bluuebunny/crossref_metadata_2025 huggingface dataset:
Halogenated biphenyls: molecular toxicology
Authors: Safe S. , Robertson L. W. , Safe L. , Parkinson A. , Bandiera S. , Sawyer T. , Campbell M. A.
Published: April 2011

The biologic and toxic effects of polychlorinated biphenyls (PCBs) are remarkably dependent on their structure. The most toxic PCBs, namely 3,3′,4,4′-tetra-, 3,3′,4,4′,5-penta- and 3,3′,4,4′,5,5′-hexachlorobiphenyl are substituted in at least one meta and para position on both phenyl rings (i.e., the lateral positions) and contain no ortho-chloro substituents. These three congeners and a fourth PCB, namely 3,4,4′,5-tetrachlorobiphenyl, are approximate isostereomers of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and, in common with TCDD, induce hepatic microsomal benzo[a]pyrene or aryl hydrocarbon hydroxylase (AHH) in rats and rat hepatoma cells in culture. The mono-ortho substituted analogs of the four laterally substituted PCBs also induce microsomal AHH activity and simultaneously enhance microsomal enzyme activities which are inducible by phenobarbitone (PB). This group of PCBs exhibits many of the properties of 2,3,7,8-TCDD and related polychlorinated dibenzo-p-dioxins; there is a close parallel in the relative potencies of these PCBs for AHH induction and their binding affinities for the Ah receptor protein and some of these PCBs are also toxic. Preliminary studies on other halogenated biphenyls confirm that the polarizability of a lateral substituent is an important factor in their activity as AHH inducers (i.e., I > Br > Cl > F). However, preliminary results with other substituted halogenated biphenyls suggest that additional structural factors are also important in determining the activity of these compounds.
Effect of hypercalcemia on renal tubular handling of calcium and magnesium
Authors: Quamme Gary A.
Published: April 2011

Tubular calcium and magnesium transport was investigated in thyroparathyroidectomized rats following acute elevation of extracellular calcium concentration. Fractional urinary excretion of calcium increased from 0.2 to 8.3% and magnesium increased from 15 to 39%, while sodium increased modestly from 0.1 to 1.1%. Superficial proximal tubules, Henle's loop, and distal tubules were perfused in vivo to determine the segmental effects of hypercalcemia. Fractional calcium absorption within the loop of Henle was significantly less in the hypercalcemie rats (58%) compared with normal animals (86%). Magnesium transport was inhibited to a greater extent compared with calcium in the loop as the fractional reabsorption decreased from 78% in the normal rats to 35% in the hypercalcemie animals. Sodium absorption was inhibited by 8%. Absolute calcium and magnesium absorption within the superficial distal convoluted tubule increased about three- to four-fold with increased delivery to this segment. These data indicate that hypercalcemia inhibits calcium and magnesium transport relatively more than sodium absorption in the loop of Henle and that this action principally accounts for the increase in urinary excretion of these electrolytes.
Factors which affect DNA strand breakage in human leukocytes exposed to a tumor promoter, phorbol myristate acetate
Authors: Birnboim H. C.
Published: April 2011

We have recently reported that phorbol myristate acetate (PMA) induces extensive DNA strand break damage in human peripheral blood leukocytes. The mechanism of action involves superoxide anion and hydrogen peroxide which are generated by phagocytes during the "respiratory burst." In this report, we describe the effect of various inhibitors and scavengers on PMA-induced DNA damage. Azide and cyanide greatly increased the level of damage; sulfhydryl compounds (glutathione, cysteine, and cysteamine) and ascorbate markedly decreased the level of damage. Hydroxyl radical scavengers such as dimethyl sulfoxide (DMSO) and glycerol also decreased the level of damage but apparently did so by inhibiting the respiratory burst. Diethyldithiocarbamate (DDC) increased the level of DNA damage at low concentrations (<1 mM), but decreased DNA damage at ≥1 mM. The results are consistent with a mechanism involving superoxide anion and hydrogen peroxide, but the precise reaction (free radical or enzymatic) responsible for DNA strand breakage has not been determined. The PMA-stimulated phagocyte is an interesting model system for looking at "active oxygen" mediated DNA damage and factors which influence it.
Role of superoxide anion radicals in microvascular permeability and leukocyte behaviour
Authors: Maestro R. F. Del
Published: April 2011

Inflammation is associated with the accumulation and activation of phagocytic cells, such as polymorphonuclear leukocytes, and with the subsequent release and generation of a group of activated oxygen species, some of which are free radicals. These studies were carried out to assess the influence of enzymatically generated free radicals on both microvascular permeability and leukocyte adhesion. The extravasation of fluorescein-labelled dextran mean molecular weight [Formula: see text] 150 000 was used to assess microvascular permeability and methodology was developed to measure in vivo leukocyte endothelial interactions. Enzymatically generated superoxide anion radical [Formula: see text] was associated with an increase in macromolecular extravasation (seen primarily from postcapillary venules) and an increase in leukocyte adhesion. Macromolecular extravasation was found to be dependent on the generation of a hydroxyl radical related interaction while leukocyte adhesion was dependent on the presence of [Formula: see text]. It is suggested that the permeability alterations and increased polymorphonuclear leukocyte adhesion seen during inflammation may be partially related to the release of free radicals from inflammatory cells.
Further studies on free-radical pathology in the major central nervous system disorders: effect of very high doses of methylprednisolone on the functional outcome, morphology, and chemistry of experimental spinal cord impact injury
Authors: Demopoulos H. B. , Flamm E. S. , Seligman M. L. , Pietronigro D. D. , Tomasula J. , DeCrescito V.
Published: April 2011

