bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies of the halothane-cooling contractures of skeletal muscle
Authors: Sudo Roberto T. , Zapata Gisele , Suarez-Kurtz Guilherme
Published: April 2011

The characteristics of transient contractures elicited by rapid cooling of frog or mouse muscles perfused in vitro with solutions equilibrated with 0.5–2.0% halothane are reviewed. The data indicate that these halothane-cooling contractures are dose dependent and reproducible, and their amplitude is larger in muscles containing predominantly slow-twitch type fibers, such as the mouse soleus, than in muscles in which fast-twitch fibers predominate, such as the mouse extensor digitorum longus. The halothane-cooling contractures are potentiated in muscles exposed to succinylcholine. The effects of Ca2+-free solutions, of the local anesthetics procaine, procainamide, and lidocaine, and of the muscle relaxant dantrolene on the halothane-cooling contractures are consistent with the proposal that the halothane-cooling contractures result from synergistic effects of halothane and low temperature on Ca sequestration by the sarcoplasmic reticulum. Preliminary results from skinned rabbit muscle fibers support this proposal. The halothane concentrations required for the halothane-cooling contractures of isolated frog or mouse muscles are comparable with those observed in serum of patients during general anesthesia. Accordingly, fascicles dissected from muscle biopsies of patients under halothane anesthesia for programmed surgery develop large contractures when rapidly cooled. The amplitude of these halothane-cooling contractures declined with the time of perfusion of the muscle fascicles in vitro with halothane-free physiological solutions. It is suggested that the halothane-cooling contractures could be used as a simple experimental model for the investigation of the effects of halothane on Ca homeostasis and contractility in skeletal muscle and for study of drugs of potential use in the management of the contractures associated with the halothane-induced malignant hyperthermia syndrome. It is shown that salicylates, but not indomethacin or mefenamic acid, inhibit the halothane-cooling contractures.
Effect of a cysteine prodrug, L-2-oxothiazolidine-4-carboxylic acid, on the metabolism and toxicity of bromobenzene: an acute study
Authors: Brodeur J. , Goyal R.
Published: April 2011

The effect of a cysteine prodrug, L-2-oxothiazolidine-4-carboxylic acid (OTCA), on certain aspects of the metabolism and toxicity of bromobenzene administered acutely to mice was investigated by (i) characterizing the influence of OTCA on the metabolic profile of low and high bromobenzene dose at 0–6, 6–12, and 12–24 h, (ii) determining the effective doses range and administration time for OTCA, as well as the optimum period for urine sampling; and (iii) measuring the efficacy of OTCA for protection against bromobenzene induced toxicity. Coadministration of OTCA and bromobenzene enhanced the urinary excretion of mercapturic acid and phenolic metabolites, during 6–12 h, by approximately 152 and 193%, respectively. Maximum efficacy was observed when OTCA (16.0 mmol/kg) was administered concomitantly with bromobenzene (4.0 mmol/kg). Finally, OTCA administration was found to afford substantial protection against elevation of plasma transaminases used as indices of bromobenzene-induced hepatotoxicity. N-acetylcysteine, another cysteine prodrug, had essentially similar effects on the metabolism and toxicity of bromobenzene. Thus, administration of cysteine prodrugs enhances the urinary excretion of several metabolites of bromobenzene and affords protection against bromobenzene-induced hepatotoxicity.
Thirty years of ion-selective microelectrodes: disappointments and successes
Authors: Hinke J. A. M.
Published: April 2011

The need to know the intracellular activity of an ion and how it changes under controlled conditions is as important today as it was 30 years ago. In 1956, one could fabricate only a H+-selective microelectrode and with a tip size not much smaller than 100 μm. Today, one can fabricate microelectrodes selective to H+, Na+, K+, Cl−, HCO3−, Ca2+, or Mg2+ (plus others) and with active tips less than 1 μm. The reduction of active tip size can be attributed mainly to the introduction of liquid ion exchanger (LIX) and neutral carrier ligands. Unfortunately, the LIX microelectrodes, as currently fabricated, do not yet function optimally as reliable and stable electrochemical measuring devices. A durable bond between the active membrane and its insulated container continues to remain the major design problem even after 30 years of development.
Design of ionophores for ion-selective microsensors
Authors: Ammann Daniel , Oesch Urs , Bührer Thomas , Simon Wilhelm
Published: April 2011

