant flow. Iproveratril (30–300 μg/kg intravenous) dilated the hindlimb and hindpaw perfused at constant flow. Responses to intra-arterial ISO, NE, and A were significantly reduced when evaluated 10 min after iproveratril. Iproveratril did not alter the vasodilator responses to GTN. These results show that iproveratril depresses the vascular responses of the hindlimb and hindpaw to stimulants of α and β adrenergic and angiotensin receptors and justify the conclusion that iproveratril is not a selective antagonist of peripheral β-receptors.
Platelet–Surface Interaction: Effect of Albumin Coating or Heparin Complexing on Thrombogenic Surfaces
Authors: Chang T. M. S.
Published: April 2011

Platelet–surface interaction was studied using activated charcoal granules (AC), cellulose nitrate coated, activated charcoal granules (CAC), albumin – cellulose nitrate coated, activated charcoal granules (ACAC), and benzokonium – heparin – cellulose nitrate coated, activated charcoal granules (BHCAC). In studies where blood from dogs was recirculated through shunts, each containing 300 g of one of the above systems, it was found that both AC and CAC lowered the systemic blood platelet levels after 2 h of hemoperfusion. In hemoperfusion across these two systems, there was also an increase in the adhesiveness of platelets. In the case of ACAC and BHCAC, hemoperfusion for 2 h did not result in any significant decrease in the systemic blood platelet levels, nor was there an increase in the adhesiveness of platelets perfused across these two systems. Scanning electron microscopic studies were carried out with the CAC and ACAC systems before and after contact with blood. There was marked platelet and fibrin deposition and entrapment of formed elements of blood in the case of the CAC. In the case of the ACAC there was no platelet adhesion, fibrin deposition, or entrapment of formed elements of blood. This study has led to the use of the ACAC microcapsule artificial kidney in the treatment of patients with chronic renal failure and acute intoxication.
Drinking Elicited by Polyethylene Glycol and Isoproterenol Reduced by Antiserum to Angiotensin II
Authors: Abdelaal A. E. , Mercer P. F. , Mogenson G. J.
Published: April 2011

The effect of the infusion of antiserum to angiotensin II on extracellular thirst was studied in rats. Drinking induced by the administration of polyethylene glycol or isoproterenol was reduced significantly when antiserum was infused. These results indicate that angiotensin is involved in drinking in response to extracellular dehydration.
Epileptiform Seizures in Domestic Fowl. II. Intermittent Light Stimulation and the Electroencephalogram
Authors: Crichlow Eugene C. , Crawford R. D.
Published: April 2011

The effects of intermittent light stimulation on chickens genetically predisposed to generalized convulsions are described. Epileptic chickens (homozygous recessive) convulse when exposed to intermittent light stimulation at 10–25 flashes per second, whereas normal (homozygous dominant) and carrier (heterozygous) hatch mates are not affected. The resting electroencephalogram (EEG) of epileptic chickens is markedly different from that of their nonconvulsive hatch mates, being characterized by high-amplitude slow waves with periodic spikes and spike–wave complexes. Prior to the onset of light-induced seizures, high-voltage spikes, at the same frequency as the stimulus, appear in all leads of the epileptic EEG. For a short time after a convulsion the EEG of epileptic chickens remains flattened, suggesting decreased electrical activity similar to the postictal depression seen in the EEG of human epileptics.
Compartmentation of "Endogenous" and Newly Absorbed Vitamin A in the Rat
Authors: Yeung D. L. , Veen-Baigent M. J.
Published: April 2011

Urinary and fecal excretion of 3H-labelled metabolites of vitamin A was followed in rats given a single oral dose of 3H-11,12-retinyl acetate (RA), followed 8 days later by a dose of non-labelled RA. The level of radioactivity in urine and feces fell to a more consistently lower level by the 8th day after administration of 3H-RA but no dilution effect was seen 24 h after administration of non-labelled RA. Dilution of 3H-metabolites became gradually evident and was statistically significant 4–6 days after the administration of non-labelled RA. The results are considered to be compatible with the theory that newly absorbed vitamin A does not immediately mix with endogenous vitamin A, but is temporarily metabolized (and stored) in a separate compartment. Plasma aqueous phase contained considerable radioactivity not due to vitamin A per se; it likely represented metabolites prior to excretion. It is doubtful these originated in the liver since all hepatic radioactivity was due to retinol and retinyl esters.
A Differential Effect of Chronically Administered Guanethidine on Sympathetic Neurotransmission to the Dog Heart and Mesenteric Arterial Blood Vessels
Authors: Clarke David E. , Jandhyala Bhagavan S. , Cavero Icilio , Dixit Balwant N. , Buckley Joseph P.
Published: April 2011