The hypothesis that pathologic free-radical reactions are initiated and catalyzed in the major central nervous system (CNS) disorders has been further supported by the current acute spinal cord injury work that has demonstrated the appearance of specific, cholesterol free-radical oxidation products. The significance of these products is suggested by the fact that: (i) they increase with time after injury; (ii) their production is curtailed with a steroidal antioxidant; (iii) high antioxidant doses of the steroidal antioxidant which curtail the development of free-radical product prevent tissue degeneration and permit functional restoration. The role of pathologic free-radical reactions is also inferred from the loss of ascorbic acid, a principal CNS antioxidant, and of extractable cholesterol. These losses are also prevented by the steroidal antioxidant. This model system is among others in the CNS which offer distinctive opportunities to study, in vivo, the onset and progression of membrane damaging free-radical reactions within well-defined parameters of time, extent of tissue injury, correlation with changes in membrane enzymes, and correlation with readily measurable in vivo functions.
A quantitative analysis of renal ammoniagenesis and energy balance: a theoretical approach
Authors: Halperin Mitchell L. , Jungas Robert L. , Pichette Carole , Goldstein Marc B.
Published: April 2011

Many theories have been proposed to explain the regulation of renal ammoniagenesis during chronic metabolic acidosis but none of these is entirely satisfactory. Since the activity of each of the enzymes in this pathway greatly exceeds the maximum rate of ammonium production in vivo, even when physiological substrate concentrations are used in this calculation, it follows that ammoniagenesis must be inhibited in the intact animal. We shall present a novel hypothesis for the regulation of the maximum rate of ammoniagenesis which emphasizes the fact that ATP is a product of this pathway and that a limited rate of ATP utilization could control its maximum velocity during chronic metabolic acidosis. To test the validity of our hypothesis, a quantitative analysis of the pathways of ATP production and utilization in the kidney will be reviewed. This approach is similar to one already proposed for the regulation of the maximum rate of ketogenesis in the liver.
Protein deficiency and endogenous pyrogen fever
Authors: Hoffman-Goetz L.
Published: April 2011

Blood monocytes have been shown to be a major source of endogenous pyrogen (EP), the protein mediator of fever. This study describes the effects of chronic dietary protein deficiency in rabbits on the in vitro production of EP by monocytes, the time course for the dietary effects on EP production, and the possible role for serum factors in the modification of EP production and (or) development of fever. EP harvested from rabbits on a protein-free diet for 4 weeks induced normal fevers when injected i.v. into recipient animals; EP produced from the protein-deprived rabbits after 6 and 8 weeks did not elicit fevers when bioassayed. Injection of EP supernatants derived from protein-deprived rabbits and containing standard protein serum resulted in less aberrant temperature responses than injection of EP supernatants containing sera from protein-deprived rabbits. These results suggest that: (i) the production of EP by rabbit blood monocytes is sensitive to dietary protein status, (ii) the effect of protein deficiency on EP production is a threshold phenomenon, and (iii) factors present in sera of protein-deprived rabbits may modify EP-induced fever.
Carotid sinus baroreceptor effects on cat livers in control and hemorrhaged states
Authors: Lautt W. Wayne
Published: April 2011

Hepatic blood volume, glucose output, and arterial conductance changes were measured in cats in response to unloading carotid sinus baroreceptors using carotid arterial occlusion or perfusion of carotid arteries in situ. Changes in all three parameters are known to be elicited by direct stimulation of the hepatic sympathetic nerves. The baroreflex did not activate glycogen breakdown, whereas nerve stimulation and hemorrhage did, indicating that not only were hepatic nerves not reflexly activated but glucagon and adrenaline levels in plasma were not significantly elevated. Hemorrhage with carotid pressure held constant produced hyperglycemia within a normal range. Hepatic blood volume responses to hemorrhage and to noradrenaline were normal but carotid baroreflexes caused no blood volume response with the vagus cut or intact and with the adrenals intact. The blood volume response to hemorrhage and to reinfusion of blood were normal when the carotid blood pressure was held steady. Hepatic arterial constriction did occur but was sufficient to exactly offset the rise in blood pressure so that blood flow remained unaltered.
The effects of imidazole-4-acetic acid on cerebral carbohydrate metaboifsm
Authors: Bovell M. , Chung T. , MacMillan V. , Shankaran R.
Published: April 2011

The effects of intravenous administration of 50–400 mg/kg imidazole-4-acetic acid (IMA) on the carbohydrate metabolism of the rat brain were assessed by measurement of the cerebral hemisphere contents of energy phosphates and glycolytic – citric acid cycle metabolites. IMA (100–400 mg/kg) produced a spectrum of electroencephalographic (EEG) change ranging from desynchronization to electrical suppression which was associated with unchanged tissue contents of ATP, ADP, and AMP, increasing levels of phosphocreatine, glucose, and aspartate, and decreasing levels of pyruvate, lactate, α-ketoglutaratc, and malate. The changes in glycolytic intermediates were present within 5 min of injecting IMA (200 mg/kg) and the pattern suggested a suppression of glycolysis. The EEG stage of electrical suppression with episodic spiking (400 mg/kg) was associated with a 30% reduction of cortical high-energy phosphate use. The lowest dose of IMA (50 mg/kg) resulted in episodic EEG desynchronization which was associated with no significant changes of the measured metabolites. The results indicate that IMA is associated with metabolite changes that are compatible with a state of cerebral depression and that the desynchronous EEG pattern is without a biochemical con-elate of increased neuronal activity.
Control hof the hyperglycemic response to hemorrhage in cats
Authors: Lautt W. Wayne , Dwan Peter D. , Singh Rajiva R.
Published: April 2011