Requirements for a reliable use of liquid membrane microelectrodes are discussed in terms of stability, response time, and lifetime on the basis of membrane technological considerations. The selectivity of H+, Li+, Na+, K+, Mg2+, Ca2+, and Cl− microelectrodes is critically evaluated using the Nikolskii-Eisenman formalism. Recent progress in the design of new ionophores is presented. A novel neutral carrier-based Ca2+-selective microelectrode with a detection limit of about 5 × 10−10 M Ca2+ at a background of 125 mM K+ has been realized. An neutral carrier-based microelectrode for H+ with extended pH range of the sample solution is now available. Promising developments in the field of Li+-, Mg2+-, and Cl−-selective ionophores are discussed.
Intracellular free magnesium in excitable cells: its measurement and its biologic significance
Authors: Alvarez-Leefmans F. J. , Giraldez F. , Gamiño S. M.
Published: April 2011

As a necessary cofactor for hundreds of enzymes, intracellular Mg2+ influences a wide range of cellular functions such as transmembrane transport of other ions, glycolysis, respiration, muscle contraction, and phosphorylation of ion channels. Unlike Ca2+, Mg2+ does not seem to have a "trigger" function. However, the wide range of enzymes requiring Mg2+ to be activated suggests that Mg2+ plays a pivotal role in fine control and coordination of cell activity, determining the "set point" of hundreds of metabolic reactions. In this sense, intracellular Mg2+ might be regarded as a static rather than a dynamic regulator of cell function. Little is known about the mechanisms by which excitable and other cells keep their [Mg2+]i within narrow limits against large electrochemical gradients. Furthermore, the actual basal level of [Mg2+]i has been the subject of recent controversy. In the present paper the roles of intracellular Mg2+ on cell function as well as four current techniques for measuring [Mg2+]i are briefly reviewed. These techniques are (i) metallochromic indicators, (ii) 31P nuclear magnetic resonance, (iii) null point for plasma membrane permeabilization using the ionophore A23187 and, (iv) Mg2+-selective microelectrodes. The relative advantages and disadvantages of each of these techniques are discussed with special emphasis on Mg2+-selective microelectrodes.
A novel concentric double-barrelled calcium-selective microelectrode for small cells
Authors: Yamaguchi H.
Published: April 2011

A novel concentric design of double-barrelled Ca2+-selective microelectrode, with an inner pipette tip that protrudes beyond an outer one, has recently been developed and is described. This configuration of pipettes was produced from concentric capillaries in one step using a horizontal pipette puller. For the tip of the inner barrel to protrude, Coming 1724 aluminosilicate glass was selected, as it has a higher melting point than the 1723 glass which is used for the outer barrel. To reduce electrode resistance the inner capillary was best made with a triangular shape. It was preferentially silanized in a dry box by injection of methyltrichlorosilane into only the inner barrel. The Ca2+ neutral carrier-based liquid membrane (ETH 1001) was back-filled from the tip to the shank of the inner pipette and above this CaCl2 solution was added. KCl, which contained EGTA and was buffered to pCa 7, was used to fill the reference barrel. These Ca2+ electrodes showed linear response with slope [Formula: see text] for changes in Ca2+ concentration between 10−3 and 10−7 M in the presence of constant [K+]. They offer a number of advantages including a low noise level achieved by the presence of the external concentric KCl electrode, and a simple mechanical structure that allows applications to a variety of small cells.
Cellular mechanisms of potassium homeostasis in the mammalian nervous system
Authors: Grafe P. , Ballanyi K.
Published: April 2011

Double-barrelled ion-sensitive microelectrodes were used to measure changes in the intracellular activities of K+, Na+, and Cl− (aKi, aNai, aCli) in neurones of rat sympathetic ganglia and in glial cells of slices from guinea-pig olfactory cortex. In sympathetic neurones, carbachol and γ-aminobutyric acid (GABA) produced a reversible decrease of aKi. The decrease of aKi during carbachol was accompanied by a rise of aNai, whereas in the presence of GABA decreases of aKi and aCli were seen. The reuptake of K+ released during the action of carbachol was completely blocked by ouabain, whereas furosemide inhibited the aKi recovery after the action of GABA. In glial cells, in contrast to the observations in the sympathetic neurones, aKi and aCli increased, whereas aNai decreased when neuronal activity was enhanced by repetitive stimulation of the lateral olfactory tract. It was found that barium ions and ouabain strongly reduced the activity-related rise of intraglial aKi in slices of guinea-pig olfactory cortex. These data show that mammalian neurones as well as glial cells possess several K+ uptake mechanisms that contribute to potassium homeostasis. Ouabain, furosemide, and Ba2+ are useful pharmacological tools to separate these mechanisms.
Calcium diffusion in the brain cell microenvironment
Authors: Nicholson Charles , Rice Margaret E.
Published: April 2011