The responsiveness of the dog heart and isolated perfused mesenteric arteries to adrenergic nerve stimulation was studied following chronic oral guanethidine administration (2.5 mg/kg per day). Treatment for 1 week abolished the mesenteric arterial vasoconstrictor response to periarterial nerve stimulation and attenuated markedly the chronotropic effect resulting from stimulation of the cardioaccelerator nerves. After 6 months, the positive chronotropic response to cardiac nerve stimulation was restored to within control values, whereas complete adrenergic neuronal blockade persisted in the mesenteric arteries. Resting heart rate and the cardiovascular responses to bilateral carotid occlusion (B.C.O.) were depressed at 1 week, but after 6 months, both the resting heart rate and the positive chronotropic response to B.C.O. were restored. However, the systemic blood pressure rise to B.C.O. remained inhibited. Biochemical and histochemical studies failed to reveal any recovery in cardiac norepinephrine (NE) content, and changes in the cardiovascular responsiveness to intravenous NE seemed largely independent of the duration of drug treatment. At 6 months, the heart rate and depressor responses to intravenous isoproterenol were unchanged, indicating the absence of any detectable postsynaptic supersensitivity.The results show a clear differential effect of chronically administered guanethidine on the sympathetic innervation to the heart compared with the mesenteric arterial blood vessels, thus underlining the importance of evaluating drug effects on a chronic basis.
Differences in Biochemical Properties of γ-Aminobutyric Acid Aminotransferase from Synaptosome-Enriched and Cytoplasmic Mitochondria-Enriched Subcellular Fractions of Mouse Brain
Authors: Buu Nguyen T. , Gelder N. M. van
Published: April 2011

Using conventional subfractionation techniques on whole mouse brains, a minimum of two distinct sources of γ-aminobutyric acid (GABA) aminotransferase were detected. GABA-T from cytoplasmic mitochondria-enriched fraction ("cytoplasmic" GABA-T) exhibited a higher apparent affinity for GABA, and for two new analogues of GABA, than a similar enzyme originating from nerve ending-enriched fraction ("synaptosomal" GABA-T). The two analogues, β-chloro GABA and β-phenyl GABA, inhibited cytoplasmic aminotransferase in a competitive manner whereas the synaptosomal enzyme was inhibited noncompetitively. "Cytoplasmic" GABA-T demonstrated an optimal activity of pH 7 whereas GABA-T of nerve endings was most active at pH 8. Per milligram of protein, the GABA-T activity in synaptosomes was five times less than in cytoplasmic mitochondria.These findings may imply that GABA absorbed in neuronal perikarya and glia (cytoplasmic mitochondria) is rapidly destroyed. In contrast, the unfavorable pH optimum displayed by the synaptosomal GABA-T, its weaker affinity for GABA, and a lower GABA-T concentration per se would favor accumulation of GABA in the nerve terminals.
Lipotropic and Adrenocorticotropic Hormones. Biological Activities of the Carboxyl-Modified Hormones
Authors: Gilardeau C. , Chrétien M. , Lis M.
Published: April 2011

The carboxyl groups of sheep adrenocorticotropic and beta-lipotropic hormones (ACTH and beta-LPH) were modified by glycine methyl ester and taurine using a water-soluble carbodiimide as a coupling agent. The biological activities of these derivatives were measured and compared with those of the native hormones. With ACTH, the lipolytic activity is almost unaffected although the adrenocorticotropic activity is completely destroyed. LPH partially looses its lipolytic activity.
An Excitatory Action of Substance P on Cuneate Neurones
Authors: Krnjević K. , Morris Mary E.
Published: April 2011

Pure Substance P was applied from 7 mM solutions by microiontophoresis to cuneate neurones in cats under barbiturate or inhalation anesthesia. The predominant effect was a slow excitation, beginning after a delay of 10–30 s, reaching a peak some 30 s later, and decreasing only gradually after the end of the application, over 1 min or even longer. It was observed with about half of all the units tested (especially those that were spontaneously active), in all experiments, with several different electrodes, and Substance P obtained from two different sources; and therefore can be considered to reflect a genuine strong but slow depolarizing action. Larger doses of Substance P depressed firing, especially when evoked by glutamate, and, in one experiment, several units showed a mainly depressant effect. This may be explained by a similar slow mechanism of depolarization but with inactivation being predominant. It is concluded that Substance P is unlikely to be the quickly acting transmitter released by primary afferent terminals but its strong excitatory action may be of functional significance in some other respects.
Cyclic Nucleotide Levels during Spontaneous Uterine Contractions
Authors: Diamond Jack , Hartle Diane K.
Published: April 2011