Rapid hemorrhage to 50 mmHg (1 mmHg = 133.322 Pa) mean arterial blood pressure led to a rise in blood glucose levels that reached a level of 500 mg% by 15 min and was then maintained with minor decreases for the full period of hemorrhage (90 min). From changes in hepatic glycogen levels it is estimated that glucose from 3.1 g of glycogen was released per kilogram of body weight over the 90-min period of hemorrhage. Bilateral adrenalectomy or hepatic denervation did not reduce the hyperglycemic response significantly although adrenalectomy tended to produce a lesser response. Removal of the adrenals and the hepatic nerves (surgically or selective hepatic sympathectomy using 6-hydroxydopamine) eliminated all but a very small hyperglycemic response which was of slow onset. Thus, the hyperglycemic response to hemorrhage is controlled by a redundant control system wherein either the adrenals or the hepatic sympathetic nerves can produce the response but elimination of both systems eliminates the response. The minor hyperglycemia that occurred with both systems eliminated shows that other hormonal changes known to occur during hemorrhage play, at most, a minor role in the direct stimulation of glycogenosis during hemorrhage.
Effects of epinephrine, clonidine, L-phenylephrine, and morphine on intestinal secretion mediated by Escherichia coli heat-stable enterotoxin in pig jejunum
Authors: Ahrens Franklin A. , Zhu Bei Lei
Published: April 2011

Perfusion of pig jejunum with Escherichia coli heat-stable enterotoxin (strain 1261) reversed net absorption of water and electrolytes to net secretion. Addition of the α-adrenergic agonists clonidine (5 × 10−7 M) or L-phenylephrine (5 × 10−6 M), or the opiate agonist morphine (3.6 × 10−6 M) to the perfusate reduced the secretory response to enterotoxin and stimulated absorption in normal jejunum. Epinephrine (5 × 10−5 M) did not stimulate absorption in controls but reduced chloride loss in the presence of enterotoxin. Mucosal sodium – potassium adenosine triphosphatase was unchanged but disaccharidase activity was decreased in the presence of enterotoxin. The results suggest that α-adrenergic agonists and opiate agonists may exert an antidiarrheal action by increasing net transport across intestinal epithelium.
Evidence for an extracellular mechanism for the action of H+ on recovery of muscles following fatigue
Authors: Mainwood G. W. , Alward M.
Published: April 2011

Isolated rat diaphragm strips were fatigued by repetitive trains of tetanic stimulation for 3 min. Maximum isometric tension fell to approximately 20% of the normal level. Tension recovered to the prefatigue level a few minutes after the fatiguing stimulation stopped. In normal, bicarbonate-buffered Tyrode solution at pH 7.4, the half recovery time (t1/2) is typically 1 – 2 min. This is not significantly changed by presoaking in Tyrode at low pH (6.2), amiloride (10−4 M), which blocks H+−Na+ exchange, 4-acetamido-4′-isothiocyanostilbene-2,2′-disulphonic acid (10−4 M), which blocks HCO3− −Cl− exchange, or a combination of these treatments. When the extracellular pH is low (pH 6.2) during recovery the recovery rate falls to approximately 10% of its normal level (t1/2 = 15 min). In the absence of external bicarbonate, using morpholinopropanesulfonic acid buffers, recovery can still be rapid (t1/2 = 2.6 min) if the pH is high but is very slow (t1/2 = 30 min) at pH 6.25. Sites on the external muscle fibre surface thus appear to influence the recovery process. These sites are pH dependent in the range of pH 6.2–7.4 which suggests that they contain a chemical group with a pK in this range.
Erratum: Evidence for mobilization of intracellular calcium during the contractile response of the rat aorta to U44069
Authors: Heaslip Richard J. , Rahwan Ralf G.
Published: April 2011

On page 745, left column, the first complete sentence should read "Contractions induced by U44069 in the absence of extracellular calcium (and in the absence or the presence of nifedipine, bu-MDI, or Q-bu-MDI) were expressed as a percentage of the maximum contraction induced by U44069 alone in the presence of 2.5 mM bath calcium."On page 745, the second sentence of the Results section should read "Although tissues which had been washed in calcium-free buffer containing no EGTA contracted tonically upon exposure to 100 mM KCl to 14% of the maximum attainable contraction in the presence of extracellular calcium, tissues which had been washed in calcium-free EGTA buffers were refractory."
Erratum: The effect of 2-n-propyl-3-dimethylamino-5,6-methylenedioxyindene on caffeine-induced contractures of skeletal muscle
Authors: Rahwan Ralf G. , Gerald Michael C.
Published: April 2011

On page 619, the first complete sentence of the left-hand column should read "Moreover, the time required for caffeine-induced contractures to reach their maximum amplitude in calcium-free medium in the presence of MD1 was 4.5 times longer than in its absence (Table 2)."
Regional release of [3H]dopamine from rat brain in vitro: effects of opioids on release induced by potassium, nicotine, and L-glutamic acid
Authors: Marien Marc , Brien James , Jhamandas Khem
Published: April 2011

