bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of L-glutamate and its analogues upon the membrane conductance of central murine neurones in culture
Authors: MacDonald J. F. , Wojtowicz J. M.
Published: April 2011

Neurones from brain and spinal cord of foetal mice were grown dissociated in monolayer cultures for 4–6 weeks prior to electropharmacological analysis. Neurones were immersed in a Hanks balanced salt solution while drugs and ions were applied by pressure microperfusion during intracellular recordings obtained by conventional techniques. L-Glutamate and its analogues, L-aspartate, DL-homocysteate, N-methyl-D-aspartate, and DL-ibotenate activated two distinct mechanisms of excitation. The primary effect was depolarization accomplished by an apparent decrease of neurone input conductance (Gm). However, in most instances an expected increase in Gm was also observed, especially if membrane potential was reduced by tonic depolarization. Another glutamate analogue, DL-kainate, never decreased Gm and invariably increased Gm at all membrane potentials tested. The decrease of Gm evoked by glutamate and related compounds was strongly dependent upon membrane potential. It was most pronounced at potentials near resting values (−40 to −60 mV) and diminished both with depolarization or hyperpolarization from this range. This apparent decrease favoured the electrogenesis of regenerative potentials that were insensitive to tetrodotoxin. A voltage-dependent increase in sodium and(or) calcium conductance (GNa, GCa) or a decrease in potassium conductance (GK) is suggested to account for this decrease in Gm. Divalent cations (Mg and Co) reduced the depolarizing actions of all amino acids except for those to kainate. The decrease in Gm was more sensitive to Mg than was the increase of Gm. However, the receptor antagonist DL-α-aminoadipate blocked both changes in conductance and responses to all amino acids with the exception of those to kainate. The possible existence of multiple receptors for glutamate is also discussed.
The effect of diazepam on adenosine uptake and adenosine-stimuiated adenylate cyclase in guinea-pig brain
Authors: York M. J. , Davies L. P.
Published: April 2011

We have used the adenosine-stimulated adenylate cyclase of guinea-pig brain to examine the potency of diazepam as an adenosine uptake inhibitor. Diazepam at concentrations in the range 10–500 μM stimulates the production of cAMP in incubated slices of guinea-pig cerebral cortex, with maximal fivefold stimulations over basal levels by 200 μM diazepam. The increases can be largely (but not completely) blocked by the adenosine antagonist theophylline or by addition of excess adenosine deaminase to the system. It appears that the stimulation of cAMP production is due to a blockade of adenosine uptake which results in an increase in extracellular adenosine and concomitant activation of the adenosine receptor coupled to adenylate cyclase. Since the cAMP response to standard adenosine uptake blockers (dipyridamole, dilazep) can be completely blocked by theophylline or adenosine deaminase, a small component of the diazepam response cannot be explained by an adenosine effect. The concentration of diazepam at which the first significant cAMP increase occurs is 10 μM or slightly lower. This is significantly higher than the concentration of diazepam needed to saturate the pharmacologically characterized central nervous system receptors for benzodiazepines.
Analysis of antigen-induced changes in pulmonary mechanics in sensitized inbred rats
Authors: Holroyde M. C. , Smith S. Y. , Holme G.
Published: April 2011

An inbred line of rats was derived which develop marked and consistent dyspnea following sensitization and then exposure to aerosolized antigen. This pulmonary response was investigated in detail by determining forced pulmonary mechanics to derive respiratory rate, peak expiratory flow rate (PEFR), forced vital capacity (FVC), forced expiratory volume in 0.1 s (FEV0.1.), and maximal midexpiratory flow rate (MMFR). Challenging anesthetized rats for 5 min with an aerosol of 3% egg albumin produced minimal change in respiratory rate, a 20% fall in PEFR, a 50% fall in FVC, and a 30% decrease in FEV0.1 and MMFR. The response could be inhibited or reversed by salbutamol (0.5 mg/kg, i.v.) and aminophylline (25 mg/kg, i.v.) administered either before or after challenge. The pulmonary changes are consistent with antigen-induced asthma in the rats. The response shows similarities to human asthma and may provide a relevant experimental model.
Naloxone and morphine inhibit gastric emptying of solids
Authors: Champion M. C. , Sullivan S. N. , Chamberlain M. , Vezina W.
Published: April 2011

Gastric emptying studies were performed on six healthy volunteers using a radioisotope test meal. Each subject was studied three times (control, morphine 7.5 mg, naloxone 2 mg). Both intravenous morphine and intravenous naloxone significantly delayed gastric emptying when compared with the control study. These results suggest that opiate receptors, opiate neurones, and enkephalin may regulate gastric motility and that under certain circumstances naloxone may act as an opiate agonist.
The effect of chronic alloxan- and streptozotocin-induced diabetes on isolated rat heart performance
Authors: Vadlamudi Rao V. S. V. , Rodgers Robert L. , McNeill John H.
Published: April 2011