A review of some of the literature on Ca2+ diffusion in free media and a variety of nervous tissues is presented. In the majority of tissue studies the apparent diffusion coefficient of Ca2+ is three to nine times smaller than that in a free aqueous medium. The methodology of using pressure microejection and Ca2+ ion-selective microelectrodes to measure Ca2+ diffusion is discussed. Our ongoing studies of Ca2+ diffusion in the cerebral cortex of the rat, using these methods, also confirm that Ca2+ diffusion is mainly influenced by the tortuosity of the tissue rather than other factors such as binding to extracellular charge sites or uptake.
Temporal relationship between neurotransmitter release and ion flux during spreading depression and anoxia
Authors: Moghaddam B. , Schenk J. O. , Stewart W. B. , Hansen A. J.
Published: April 2011

Brain ion homeostasis is severely perturbed during spreading depression of Leao and during anoxia. The ionic composition of the extracellular space changes abruptly and approaches the intracellular concentrations owing to an increase in cell permeability. In spreading depression, synchronous transmitter efflux caused by a depolarization of the presynaptic terminals has been implicated as a possible mechanism that would explain the concomitant movement of ions. Anoxia, having many features in common with spreading depression, may follow the same mechanism. We have measured the concentrations of extracellular potassium with ion-selective microelectrodes and dopamine by in vivo voltammetry with carbon fiber microelectrodes during spreading depression and anoxia to compare the temporal relationship between the release of dopamine and ion movements in the striatum. There is a pronounced release of dopamine during both spreading depression and anoxia. In spreading depression, the sharp increase of potassium concentration that follows an initial smaller and slower increase of potassium is accompanied by the release of dopamine. In anoxia, the dopamine release clearly precedes the fast rise of extracellular potassium concentration. We conclude that in striatum, there is a pronounced dopamine release during spreading depression and anoxia, but that the relationships between ionic changes and transmitter release for these two phenomena are different and probably reflect different mechanisms.
Effects of liver blood flow on hepatic uptake kinetics of galactose in anesthetized cats: parallel tube model
Authors: Greenway C. V. , Burczynski F. J.
Published: April 2011

Hepatic galactose uptake in cats anesthetized with pentobarbital was determined during (i) steady-state infusions at several doses, (ii) rapidly increasing infusion rates at different blood flows, and (iii) prolonged infusion of a single dose at different blood flows. The hepatic venous long-circuit technique was used to allow frequent sampling of arterial, portal, and hepatic venous blood without depletion of the animal's blood volume and to allow measurement and alteration of total hepatic blood flow. Uptake was shown to follow Michaelis–Menten kinetics and was consistent with the "parallel tube model." The kinetic parameters Vmax and Kmax could be determined under steady-state and nonsteady-state conditions and were independent of hepatic blood flow over the range 60–150% of control flow. Mean Vmax was 80 μmol/(min∙100 g liver) and mean Km was 215 μM. Vmax declined by 50% when flow was reduced to half normal. It is concluded that the parallel tube model can be used to describe and predict hepatic galactose kinetics in anesthetized cats, although other models may fit the data equally well.
Anticonvulsants modify inactivation but not activation processes of sodium channels in Myxicola axons
Authors: Schauf C. L.
Published: April 2011

The effects of pronase and the anticonvulsant drugs diphenylhydantoin, bepridil, and sodium valproate on fast and slow Na+ inactivation were examined in cut-open Myxicola giant axons with loose patch-clamp electrodes applied to the internal surface. Pronase completely eliminated fast Na+ inactivation without affecting the kinetics of Na+ activation or the maximum Na+ conductance. The time and voltage dependences of slow inactivation following pronase treatment were identical to those measured before enzyme application in the same axons. All three anticonvulsants slowed the time course of recovery from fast Na+ inactivation in untreated axons, and shifted the steady-state fast inactivation curve in the hyperpolarizing direction along the voltage axis. Anticonvulsants enhanced steady-state slow inactivation and retarded recovery from slow inactivation in both untreated and pronase-treated axons. Although some quantitative differences were seen, the order of potency of the anticonvulsants on slow Na+ inactivation was the same as that for recovery from fast inactivation.
Role of the anteroventral third ventricle region in fever in sheep
Authors: Blatteis C. M. , Hales J. R. S. , McKinley M. J. , Fawcett A. A.
Published: April 2011