Previous studies have suggested that the release of dopamine (DA) in the rat brain may be sensitive to modulation by opioid agents, including the endogenous opioid peptides (enkephalins and endorphins). The present study examined the effects of morphine and the enkephalin analogue D-Ala2-Met5-enkephalinamide (DALA) on the release of radiolabeled DA from superfused slices of rat brain regions. The release of preloaded [3H]DA was evoked from slices of the caudate–putamen (CP) by application of potassium (K+), nicotine (NIC), or L-glutamic acid (L-GLU). The release of [3H]DA from slices of the nucleus accumbens (NA), olfactory tubercle (OT), and substantia nigra (SN) was evoked by L-GLU. Both K+ and NIC evoked a concentration-related release of [3H]DA from CP slices. K+-induced release was only partially dependent on calcium (Ca2+), while NIC-evoked release was completely Ca2+ independent. Neither morphine nor DALA influenced the release of [3H]DA evoked by K+ or NIC. L-GLU produced a concentration-dependent release of [3H]DA from slices of CP, NA, OT, and SN. In all four brain regions, this release was (a) Ca2+-dependent, (b) strongly inhibited by low concentrations of magnesium (Mg2+), (c) greater than the release evoked by D-GLU, (d) attenuated by the putative L-GLU receptor antagonist glutamic acid diethylester (GDEE), and (e) insensitive to tetrodotoxin (TTX) except in the SN. Morphine produced a significant inhibition of L-GLU-evoked [3H]DA release from all four regions. Naloxone, which by itself had no significant effect on the L-GLU-evoked release of [3H]DA, blocked the inhibitory effect of morphine on this release in the CP but not in the other regions. Levorphanol and dextrorphan were equipotent in reducing the glutamate-stimulated release of [3H]DA from CP slices. DALA had no effect on L-GLU-induced release in any of the brain regions examined. The results indicate that L-GLU provokes regional release of DA by acting at a Mg2+-sensitive glutamate receptor. This release is selectively modified by morphine through a mechanism which is insensitive to naloxone.
Are enlarged fenestrations in the internal elastic lamina of the rabbit thoracic aorta associated with poststenotic dilatation?
Authors: Potter Richard F. , Roach Margot R.
Published: April 2011

A stenosis amounting to 45–60% of the luminal diameter was made in the thoracic aorta of six New Zealand White rabbits. The progress of the ensuing poststenotic dilatation (PSD) was followed by daily X-ray analysis after which angiograms were taken for the calculation of luminal diameters. Specimens of the aorta proximal and distal (PSD) to the stenosis were digested to expose the internal elastic lamina (IEL) and viewed using a scanning electron microscope. The dilatations, which ranged between 7 and 30% reached their maximum diameter after only 8–10 days. The average diameter of the fenestrations distal (2.30 ± 0.53 SEM) to the stenosis were significantly larger (p < 0.01) than proximal (1.33 ± 0.16 SEM) and covered a significantly larger (p < 0.005) percent of the surface area of the IEL. It is suggested that the enlarged fenestrations may result in changes to the mechanical properties of the IEL which would play an important role in the genesis of PSDs.
Effects of 5-hydroxytryptamine on carbohydrate metabolism in Hymenolepis diminuta (Cestoda)
Authors: Rahman M. S. , Mettrick D. F. , Podesta R. B.
Published: April 2011

Under in vitro anaerobic and aerobic incubations the presence of 5-hydroxytryptamine (5-HT) resulted in an accelerated rate of carbon transfer through the carbohydrate metabolic pathways of Hymenolepis diminuta resulting in an increase in worm tissue total carbon pools. Under aerobic incubation, levels of phosphoglycerates, phosphoenolpyruvate (PEP), and pyruvate were significantly increased over the corresponding levels under anaerobic incubation. Excreted end products of carbohydrate metabolism also differed significantly depending on the gas phase and the presence of 5-HT. Under atmospheric (21%) oxygen concentrations excreted levels of lactate, succinate, and acetate were all significantly elevated; under a 95% O2–5% CO2 gas phase only lactate excretion was increased, and under a 95% N2–5% CO2 gas phase only succinate and acetate excretion increased. The presence of oxygen reduced acetate excretion by up to 55% and under the 95% O2–5% CO2 gas phase succinate excretion was reduced 48%. Irrespective of gas phase or the presence of 5-HT, adenine nucleotide pool sizes and the adenylate energy charge remained constant. The addition of 5-HT had no significant effect in increasing the specific activity of phosphofructokinase (PFK). In the presence of ATP the addition of cAMP increased PFK activity by up to 48%; AMP enhanced the enzyme activity by up to 69%, irrespective of the presence or absence of 5-HT. These results are discussed in terms of the effects of 5-HT, gas phase, and nucleotide pools on the motility, metabolism, and control of H. diminuta, and of other parasites which respond to 5-HT.
Stable membrane potentials and mechanical K+ responses activated by internal Ca2+ in HeLa cells
Authors: Roy G. , Sauvé R.
Published: April 2011

Stable membrane potentials have been measured with microelectrodes in HeLa cells and their average value (−38 mV) compares well with the Cl− electrochemical potential (−34 mV). A hyperpolarizing response is observed upon microelectrode penetrations and following a mechanical or electrical shock; this response is due to a large increase in the K+ permeability, which can also be triggered by Ca2+ injection or blocked by EGTA injection through the microelectrode. Stable hyper-polarizations are obtained with the Ca2+ ionophore A 23187.
Dose-related effects of furosemide, bumetanide, and piretanide on the thick ascending limb function in the rat
Authors: Gutsche Hans-Ulrich , Muller-Ott Klaus , Brunkhorst Reinhard , Niedermayer Walter
Published: April 2011

