bluuebunny/crossref_metadata_2025 huggingface dataset:
Stereospecific presynaptic inhibitory effect of Δ9-tetrahydrocannabinol on cholinergic transmission in the myenteric plexus of the guinea pig
Authors: Roth Sheldon H.
Published: April 2011

Δ9-Tetrahydrocannabinol (THC) is very lipid soluble, as are many anesthetic agents. The action of anesthetics is nonspecific; isomers are equieffective. THC is optically active; therefore, the effects of its stereoisomers were studied on the electrically and chemically stimulated longitudinal muscle strip of guinea pig ileum. The results demonstrate that both isomers depress the response to electrical stimulation in a dose-related manner. The maximum effect is gradually reached in approximately 20 min. The (−) isomer is 24.6-fold more active than the (+) isomer (ED50 for (−) THC is 1.25 × 10−7 M, for (+) THC, 3.08 × 10−6 M) and the site of action appears to be presynaptic because responses to ACh are not significantly depressed. The depressant effects are relatively nonreversible. Membrane concentrations calculated at the ED50 values for the (−) isomer are of the order of 0.5 mM/kg dry membrane, well within the range for anesthesia. Thus THC may be regarded as a partial anesthetic since some of its actions are similar to those of the classical anesthetics, yet it possesses selective action at the neuronal membrane or tissue level.
Effect of ovine prolactin on serum somatomedin bioactivity in hypophysectomized female rats
Authors: Bala R. M. , Bohnet H. G. , Carter J. N. , Friesen H. G.
Published: April 2011

Ovine prolactin (oPRL) increased serum somatomedin (SM) bioactivity in hypophysectomized female rats. ACTH, in small but not large doses, augmented this oPRL effect. These results suggest that in the female rat PRL may regulate SM production. Adrenal factors may variably modulate SM production or serum SM bioactivity.
Voluntary increase in finger temperature in man in a cooling environment
Authors: Carter Stefan A.
Published: April 2011

To test whether man can increase voluntarily skin temperature in a cool environment, 14 subjects (age 15–51) were studied. They came once or twice a week for five to eight sessions of 1 h. The room temperature of various sessions varied from 21.2 to 15.6 °C. Temperatures of six fingers were recorded using thermocouples. During trials to increase temperature, subjects were shown a dial indicating temperature of an index linger and were instructed to try to warm their hands. The trials were begun when skin temperatures were stable or were falling, indicating that vasoconstriction was occurring. They were preceded and followed by a rest period. The differences between changes in temperature during the trials and the rest periods were significant for the group of 14 subjects (p < 0.01). In 10 subjects with individually significant results, differences between the trial and rest periods averaged 5.0 °C for 'the best' and 3.9 °C for 'the worst' finger. The maximum temperatures during the trials averaged 30.9 ± 1.0 °C(mean ± SE) in 'the best' finger. During later sessions, subjects were able to increase temperatures without seeing the dial. The results indicate that humans are able to increase voluntarily cutaneous finger blood How in a cool environment.
Role of cardiac lymph and interstitial fluid in lipid metabolism of canine heart
Authors: Julien Pierre , Dagenais Gilles R. , Gailis Laimonis , Roy Paul-E.
Published: April 2011

To determine whether cardiac interstitial spaces participate in cardiac fatty acid pool, the relationship between cardiac lymph and arterial plasma free palmitate and triglycerides was studied in anesthetized dogs. [14C]Sucrose, infused at a constant rate in a femoral vein, appeared in the lymph at 90% of its arterial concentration within 60 min. On the other hand, when [1-14C]palmitate was infused at the same rate and at the same site, the ratio of lymph to arterial plasma 14C-labelled free fatty acids (FFA) was only 21% at 60 min and 25% at 120 min, even though the concentrations of endogenous FFA in lymph and arterial plasma were the same. The ratio reached 90% only 24 h after a bolus injection of [3H]palmitate. [1-14C]Palmitate in the lymph triglyceride fraction was only 8% of that in plasma. Although the lymph composition may be influenced by the metabolism of heart muscle, cardiac adipose tissue, and serum lipoproteins, these results indicate the presence of a pool of myocardial fatty acids which may be partly located in the interstitial spaces.
Acetaldehyde affects mammalian neuromuscular transmission without observable postsynaptic effects
Authors: Carlen Peter L. , Staiman Allan L. , Corrigall William A.
Published: April 2011

Acetaldehyde, the first metabolite of ethanol, caused a reversible block of the end-plate potential (EPP) in the rat and mouse phrenic nerve – hemidiaphragm preparation. Decrease and block of the EPP occurred over a bath concentration range from 3 to 25 mM. The phrenic nerve compound action potential was blocked along with the EPP, and this block was not reversed by high bath Ca2+ concentration. The muscle action potential was unaffected even at concentrations up to 50 mM. Over the same concentration range (3–25 mM), miniature end-plate potential (MEPP) frequency sometimes decreased a few minutes after application, and over the ensuing 10–20 min would steadily increase to as much as 11 times the base-line frequency, particularly with higher doses. However, the shape of averaged MEPPs remained unchanged after acetaldehyde application, suggesting that this aldehyde does not have postsynaptic effects.
Some effects of superior laryngeal nerve stimulation on sympathetic preganglionic neuron firing
Authors: Gerber Urs , Polosa Canio
Published: April 2011