Tissue levels of adenosine 3′,5′-cyclic monophosphate (cyclic AMP) and guanosine 3′,5′-cyclic monophosphate (cyclic GMP) were determined in uterine muscles frozen at various points during spontaneous contraction–relaxation cycles. No significant changes in cyclic nucleotide levels were detected at any of the stages of contraction studied. Exposure of uterine segments to 1 μM isoproterenol resulted in an eightfold increase in cyclic AMP levels but no change in cyclic GMP, whereas exposure to 2 mM theophylline resulted in a doubling of cyclic GMP levels and a 42% increase in cyclic AMP content. Thus, the methods used were capable of detecting changes in cyclic nucleotide levels when they did occur. It was concluded that changes in cyclic nucleotide levels do not play a role in the initiation or regulation of spontaneous contractions of isolated rat uterus.
Turnover and Metabolism of Polychlorinated Biphenyls in Relation to their Chemical Structure and the Movement of Lipids in the Pigeon
Authors: Freitas A. S. de , Norstrom R. J.
Published: April 2011

Experiments with White Carneau pigeons have established that the ease of metabolism of polychlorinated biphenyls (PCBs) composing Aroclor 1254® is determined principally by chlorine substitution patterns rather than degree of chlorination. Rapidly metabolized PCBs have 2,3, 3,4, or 2,3,6 chlorine substitution on at least one phenyl ring. Those PCBs which are not metabolized have a combination of 2,4,5, 2,3,4, and 2,3,4,5 chlorine substitutions on both rings. PCBs containing 2,5 substitutions were metabolized over a 31 day period, but much more slowly than PCBs with 2,3 or 3,4 chlorine substitutions.Chemical structure of PCBs does not affect their rate of mobilization from adipose tissue and subsequent movement through the circulation. The fractional turnover of all PCBs is approximately equivalent to the fractional turnover of the lipid pool under fully fed conditions as well as during periods of starvation induced depletion of lipid reserves. A net movement of PCBs from adipocytes to other lipid pools, principally muscle cells, occurred during starvation. On subsequent refeeding, the net movement of PCBs from muscle back into adipose tissue was similar to the net movement out of adipose tissue. PCB metabolites tend to be rapidly excreted and do not accumulate in adipose tissue, muscle, or liver. Brain and, to a lesser extent, kidney tissue appear to accumulate PCB metabolites, particularly during the refeeding stage in a starvation/refeeding cycle.
Erythrocyte Settling
Authors: Kernick D. , Jay A. W. L. , Rowlands S.
Published: April 2011

The mechanism of erythrocyte settling has been observed directly by microscope. The results have been correlated with the standard method of measuring erythrocyte sedimentation rate (E.S.R.) and with theories of the settling of suspensions. Downward movement of cells and aggregates causes rapid upward currents in the suspending medium carrying with them other cells and smaller aggregates that may collide and result in attachment or break-up. The fall of the interface at the top of the cell column has three phases: (a) an initial acceleration, (b) a long phase at a constant rate of fall and (c) a deceleration phase as the aggregates pack at the bottom of the tube. During phases a and b, the aggregate size at the top of the column is constantly increasing to reach saturation when the interface meets the pile-up of cells at the bottom of the chamber, when phase c starts. The results for cells suspended in Ringer's solution, in which there is no aggregation, are compatible with the theory of "hindered settling" of slurrys in the chemical engineering literature. Settling in plasma is complicated by the formation and break-up of aggregates during settling, and will require a more elaborate theory.
Phosphate-Transport Appearance in the Sea-Urchin Egg. II. Analysis of the Genome Function with Centrifuged Eggs and Ethidium Bromide
Authors: Noüe Joël de la
Published: April 2011

Ethidium bromide, an inhibitor of mitochondrial transcription, inhibits phosphate uptake, valine incorporation, and uridine incorporation in fertilized eggs of Strongylocentrotus purpuratus, the purple sea urchin. Phosphate uptake, valine incorporation, and valine influx are also inhibited by this drug in artificially activated nucleate and anucleate egg fragments. Ethidium bromide does not affect the egg respiration and it has no measurable effect on ATP level and labeling. It is concluded that the post-fertilization appearance of the phosphate-carrier system does not require the participation of the nuclear genome but that of the mitochondrial one. It is likely that the same proposal holds for the L-valine-transport system. Some effects of ethidium bromide on development are exposed.
Influence of Starvation on Absorption, Distribution, and Action of Barbital in Mice and Rats
Authors: Brodeur J. , Lalonde S. , Leroux J.
Published: April 2011