Cardiac disease is a common secondary complication appearing in chronic diabetics. Isolated perfused working hearts obtained from both acute and chronic diabetic rats have also been shown to exhibit cardiac functional abnormalities when exposed to high work loads. We studied cardiac performance at various time points after induction of diabetes in rats to determine exactly when functional alterations appeared and whether these alterations progressed with the disease state. Female Wistar rats were made diabetic by a single i.v. injection of either alloxan (65 mg/kg) or streptozotocin (STZ 60 mg/kg). Cardiac performance was assessed at 7, 30, 100, 180, 240, and 360 days after induction of diabetes using the isolated perfused working heart technique. No changes were observed in the positive and negative dP/dt development at various atrial filling pressures in the diabetic hearts 7 days after treatment. Alloxan diabetic rat hearts exhibited depressed left ventricular pressure and positive and negative dP/dt development when perfused at high atrial filling pressures, at 30. 100, and 240 days after treatment. STZ diabetic rat hearts exhibited depressed cardiac performance at high atrial filling pressures at 100, 180, and 360 days after treatment, but not at 30 days after treatment. Control hearts exhibited slight but significant depressions in cardiac function with age. These results suggest that cardiac functional alterations appear in diabetic rats about 30 days after induction and progress with the disease. These alterations may indicate the development of a cardiomyopathy.
Perspectives on the central nervous system toxicity of methylmercury
Authors: Racz William J. , Vandewater Laurie J. S.
Published: April 2011

Methylmercury is a widespread and highly toxic environmental pollutant. The source of the substance in the environment is industrial and agricultural use. Chronic methylmercury poisoning is characterized by peripheral and central nervous system damage. The rate of absorption and distribution of this organomercurial into neural tissue determines the rate of development and the severity of the neural lesion. Furthermore, the rate of metabolism and excretion of an organomercurial will greatly influence its neural toxicity. There are differences in the accumulation of methylmercury in different regions of the brain, as well as by the different cell types in these regions. The significance of this variable accumulation of methylmercury is not known. Methylmercury influences a large number of neurocellular functions ranging from inhibition of membrane integrity to alteration in the synthesis and release of transmitter substances.
Reduction by cytoprotective agents of ethanol-induced damage to the rat gastric mucosa: a correlated morphological and physiological study
Authors: Wallace John L. , Morris Gerald P. , Krausse Elisabeth J. , Greaves Susan E.
Published: April 2011

Acute haemorrhagic erosions were produced in chambered gastric mucosae of rats by infusion into the chamber of 40% ethanol (v/v) for 10 min, followed by 50 mM HCl for 1 h. This procedure produced erosions which extended over nearly 70% of the glandular mucosa. When one of 2% ethanol, prostaglandin E2 (75 μg/kg in either 2% ethanol or in aqueous solution), or isoproterenol (50 μg/kg) was placed in the chamber for 10 min prior to infusion of 40% ethanol, the resultant lesions were significantly reduced in area (mean lesion area 25–31% of the glandular mucosa). When compared with the effects of 40% ethanol without pretreatment, there was no consistent correlation between pretreatment with these agents and changes in mucosal potential difference (PD) or net fluxes of Na+ and H+. All of the pretreatment groups did show a reduced loss of Cl+ from the chamber in the final 10-min period of the experiments. Exposure to the "protective" agents did not result in qualitative changes in mucosal structure at either the light or electron microscopic levels. Rather, the ultimate effect of pretreatment was to reduce the extent of deep mucosal vasocongestion. The reduction in lesion area could be directly related to these reductions in vasocongestion and not to any enhanced resistance of the luminal epithelium to the damaging effects of 40%) ethanol.
Calcium-channel antagonist binding to isolated vascular smooth muscle membranes
Authors: Triggle C. R. , Agrawal D. K. , Bolger G. T. , Daniel E. E. , Kwan C. Y. , Luchowski E. M. , Triggle D. J.
Published: April 2011

The binding characteristics of the calcium-channel antagonist nitrendipine, an analog of nifedipine, have been measured in plasma membrane enriched microsomal fractions from the canine thoracic aorta, canine mesenteric artery, and rat mesenteric artery. The dissociation constants, KD, for the high-affinity binding sites were, respectively, 0.308, 0.254, and 0.101 nM and Bmax values for binding capacity were 20.3, 25.0, and 18.0 fmol/mg of microsomal protein. Studies with isolated tissues, in which the sensitivity of the high potassium mechanical response to nitrendipine was determined, indicate that the apparent KD for nitrendipine in the canine mesenteric artery, as reflected by the IC50 (mean inhibition constant) value, is 4.5 – 5.3 nM and for the rat mesenteric artery 2.5 – 6.6 nM.
Chemical sympathectomy and serotonin inhibition reduce monocrotaline-induced right ventricular hypertrophy in rats
Authors: Tucker A. , Bryant S. E. , Frost H. H. , Migally N.
Published: April 2011

Young male rats were administered monocrotaline (40 mg/kg, s.c.) either after chemical sympathectomy with 6-hydroxy-dopamine (6-OHDA, 100 mg/kg), after serotonin synthesis inhibition with p-chlorophenylalanine (PCPA, 500 mg/kg), or after saline injection. Monocrotaline rats exhibited a loss of body weight, marked right ventricular hypertrophy (RVH), increased pulmonary vascular muscularization, but no change in left ventricular weight or hematocrit at 20 days post-monocrotaline. Pretreatment with 6-OHDA or PCPA reduced the degree of RVH; however, neither 6-OHDA nor PCPA pretreatment prevented or reduced the pulmonary vascular muscularization associated with monocrotaline. Control, 6-OHDA-, and PCPA-treated rats exhibited only changes in ventricular weights associated with changes in their body growth. Thus, the sympathetic nervous system and serotonergic mechanisms seem to be involved in the development of monocrotaline-induced right ventricular hypertrophy, but are not responsible for the pulmonary vascular lesion.
The acute hypocalcaemic effect of ethanol and its mechanism of action in the rat
Authors: Krishnamra Nateetip , Limlomwongse Liangchai
Published: April 2011