To assess the action of piretanide, bumetanide, and furosemide on the thick ascending limb of Henle's loop, perfusion experiments were performed on rat kidneys, using a recently developed conductivity microprobe for the analysis of distal tubular fluid. Surface nephrons were perfused downstream from a solid paraffin block through Henle's loop with isotonic saline solution containing either 10−6, 3 × 10−6, or 10−5 mol/L piretanide, bumetanide, or furosemide, respectively. For control values, diuretic-free saline was used. Conductivity measurements of early distal tubular fluid were perfomed in situ with a conductivity microprobe and were recorded continuously during variations of loop perfusion rate. A recently described micro-stop-flow technique was used to measure the conductivity of fluid emerging from the ascending limb, thereby evaluating the amount of sodium chloride reabsorbed. A significant electrolyte transport inhibition occurred within the concentration range between 10−6 and 10−4 M. Bumetanide and piretanide were slightly more effective than furosemide. Luminal diuretic concentrations of 10−6 M or below were without influence on electrolyte reabsorption. Concentrations of 10−4 M resulted in complete inhibition of the diluting segment electrolyte transfer.
Effects of protein malnutrition and ascorbic acid levels on drug metabolism
Authors: Basu Tapan K.
Published: April 2011

The duration of action of drugs (or other environmental chemicals) is dependent on their rate of metabolic deactivation and elimination from the body. Termination of activity is achieved either through excretion of the drug via the kidney and bile or, more commonly, through metabolic deactivation by enzymes of the liver and other tissues. In recent years, it has become increasingly obvious that nutritional status is one of the major factors capable of modifying the pharmacological effect of drugs. Numerous studies have indicated that the process of drug metabolism may be affected by acute starvation, undernutrition, protein nutrition, and deficiencies of minerals, vitamins, and lipids. Although most of the evidence concerning the effects of nutrition on the metabolism of drugs has been derived from studies on experimental animals, there is significant fragmentary-human data to show that the same effects may occur in man. This paper will discuss the influence of nutritional status with particular references to protein and ascorbic acid on the metabolism of foreign compounds including drugs. The interrelationships of nutrition and the metabolism of drugs are an important consideration in view of the widespread recurrence of primary malnutrition in the developing countries, and of secondary malnutrition in more affluent societies, especially in debilitated chronically ill patients, in postoperative patients, and in those whose dietary manipulations are carried out in weight-reducing regimens. The effects of nutrition on drug metabolism may be viewed as an extension of the search for one of the environmental factors that modify drug action.
Alterations in myocardial RNA synthesis and RNA polymerase activity during normal growth
Authors: McCully James D. , Taylor Paul B. , Morrison Nancy L.
Published: April 2011

The effect of normal growth (hypertrophy) on myocardial nuclear activity was investigated using male Wistar rats at 21, 50, and 100 days of age. Cardiac mass increased sevenfold during this age range. The concentration of RNA (mg∙g−1) was the highest at 21 days and decreased 48% by 50 days of age and 68% after 100 days of development. RNA synthesis, corrected for alterations in the specific activity of the cytoplasmic nucleotide pool, was the highest at 21 days of age. After 50 days of growth, uridine incorporation was decreased fivefold. With continual growth (100 days), RNA synthesis was still reduced compared with the 21-day animals. RNA polymerase activity in myocyte nuclei showed little change in activity from 21 to 100 days of age. However, in the nonmyocyte fraction, RNA polymerase decreased threefold after 50 days of development. Collectively, these data suggest that the large decrease in myocardial RNA synthesis cannot be accounted for by a change in nuclear RNA polymerase activity and that an alteration in chromatin template capacity may be involved during this form of cardiac growth.
Failure of delta-aminolaevulinic acid and porphobilinogen to alter renal salt and water excretion in the dog
Authors: Unikowsky Bernard , Levy Mortimer
Published: April 2011

We tested the hypothesis that the hyponatremia commonly observed in patients with acute hepatic porphyria is mediated by the presence of aminolaevulinic acid (ALA) and (or) porphobilinogen (PBG) at the level of the renal tubule to alter water handling, or at the level of the nervous system to release antidiuretic hormone (ADH). When these substances were infused intravenously into hydropenic dogs, there was no effect on systemic hemodynamics or renal function. Neither ALA or PBG, when infused directly into the renal circulation of water-loaded dogs, could effect a decrease in urinary flow, osmolar clearance, or renal perfusion. Similar results were obtained when these substances were infused directly into the renal circulation of hydropenic dogs. When ALA was administered directly into the carotid artery of nine water-loaded dogs and eight hydropenic dogs, there was again no effect on systemic hemodynamics or renal function. These data suggest that ALA (and PBG) have no effect on the renal excretion of sodium or water, and ALA does not cause the release of ADH. The hyponatremia of porphyria may be related to factors other than the elevated plasma levels of ALA and PBG.
Monosaccharide transport and hexokinase activity in leg muscles from cardiomyopathic hamsters
Authors: Phipps Burnell A. , Elbrink Just
Published: April 2011