Ablation of the anteroventral third ventricle (AV3V) region, which includes the organum vasculosum laminae terminalis (OVLT), blocks the febrile response of guinea pigs to systemically injected endotoxin; by contrast, discrete lesions of the OVLT transiently enhance fever in rabbits and rats. To assess whether separate subdivisions of the AV3V may mediate these different effects, the thermal responses to Escherichia coli lipopolysaccharide (LPS, 0.25 μg/kg, i.v.) were measured in eight sheep before and 12–13 days after placement of lesions at various levels within the AV3V. The responses of four of these sheep to crude homologous endogenous pyrogen (EP, 1–2 mL, i.c.v.) were also evaluated. Additionally, five other sheep were tested with LPS 2–8 months postlesion. All the experiments were performed at thermoneutrality. Sheep were used because most of the frontal wall of their 3V forms an elongated OVLT consisting of an avascular body and a vascular base. The animals were classified postmortem according to the extent of tissue ablated. Lesion overlap analyses showed that (i) medial lesions which extended from the floor of the 3V to the anterior commissure and laterally into adjacent preoptic periventricular tissue were associated with significantly depressed fever after LPS (n = 2); (ii) comparable lesions, but which excluded the ventral portion of the AV3V, i.e., the base of the OVLT, did not alter the magnitude of the febrile response to LPS (n = 4); (iii) lesions of the lateral walls of the 3V and (or) of the adjacent medial preoptic and anterior hypothalamic areas but excluding the frontal 3V wall also did not affect fever height after LPS (n = 7). Damage to aspects of the walls of the lateral ventricles attenuated the febrile response to EP i.c.v. (n = 3). Hence, although no separate fever-inhibiting and fever-enhancing regions were found within the AV3V, these results indicate that the ventral portion of the AV3V, i.e., the vascular plexus of the OVLT, is critical for normal fever development in sheep.
Thermoregulatory responses of guinea pigs with anteroventral third ventricle lesions
Authors: Blatteis C. M. , Hunter W. S. , Wright J. M. , Ahokas R. A. , Llanos-Q. J. , Mashburn Jr. T. A.
Published: April 2011

Guinea pigs with anteroventral third ventricle region (AV3V) lesions fail to develop fever and the associated rise in acute-phase plasma protein levels following systemic injections of lipopolysaccharide (LPS). Since endogenous pyrogen (EP) injected directly into the preoptic area of animals with AV3V lesions causes appropriate elevations in core temperature (Tco) and acute-phase plasma proteins levels, the blocked responses to LPS probably are not due to damage to the adjacent preoptic area. We proposed, therefore, that EP may pass from blood into brain in the AV3V, presumably through the organum vasculosum laminae terminalis. However, the possibility that a more generalized impairment due to damaged pathways within the AV3V could account for the observed effects was not examined. To investigate this possibility, guinea pigs were given AV3V lesions. Pending histological verification of the ablated sites, AV3V lesions were presumed to be placed correctly if the animals did not develop fever following LPS (Salmonella enteritidis, 2 μg/kg i.p., at ambient temperature (Ta) 22 °C); those failing to meet this criterion were designated as sham-operated. Two experiments were conducted. In the first, metabolic rates, Tco, and two skin temperatures (Tsk) were measured at Ta 12°, 22°, and 32 °C over an 8-month postlesion period during which failure to fever persisted; the data were collected during a 30-min period after thermal balance had been achieved at any given Ta. There were no differences in the variables measured between sham-operated and AV3V-lesioned animals at Ta 22 °C. At Ta 12° and 32 °C, the Tsk of both the sham-operated and the AV3V-lesioned guinea pigs were reduced and elevated, and metabolic rate increased and decreased, respectively. However, Tco at Ta 32 °C and metabolic rate at Ta 12° and 32 °C were significantly higher in the AV3V-lesioned than in the sham-operated animals. In the second experiment, only Tco was measured, but under more severe ambient conditions and over a briefer duration. Thus, 11 and 14 days postlesion, the animals were exposed to Ta 35.5 ± 1.8 °C (means ± SD) until their Tco stabilized between 40.5 and 41.5 °C, and to Ta 2.7 ± 1.5 °C for 2.5 h, respectively. In addition, as indices of the acute-phase plasma protein response, their plasma levels of copper (Cu) and N-acteylneuraminic acid (NANA) were assayed 28 h after the onset of these exposures. There were no significant differences in the Tco changes between sham-operated and AV3V-lesioned guinea pigs induced by each of these conditions. Plasma Cu and NANA levels also were not affected by the lesions or the environments. It would appear, therefore, that ablation of the AV3V causes enhanced metabolic responses to thermal stress; but since these changes lead to elevated rather than to depressed Tco and do not alter acute-phase plasma protein levels, they cannot account for the blocked febrile and acute-phase plasma protein responses to LPS.
Body temperature related factors diminishing the drive to exercise
Authors: Brück K. , Olschewski H.
Published: April 2011