The hypocalcaemic action of ethanol (3 g/kg body weight) was investigated in intact, thyroparathyroidectomized and antrectomized rats. It was found that ethanol administered either intraperitoneally or orally reduced plasma calcium concentrations within 30 min and that this response lasted for 8 h. Additional studies performed in antrectomized and thyroparathyroidectomized rats indicated that neither gastrin nor the hormones parathormone and calcitonin had any effect on the hypocalcaemic effect of ethanol. Investigation of the mechanism of action of ethanol-induced hypocalcaemia involved measurements of calcium efflux from and influx into the plasma pool. Ethanol did not have any effect on the disappearance from plasma of 45Ca administered intravenously at 0 min. In contrast, ethanol was found to enhance the disappearance of 45Ca administered intraperitoneally 17 h prior to the experiment. The interpretation of 45Ca studies was discussed and it was concluded that ethanol-induced hypocalcaemia resulted from a decrease in calcium influx into the plasma. Additional in vitro studies did not indicate the suppressive action of ethanol on the release of calcium from tibias. In conclusion, our results show that the mechanism of hypocalcaemia caused by ethanol is the suppression of calcium release from some tissue(s) into the plasma.
Diacetylmorphine (heroin) hydrolases in human blood
Authors: Owen J. A. , Nakatsu K.
Published: April 2011

Human blood esterases responsible for diacetylmorphine (DAM, heroin) metabolism were examined by means of an HPLC assay system for DAM, 6-monoacetylmorphine (MAM), and morphine. Four kinetically distinct enzymes capable of hydrolyzing DAM to MAM were observed in the plasma, erythrocyte (RBC) cytosol, and RBC membrane fractions of human blood. Under physiological conditions (pH 7.4, 37 °C), the Km (micromolar) and Vmax (micromolar per minute) values, respectively, for these enzymes were as follows: plasma, 200 and 210; RBC cytosol, 710 and 815; RBC membranes, 2000 and 748, and 38 and 80. For DAM blood concentrations [Formula: see text], RBC associated esterases are responsible for the majority (76%) of DAM hydrolysis in blood.
Physiological and pathophysiological aspects of cardiac prostaglandins
Authors: Karmazyn Morris , Dhalla Naranjan S.
Published: April 2011

It has now been demonstrated that prostaglandins produce a wide variety of actions on cardiac tissue. These effects are quite complex and are dependent on such factors as type of prostaglandin, animal species, experimental format, as well as the amount of prostaglandin employed. The last factor is of particular concern since the administration of large amounts of prostaglandins may not truly reflect the actual actions of the endogenously synthesized prostaglandins which are likely to be at a very low concentration. In this review we have attempted to analyze the pharmacological properties of prostaglandins on cardiac tissue including coronary arteries and myocardium as well as the subcellular basis for their actions. The possible reasons for the diverse effects of prostaglandins under different experimental conditions have been pointed out. An effort has also been made to synthesize the existing information concerning the actions of prostaglandins on heart in terms of current concepts. A discussion is presented concerning the role of endogenously synthesized prostaglandins in physiological and pathological aspects of cardiac performance and the potential use of prostaglandins and prostaglandin synthesis inhibitors in the treatment of heart disease.
Feedback suppression of ACTH secretion by Cortisol in dogs: lags after large signals equal those following very small signals
Authors: Cowan John S. , Layberry Ross A.
Published: April 2011

Previously, low stepwise infusions of Cortisol in resting adrenalectomized dogs (plateaux ≤ 6 μg/dL) were shown to reduce ACTH secretion only after 20 min. In the present study, large, steep-sloped cortisol signals were used to try to evoke faster feedback. Adrenalectomized male mongrel dogs were maintained on exogenous steroids until 48 h before the experiment. Of the 23 experiments on 15 dogs (under light pentobarbital anesthesia), 12 were on resting dogs, 7 on dogs stressed by variable insulin infusion (keeping plasma glucose at 18–40 mg/dL), and 4 stressed as above but with 4 h of low cortisol infusion (plasma [Formula: see text] 5 μg/dL) before applying the feedback signal. After a 50-min control period, a 30-min feedback period was initiated by one of two i.v. cortisol signals: (a) injection of 0.3 mg/kg or (b) infusion of 46 μg kg−1 min−1. Both raised plasma cortisol above physiological limits (within 2 and 6 min, respectively). In each experiment, 23 timed venous blood samples were assayed for plasma ACTH and cortisol. ACTH secretion rates were calculated continuously using a validated single-compartment method. Results from both types of cortisol signals were indistinguishable, and were thus pooled. In the unstressed dogs, control-period ACTH secretion of 0.97 ± 0.12 mU kg−1 min−1 showed no significant decline due to the feedback signal for 20.3 ± 1.4 min. In the stressed dogs the comparable values were 3.18 ± 0.92 mU kg−1 min−1 and 21.9 ± 3.2 min, and in the stressed Cortisol preconditioned dogs 0.78 ± 0.23 mU kg−1 min−1 and 21.0 ± 3.2 min. Thus at rest or in stress, these large cortisol signals evoked no more evidence of fast, rate-sensitive feedback than did very small signals.
Studies of wet-dog shake behavior induced by septohippocampal stimulation in the rat
Authors: Salle G. Le Gal La , Cavalheiro E. A. , Feldblum S. , Maresova D.
Published: April 2011