Repetitive electrical stimulation of afferent fibers in the superior laryngeal nerve (SLN) evoked depressant or excitatory effects on sympathetic preganglionic neurons of the cervical trunk in Nembutal-anesthetized, paralyzed, artificially ventilated cats. The depressant effect, which consisted of suppression of the inspiration-synchronous discharge of units with such firing pattern, was obtained at low strength and frequency of stimulation (e.g. 600 mV, 30 Hz) and was absent at end-tidal CO2 values below threshold for phrenic nerve activity. The excitatory effect required higher intensity and frequency of stimulation and was CO2 independent. The depressant effect on sympathetic preganglionic neurons with inspiratory firing pattern seemed a replica of the inspiration-inhibitory effect observed on phrenic motoneurons. Hence, it could be attributed to the known inhibition by the SLN of central inspiratory activity, if it is assumed that this is a common driver for phrenic motoneurons and some sympathetic preganglionic neurons. The excitatory effect, on the other hand, appears to be due to connections of SLN afferents with sympathetic preganglionic neurons, independent of the respiratory center.
The characteristics of tetraethylammonium-induced rhythmic contractions in canine tracheal smooth muscle: Effect of Na-pump inhibition
Authors: Watanabe Minoru , Imaizumi Yuji , Kasuya Yutaka
Published: April 2011

Tetraethylammonium ions (TEA) induced rhythmic contractions (RC) in canine tracheal smooth muscle (frequency, 0.09 ± 0.01 contractions/min; tension development, 279 ± 36 mg/mg tissue wet weight, at a TEA concentration of 15 mM). The rhythmicity coupling with various electrical activities (e.g., oscillation or action potentials) was suppressed or reduced by metabolic depletion – anoxia, 2,4-dinitrophenol (DNP), monoiodoacetic acid (MIA), or KCN. DNP (3 × 10−6 M) or MIA (5 × 10−4 M) completely inhibited the RC. Anoxia or 1 mM KCN decreased the tension development by 50%. Under these conditions, basal tension was unaffected. During prolonged incubation in K+-free Krebs solution or in the medium containing 10−5 M ouabain in the presence of 10−7 M atropine, the tension development was minimal. Membrane potential was also unaffected by 1-h incubation with 10−5 M ouabain. In contrast, after the rhythmicity was induced by TEA, ouabain (1 × 10−6 to 3 × 10−6 M) was especially effective in depolarizing the membrane. At the same time, the RC was also changed into tonic contraction, which was relaxed by 10−6 M D 600 or 2.5 mM glycoletherdiamine-N,N,N′,N′-tetraacetic acid. An extracellular K+ concentration of 1–2 mM was necessary for initiation of the RC by TEA. Rb+ was as effective as K+, but Cs+ could not replace K+. When extracellular Na+ was substituted with Li+, the RC turned to tonic contraction. These results suggest that the Na pump takes part in the mechanism of the RC.It may be concluded that augmentation of membrane excitability and resulting excitation–contraction coupling in the presence of TEA can occur without the action of the Na pump, but that succession of the RC inevitably requires it.
Nonparticipation of extracellular glutathione in renal transport of dibasic amino acids
Authors: Craan André G. , Bergeron Michel
Published: April 2011

Microinjections of L-[14C]arginine (2.9 mM) and L-[14C]ornithine (3.4 mM) were made into renal proximal tubules of rats in the presence of methionine sulfoximine (MSO) (10, 20 mM), ATP (10 mM), and MgCl2 (20 mM) together. Absorption of both labelled amino acids dropped, respectively, by 31.1 and 49.1% compared with control microinjections. The MSO alone or ATP plus MgCl2 had no effect. These data suggest that the inhibition by MSO plus ATP plus MgCl2 is not due to direct competition between MSO and dibasic amino acids but rather to suppression of the renewal of intracellular glutathione. Such an effect is discussed in comparison with cycloleucine inhibition of dibasic amino acid transport. Addition of exogenous glutathione to microinjectates did not reverse either type of inhibition. This study shows that while intracellular glutathione may affect amino acid transport, extracellular glutathione has no effect.
Glucose oxidation in fresh guinea pig cornea
Authors: Liao Horng-Miao R. , Lin Boniface J. , Hasany Syed M. , Basu Prasanta K.
Published: April 2011

The rate of glucose oxidation of fresh corneas of guinea pigs at different ages has been determined.Full-thickness corneal discs, 4 mm in diameter, were incubated in radioactive glucose solution. The quantity of the released CO2 was expressed in terms of the corneal discs, their dry weights, and DNA and protein contents. The rate of glucose metabolized to CO2 per hour was about 300 pmol/μg DNA for guinea pigs weighing approximately 800 g. Glucose oxidation decreased as the age of the animals increased.Our results compared well with those obtained in other species. We therefore feel that the guinea pig should be a suitable model for research on the metabolism of corneas.
Use of the overturn end point in goldfish to measure the interaction of diazepam and ethanol and the effects of the binding of diazepam to bovine serum albumin
Authors: Giles H. G. , Kadar G. , MacLeod S. M. , Sellers E. M.
Published: April 2011

Over the ranges 2.8 × 10−6 to 8.78 × 10−5 M diazepam and 4.85 × 10−2 to 1.22 × 10−1 M ethanol, addition of the effects of these agents on the overturn end point in goldfish was observed. The addition of bovine serum albumin (1.56 × 10−5 M) to aqueous solutions of diazepam modifies the diazepam effect by reducing the "free" drug concentrations.
Inhibition by dopamine of the stimulation-induced efflux of [3H]noradrenaline in renal arteries: limitations of the unitary hypothesis of presynaptic regulation of transmitter release
Authors: Kalsner Stanley , Chan Chi-Chung
Published: April 2011