The facilitated diffusion system for monosaccharides was studied with nonmetabolized 3-O-methyl-D-glucose (3-O-MG) and hexokinase activity was determined with 2-deoxyglucose (2-DG) in extensor digitorum longus (EDL) and soleus muscles from BIO 14.6 (dystrophic) hamsters. Motor activity was recorded at 2 months of age. FIB (normal) hamsters were controls. In EDL (fast-twitch) muscle, sugar transport was unaltered at 6 weeks; at 2 to 5 months the normal decrease in sugar transport with time was reduced, decreasing stimulation of the facilitated diffusion system by anoxia. Phosphorylation in EDL muscles, measured at 2 months, probably was decreased. In soleus (slow-twitch) muscle, 3-O-MG transport was unaltered with age but hexokinase activity, determined at 2 months, was greatly increased in the quiescent state and during stimulation at 2 Hz. Motor activity was less, but not significantly, in the dystrophic hamsters. The results indicate that the alterations in glucose metabolism depend upon both muscle type and age. We interpret the changes in dystrophic fast- and slow-twitch muscles as reflecting compensatory mechanisms to increase the generation of energy.
Release of epinephrine during carotid artery occlusion following vagotomy in dogs
Authors: Carrière Serge , Demassieux Sylvain , Cardinal Jean , Grimellec Christian Le
Published: April 2011

The blood pressure (BP), serum norepinephrine (NE), and epinephrine (E) responses to carotid artery occlusion (CAO) were examined in three different groups of anesthetized dogs. The response was first examined under control conditions in the three groups and then following vagotomy and adrenalectomy in the first group, following adrenalectomy and vagotomy in the second group, and following atropine administration and vagotomy in the third group. The results obtained in these three groups of dogs during the control period demonstrate that CAO produces significant increases in BP (from 144 ± 5 to 182 ± 8, 154 ± 7 to 202 ± 9, and 143 ± 3 to 185 ± 2 mmHg, respectively) (1 mmHg = 133.322 Pa) and in NE serum level (from 218 ± 36 to 337 ± 45, 215 ± 51 to 275 ± 46, and from 163 ± 23 to 247 ± 22 pg/mL, respectively), thus confirming previous studies. No rise in E serum level occurred in these three conditions (226 ± 100 vs. 275 ± 87, 280 ± 161 vs. 205 ± 88, and 183 ± 75 vs. 157 ± 46 pg/mL, respectively), as also previously reported. The first series of experiments demonstrated that following vagotomy, CAO induced a marked elevation of E serum levels from 275 ± 87 to 1145 ± 274 pg/mL (P < 0.005). These CAO-induced changes in E were abolished by previous (group 2) or subsequent (group 1) adrenalectomy which also attenuated BP and NE elevations, although these remained significant. By comparison with these changes, vagotomy only had a modest effect on BP and serum NE increase following CAO. These results demonstrate that vagal inhibition upon vasomotor tone was most important in controlling the adrenal release of catecholamines (CA), particularly E. In the third series of dogs atropine sulfate could not reproduce the BP, NE, and E changes observed after vagotomy, as the results were comparable to those observed under control conditions. Subsequent vagotomy produced results analogous to those observed in the first group of animals and confirmed that vagal afferent fibers are responsible for tonic inhibition of vasomotor centers.
Investigation of the role of prostaglandins in nitroglycerin-induced relaxation of isolated rabbit blood vessels
Authors: Bennett Brian M. , Moffat Joyce A. , Armstrong Paul W. , Marks Gerald S.
Published: April 2011

The effect of inhibition of prostaglandin synthesis on nitroglycerin-induced relaxation was examined in isolated rabbit mesenteric and celiac arterial rings. An indomethacin dose of 5 μM was selected as adequate to inhibit prostaglandin synthesis as this dose prevented relaxation of the arterial rings by sodium arachidonate (3.3 μM) and by bradykinin, a peptide thought to induce vasodilation via stimulation of prostaglandin synthesis. Following 20 min pretreatment with indomethacin (5 μM), indomethacin solvent, or Krebs solution (control), the arterial rings were contracted submaximally with phenylephrine (0.5–10 μM). The degree of inhibition of phenylephrine-induced tone produced after cumulative additions of nitroglycerin (10−10 – 5 × 10−7 M) was assessed. In control celiac and mesenteric rings the responses to nitroglycerin were as follows: mean effective dose (ED50), 5.6 × 109 ± 4.5 × 10−9 M (SD) and 1.1 × 10−8 ± 5 × 10−9 M (SD), respectively; maximum relaxation, 97 ± 3% (SD) and 93 ± 7% (SD), respectively. Neither indomethacin nor indomethacin solvent affected the ED50 or maximum relaxation with nitroglycerin. We conclude that nitroglycerin-induced relaxation of rabbit celiac and mesenteric arteries appears to be mediated through a mechanism other than stimulation of prostaglandin synthesis.
Aminophylline ameliorates glycerol-induced acute renal failure in rats
Authors: Bidani K. , Churchill P. C.
Published: April 2011

The effect of aminophylline (theophylline complexed with ethylenediamine) on the severity of glycerol-induced myohemoglobinuric acute renal failure was examined in rats. In the first series of experiments, one group of rats received twice daily injections of aminophylline following the induction of acute renal failure, and a second group (controls) received twice daily injections of saline. Only one of the aminophylline-injected rats but five of the saline-injected rats died during the 3-day follow-up period. Moreover, mean serum creatinine was lower in the aminophylline-injected rats than in the saline-injected controls on each of the 3 days, demonstrating that aminophylline reduced the renal functional impairment. In the second series, single injections of aminophylline were given at the time of glycerol injections or 3, 6, or 24 h later. As assessed by mean serum creatinine during the 3-day follow up, even single injections had protective effects if given during the initiation phase (0–3 h after glycerol). Since aminophylline dissociates into theophylline in biological fluids, and since theophylline is an adenosine-receptor antagonist, these observations are consistent with the hypothesis that adenosine plays a pathogenic role in myohemoglobinuric acute renal failure in rats.
Comparison of longitudinal elastic properties of proximal and distal strips of aorta-branch junctions from the abdominal aorta of sheep
Authors: Cleave Janet , Roach Margot R.
Published: April 2011