Stimulation of the septum and the hippocampus were found to elicit a great number of "wet-dog" shakes (WDS). Their occurrence is strongly related to the evocation and to the time course of the afterdischarges elicited by the stimulation. Morphine, apomorphine, diazepam, and antiserotoninergic drugs greatly reduce the incidence of these WDS but do not alter the afterdischarge duration. Based on electroencephalographic and pharmacological data we propose that WDS induced by stimulation of the septohippocampal system may share some common mechanisms with many other models inducing WDS and offer a useful method to study further the neuroanatomical substrate of this behavior.
Renal blood flow in normal dogs and in dogs with experimental liver cirrhosis following the acute continuous infusion of endotoxin
Authors: Levy Mortimer , Liszauer Alan , Wexler Marvin J.
Published: April 2011

The purpose of this study was to determine if the renal circulation of normal and cirrhotic dogs behave similarly in response to an acute endotoxin infusion. Endotoxin was administered as a slow continuous infusion (13–26 μg/min) to a total of 20 normal dogs through the femoral vein, portal vein, or into the left renal artery. In each case, there was an initial increment in renal blood flow, of the order of 46%, while arterial blood pressure was actually declining. After 8–20 min, blood flow fell as perfusion pressure declined further. The initial increment in renal perfusion was not due to a hyperthermic response following the endotoxin. When similar doses were given to five dogs with chronic biliary cirrhosis and ascites, the biphasic response in renal perfusion was not observed, rather blood flow declined as perfusion pressure declined. When normal dogs were infused with bilirubin, bile salts, noradrenaline, and angiotensin in pressor doses, the subsequent infusion of endotoxin still produced the usual biphasic response in renal perfusion. Chronic elevation of portal pressure (but not acute elevation), volume contraction by diuresis or hemorrhage, and the infusion of bile intravenously, all abolished the biphasic response in renal perfusion and reproduced in normal dogs the response to endotoxin observed in cirrhotic dogs. Investigation of the factors causing the initial decrease in intrarenal vascular resistance in normal dogs following the endotoxin infusion implicated a role for histamine, kinins, and prostaglandins. We conclude there is a fundamental difference in the response of the renal circulation of normal and cirrhotic dogs to an endotoxin infusion, which may depend on failure of this latter group to release one or more humoral agents. This difference may be due to elevated portal pressure, a decreased effective arterial blood volume, or the products of bile having access to the circulation in cirrhotic dogs.
Substitution of extracellular sodium ions blocks the voltage-dependent decrease of input conductance evoked by L-aspartate
Authors: MacDonald J. F.
Published: April 2011

The response of cultured spinal cord neurones to L-aspartic acid consists of membrane depolarization accompanied by an apparent voltage-dependent reduction in input conductance (Gm). Depolarizations evoked by this amino acid and the decrease in Gm were reduced or eliminated when cultured spinal cord neurones were superperfused with solutions where Na was substituted with choline or Tris. Responses to L-aspartate recovered rapidly upon return to the control (Na-containing solution). The voltage-dependent component of the response to L-aspartate is dependent upon the presence of external Na.
Effect of experimental diabetes on isolated rat heart responsiveness to isoproterenol
Authors: Vadlamudi Rao V. S. V. , McNeill John H.
Published: April 2011

The isolated perfused working rat heart was used to study experimental diabetes-induced alterations in the sensitivity and responsiveness of the myocardium to the effects of isoproterenol. Experimental diabetes was induced by intravenous administration of either 65 mg/kg alloxan or 60 mg/kg streptozotocin. The positive inotropic and cardiac relaxant effects of isoproterenol were studied at various time points after the induction of diabetes. There were no changes either in the sensitivity or in the maximum responses of diabetic rat hearts to the positive inotropic effect of isoproterenol at any time point studied. However, the cardiac relaxant effect of isoproterenol was depressed in acute as well as chronic diabetic rat hearts when compared with age-matched controls. Ventricular noradrenaline content was unchanged in 180-day diabetic rat hearts indicating the absence of a diabetes-induced sympathetic neuropathy in the heart. The depressed relaxing effect of isoproterenol may have resulted from alterations in energy utilization and sarcoplasmic reticular function in diabetic rat hearts.
Effects of bile and bile salt infusions on renal function in dogs
Authors: Finestone Hillel , Fechner Christine , Levy Mortimer
Published: April 2011

A previous study in dogs indicated that 4 h of acute biliary obstruction was associated with an increment in the glomerular filtration rate (GFR), renal perfusion, and urinary sodium excretion. These effects could also be transmitted to a "recipient" dog following 2 h of cross circulation. In this study we examined the possible role of bile and bile products in reproducing these effects. The i.v. infusion of 15 mL of undiluted gallbladder bile produced a marked diuresis and natriuresis, while arterial pressure and GFR declined. Bile diluted as much as 1/100 in isotonic saline could produce an effect when infused intravenously. When bile diluted to 1/250 was infused into the left renal artery at 0.5 mL/min, a diuretic and natriuretic response was obtained. GFR and renal blood flow declined with more concentrated solutions, though blood pressure remained normal. Dialysis of bile, or prior incubation with cholestyramine or plasma, failed to uncover a renal vasodilator effect. Following the first two procedures, the diuretic properties of infused bile were lost. The infusion of small amounts of synthetic bile salts (taurocholate or glycocholate) into the left renal artery caused marked increments in urinary sodium excretion without any change in renal hemodynamics. The infusion of bilirubin was without effect on renal function. Taurine and glycine, the amino acids present in the conjugated bile acids, were injected i.v. Both caused marked diuresis and natriuresis, but only glycine increased GFR and renal perfusion. The plasma levels of these substances, however, were unchanged following 4 h of acute biliary obstruction. We conclude that while bile salts probably cause the diuresis of biliary obstruction, the mechanism for the increase in GFR has not yet been identified.
Plasma glucose and insulin responses in growing rats fed a total parenteral nutrition diet either intravenously or intragastrically
Authors: Track Norman S. , Cutz Ernest , Witt Barbara H.
Published: April 2011