The supposition was tested that a pattern of agonist inhibition of 3H-labelled transmitter efflux which shows a decline in intensity as the frequency of stimulation rises provides major evidence for the existence of a functional autoinhibitory feedback loop mediated by released transmitter and located on adrenergic nerve terminals. For these experiments dopamine was used, as it is not released in significant quantities in the ordinary course of sympathetic nerve activation and it appears to act presynaptically in several tested tissues at a locus discrete from that acted on by noradrenaline. Dopamine (3 × 10−7 and 3 × 10−6 M) inhibited the stimulation-induced efflux of [3H]noradrenaline from cattle renal arteries and did so to a declining extent with increasing frequency (1–15 Hz). Known antagonists of dopamine action, pimozide and metoclopromide, antagonized this effect of dopamine but did not by themselves enhance stimulation-induced transmitter efflux or block the inhibiting effects of exogenous noradrenaline on efflux, establishing the specificity of dopamine action in renal artery and indicating the absence of an operative negative feedback loop mediated by dopamine. This interpretation was substantiated by the finding that although dopamine reduced the magnitude of contractile responses to nerve stimulation neither pimozide nor metoclopromide enhanced the amplitude of nerve-induced contractions. It thus appears that a pattern of agonist effect on transmitter efflux which manifests a diminution in intensity as the frequency of stimulation climbs is not derived from the operation of an ongoing autoinhibitory feedback system regulating transmitter release but by a yet to be established factor.
The increase in calcium binding of cardiac plasma membrane lipoprotein caused by general anesthetics and alcohol
Authors: Ohnishi S. Tsuyoshi , Obzansky David M. , Price Henry L.
Published: April 2011

(1) Ca2+-binding lipoprotein was purified from dog heart plasma membrane and the effect of several general anesthetics, ethanol, and acetaldehyde on the Ca2+ binding was studied.(2) These drugs, which are known to cause myocardial depression increased the Ca2+ binding at clinically useful concentrations.(3) These results raise the possibility that these drugs, by increasing the Ca2+ binding to the plasma membrane, limit the availability of superficially located Ca2+ for excitation–contraction coupling and result in depression of myocardial contractile force.
Long-term administration of atropine, imipramine, and viloxazine alters responsiveness of rat cortical neurones to acetylcholine
Authors: Jones Roland S. G.
Published: April 2011

Rats were treated daily with atropine (2.5 mg/kg), imipramine (5 mg/kg), viloxazine (5 mg/kg), or saline for 14 days. Thirty-six hours following the final injection the rats were anaesthetized with urethane and the sensitivity of neurones in the somatosensory cortex to iontophoretically applied acetylcholine (ACh) was determined. In saline-treated animals the large majority of neurones was excited by ACh with depression being observed infrequently. This was reversed in drug-treated animals, the predominant response to iontophoretic ACh becoming one of depression. The results indicate that long-term administration of antidepressant drugs may induce qualitative changes in the sensitivity of central cholinergic systems.
Active and passive control of hepatic blood volume responses to hemorrhage at normal and raised hepatic venous pressure in cats
Authors: Lautt W. Wayne , Brown L. Cheryle , Durham J. Scott
Published: April 2011

Hepatic blood volume decreases in response to a rapid hemorrhage (15.3 mL/min) were measured in cats anesthetized with pentobarbital or ketamine–chloralose, by use of in vivo plethysmography alone or in combination with various surgical procedures and vascular circuits. The hepatic blood volume contracts during hemorrhage to compensate for a constant proportion (26 ± 6%) of the blood loss regardless of the extent of the actual blood loss. Following denervation of the liver and α adrenoreceptor blockade (3 mg phentolamine, intraportal) the liver compensation was unaltered. After denervation, nephrectomy, hypophysectomy, and adrenalectomy the liver was still able to compensate for 20 ± 7.4% of the hemorrhage. Decreases in liver volume were linearly related to decreases in total hepatic blood flow that ensued whether the decreased blood flow was induced by hemorrhage or by clamping of the arteries supplying the splanchnic organs (superior mesenteric artery, celiac artery). The hepatic volume response to hemorrhage could be predicted accurately (97 ± 6.6%) simply from the linear passive relationship between flow and volume for a particular animal. However when hepatic venous pressure was experimentally elevated, the volume response to passive flow decrease was markedly reduced whereas the response to hemorrhage and noradrenaline infusion was unimpaired suggesting that active control factors were required to produce normal hepatic volume responses to hemorrhage at raised venous pressure. Phentolamine reduced the response at raised venous pressure but was without effect at normal venous pressure in the same animal, indicating that the hepatic nerves and (or) adrenal catecholamines are of paramount importance in control of the response at raised venous pressure when the passive flow influence is much reduced.
Increased uptake of [3H]deoxyglucose and [14C]deoxyglucose in localized regions of the brain during stimulation of the motor cortex
Authors: Goldberg L. , Courville J. , Lund J. P. , Kauer J. S.
Published: April 2011

A part of the motor area which evokes short-latency activity in jaw-opening muscles was stimulated for 30–45 min in guinea pigs which had received an injection of [3H]deoxyglucose or [14C]deoxyglucose. In a number of specific regions of the upper brainstem and basal ganglia, bilateral increases of metabolic activity were demonstrated by autoradiography. These included the putamen, globus pallidus, substantia nigra, subthalamic nucleus, dorsomedial region of red nucleus, deep layers of the superior colliculus, and pretectal nuclei. A ventral region of the thalamus was labeled ipsilateral to the stimulation. It is suggested that these regions represent stations in the circuits involved in the production of the evoked muscular activity. Using [3H]deoxyglucose instead of [14C]deoxyglucose as a tracer improved the quality of the autoradiographic images.
Influence of sodium intake on catecholamine release by angiotensin and renal nerve stimulation in dogs
Authors: Carrière Serge , Cardinal Jean , Grimellec Christian Le
Published: April 2011