The influence of food deprivation on the disposition of barbital during the early phase following administration of the drug was studied in mice and rats. Starvation consisted of withholding solid food, but not water, for 24–72 h in mice, and 72 h in rats. The results show that starvation leads to higher blood concentrations of barbital given intraperitoneally (i.p.) and subcutaneously to mice and rats, and intramuscularly to rats. This effect was observed 2.5–10 min following the injection of the barbiturate. In mice, starvation significantly reduced the interval between injection of the drug and loss of the righting reflex, but it extended the duration of the sleeping period. When barbital was given intravenously, starvation no longer resulted in higher blood concentrations of the drug, although starved mice went to sleep more rapidly than fed controls. At the moment of loss of the righting reflex. starved mice had significantly lower concentrations of barbital in the brain than fed controls. The total blood and plasma volumes of starved animals were moderately increased when expressed as a percentage of the body weight. These results suggest that starvation might influence the early phase of barbital absorption following its parenteral administration. There is also an indication that starvation could induce a state of hypersensitivity of the central nervous system to barbital.
The Effect of Insulin on Glucose Uptake in Soleus Muscle during Hemorrhagic Shock
Authors: Chaudry Irshad H. , Sayeed Mohammed M. , Baue Arthur E.
Published: April 2011

Hemorrhagic shock was produced by bleeding conscious rats to a mean arterial pressure of 40 mm Hg, which was maintained for 2 h. Basal glucose uptake by isolated soleus muscle from normal rats and rats subjected to hemorrhagic shock ('shock' muscles) increased with the increase in medium glucose concentration. Uptake values were similar in both groups of muscles. This indicates that there were no alterations in the basal glucose carrier mechanism during shock. Whereas insulin (0.1 U/ml) stimulated glucose uptake in control muscles under aerobic as well as under anaerobic conditions, it had no stimulatory effect in 'shock' muscles under either environment. Maximal stimulation of glucose uptake in 'shock' muscles was observed at an insulin concentration of 0.2 U/ml. The ability of muscle to bind insulin was not altered during shock. The present experiments indicate that insulin responsiveness to tissues is altered in shock. This could be due to alterations in the insulin sensitivity of the glucose carrier mechanism during shock.
Further Observations on the Response of the Glomerular Filtration Rate to Glucagon: Comparison with Secretin
Authors: Levy Mortimer
Published: April 2011

Glucagon causes marked elevations of glomerular filtration rate (GFR) in dogs when administered intravenously (i.v.) in small doses. The associated natriuresis is thought to be entirely due to increments in the filtered sodium load. In this study, renal denervation, thyroparathyroidectomy, and blockade of cholinergic, α- and β-adrenergic, dopaminergic and histaminergic receptors did not prevent the usual glucagon-induced elevations of GFR or rate of sodium excretion (UNaV). This effect of glucagon was not mediated through the release of cyclic AMP, or by plasma compositional changes of Ca2+, K+, or amino acids. Pure porcine secretin, in doses of 5–10 μg/min delivered either i.v. or into the left renal artery did not alter GFR; clearance rate of p-aminohippurate (CPAH) or UNaV in either hydropenic or saline-loaded dogs. Nor did this polypeptide, structurally very similar to glucagon, abolish the effect of glucagon on GFR. It did, however, partially inhibit the glucagon-induced natriuresis, presumably by preventing a previously undetected glucagon action on tubular reabsorption of sodium.
Exercise-Induced Increase in the Capacity of Rat Skeletal Muscle to Oxidize Ketones
Authors: Winder W. W. , Baldwin K. M. , Holloszy J. O.
Published: April 2011

During and after strenuous prolonged exercise, sedentary individuals develop high blood levels of acetoacetate and β-hydroxybutyrate whereas exercise-trained animals and human subjects do not. We have investigated the possibility that exercise training can increase the capacity of skeletal muscle to oxidize ketones. In this study we measured rates of d-β-[3-14C]-hydroxybutyrate and [3-14C]acetoacetate oxidation, and the levels of activity of the enzymes involved in the oxidation of ketones in homogenates of gastrocnemius muscles of exercise-trained and of untrained male rats. The trained animals had markedly lower blood ketone levels immediately and 60 min after a 90 min long bout of exercise than did the sedentary animals. The rates of D-β-[3-14C]hydroxybutyrate and [3-14C]acetoacetate oxidation were twice as high in homogenates of muscles from the trained as compared to the sedentary rats. The increases in levels of activity in gastrocnemius muscle in response to the exercise program were: β-hydroxybutyrate dehydrogenase threefold; 3-ketoacid CoA-transferase twofold; and acetoacetyl-CoA thiolase 55%. This exercise-induced increase in the capacity of skeletal muscle to oxidize ketones could play a role in preventing development of ketosis in the physically trained animal during and following prolonged strenuous exercise.
Response of Hepatic Carbohydrate and Cyclic AMP Metabolism to Cadmium Treatment in Rats
Authors: Merali Z. , Kacew S. , Singhal R. L.
Published: April 2011