The effect of administering either intravenously (group I) or intragastrically (group II) a glucose – amino acid total parenteral nutrition diet over a 12-day period upon plasma glucose and insulin responses was examined in adolescent rats. Infusion of the 25% glucose – 12.2% amino acid diet at a rate of 300 kCal∙kg body weight−1∙24 h−1 supported normal weight gain over the 12-day study period in both intravenously (group I) and intragastrically (group II) alimented rats. Mean plasma glucose levels rose dramatically in both groups by the end of day 1; group I had significantly higher mean plasma insulin levels. By day 3, the group I mean plasma glucose value decreased significantly while the group II mean glucose value remained virtually unchanged. Mean plasma insulin values more than doubled in both groups with the group I level still remaining significantly above the group II level. At days 6 and 12, group I mean plasma glucose levels were significantly below group II while both groups had similar plasma insulin levels. Data from this 12-day intravenous–intragastric alimentation study reveals quite different metabolic responses compared with acute (120–180 min) studies of the enteroinsular axis.
Dietary tyrosine supplementation enhances weight gain in streptozotocin-diabetic rats
Authors: Glanville N. Theresa , Anderson G. Harvey
Published: April 2011

The effect of dietary protein concentration and tyrosine supplementation on growth in streptozotocin (65 mg/kg, ip) diabetic rats was evaluated. When rats were fed diets ranging from 15 to 60% protein, weight gain and feed efficiency were greatest in rats fed the 45% protein diet. Adding tyrosine to this diet (8%, incorporated as a percentage of protein) did not promote further weight gain relative to nonsupplemented diabetic animals. In contrast, rats choosing 45% of total calories as protein by selecting from 10 and 60% protein diets supplemented with either 0, 4, or 8% tyrosine demonstrated a 35% (4% tyrosine) to 45% (8% tyrosine) increase in weight gain. Proximate analysis indicated similar body composition in tyrosine supplemented and nonsupplemented diabetic animals. Including tryptophan (1.45%) with tyrosine in the self-selection diet was without effect. Thus, tyrosine supplementation promoted a modest but consistent and specific increase in weight gained by self-selecting diabetic rats.
Potentiation of in vivo thermogenesis in rat brown adipose tissue by stimulation of α1-adrenoreceptors is associated with increased release of cyclic AMP
Authors: Ma Stephanie W. Y. , Foster David O.
Published: April 2011

Release of cyclic AMP (cAMP) from the interscapular brown adipose tissue (IBAT) of barbital-anesthetized, cold-acclimated rats given activators and inhibitors of brown adipose tissue (BAT) thermogenesis was assessed by measuring IBAT blood flow (microsphere method) and the arteriovenous difference in plasma cAMP across the tissue. The release was taken as an index of the generation of cAMP in the IBAT. During thermogenesis induced by infusion of graded doses of noradrenaline (NA), release of cAMP increased from no significant release without NA to 68 pmol/min at a NA dose that effected maximal thermogenesis. The α-adrenoreceptor antagonist dihydroergotoxin inhibited NA-induced BAT thermogenesis and markedly reduced the release of cAMP. The α1-adrenoreceptor agonist phenylephrine potentiated the in vivo thermogenic response of BAT to isoproterenol or to a suboptimal dose of NA and enhanced the release of cAMP elicited by these catecholamines. But given alone, phenylephrine or dihydroergotoxin had very little or no effect on thermogenesis and cAMP release. These results suggest that stimulation of the α1-adrenoreceptors on BAT adipocytes potentiates the thermogenic response originating from stimulation of the adenylate cyclase-coupled β1-adrenoreceptors by increasing, in some indirect way, the generation of cAMP, the intracellular messenger for activation of thermogenesis. However, in the absence of proof that adipocytes are the principal source of the cAMP released from IBAT, during catecholamine-induced thermogenesis, this explanation for the effect of α1-adrenoreceptor stimulation on thermogenesis remains tentative.
Toxic effects of acid rain on aquatic and terrestrial ecosystems
Authors: Rutherford G. K.
Published: April 2011

The historical perspective as well as the nature and causes of acid precipitation are presented. The toxicological effects of acid precipitation on lakes, other water bodies, fish, and invertebrate fauna are reviewed. In addition, the effects of this phenomenon on soil productivity and forest growth are examined. It appears that grave toxic effects have been and are being experienced by aquatic systems, but there is little reliable evidence of economic damage to crops, natural vegetation, and soil and biological processes. There may be insidious long-term effects on terrestrial ecosystems, particularly in the more susceptible areas.
Estimation of dermal exposure to pesticides and its use in risk assessment
Authors: Franklin C. A.
Published: April 2011