The effects of slightly below-normal body temperatures (ΔTcore –0.5 to 1 °C) on exercise performance were examined in four series of studies employing a standardized precooling maneuver. In both the precooling tests and the control tests the subjects exercised on a cycle ergometer at an ambient temperature of 18 °C with the following results. In series 1, the subjects were exercising at a heart rate of 120 beats∙min−1. Work rate and oxygen pulse were significantly increased, and sweat rate was less elevated in precooling tests than in controls. In series 2, in 12 well-trained rowers subjected to an incremental performance test, maximum work rate, peak [Formula: see text], time to exhaustion, and total work were not reduced in precooling tests. Eight well-trained rowers in series 3 were requested to work as hard as possible for 1 h. The mean work rate, [Formula: see text], and oxygen pulse were increased in the precooling tests by 6.8, 9.6, and 5.6%, respectively, whereas the sweat rate was 20% lower. In series 4 after a 16-min period of easy exercise (phase 1) the subjects exercised at a work rate corresponding to 80% [Formula: see text] up to exhaustion. Endurance time at this work rate was increased in precooling tests by 12% (18.5 vs. 20.8 min, p = 0.035). Heart rate was lower throughout the exercise period in precooling tests. Oxygen pulse, as well as stroke volume and arteriovenous oxygen difference (AVDo2), measured by impedance cardiography were increased in phase 1; during min 16–28 (phase 2) precooled–control differences in stroke volume and AVDo2 disappeared, but pedal rate (which is related to muscle force, muscle metabolism efficiency, and fatigue) was significantly reduced in precooling tests. Sweat rate and skin blood flow increased less in phase 2 of the precooling test. In conclusion, changes in circulatory, thermoregulatory, and muscular factors have been demonstrated after precooling. These may account for a smaller increase in exercise discomfort counteracting the drive to exercise.
No dynamic effector responses to fast changes of core temperature at constant skin temperature
Authors: Roos Ulrike , Jessen Claus
Published: April 2011

Experiments in conscious goats were done to see whether heat production and respiratory evaporative heat loss show dynamic responses to changing core temperature at constant skin temperature. Core temperature was altered by external heat exchangers acting on blood temperature, while skin temperature was maintained constant by immersing the animals up to the neck in a rapidly circulating water bath. Core temperature was altered at various rates up to 0.9 °C/min. Step deviations of core temperature from control values were always followed by a positive time derivative of effector response, but never by a negative time derivative during sustained displacement of core temperature. Ramp experiments showed that the slopes at which heat production or heat loss rose with core temperature deviating from its control level grew smaller at higher rates of change of core temperature. It is concluded that neither heat production nor respiratory evaporative heat loss respond to the rate of change of core temperature. At constant skin temperature, thermoregulatory effector responses appear to be proportional to the degree to which core temperature deviates from its set level.
Thermoregulatory behavior and temperature gradient perception in a juvenile fish (Poecilia reticulata)
Authors: Williams E. Eugene , Brauer Ralph W.
Published: April 2011