Daily intraperitoneal injection of cadmium chloride (0.25 or 1 mg/kg) for 21 or 45 days into rats significantly stimulated the activities of hepatic pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-diphosphatase, and glucose-6-phosphatase, increased the concentrations of glucose and urea in the blood, and decreased the levels of glycogen in the liver. Whereas chronic cadmium treatment failed to alter adenosine-3′,5′-monophosphate phosphodiesterase (phosphodiesterase) activity, the endogenous levels of cyclic AMP (cAMP) and the activity of basal- and fluoride-stimulated forms of hepatic adenylate cyclase (AC) were markedly increased in cadmium-injected animals. Treatment with the higher dose (1.0 mg/kg) of cadmium chloride for 45 days produced greater metabolic alterations in hepatic tissue than those seen with the lower dose (0.25 mg/kg) given for a shorter period of time (21 days). Discontinuation of cadmium administration for 14 days in rats previously injected with cadmium chloride (1 mg/kg per day) for 21 days, failed to reverse the observed changes in hepatic cAMP or carbohydrate metabolism. A similar persistence of metabolic alteration was noted in rats treated with cadmium (1 mg/kg per day) for 45 days and subsequently maintained without additional treatment for 28 days. Administration of an acute dose of cadmium chloride (60 mg/kg) decreased hepatic phosphodiesterase activity and glycogen content 1 h after the injection. In addition, acute cadmium exposure increased blood glucose, serum urea, and hepatic cAMP levels, and produced an augmentation of basal- and fluoride-activated AC. However, the activities of various hepatic gluconeogenic enzymes remained unaffected in animals given an acute dose of cadmium chloride (60 mg/kg). Data provide evidence that suggests that the gluconeogenic potential of liver is markedly enhanced following chronic exposure to cadmium and that the cadmium-induced changes in carbohydrate metabolism may be associated with an enhanced synthesis of cAMP. In addition, the present study shows that the cadmium-induced metabolic alterations persist even after the cessation of cadmium treatment for a period of 28 days.
The Metabolism of 4-Chlorobiphenyl in the Pig
Authors: Safe S. , Ruzo L. O. , Jones D. , Platonow N. S. , Hutzinger O.
Published: April 2011

4-Chlorobiphenyl was administered retrocarotidly in a saline oil emulsion to anesthetized pigs. The urine obtained from the pigs 2 h after injection of the 4-chlorobiphenyl was analyzed for metabolites. Mass spectrometric analysis indicated the presence of a monohydroxylated species (M+ 204) and a dihydroxylated compound (M+ 220) and these were identified as 4′-chloro-4-biphenylol and 4′-chloro-3,4-biphenyldiol, respectively. Examination of the urine extracts from pigs 0.5, 1, and 2 h after administration of the 4-chlorobiphenyl indicated an increase in both urinary metabolites with time, however, neither compound was detected in the bile. Blood and organ samples were examined also for metabolites and the results clearly showed the presence of 4′-chloro-4-biphenylol in the blood, kidney, and liver and absence in the lung, brain, and heart. The diol was not observed in any of these samples.
An Adrenal Cell System Suitable for Long Term Study of Factors Affecting Steroidogenesis
Authors: Price Carman S. , Ruse James L. , Laidlaw John C.
Published: April 2011

Cell suspensions of normal adult rat adrenals have been prepared by trypsinization and incubated in Ham's nutrient mixture F10 containing horse serum, fetal calf serum, and lima bean trypsin inhibitor. In most experiments culture medium was not changed during incubation. In this system the number of cells fell to 50% after 2 days, then slowly declined to 20% after 1 month of incubation. A corticosterone (B) response was seen to as little as 5 μU of ACTH per millilitre, a concentration which is within the range found in normal rat serum. With maximal stimulation (100 mU ACTH/ml) the rate of accumulation was highest during the first 24 h then slowly decreased over the following 9 days. When in separate experiments ACTH was added after various times of incubation up to 3 weeks, there was a B response which continued for as long as 1 week after the ACTH was added; the later the time at which ACTH was added the lesser was the initial B response and the longer the lag period before a substantial response occurred. In cell suspensions in medium containing 5.0 mequiv. of K+ per litre, aldosterone content increased for approximately 24 h, then showed little or no change over the next 9 days. With increased K+ concentration, aldosterone was found in greater amounts and accumulation continued for longer periods, both without and with ACTH. This adrenal cell system appears suitable for long term study of factors affecting steroidogenesis.
Comparative Effects of Opiate Agonists Methadone, Levorphanol, and Their Isomers on the Release of Cortical ACh in Vivo and in Vitro
Authors: Jhamandas K. , Hron V. , Sutak M.
Published: April 2011