The potential risks to humans resulting from the usage of a pesticide must be carefully assessed before the product is registered. One of the components in the risk assessment is the determination of the amount of pesticide to which the applicator is exposed. Traditional methods estimated dermal exposure by measuring the amount of pesticide deposited on absorbent patches worn on the applicator's body. A more recent approach consists of measuring urinary metabolite levels. A review of data obtained in humans and in rats suggests that the urinary concentration of dimethyl thiophosphate is a good indicator of dermal exposure to azinphos-methyl.
Effects of tetrodotoxin-induced disuse on properties of developing rat gastrocnemius muscle
Authors: Lapointe M. A. , Gardiner P. F.
Published: April 2011

Our goal was to determine the influence of a complete lack of neuromuscular activity, during a period of rapid muscle growth, on muscle morphology and contractile function. Rats, 21 days old, had one hindlimb paralyzed for a period of 7–9 consecutive days by repetitive implantation of a silastic cuff containing tetrodotoxin (TTX), a specific nerve impulse conduction blocker, around the sciatic nerve. In situ isometric contractile properties of gastrocnemius were measured at 31 days of age, and muscles were subsequently examined histologically. Normal growth during this period resulted in a two- to three-fold increase in muscle weights, mean muscle fiber cross-sectional areas and increases in absolute twitch and tetanic tensions. After inactivity from 21 to 30 days of age, gastrocnemius muscles were smaller, and tetanically weaker, than age-matched controls. The normal cross-sectional area increase of fast-twitch fibers was preferentially affected. Inactive muscles also demonstrated significantly slower twitch responses, had higher twitch: tetanus ratios and relative tensions at 25 Hz than age-matched controls, suggesting a "slower" contractile response. On the other hand, maximum rate of tetanic tension development was elevated. These effects of inactivity appeared to be reversed by resumption of normal activity for 4 days. Neuromuscular inactivity during a relatively short period of rapid muscle growth causes significant muscle morphological and contractile changes, which are most likely reversible.
Effect of glucocorticoids on testosterone production by porcine Leydig cells in primary culture
Authors: Bernier M. , Gibb W. , Collu R. , Ducharme J. R.
Published: April 2011

For this study, purified immature porcine Leydig cells in primary culture were used. After 2 days of culture, the cells were incubated with dexamethasone (5 × 10−9, 1 × 10−7 M) for various periods of time (3–45 h). The media were discarded and treatment was repeated with or without the addition of human chorionic gonadotropin (HCG, 10 mIU/mL) for 3 h. Dexamethasone (10−7 M) decreased testosterone production of HCG-treated cells (up to 40%) in a time-dependent fashion while the lower dose was ineffective. The effect of varying doses (10−8 and 10−6 M) of natural glucocorticoids (corticosterone, cortisol) or synthetic glucocorticoids (triamcinolone, triamcinolone acetonide, betamethasone, dexamethasone) and that of a synthetic progestin (R-5020) on cultured Leydig cells was also studied. After 18 h of preincubation, the various synthetic but not the natural steroids nor R-5020, were able to decrease testosterone production of control and HCG-treated cells by 20–40%. Of a number of other hormonal and nonhormonal substances studied at concentrations of 10−9 – 10−5 M, only lysine8-vasopressin at a concentration of 10−6 M was able to inhibit testosterone production by these cells. These results indicate that dexamethasone and other synthetic glucocorticoids, and to a lesser degree lysine8-vasopressin, may exert a direct inhibitory effect on testosterone production by purified porcine immature Leydig cells in vitro.
Effect of disulphonic stilbenes on Ca2+ transport in smooth muscle plasma membranes
Authors: Rangachari P. K. , Grover A. K. , Daniel E. E.
Published: April 2011

We studied the effects of two disulphonic stilbenes, 4′,4′-diisothiocyano-2,2′-stilbene disulphonic acid (DIDS) and 4-acetamido-4′-isothiocyano-2,2′-stilbene disulphonic acid (SITS), on Ca2+ transport by plasma membrane vesicles from the circular muscle of the dog stomach. Both compounds inhibited ATP-dependent Ca2+ uptake and reduce the leak from loaded vesicles. The inhibition produced could not be significantly reduced by either permeant anions or by increasing the level of free Ca2+. The effects of DIDS could be rendered irreversible by incubating the membranes with this agent at 37 °C.
Lipogenesis and lipoprotein lipase in human adipose tissue: reproducibility of measurements and relationships with fat cell size
Authors: Savard Roland , Deshaies Yves , Després Jean-Pierre , Marcotte Martine , Bukowiecki Ludwik , Allard Claude , Bouchard Claude
Published: April 2011