For 10 days, dogs were fed a normal salt diet containing 70 mequiv. Na+/day (NSD) followed by a high salt diet containing 170 mequiv. Na+/day (HSD) or 240 mequiv. Na+/day (VHSD), or the order was reversed. K+ in these diets was fixed at 40 mequiv./day. The different diets did not influence the basal level of serum catecholamines (CA). Intravenous angiotensin II (ATII) in subpressor doses produced, under NSD and HSD, an increase in serum CA accompanied by reductions in total renal blood flow as well as regional blood flow rates (microspheres), mostly in the deeper regions of the cortex. Under VHSD, ATII did not affect serum CA and barely decreased total renal blood flow, reducing regional blood flow rate in C3 and C4 only. The increase in renal vein serum CA produced by renal nerve stimulation was potentiated by ATII but under constant plasma levels of the latter, progressive increments of Na+ in the diet markedly exaggerated the liberation of CA following renal nerve stimulation and the hemodynamic response of the kidney. We conclude that the Na+ content in the diet markedly influences the increase in serum CA after renal nerve stimulation and greatly influences the response of that organ to renal nerve stimulation.
Expired air volumes of maies and females during cold water immersion
Authors: Malkinson T. J. , Martin S. , Simper P. , Cooper K. E.
Published: April 2011

Expired air volumes were measured from a random population of adult male and female human volunteers before and during short-term immersion in either cold (13.53 ± 0.13 °C) or warm (33.18 ± 0.11 °C) water. A statistically significant difference was found in the pulmonary ventilation over the first 4 min of immersion between males and females when immersed in cold water. The swim suits worn could not account for the differences observed. No statistically significant difference in pulmonary ventilation was found between males and females during warm water immersion. A numerically smaller group of volunteers was preheated in a sauna before immersion in cold or warm water and this resulted in an attenuated ventilatory response. In this instance there is no statistically significant difference in ventilation between males and females. Also, in another small group of volunteers, surface and deep skin temperatures were continuously measured before and during immersion in cold water. The rates of change of deep skin temperature between males and females were found to be similar.
Enkephalin-induced inhibition of the isolated rat ileum is not blocked by naloxone
Authors: Nakatsu K. , Goldenberg E. , Penning D. , Jhamandas K.
Published: April 2011

Both methionine- and leucine-enkephalin caused the isolated rat ileum to relax in a concentration-dependent manner; the EC50 values were in the order of 10−8 to 10−7 M. This isolated preparation was generally not sensitive to morphine. The enkephalin-induced inhibitions were not blocked by the classical narcotic antagonist, naloxone.
Distribution of serum paraoxon hydrolyzing activities in a Canadian population
Authors: Carro-Ciampi Giovanna , Kadar Deszo , Kalow Werner
Published: April 2011

The serum paraoxon hydrolyzing activities in a Canadian population were bimodally distributed and interethnically variable. A clear separation between the two phenotypes was obtained by determining the ratio of activity in the presence of 5 × 10−3 M CaCl2 plus 5 × 10−1 M NaCl over that in 5 × 10−3 M CaCl2 alone. The data strongly suggest that the crucial discriminatory role was played by Ca2+.
Single cells from adult mammalian heart: Isolation procedure and preliminary electrophysiological studies
Authors: Bustamante J. Omar , Watanabe Toshifumi , McDonald Terence F.
Published: April 2011

Single ventricular cells have been isolated from adult guinea pig heart using a collagenase enzyme method. The procedure is straightforward, takes about 20 min, and yields 40–65% rod-shaped cells which are quiescent in millimolar Ca2+ solution. Electrophysiological studies involving external ion changes and ionic channel inhibitors suggest that the cells retain their active membrane properties following this enzymatic dissociation.
Effect of myocardial ischemia on uridine incorporation and histone acetylation
Authors: Taylor Paul B. , Young Bruce G.
Published: April 2011

The influence of transient myocardial ischemia on recovery uridine incorporation into RNA and histone acetylation was investigated in an isolated perfused rat heart. Hemodynamically, hearts recovered from 15 min of ischemic arrest and were stable for at least 60 min of perfusion. Uridine incorporation was reduced (P < 0.05) in ischemic hearts by 24 and 26% after 30 and 60 min of recovery perfusion. The incorporation of uridine into RNA from purified myocytes was decreased by 50% in the ischemic muscle cells. The covalent acetylation of total nucleohistones was diminished by 37%. Histone fractionation by urea polyacrylamide gel electrophoresis clearly indicated that histones H3 and H4 preferentially incorporated less acetate during ischemic recovery. However, histone acetylation for proteins H2A + H2B was not effected. These data suggest that a brief period of ischemia disrupts nucleotide incorporation during the recovery phase, with a marked decrease associated with the muscle cell. The similar change in histone acetylation indicates a possible link between nucleoproteins and chromatin function during ischemic insult to the heart.
Acetaminophen toxicity in fed and fasted mice
Authors: Walker Robin M. , Massey Thomas E. , McElligott Timothy F. , Racz William J.
Published: April 2011