Narrow longitudinal continuous strips were cut from the abdominal aorta and its major branches so that each strip contained the same width of aorta, bifurcation, and branch although the lengths of the three segments were different. A grid was marked on each region, and photographs made at a variety of strains as the whole strip was stretched at a strain rate of 2 cm/min with an Instron tensile testing machine. Measurements from the grids gave the strains for each region, and stress–strain curves were calculated. The proximal bifurcation zone was much more extensible than any of the other regions, owing mainly to changes in the "slack" of the collagen fibers (p < 0.01). This would imply that the shape and cross-sectional area of the bifurcation region are apt to change between diastole and systole, and implies that model studies which assume the shape of the bifurcation region is constant may not be accurate.
Redundant nature of the vasopressin and rennin–angiotensin systems in the control of mesenteric resistance vessels of the conscious fasted cat
Authors: McNeill J. R.
Published: April 2011

[1-deaminopenicillamine, 4-valine, 8-D-arginine]Vasopressin (DPVDAVP), a specific antagonist of the pressor activity of vasopressin, and teprotide, a converting enzyme inhibitor, were infused intravenously in conscious, fasted (24–30 h) but not water-deprived cats which had been implanted previously with flow probes on their superior mesenteric arteries and with arterial and venous cannulae. Infusion of DPVDAVP (20 μg/min) alone or teprotide (1 mg over 5 min) alone caused only small and statistically nonsignificant changes in mesenteric conductance and arterial pressure. However, infusion of DPVDAVP during the plateau phase of the response to teprotide or, conversely, administration of teprotide during the plateau phase of the response to DPVDAVP caused large increases in mesenteric conductance and small but significant decreases in arterial pressure. The results are consistent with the hypothesis that vasopressin and angiotensin are redundant overlapping mechanisms that play a significant role in the control of the mesenteric resistance vessels of the conscious fasted cat; when one system is inhibited, the other compensates to maintain resistance.
Tip potential of open-tip glass microelectrodes: theoretical and experimental studies
Authors: Gagné Simon , Plamondon Réjean
Published: April 2011

A mathematical analysis of the tip potential based on the main physicochemical phenomena occurring at the tip of a glass microelectrode is presented. The factors considered in the theoretical analysis are the diffusion of ions through the open tip, the conduction in the bulk solutions, the longitudinal conduction in the double layers at the glass-electrolyte interfaces, and to some extent, in a hydrated glass layer. A graphical analysis of the mathematical expressions as a function of the resistivity of test solutions is done and the distribution of the source potentials giving rise to the tip potential is studied. The experimental results presented in the paper confirm the validity of the proposed theoretical model. Comments for an improved use of glass microelectrodes in electrophysiological experiments are given throughout the paper.
Distension of the pulmonary vein – atrial junctions and plasma vasopressin in the chloralose-anaesthetized dog
Authors: Wilson N. , Ledsome J. R.
Published: April 2011

The effects of localized distension of the pulmonary vein–left atrial junctions on plasma arginine vasopressin (AVP) have been examined in chloralose anaesthetized dogs. Pulmonary vein distension caused an increase in heart rate and a decrease in plasma AVP concentration. Cooling the vagosympathetic nerves to 10 °C caused an increase in arterial pressure and plasma AVP concentration and prevented the changes in heart rate and plasma AVP concentration caused by pulmonary vein distension. Cooling the vagus nerves to 16 °C did not change heart rate, arterial pressure, or plasma AVP concentration but significantly reduced the changes in heart rate and plasma AVP concentration caused by pulmonary vein distension. Propranolol (0.5 mg/kg) decreased heart rate and prevented the increase in heart rate associated with pulmonary vein distension but did not abolish the decrease in plasma AVP concentration. It is concluded that distension of the pulmonary vein – left atrial junctions causes a decrease in plasma AVP concentration by stimulating atrial receptors with myelinated afferent fibres. The decrease in plasma AVP concentration is not secondary to the reflex changes in heart rate caused by pulmonary vein distension.
A two-dimensional analysis of regional myocardial function in the dog
Authors: Nomura Hideo , Nagata Kazuhiko , Futamura Yoshihiro , Hama Yoshiyuki , Sotobata Iwao
Published: April 2011

The pattern of left ventricular contraction or relaxation is not uniform and also changes depending on hemodynamic states. Accordingly, the measurement of myocardial segment length only may have limitations for the analysis of regional myocardial function, and a two-dimensional analysis of regional myocardial function was developed and characterized by utilizing measurement of regional myocardial surface area on the epicardial surface. In eight anesthetized open-chest dogs, the relationship between regional myocardial function and total cardiac function was examined. The extent of the reduction of regional myocardial surface area during the ejection phase or during the systolic phase correlated more closely with stroke volume over wide ranges of left ventricular end-diastolic pressure, aortic pressure, left ventricular contractility, and heart rate (r = 0.75–0.96) than the shortening of myocardial segment length alone. Thus, the results demonstrated that regional myocardial function estimated by the measurement of regional myocardial surface area represents total cardiac function more accurately than myocardial segment length over wide ranges of hemodynamic states despite the changes in the left ventricular contraction and relaxation pattern.
Calcium antagonist blockade of slow action potentials in cultured chick heart cells
Authors: Li Tung , Sperelakis Nick
Published: April 2011