Lipogenesis from glucose and lipoprotein lipase activity were investigated in humans. The reliability of measurements was quantified and correlations with fat cell weight were assessed. Twenty-four subjects (7 women, 17 men) were studied twice within a 2-week period, along with 17 additional male subjects who were studied once and used only in the correlation analyses. All subjects were not regularly involved in an exercise-training program and were between 18 and 30 years of age. Following an overnight fast, adipose tissue specimens were obtained by suprailiac biopsy and fat cells were collagenase isolated. Mean fat cell weight was obtained from 400 to 500 cell diameter determinations per subject. Basal and insulin-stimulated fat cell lipogenesis from glucose were determined using D-[U-14C]glucose and were reported in nanomoles of glucose per hour per 106 cells. Adipose tissue heparin-releasable lipoprotein lipase activity was also determined and expressed in micromoles of free fatty acids per hour per gram of tissue and per 106 cells. Fat cell weight, basal and insulin-stimulated lipogenesis and lipoprotein lipase activity per gram showed high reliability of measurement, interclass and intraclass coefficients being 0.83 and over. Lipoprotein lipase activity per 106 cells showed a somewhat lower degree of reliability, interclass and intraclass coefficients being, respectively, 0.69 and 0.81. On the other hand, fat cell weight was positively correlated with lipoprotein lipase activity (r = 0.80), while no significant correlation was observed between basal lipogenesis and fat cell weight. Moreover, basal lipogenesis presented no significant correlation with lipoprotein lipase activity. These results suggest that, under standardized conditions, and from a single tissue sample, human adipose tissue lipoprotein lipase activity and fat cell lipogenesis can be measured with a satisfactory level of reliability. They also suggest that lipoprotein lipase activity is highly related with adipocyte lipid content.
Evidence for oxytocin receptors in the urinary bladder of the rabbit
Authors: Romine Mary T. , Anderson Gordon F.
Published: April 2011

Experiments were performed on isolated detrusor smooth muscle from New Zealand White rabbits. Oxytocin was shown to exhibit high intrinsic contractile activity on isolated strips of detrusor muscle, where the maximum contractile amplitude was 12% greater than control responses to 1 μM carbachol. Repeated applications of 1 μM oxytocin were associated with tachyphylaxis representing a 49% decrease in the amplitude which became reproducible after several applications without further decay of contractile strength. Dose–response experiments indicated that threshold contractions to oxytocin occur at 3 μM and were maximum at 10 μM with mean effective concentration of 125 μM. The contractile responses to 1 μM oxytocin were not antagonized by phentolamine, atropine, methysergide, saralasin, or naloxone, but were partially inhibited by 1 μM of indomethacin. Ligand binding studies on partially purified membrane preparations from detrusor smooth muscle were performed over a range of 78 pM to 10 nM with 125I-labelled oxytocin. Scatchard analysis of specific bound receptors indicated a KD of 2.5 nM and Bmax of 187 fmol/mg protein and a second compartment that was unsaturable at the concentrations of ligand employed. Nonspecific binding ranged from 36 to 77% of the total binding.
Primary versus secondary structural changes of the blood vessels in hypertension
Authors: Lee Robert M. K. W. , Smeda John S.
Published: April 2011

Various researchers have hypothesized that the thickening of the vascular wall plays an important role in the maintenance of hypertension. Such an alteration can increase the vascular resistance by exerting two effects. A thickened vascular wall could occlude the lumen of the blood vessel and (or) cause the artery to hyperreact to contractile stimuli. Until recently, it has been a general conclusion that such alterations were a secondary adaptation produced by the elevation of blood pressure. Consistent with this view, certain classes of larger arteries do exhibit a thickened vascular wall late during hypertension development and such changes can be prevented from occurring by antihypertensive treatment. However, recent studies involving the mesenteric and renal arteries of Wistar-Kyoto spontaneously hypertensive rats have shown that wall thickening of the vasculature occurs prior to hypertension development and is present even under conditions where the blood pressure has been normalized throughout the animal's life. These latter observations suggest that some structural alterations in the blood vessels observed in hypertension are pressure independent and could be of etiological importance in the initiation of hypertension.
Role of carnitine during development
Authors: Borum Peggy R.
Published: April 2011

Fatty acids are an important fuel source for neonates. The utilization of long chain fatty acids as a fuel source is dependent upon adequate concentrations of carnitine. Carnitine also has functions in other physiological processes critical to the survival of the neonate such as lipolysis, thermogenesis, ketogenesis, and possibly regulation of certain aspects of nitrogen metabolism. Plasma and tissue carnitine concentrations in neonates are depressed compared with those of older individuals. The capability for carnitine biosynthesis is much less in the neonate than in the adult. Human milk contains carnitine and appears to be the major source of carnitine to meet the neonate's metabolic needs. However, total parenteral nutrition solutions and soy-based infant formulas contain no carnitine. Evidence is accumulating that all infant diets may need to supply carnitine to meet the neonate's metabolic needs.
The binding of [3H]mepyramine to histamine H1 receptors in monkey brain
Authors: Bielkiewicz B. , Cook D. A.
Published: April 2011

Several laboratories have reported ligand binding studies using radioactive histamine H1 antagonists to label the H1 receptors in mammalian brain. We have extended these studies to a detailed examination of the binding of [3H]mepyramine to monkey brain and have shown that the distribution is similar to that in man, with specific binding sites being concentrated in the frontal cortex with relatively low binding to the pons and basal ganglia. The binding shows a single saturable component with a KD of about 1 nM and a Hill plot slope close to unity. These observations are the same for all structures tested. Comparison with data from other laboratories suggests that in this species, the histamine receptor is the same as that in peripheral tissues. From Ki values for various ligands and comparison of KD estimates in other species, the receptor seems to be essentially identical to the H1 receptor in central and peripheral tissues of the guinea pig and also to that in human brain. The rat and possibly the dog have minor differences from the monkey in terms of KD values for [3H]mepyramine binding.
Physical, chemical, and physiological characteristics of isolates of pulmonary surfactant from adult rabbits
Authors: Keough K. M. W. , Farrell E. , Cox M. , Harrell G. , Taeusch Jr. H. W.
Published: April 2011