The thermoregulatory behavior of guppies in a temperature gradient was studied under conditions offering one degree of locomotor freedom, in which displacement of the fish was coupled to a change of occupied temperature, and two degrees of locomotor freedom, in which the added dimension allowed for thermally neutral movement, thus uncoupling any obligatory link between displacement and temperature change. More animals failed to thermoregulate in the second than in the first geometrical system (32% vs. 7%); however, the means of the temperature preferenda (Tp) were the same in both gradient configurations and the frequency distributions along the temperature axis were indistinguishable. In both geometrical systems, mean swimming speed along the temperature axis showed well-defined minima coinciding with the Tp. It was shown that the mean components of movement with respect to the thermal and thermally neutral axes both showed minima at Tp. Further analyses of the actual behavior confirm that in the vicinity of Tp the movements of the fish show little dependence on direction. The analyses thus suggest that thermoregulatory movements are not adjusted in response to movement-generated directional information derived from the temperature gradient. The primary determinant of thermoregulatory behavior in fish may require a more complex awareness of the thermal arrangement of the environment than can be furnished by the instantaneous perception of the local gradient structure.
Reversal of renovascular hypertension: role of the renal medulla
Authors: Swales J. D. , Bing R. F. , Edmunds M. E. , Russell G. I. , Thurston H.
Published: April 2011

The fall in blood pressure, which occurs when renovascular hypertension is corrected surgically, offers a means of elucidating the factors responsible for blood pressure control. When Goldblatt two-kidney, one-clip hypertension in the rat is reversed by unclipping the renal artery, or by removal of the ischaemic kidney, restoration of normal blood pressure is due to a fall in peripheral resistance. This is associated with sodium retention and cannot be modified by inhibition of the renin–angiotensin system. The fall is, however, partially inhibited by chemical removal of the renal medulla by means of 2-bromo-ethylamine hydrobromide. When normal rats are chemically medullectomized, moderate hypertension is produced, which cannot be attributed to the renin–angiotensin system or sodium retention. It is concluded that a renomedullary vasodepressor system is ablated by chemical medullectomy: further, this system plays a role in the surgical correction of Goldblatt hypertension.
Cerebral osmoregulation of renal sodium excretion—a response analogous to thirst and vasopressin release
Authors: McKinley Michael J. , Denton Derek A. , Coghlan John P. , Harvey Rodney B. , McDougall John G. , Rundgren Mats , Scoggins Bruce A. , Weisinger Richard S.
Published: April 2011

Studies in sheep have shown that renal excretion of sodium may be under osmoregulatory control. When sheep become dehydrated, or are infused intravenously with hypertonic saline, they increase renal Na excretion in addition to secreting vasopressin and developing a thirst. These natriuretic, antidiuretic, and dipsogenic responses to dehydration and hypertonicity can be greatly reduced by lowering the cerebrospinal fluid NaCl concentration or by prior ablation of tissue in the anterior wall of the third ventricle. Lowering of cerebrospinal fluid NaCl concentration also prevents postprandial natriuresis which normally occurs in association with a postprandial increase in plasma Na concentration and tonicity. We propose that there is a cerebral osmoregulatory control of Na excretion which may interact with volume influences from the cardiovascular system to regulate renal Na output. The effector mechanism from brain to kidney mediating such cerebral control of Na excretion is probably hormonal.
Carnitine and carnitine esters in rat bile and human duodenal fluid
Authors: Hamilton J. J. , Hahn P.
Published: April 2011

The recent discovery of carnitine and its esters in rat bile has led to much speculation about its role. The objectives of these studies were to investigate the origin of carnitine esters in rat bile and to study the presence of carnitine in human bile-rich duodenal fluid. Bile was collected from chow-fed (n = II), fasted (72 h, n = 6), and fasted plus 2-tetradecylglycidic acid administered (72 h, n = 5) male adult rats under sodium pentobarbital anaesthesia. Carnitine and carnitine ester content was measured in the bile and compared with serum and liver carnitine. Bile from fed rats was found to contain 80% acylcarnitine, one-third of this as long chain carnitine esters. Fasting caused no change in the secretion rate of acylcarnitine into the bile, although long chain carnitine ester secretion almost doubled. Conversely, 2-tetradecylglycidic acid treatment caused a decrease in long chain carnitine ester secretion into bile. Duodenal fluid was collected from patients with suspected cholelithiasis (n = 10) before and after pancreozymin–cholecystokinin injection. Although carnitine concentration was variable, it was consistently 80% esterified. These data associate bile carnitine with hepatic carnitine metabolism and establish the presence of carnitine and carnitine esters in the human intestinal lumen.
Multiple effects of phorbol ester on secretory activity in rabbit gastric glands and parietal cells
Authors: Brown Milton R. , Chew Catherine S.
Published: April 2011