The effect of analgesically active opiate agonists dl-methadone, levorphanol, and their less active forms d-methadone and dextrorphan, respectively, were tested on, (a) the spontaneous release of cortical acetylcholine (ACh) in vivo; (b) the spontaneous and K+-evoked release of cortical ACh in vitro. The injections of dl-methadone, but not d-methadone, inhibited the output of ACh in vivo. Naloxone completely reversed this effect of methadone. Levorphanol in small doses inhibited, and in larger doses stimulated, the in vivo release of ACh. Both effects were antagonized by naloxone. Its dextroisomer dextrorphan was completely inactive. The in vitro release of ACh from cortical slices was inhibited by all four agents. The effects of analgesically active opiates dl-methadone and levorphanol on the in vitro release were not clearly separable from the effects of their inactive forms d-methadone and dextrorphan.
Endogenous Prostaglandin Release Contributes Directly to Coronary Artery Tone
Authors: Kalsner Stanley
Published: April 2011

An in vitro coronary artery preparation of beef heart was found to synthesize and release continuously large amounts of a prostaglandin of the E type. Inhibition of prostaglandin synthesis with aspirin, indomethacin, or eicosa-5,8,11,14-tetraynoic acid induced a sustained contraction of the coronary artery, and pretreatment with indomethacin diminished markedly the output of prostaglandin into the bathing medium. It appears that prostaglandin E1, generated from within the vessel wall itself, may act as an intrinsic regulator of coronary artery tone in the beef heart, and that blockade of this function leads to vasospasm.
Endogenous Acetylcholine Release and Labelled Acetylcholine Formation from [3H]Choline in the Myenteric Plexus of the Guinea-Pig Ileum
Authors: Szerb John C.
Published: April 2011

The spontaneous release of acetylcholine (ACh) from the guinea-pig myenteric plexus – longitudinal muscle preparation superfused at a constant rate in the presence of physostigmine was 10 nmol∙g−1∙h−1. This release was decreased to one-third by tetrodotoxin or by MnCl2 and increased 2.5 times by 0.1 Hz and 20 times by 16 Hz stimulation. The formation of [3H] ACh from [3H]choline increased from 3 to 33 nmol∙g−1∙h−1 when the concentration of [3H]choline was increased from 1 μM to 50 μM. The rate of [3H] ACh formation was not affected by tetrodotoxin, MnCl2, or physostigmine in the absence of stimulation. It was increased by 50% by 0.1 Hz and by 100% by 16 Hz stimulation during the first 9 min of exposure to [3H]choline but not subsequently. The myenteric plexus – longitudinal muscle preparation contains 200 nmol/g choline. Results suggest that the apparent small [3H]ACh formation from low concentrations of [3H]choline is due to the dilution of [3H]choline by endogenous choline. The major part of [3H]ACh formation appears to be due to the intracellular turnover of ACh while the evoked release of [3H]ACh appears to originate from a small pool.
Uncoupling of Lipolysis from Cyclic AMP by Procaine: a Tool for Studying the Mechanism of Action of Antilipolytic Agents
Authors: D'Costa Mario , Angel Aubie
Published: April 2011

The initial rate of net glycerol release in norepinephrine-stimulated adipose tissue fragments was inhibited (40–78%) by procaine–HCl (1–5 mM), whereas basal (unstimulated) lipolysis was unaffected. A dose-related inhibition of norepinephrine-induced lipolysis by procaine–HCl (0.1–1 mM) also occurred in adipocytes. Procaine-induced antilipolysis was associated with an augmented rather than a reduced hormone-stimulated increment in intracellular cyclic AMP. The dissociation of lipolysis from cyclic AMP accumulation has been termed the uncoupling effect of procaine. This effect of procaine was employed to define the precise mechanism of action of the antilipolytic drug clofibrate (Atromid-S®) which inhibits lipolysis by reducing cyclic AMP. A reduction in cyclic AMP by clofibrate was demonstrated in norepinephrine-stimulated cells exposed to procaine (uncoupled system). Thus, the inhibitory effect of clofibrate on cyclic AMP could not be attributed to accumulation of products of lipolysis. Because neither procaine–HCl nor clofibrate had any effect on the low Km 3′:5′-cyclic-AMP phosphodiesterase (EC 3.1.4.17) activity in hormone stimulated cells, the clofibrate-induced reduction in cyclic AMP was attributed to its direct action on adipocyte adenylate cyclase.
The Influence of Chronic Ethanol Consumption on the Distribution of Thiopental in Rats
Authors: Patel V. K. , Johnson G. E.
Published: April 2011