Physical and chemical characteristics of two types of preparations of surface active material from adult rabbits were determined. A procedure using multiple centrifugations produced a surface active material (type A) which had 6.6% by weight protein and a phosphorus/protein ratio of 13.1 nmol P/μg protein. A simpler protocol involving two centrifugations yielded a surface active material (type B) with more protein (10.8%) and a lower phosphorus/protein ratio (8.4 nmol/μg). Lipid compositions of both types were similar with phosphatidylcholine being the major phospholipid (80%) and palmitate the major fatty acid in the total lipid (65–71%) and in phosphatidylcholine (80%). Both types exhibited broad thermotropic phase transitions encompassing 37 °C. Measurements of aqueous dispersions of surface active material on the surface of a Langmuir–Wilhelmy balance or in a pulsating bubble apparatus indicated that there was variability both between types and between batches of the same type in the capacity to reach low surface tension on the surface balance and in the rates at which low surface tension was achieved on the bubble apparatus. Type A preparations were somewhat more reliable in meeting these ends than were type B. Both types of isolates were effective in normalizing pressure–volume characteristics when instilled into the lungs of immature rabbit fetuses.
Effects of manganese chloride on the outward currents in frog atrial trabeculae
Authors: Alvarez Julio L. , Garcia Miguel , Dorticós Francisco R. , Morlans Jesús A.
Published: April 2011

The effects of MnCl2 on outward currents in frog atrial muscle were investigated under voltage-clamp conditions. MnCl2 (3 mmol/L), which completely abolished the slow inward current, produced a decrease in the outward background current (Ib) at potentials positive to −50 mV. The delayed outward current (Ix, time dependent) was not altered by Mn. "Isochronic activation curves" for Ix and decay of current tails at −40 mV remained unaffected after Mn. Effects on Ib probably reflect a decrease in [Formula: see text] related to the decrease in Ca influx as well as a reduction in the Na–Ca exchange current.
On the metabolism of amygdalin. 2. The distribution of β-glucosidase activity and orally administered amygdalin in rats
Authors: Adewusi S. R. A. , Oke O. L.
Published: April 2011

The organs of 15-day-old rats had the highest capability to hydrolyze amygdalin and prunasin, and most of this activity is concentrated in the tissues of the small and large intestines. The activity decreased with age. In adult rats, the ability of the organs to hydrolyze prunasin is higher than that of amygdalin and is concentrated in the spleen, large intestine, and kidney (35.0, 15.0, and 8.9 μg prunasin hydrolyzed∙h−1∙g tissue−1). Minced tissues of the liver, spleen, kidney, and stomach contain more hydrolytic capability than the homogenate of these organs, while the reverse is the case with the small and large intestines. When 30 mg amygdalin was orally administered to adult rats, its distribution after the 1st h was as follows: stomach (0.89 mg), small intestine (0.78 mg), spleen (0.36 mg), large intestine (0.30 mg), kidney (0.19 mg), liver (0.10 mg), and serum (5.6 μg/mL). At the end of the 2nd h, the highest amygdalin content was found in the large intestine (0.79 mg).
The in vitro metabolism of benzo[a]pyrene by polychlorinated and polybrominated biphenyl induced rat hepatic microsomal monooxygenases
Authors: Haake J. M. , Merrill J. C. , Safe S.
Published: April 2011

The metabolism of benzo[a]pyrene by halogenated biphenyl-induced rat hepatic microsomal monooxygenases was determined using a high pressure liquid chromatographic assay system. Incubation of benzo[a]pyrene with microsomes from rats pretreated with phenobarbitone or phenobarbitone-type inducers (2,2′,4,4′,5,5′-hexachlorobiphenyl, 2,2′,4,4′,6,6′-hexachlorobiphenyl, 2,2′,5,5′-tetrachlorobiphenyl, 2,2′,4,4′,5,5′-hexabromobiphenyl, and 2,2′,5,5′-tetrabromobiphenyl) resulted in increased overall metabolism of the hydrocarbon (less than fourfold) into phenolic, quinone, and diol metabolites, with the most striking increase observed in the formation of 4,5-dihydro-4,5-dihydroxybenzo[a]pyrene. In contrast, the metabolism of benzo[a]pyrene by microsomes from rats induced with 3-methylcholanthrene or 3,3′,4,4′-tetrachlorobiphenyl resulted in a >10-fold increase in overall benzo[a]pyrene metabolism, with the largest increases observed in the formation of the trans-7,8-and -9,10-dihydrodiol metabolites of benzo[a]pyrene. However, in comparison to control and phenobarbitone-induced microsomes, the oxidative conversion of benzo[a]pyrene by microsomes induced with 3-methylcholanthrene and 3,3′,4,4′-tetrachlorobiphenyl into the 6,12-quinone was substantially inhibited. Previous reports have shown that the commercial halogenated biphenyl mixtures, fireMaster BP-6, and Aroclor 1254 are mixed-type inducers and that microsomes from rats pretreated with these mixtures markedly enhance the overall metabolism of benzo[a]pyrene. Not surprisingly, the metabolism of benzo[a]pyrene by microsomes from rats pretreated with the mixed-type inducers, 2,3,3′,4,4′-penta-, 2,3,3′,4,4′,5-hexa-, and 2′,3,3′,4,4′,5-hexa- chlorobiphenyl was also increased and the metabolic profile was similar to that observed with fireMaster BP-6 and Aroclor 1254 induced microsomes.