Acetaminophen (750 mg/kg) toxicity and its modification by N-acetylcysteine (NAC, 1200 mg/kg) have been compared in fed and fasted mice. There was no significant difference between fed and fasted animals with respect to microsomal protein content, cytochrome(s) P-450 content, and aryl hydrocarbon hydroxylase activity. Glucuronyl transferase activity was significantly higher in fasted mice. Hepatotoxicity, as determined histologically and by liver enlargement was greater in fasted than fed mice. Covalent binding of [3H]acetaminophen metabolite(s) to liver proteins was also greater in fasted animals. NAC administration prevented acetaminophen-induced microscopic changes and liver enlargement and reduced the magnitude of covalent binding of acetaminophen metabolites. Fasting caused a marked fall in liver reduced sulfhydryl concentration. The incidence of acetaminophen-induced hypothermia was greater in fasted than in fed animals. NAC administration reduced hypothermia in fasted mice and abolished it in fed animals. It is concluded that enhanced acetaminophen toxicity in fasted mice compared with fed mice is unlikely to be a consequence of increased reactive metabolite formation, but rather a result of reduced inactivation of reactive metabolite(s) due to reduced hepatic glutathione stores in fasted mice.
Nonparallel transport of exportable proteins in rat pancreas in vitro
Authors: Singh Manjit
Published: April 2011

The relative change in in vitro discharge of amylase (or total protein) versus pulse-labeled protein from rat pancreatic fragments was studied after in vivo stimulation with bethanechol or saline injections. Bethanechol was injected three times in a dose of 2 mg∙kg−1 at hourly intervals. Fragments of pancreas obtained 30 min after the last injection were pulse-labeled for 5 min with [14C]L-phenylalanine. The pulse was chased for 60 min. In fragments derived from animals injected with saline, ratio of amylase (or total protein) to new secretory protein decreased at 5 and 15 min but there was no change at 45 min of in vitro incubation with 5 × 10−5 M bethanechol. In fragments derived from animals injected with bethanechol, ratio of amylase to radiolabeled secretory protein decreased at 5, and 15 min and the ratio of total protein to radiolabeled secretory protein secretion decreased at 5 but not at 15 and 45 min. There was a lack of parallelism between the ratios of amylase to radiolabeled protein secretion and total protein secretion to radiolabeled protein secretion in animals injected with bethanechol in vivo followed by in vitro incubations. These experiments indicate that the older proteins are preferentially secreted under nonstimulated conditions and mixing of granules occurs following stimulation. The time required for mixing varies depending on whether the cells are stimulated or not. These data provide support for the concept that there may be more than one subpopulation of zymogen granules in the acinar cell leading to nonparallel enzyme secretion.
Pharmacological study of the contractile activity of leukotriene C4 and D4 on isolated human airway smooth muscle
Authors: Jones Thomas R. , Davis Clive , Daniel Edwin E.
Published: April 2011

Synthetic leukotriene C4 (LTC4) and leukotriene D4 (LTD4) were examined on isolated human tracheal and bronchial smooth muscle. Both LTC4 and LTD4 produced slowly developing contraction of trachealis and bronchus which were submaximal (70–85% of the carbachol maximum) and were not blocked by 1.0 μM atropine, 5.0 μM mepyrarnine, or 5.6 μM indomethacin. The EC50's for LTC4 and LTD4 were 10.3 and 1.8 nM on trachealis and 1.8 and 1.7 nM on bronchus, respectively. LTD4 was in excess of 20 000 times more potent than acetylcholine on some bronchial and tracheal tissues. Similar differences in potency were obtained in some tissues when LTC4 and LTD4 were compared with histamine. Tissues pretreated for 30 min with 2.0–4.0 μM FPL-55712 were less reactive to LTC4 and LTD4 than untreated control tissues. Established contractions to LTC4 and LTD4 persisted despite washing with fresh Krebs solution, were partially reversed by FPL-55712 (0.5–10 μM) and the Ca2+ channel blocker D-600 (5–10 μM), but were completely reversed by the catecholamine adrenaline (1.0 μM) and by high concentrations of FPL-55712 (>20 μM). The marked potency of the leukotrienes on human tracheal and bronchial smooth muscle suggests an important role for these lipoxygenase products in respiratory disease.
Interaction of the level of dietary fat and type of carbohydrate in the regulation of hepatic lipogenesis in the mouse
Authors: Herzberg Gene R. , Rogerson Minda
Published: April 2011

We have studied hepatic and extrahepatic lipogenesis in mice fed diets containing 0, 5, 10, or 15% corn oil in which the carbohydrate was one of fructose, sucrose, glucose, or wheat starch. Meal-fed animals were trained to eat a quantity of food such that at a given level of fat ail animals consumed the same amount of carbohydrate. Fatty acids synthesis in vivo, acetyl CoA carboxylase, fatty acid synthetase, ATP citrate lyase, glucose-6-phosphate dehydrogenase, and malic enzyme were determined. At 0 and 5% corn oil the values generally decreased in the order fructose > sucrose > glucose > wheat starch. At 10 and 15% corn oil differences due to the type of carbohydrate were less pronounced. The effect of dietary carbohydrate on glucokinase activity followed the reverse pattern with the values decreasing in the order wheat starch > glucose > sucrose > fructose. The results obtained demonstrate that hepatic lipogenesis was increased in mice consuming fructose or sucrose independent of carbohydrate intake or the level of dietary fat. However, total capacity for lipogenesis was greater in glucose-fed mice than those consuming wheat starch, fructose, or sucrose. Regardless of the carbohydrate in the diet, as dietary fat increased all the lipogenic parameters measured declined.Increasing corn oil from 0 to 15% caused a greater change in lipogenic capacity than the change due to the various carbohydrates. The percentage of total synthesis which occurred in liver was greater in mice fed fructose or sucrose. This increased contribution by the liver was unaltered by dietary fat which may contribute to the hypertriglyceridemia in such animals. Compared with diets based on glucose or wheat starch, diets based on fructose or sucrose do not cause increased lipogenesis in meal-fed mice if the diets contain more than 30 calorie percent fat. Our results suggest that when diets contain fat a a level similar to that in North American diets, the effects of the type of dietary carbohydrate on lipogenesis are minimal.
Preparation and stability of indomethacin solutions
Authors: Curry Stephen H. , Brown Edgar A. , Kuck Hilken , Cassin Sidney
Published: April 2011