Ethanol was administered chronically for 14 days to male Sprague–Dawley rats. Day 15 was ethanol-free. On day 16 the rats received 25 mg of thiopental per kilogram (intravenously). One minute after the injection, the ethanol-treated rats showed lower blood levels of thiopental and higher liver levels of the drug than control rats given sucrose in place of ethanol. Samples of blood drawn 5 and 10 min after injection showed no significant difference in thiopental levels between the ethanol and control groups. The ethanol-treated group slept for a significantly shorter period of time. It is concluded that chronic ethanol consumption for 14 days decreases the pharmacological effects of thiopental and alters its initial distribution in the body.
Evidence for Sodium Specificity of the Receptors in the Fourth Cerebral Ventricle Affecting Sodium Excretion in the Cat
Authors: Borough J. R. Thorn , Passo S. S.
Published: April 2011

Perfusion of the fourth cerebral ventricle with artificial cerebrospinal fluid, made hypertonic by the addition of 0.89 M sucrose, resulted in no change in the rate of renal sodium excretion. These data lead us to conclude that the putative receptive field in the area of the fourth ventricle which is capable of affecting urinary sodium excretion contains elements that are sodium-specific.
Ontogenic Pattern of Dopamine, Acetylcholine, and Acetylcholinesterase in the Brains of Normal and Hypothyroid Rats
Authors: Hrdina P. D. , Ghosh P. K. , Rastogi R. B. , Singhal R. L.
Published: April 2011

The influence of neonatal thyroidectomy (Tx) on developmental changes in dopamine (DA), acetylcholine (ACh), and acetylcholinesterase (AChE) was studied in the whole brain of rats. In control animals, brain levels of ACh gradually increased and attained adult values at the 70th day. In contrast, AChE activity showed a rapid increase between the 7th and 30th days. Levels of DA were low during early postnatal life but markedly increased to reach adult values of 1.47 μg/g at the 30th day, after which no further enhancement was noted. Neonatal Tx interfered with the normal growth of the animals, decreased brain weights, and markedly influenced the developmental pattern of both DA and ACh in the brain. The concentration of DA in 30-day-old hypothyroid rats was 46% of the control values. In contrast, brain ACh levels in Tx rats were consistently above those seen in controls, being significantly higher, by 49 and 64%, at 15 and 30 days, respectively. Activity of AChE in brains of hypothyroid animals was not significantly different from that in controls. Treatment of Tx rats with thyroid hormone virtually restored the levels of DA and ACh to values in control animals.
Respiratory Effects of H+ and Dinitrophenol Injections into the Brain Stem Subarachnoid Space of Fetal Lambs
Authors: Jansen A. H. , Russell B. J. , Chernick V.
Published: April 2011

Mock cerebrospinal fluid (pH 5.37–8.38) or 2,4-dinitrophenol (DNP) (0.15–1.5 mg) was injected into the subarachnoid space of the ventral brain stem of exteriorized fetal sheep. Changes in pH on the ventral surface of the medulla did not stimulate respiratory efforts or induce significant cardiovascular changes. The respiratory response to DNP injections ranged from no response to prolonged rhythmic ventilation that was independent of the peripheral chemoreceptors or the control arterial pH and blood gas tensions. This inconsistency suggests an effector site somewhat removed from the immediate surface of the medulla. The heart rate and blood pressure were not affected. It is concluded that increased H+ concentration in the extracellular fluid of the fetal ventral medulla does not initiate respiration, and any respiratory response to metabolic inhibitors applied to this area therefore is not attributable to a secondary change in surface pH.
Growth Hormone and Cortisol Levels in the Annual Cycle of White-Tailed Deer (Odocoileus virginianus)
Authors: Bubenik G. A. , Bubenik A. B. , Brown G. M. , Trenkle A. , Wilson D. I.
Published: April 2011

The annual cycles of growth hormone and cortisol levels in white-tailed deer were followed. No significant difference was found in the average cortisol levels in a large group of animals during the year. In contrast to cortisol, growth hormone (GH) investigated by heterologous bovine GH radioimmunoassay, seems to have a distinct annual rhythm. High levels of GH in plasma were found between casting and the first week of antler growth with the peak of 23.1 ng/ml (estimated in bovine GH equivalents) in the middle of April, From the middle of June until the middle of November a plateau averaging 3 ng/ml was found.The relationships between very rapid growth of a bone tissue and the influence of GH and sex hormones are discussed.
The Bronchodilator Activity of an 11-Deoxyprostaglandin (AY-23 578)
Authors: Greenberg R. , Smorong K.
Published: April 2011