The effects of four Ca antagonists, bepridil, diltiazem, nifedipine, and verapamil, on slow channels were studied in cultured cell reaggregates prepared from 14-day-old chick embryonic, hearts. The cell membrane was partially depolarized to about −45 mV by using 22 mM KCl to inactivate the fast Na+ channels. Slow action potentials were induced by 10−6 M isoproterenol with electrical stimulation. Cumulative dose – response curves for the effect of the four drugs on the blocking of slow action potentials (using [Formula: see text] as the indicator) were analyzed by Hill plots. The dose values for 50% of maximal effect, at a stimulation frequency of 60/min, were (in order of decreasing potencies) as follows: 5.2 × 10−9 M for nifedipine, 3.1 × 10−7 M for diltiazem, 1.2 × 10−6 M for verapamil, and 5.1 × 10−6 M for bepridil. The effect of all four Ca antagonists showed use (or frequency)-dependency, i.e., the drugs were more effective at higher stimulation rates. This may reflect a blocking action of the drugs on the nonresting states of the channels and (or) a slowing of the recovery kinetics of the channels from the inactivated state back to the resting state. In a separate type of experiment utilizing a 5-min rest period in the presence of the drugs, nifedipine blocked and bepridil exhibited some depression of the first action potential elicited, i.e., use-independent effect, indicating that these drugs may also act on resting channels. Thus, these four Ca antagonists have a prominent use-dependent component in their actions, and one or two may also have a use-independent component.
Kinetics of uptake of glucose in rabbit jejunum: influence of sodium, unstirred layers, and passive permeation
Authors: Thomson A. B. R.
Published: April 2011

Failure to account for the effect of the unstirred water layer and the contribution of passive permeation will lead to errors in the estimation of the kinetic constants of glucose uptake into the intestine. It is widely accepted that variations in the concentration of sodium in the bulk phase profoundly influence the rate of uptake of glucose in the intestine, but the kinetic basis for this effect remains in dispute. Accordingly, a previously validated in vitro technique was used to assess the effect of Na+ on the uptake of glucose into rabbit jejunum under conditions selected to reduce the unstirred layer resistance. Varying Na+ had no effect on the uptake of lauryl alcohol and therefore on unstirred layer resistance. The passive permeability coefficient for glucose uptake was estimated from the uptake of L-glucose, of D-glucose at 4 °C, or in the presence of 1 mM phlorizin or 40 mM galactose. The permeability for glucose increased as Na+ rose. The values of both the maximal transport rate and the Michaelis constant (Km) were influenced by Na+. A linear relationship was noted between Na+ and the maximal transport rate; the value of Km fell as Na+ was increased to 75 mequiv./L, but Km did not decline further with higher values of Na+. These results support the theoretical predictions of the presence of both an affinity and a velocity effect of the sodium gradient on the intestinal transport system for glucose.
Inhibitory effects of ketamine on the isolated uteri of the rat: evidence for the mechanism of action
Authors: Calixto Joāo Batista , Aucélio José Gilberto , Duarte Danilo Freire
Published: April 2011

The inhibitory effect of ketamine on the agonist-induced contraction of isolated rat uteri was compared with that of papaverine and verapamil. Under similar experimental conditions papaverine and verapamil were found to be more potent than ketamine. When preparations were preincubated for 20 min with either ketamine (3 × 10−5 to 10−3 M) or papaverine (10−6 to 10−5 M), a noncompetitive antagonism was observed against oxytocin with [Formula: see text] values of 3.67 ± 0.07 and 5.13 ± 0.10, respectively. A noncompetitive form of antagonism was also observed by papaverine against BaCl2 with [Formula: see text] values of 4.59 ± 0.15, while ketamine produced competitive antagonism with a pA2 value of 4.68 ± 0.12. It was also demonstrated that all three inhibitory drugs interfere competitively with Ca2+ on the rat uteri. However, ketamine was shown to be less potent than verapamil and papaverine in antagonizing the effects owing to an increased Ca2+ concentration in the medium. These results are consistent with previous publications that ketamine has a papaverinelike effect on the rat uteri and suggest that the relaxation promoted in this preparation is due, at least in part, to blockade of the Ca2+ translocation processes.
Aging: its influence on the intestinal unstirred water layer thickness, surface area, and resistance in the unanesthetized rat
Authors: Hollander Daniel , Dadufalza Violetta D.
Published: April 2011

The intestinal absorption of some nutrients changes with aging. As the unstirred water layer (UWL) is an important rate limiting step in the absorption of nutrients in general and of lipid soluble nutrients in particular, we investigated possible changes in the UWL dimensions in the aging rat in vivo. We measured the thickness (d) of the UWL using rapid changes in the luminal sodium concentration to induce changes in the transmucosal potential differences. We assessed the surface area (Sw) and resistance (d/SwD) of the UWL at varying flow rates by using increasingly lipophilic medium chain saturated alcohols as probes. At high UWL resistance, d decreased from 318 to 268 μm between 1 and 29 months of age. As the animals aged, Sw changed from 114 to 106 cm2/100 cm and from 262 to 214 cm2/100 cm at low and high flow rates, respectively, using dodecanol as a probe. The resistance of the UWL (d/SwD) remained relatively stable at all ages studied. These experiments demonstrate that age-related changes in absorption are dependent on the aqueous diffusion coefficient and degree of lipid solubility of the specific nutrients. At low UWL resistance, absorption of compounds with higher diffusion coefficients and greater aqueous solubility is decreased with aging. In contrast, previous studies have demonstrated that the absorption of nutrients with low diffusion coefficients and high lipid solubility increases with aging especially when the resistance of the UWL is high.