Indomethacin is used in closure of the ductus arteriosus in newborn humans as well as in related research in near-term sheep and goats. Conflicting data in these studies have led to a reexamination of indomethacin stability. Solutions at various pH values, at two temperatures, and in polyethylene glycol (PEG-400), were assessed by high-pressure liquid chromatography for indomethacin and its products. Solutions below pH 7.4 were stable. Decomposition was rapid in alkaline solutions. Solutions at pH 7.4 showed no changes up to 24 h. Solutions of sodium indomethacin, and of indomethacin in PEG were stable. Solutions in aqueous Na2CO3 were variably stable depending on the mode of mixing. A solution prepared directly in 0.1 M Na2CO3 (pH 10.7) lost 75% of its content in 80 min; a similar solution diluted immediately with two volumes of pH 7.4 buffer (final pH 9.9) showed less decomposition. A solution in Na2CO3 adjusted to pH 7.4 with HCl was stable (at least 24 h). Solutions prepared by suspending indomethacin in 0.9% NaCl and adding Na2CO3 slowly were stable for 80 min; rapid mixing led to decomposition. Solutions in plasma were stable at −20 °C (2 months). Lack of indomethacin activity in some biological studies may have resulted from injection of inactive solutions.
Present status: toxic substances in the environment
Authors: Plaa Gabriel L.
Published: April 2011

"Environmental toxicology" and "ecotoxicology" are defined and the characteristic components of each discussed. The sources of chemical pollution (production and use of energy sources and industrial chemicals; increased agricultural practices) and their dispersion in the environment are put into perspective. Characteristics of some chemical pollutants are summarized. The problems facing these branches of toxicology as predictive disciplines are briefly presented.
Aerial spraying of fenitrothion in forest programs: some problems and some solutions
Authors: Ecobichon D. J.
Published: April 2011

Annually, large tracts of forest in eastern Canada are sprayed aerially with insecticides (fenitrothion, aminocarb) in attempts to control an epidemic infestation by an indigenous forest pest, the spruce budworm (Choristoneura fumiferana, Clemens). The massive size of the spraying programs, the anecdotal reports of human exposure, and the potential for hazard to human health have led one province, New Brunswick, to initiate and fund specific environmental and laboratory studies which will provide adequate data upon which the government can base realistic legislation to protect both the forests and the population. These studies have included some unique field analyses of aerial spray drift conducted by a research group from the National Research Council; comparative subchronic studies in rats of fenitrothion and a new formulation; a nose-only inhalation study of this formulation in rats; field testing of the formulation for drift characteristics. Ongoing research involves the subchronic testing of the emulsifying agents being used routinely in the new formulation and studies of a low-drift additive which will stabilize the particle size of the spray. On the basis of the results to date, the government has been able to modify spraying techniques and to establish realistic buffer zones around human habitation.
Dietary influences on excretory pathways and tissue residues of zearalenone and zearalenols in the rat
Authors: Smith T. K.
Published: April 2011

Experiments were conducted with male weanling rats to determine the effect of high dietary protein (40% casein), alfalfa (25%), protein + alfalfa (25% casein + 25%) alfalfa), or anion-exchange resin (5%) on the relative proportions of free and conjugated zearalenone and zearalenols excreted in urine and feces following a single oral dose of zearalenone. About 90% of the dose was excreted in feces after 48 h while the remaining 10% was excreted in urine. Zearalenone and metabolites were excreted mainly in free form with conjugates being found only in urine. Rats fed high-protein diets excreted more free zearalenone and α-zearalenol in urine than did controls (16.3% casein). The feeding of protein + alfalfa also resulted in increased urinary losses of free zearalenone. A reduction in urinary losses of conjugated zearalenone and α-zearalenol was seen when 5% anion-exchange resin was fed. Fecal excretion of zearalenone and α- and β-zearalenol increased when alfalfa + protein was fed. Residual zearalenone and zearalenols were measured in liver and kidney 18 h after dosing. All treatments except high protein reduced residues of zearalenone and α-zearalenol in liver when compared with controls. Renal residues of zearalenone were lowered only by supplements of protein + alfalfa or anion-exchange resin. Each of the treatments fed has been shown to reduce zearalenone toxicosis in rats, but it was concluded that each does so by a different mechanism.
Effect of l,3-diaminopropan-2-o1, an inhibitor of ornithine decarboxylase, on the metabolic response of liver to insulin
Authors: Hu Yu-Wan , Hall Douglas E. , Brosnan Margaret E.
Published: April 2011

The effect of diaminopropanol, an inhibitor of polyamine synthesis, on the metabolic response of liver to insulin was studied in streptozotocin-diabetic rats. Insulin elicited a prompt and very marked increase in ornithine and S-adenosylmethionine decarboxylase activities and in putrescine concentration. Pretreatment of rats with diaminopropanol prevented the increase in the decarboxylases and resulted in decreased spermidine and spermine content of liver. The insulin-induced increase in glycogen content was depressed by 50% and the increase in the rate of lipogenesis in vivo was completely prevented by prior injection of diaminopropanol. These studies implicate altered polyamine metabolism in the metabolic response of liver of streptozotocin-diabetic rats to insulin.
Net urate reabsorption in the Dalmatian coach hound with a note on automated measurement of urate in species with low plasma urate
Authors: Moulin B. , Vinay P. , Duong N. , Gougoux A. , Lemieux G.
Published: April 2011