The bronchodilator activity of AY-23 578 was studied using in vivo and in vitro techniques. In the conscious guinea pig, aerosols of AY-23 578, prostaglandin (PGE2) E2, and isoproterenol afforded significant protection against histamine-induced convulsions. In the anesthetized guinea pig, where changes in tracheal pressure were taken as an index of bronchoconstriction, AY-23 578, PGE2, and isoproterenol were equipotent in inhibiting the bronchoconstriction induced by histamine. AY-23 578, PGE2, and isoproterenol reduced or prevented neostigmine-, prostaglandin F2α- or carbachol-induced increases in pulmonary resistance, and decreases in dynamic compliance in the anesthetized cat. The activities of the former two compounds were qualitatively similar but less potent than isoproterenol. In both the guinea pig and the cat, the aerosol administration of effective bronchodilator doses of AY-23 578 did not exhibit any significant cardiovascular effects. Both AY-23 578 and PGE2 caused relaxation of the isolated guinea pig tracheal strip; PGE2 was about six times more potent than AY-23 578.It is concluded that AY-23 578 is an effective bronchodilator in both the guinea pig and cat.
Effective Body Water Half-life and Total Body Water in Rhesus and Cynomolgus Monkeys
Authors: Azar Efteem , Shaw Jr. Seth Thomas
Published: April 2011

Although body water content and effective water half-life have been determined in several mammalian species, including man, these measurements are not available for sub-human primates to our knowledge. Values were therefore determined in a group of rhesus and cynomolgus monkeys.A fairly wide range of water half-life values was found in each of the two species between animals, but there was little variation within animals who had more than one determination over the course of 1 year. Mean values for effective water half-life were 7.2 days and 3.7 days for naturally menstruating females of the cynomolgus and rhesus species, respectively. Water half-life in female rhesus monkeys with artificial menstrual cycles averaged 6.2 days. Females of both species had a similar percentage of body water content of 64%. Water half-life measured 7.1 and 8.5 days in two male rhesus; and water content was 62% of body weight in one of these animals.
Absence of 'Superfast' Axonal Transport in Rat Sciatic Nerve
Authors: Bisby M. A.
Published: April 2011

Axonal transport of labelled protein was studied in rat sciatic nerve by analyzing nerve segments at intervals after injection of L-[3H]leucine into the lumbar spinal cord. Some nerves were sectioned before injection so that material in transit accumulated proximal to the section. The segments distal to the section served as controls for incorporation into the nerve of blood-borne label. An analysis of TCA-soluble and TCA-insoluble activity in cut and intact nerve segments was also made. No evidence was found for the existence of a 'superfast' component of axonal transport (velocity 2000 mm/day). Results showed that the most rapidly transported protein derived from the neuron soma had a conventional 'fast' velocity of 350–420 mm/day. There was no transport of TCA-soluble material. It is suggested that 'superfast' transport, detected in mice by other investigators, is an artefact resulting from failure to control for incorporation of circulating label into the sciatic nerve.
Inhibition of Choline Transport into Human Erythrocytes by Choline Mustard Aziridinium Ion
Authors: Clement John G. , Colhoun E. Howard
Published: April 2011

Acetylcholine mustard aziridinium ion inhibited the transport of [3H]choline into human erythrocytes. Treatment of the erythrocytes with 1 × 10−4 M tetraethylpyrophosphate prevented the inhibition of [3H]choline transport by acetylcholine mustard aziridinium ion. Hydrolyzed acetylcholine mustard aziridinium ion inhibited choline transport both in the presence and absence of 1 × 10−4 M tetraethylpyrophosphate. The product of hydrolysis was equipotent with acetylcholine mustard in its ability to inhibit choline transport; incubation of this product with sodium thiosulfate prevented inhibition of choline transport thereby indicating the presence of an aziridinium ion. The hydrolysis product is likely to be choline mustard aziridinium ion. Results on the efflux of [3H]choline from erythrocytes in the presence of the proposed choline mustard aziridinium ion showed that the mustard moiety was transported into the red cells on the choline carrier. The rate of efflux of [3H]choline produced by choline mustard aziridinium ion was 55% of that produced by the same concentration of choline. It is concluded that acetylcholinesterase (EC 3.1.1.7) of red cells rapidly hydrolyzes acetylcholine mustard aziridinium ion to acetate and choline mustard aziridinium ion and the latter compound can act as a potent inhibitor of choline transport. This finding would indicate that the hemicholinium-like toxicity of acetylcholine mustard in the mouse is due to the formation of choline mustard aziridinium ion.