A progressive reduction of renal blood flow and glomerular filtration rate induced by the stepwise clamping of a Goldblatt clamp increases the urate over creatinine clearance ratio from 1.2 to 1.9 in normal urate-secreting Dalmatian dogs. These clearance data support the existence of a predominant postreabsorptive secretory flux of urate in the normal Dalmatian dog. In contrast, in Dalmatians loaded with pyrazinoic acid which suppresses urate secretion, net reabsorption of urate is unmasked and the urate over creatinine clearance ratio decreases with the progressive reduction in glomerular filtration rate (down to 0.44). It is concluded that the net reabsorption of urate measured by conventional clearance techniques after pharmacologic depression of the urate secretory flux probably reflects true urate reabsorption in the nephron of this species.
Ovarian hormones are not necessary for postpartum regression of gap junctions
Authors: Berezin Irene , Daniel E. E. , Garfield R. E.
Published: April 2011

We tested the hypothesis that gap junction degradation in myometrium after parturition in rats requires an ovarian hormone. Compared with unoperated or sham-operated controls, ovariectomy on day 21 slightly delayed parturition (nearly all animals delivered on day 23 instead of day 22). It also significantly reduced the number and membrane area occupied by gap junctions in delivering animals. However, it did not alter the disappearance of gap junctions which occurs less than 24 h after parturition or disassociate gap junction disappearance from parturition. These results do not support the hypothesis of a necessary role for ovaries in gap junctions degradation after parturition and suggest that events associated with parturition may initiate this event.
The effect of glucose loading on steady-state lactate levels and contraction in the isolated rat diaphragm
Authors: Mainwood G. W.
Published: April 2011

Isolated rat diaphragm strips were used to investigate two questions: (a) can the steady-state level of lactate in contracting muscles be increased by glucose loading resulting from the addition of increased external glucose (50 mM) in the presence of inslulin (10 mU/mL)? (b) is the isometric tension developed by muscles contracting at different frequencies (0.125 to 1.0 Hz) affected by glucose loading? The results show that lactate levels in contracting muscles are increased by glucose loading over the whole range of contraction frequencies studied. Suppression of isometric contraction increases with contraction frequency but the extent of the suppression is not influenced by glucose loading. Steady-state lactate levels are well correlated with suppression in glucose-loaded muscles (r = 0.89) but not well correlated with suppression in normal muscles (r = 0.46). Isometric tension in the steady-state condition is well correlated with creatine phosphate levels (r = 0.98, 0.92 in glucose-loaded and normal muscles) and reasonably well with ATP (r = 0.88, 0.86, glucose loaded and normal). The increase in resting tension seen during development of steady-state conditions is reduced by glucose loading. It is concluded that several factors may contribute to the suppression of tension in contracting muscle but metabolic product inhibition, at least by products of glycolysis, does not normally play an important part in the isolated rat diaphragm preparation.
Hyperkalemia, hyperglycemia, and plasma levels of cyclic AMP and cyclic GMP induced by portal vein injection of cyclic nucleotides and their butyryl derivatives into dogs
Authors: Nakashima Toshikatsu , Morita Naofumi , Nakanishi Yasumasa , Inoki Masayuki , Kurogochi Yutaka
Published: April 2011

The levels of serum potassium, blood glucose, and plasma adenosine cyclic 3′:5′-monophosphate (cAMP) and guanosine cyclic 3′:5′-monophosphate (cGMP) were studied after the portal vein injection of cyclic nucleotides and their derivatives, (cAMP, cGMP, N6, O2′,-dibutyryl adenosine 3′:5′-monophosphate (DBcAMP), N6-monobutyryl adenosine cyclic 3′:5′-monophosphate (NMBcAMP), and O2′-monobutyryl adenosine cyclic 3′:5′-monophosphate (OMBcAMP)), into dogs. Dose-related hyperglycemic responses were observed after the injection of DBcAMP (1–8 mg/kg). Transient and prominent hyperkalemia and hyperglycemia were caused by the injection of DBcAMP, NMBcAMP, and OMBcAMP (4 mg/kg). The hyperkalemic response was highest with NMBcAMP (1.22 mequiv./L), followed by OMBcAMP (0.64), DBcAMP (0.54), cGMP (0.47), and cAMP (0.41), whereas the hyperglycemic response was highest with NMBcAMP (146 mg/100 mL), followed by DBcAMP (93.6), OMBcAMP (77.1), and cAMP (56.0), and there was only a slight change with cGMP (28.4) compared with the control. The plasma level of cAMP was maximal with DBcAMP (1.92 nmol/mL), followed by NMBcAMP (1.28) and OMBcAMP (0.76), whereas the plasma levels of cGMP showed no evident change, except that caused by DBcAMP (0.27). Of the cyclic nucleotides tested, NMBcAMP was found to be most potent in causing both hyperkalemia and hyperglycemia. Based on these results, possible correlations between hyperkalemia, hyperglycemia, and plasma levels of cAMP and cGMP are discussed.
Evidence for a blood – uterine lumen permeability barrier in rats treated with hormones to mimic early pseudopregnancy
Authors: McRae Ann C. , Kennedy T. G.
Published: April 2011

Experiments have been carried out to investigate whether a blood – uterine lumen permeability barrier exists in rats treated with hormones to mimic the implantation period of gestation. Levels of radioactivity in fluid from the uterine lumen and in serum of rats at the equivalent of day 4, 5, or 6 of pseudopregnancy (day 1 = day of induced ovulation) were determined either 20 or 60 min after intravenous injection of a radiolabelled test substance. Following injection of [14C]urea or [3H]sucrose, uterine fluid (UF) radioactivity concentrations did not differ significantly between 20 and 60 min irrespective of day of pseudopregnancy. With [14C]urea, UF radioactivity concentrations were significantly less than those in serum in all groups except at the equivalent of day 6 of pseudopregnancy. After injection of [3H]sucrose, the UF radioactivity concentrations were significantly less than those in serum in all groups except at 60 min at the equivalent of day 6 of pseudopregnancy. Additionally, the UF radioactivity concentrations after injection of either [14C]urea or [3H]sucrose were significantly higher on the equivalent of day 6 of pseudopregnancy than on day 4. By contrast, when tritiated water was injected, the UF radioactivity concentrations were not markedly different from those in serum in all groups.not available
The gastrointestinal peptides and nutrition
Authors: Brown J. C. , McIntosh C. H. S. , Pederson R. A.
Published: April 2011

Gastrointestinal (GI) peptides have been identified in endocrine cells and nerve fibres throughout the GI tract. They play both a direct and indirect role in the regulation of food intake, digestion, and absorption. The rate at which food is absorbed is dependent upon the rates of gastric emptying, intestinal transit, membrane transport, and enzymatic degradation. The control of pepsin secretion is intimately linked to that of acid secretion and stimulatory peptides, e.g., gastrin and bombesin. Inhibitors of acid secretion such as gastric inhibitory polypeptide (GIP), vasoactive intestinal peptide (VIP), secretin, and glucagon also control pepsin secretion. Powerful inhibitory reflexes, both nervous and hormonal, operate from the duodenum to slow gastric emptying and the most compelling evidence exists for the involvement of neurally released VIP. However, a unifying concept for the role of peptides in the control of intestinal motility is lacking. It is well established that the enzyme component of pancreatic secretion is controlled by the peptide cholecystokinin (CCK) and the aqueous component by secretin. Nutrient absorption can be affected by the endocrine pancreas and by somatostatin. Control of luminal enzyme secretion is increased by CCK, secretin, GIP, VIP, glucagon, and gastrin. Peptides influence the rate and direction of electrolyte and attendant water movement. The secretory actions of VIP are well documented. Peptides, again notably VIP, probably influence digestion and absorption via blood flow changes. Evidence has accumulated that gut hormones stimulate insulin release from the pancreas. The peptide, GIP, has been demonstrated to be a hormone involved in this mechanism and has been hypothesized to be a causal agent in disease states involving hyperinsulinemta, e.g., obesity and maturity onset diabetes. The hypothalamus is recognized to be the major regulatory area for appetite. It receives rich peptidergic innervation as well as being influenced by exogenous peptides. CCK has been shown to inhibit food intake. The presence of this peptide in the brain as well as the gut has led to the suggestion that it is a satiety hormone. However, problems with experimental design render equivocal the role of CCK and other peptides in the control of food intake.
Paraoxonase phenotype distribution in Canadian Indian and Inuit populations
Authors: Carro-Ciampi Giovanna , Gray Sidney , Kalow Werner
Published: April 2011

Test objects were the sera of 57 North American Indian and 67 Inuit subjects. The paraoxon-hydrolyzing activity, a, was determined, as well as the paraoxonase-phenotyping ratio, c/b, a ratio designating enzyme activation by Na+ in the presence of Ca2+. The values of c/b were clearly bimodally distributed. Location of the modes and of the antimodal gap were in perfect agreement with the results previously obtained on Caucasian sera. This allowed us to retain the criterion which had been already established in the study of Caucasians, i.e., c/b < 1.5 = "low-activity" phenotype, and c/b > 1.5 = "high-activity" phenotype. The proportions of individuals in each mode differed, however. In Caucasians, the frequency of the "low-activity" phenotype had been estimated as 51.2%. In Indians and Inuits, it was 7.0% and 6.0%, respectively. Independent of phenotype, Indian and Inuit sera displayed lower paraoxon-hydrolyzing activity than did Caucasian sera.
The development of the early atrioventricular conduction system in the embryonic heart
Authors: Virágh Sz. , Challice C. E.
Published: April 2011

Recent electrophysiological evidence indicates that periodic spontaneous depolarizations occur in the primordial heart of the bird (and presumably mammal) even before the myocardial cells can contract, and these are initiated in the primordial sinoatrial region. As contractions are generated, these then establish a peristaltic wave. From that time on, during ontogenesis, the contractile sequence follows a regular pattern of development. As chambers form they contract sequentially in the direction of blood flow, even though, in the twisted configuration, myocardial continuities suggest the possibility of short-circuiting the electrical conduction pathways from atrium to bulbus. This implies that, even at these early stages, the electrical properties of the myocardium are not isotropic, and that specialized conduction pathways must exist. To the present time, electrophysiological techniques have limited the direct evidence that can be obtained on these delicate electrically specialized pathways. However, microscopical techniques have permitted studies on the morphological development of the tissue and of the cells in the various regions of the myocardium. The present paper traces the development of cell morphology in these regions, including the development of structural nodes and proximal ventricular fibre pathways, and from these observations, the manner in which the electrical conduction pathways are believed to develop is suggested.