Acid secretory activity and respiration in rabbit gastric glands are stimulated by cAMP-dependent and -independent agonists. Potentiation between agonists suggests interaction of the activation pathways. Regulation of secretory response by protein kinase C was investigated with 12-O-tetradecanoyl phorbol-13-acetate (TPA). TPA elevated basal respiration, pepsin release, and acid secretion but inhibited histamine and carbachol stimulation of acid secretion by gastric glands, as measured by [dimethylamino-14C]aminopyrine accumulation. The inhibition of histamine response was specific for protein kinase C activators, occurred after a 20-min lag, and was not reversed by removal of TPA after 3 min of preincubation. TPA pretreatment inhibited acid secretory responses to cholera toxin and forskolin but enhanced the response to cAMP analogues. Cholera toxin and pertussis toxin simulated ADP-ribosylation of 45 and 41 kDa proteins, respectively, in parietal cell membranes. Therefore, both stimulatory (Gs) and inhibitory (Gi) GTP binding proteins of adenylyl cyclase appear to be present in parietal cells. Pretreatment with pertussis toxin attenuated PGE2 but not TPA inhibition of histamine stimulation of aminopyrine accumulation. Thus, the inhibitory effect of TPA does not appear to be associated with an action on Gi. The results with histamine and carbachol suggest that protein kinase C may regulate both cAMP-dependent and -independent stimulation of parietal cell acid secretion.
Extensibility changes of calcified soft tissue strips from human aorta
Authors: Sherebrin M. H. , Bernans H. A. , Roach Margot R.
Published: April 2011

Some degree of calcification was noted in more than half of the 59 aortas of individuals aged from 15 to 88 we have examined at autopsy. The calcification, which is determined by x-raying the opened and flat aorta, is in patches. We have studied the influence of calcification on stress versus strain, breaking strength, and modulus of elasticity of strips of aorta to determine its importance in vascular disease. Strips of aortic wall 5 × 30 mm were cut with orientation parallel or perpendicular to the vessel axis. Elongation versus load was measured with an Instron tensile testing machine. The true stress and true strain were calculated for both calcified and uncalcified strips from the thoracic and abdominal regions in both orientations. From the stress–strain curve the following values were selected: strain, stress, and slope at 80 mmHg equivalent pressure (1 mmHg = 133.3 Pa); maximum stress, strain, and slope; and breaking stress, strain, and slope if the sample broke. There were statistically significant differences in 13 of the 36 categories between calcified and uncalcified strips. The breaking strength and strain is lower in the calcified strips. The stress–strain curve for the uncalcified strip was mathematically transformed by reducing the amount of elongation so that the curve coincided with that of the calcified strip for eight matched pairs from the same individuals. The calcification appears to immobilize part of the strip, probably causing the boundary of the calcified tissue to be a region of high stress where tissue breakdown can occur.
Nonadditive interactive effects of polychlorinated biphenyl congeners in rats: role of the 2,3,7,8-tetraehlorodibenzo-p-dioxin receptor
Authors: Leece Brian , Denomme Mary Anne , Towner Rheal , Li Angela , Landers Jamie , Safe Stephen
Published: April 2011

Administration of 3,3′,4,4′,5,5′-hexa-, 3,3′,4,4′,5-penta-, and 2,3,3′,4,4′5-hexa-chlorobiphenyl to immature male Wistar rats caused a thymic atrophy at high dose levels (1.25, 1.0, and 100 μmol/kg, respectively) and induced the hepatic cytochrome P-448 dependent monooxygenases (benzo[a]pyrene hydroxylase and ethoxyresorufin O-deethylase) at both high and low (0.25, 0.01, and 5 μmol/kg, respectively) doses. In contrast, 2,2′,4,4′,5,5′-hexachlorobiphenyl (HCBP) (300 μmol/kg) did not elicit any of these effects but elevated hepatic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cytosolic receptor protein levels (threefold) as previously reported. The effects of hepatic receptor modulation by 2,2′,4,4′,5,5′-HCBP (300 μmol/kg) on the enzyme induction activities of 3,3′4,4′,5-penta-, 3,3′,4,4′,5,5′-hexa-, and 2,3,3′,4,4′,5-hexa-chlorobiphenyl were dose-dependent; no interactive effects were observed at high (toxic) doses of these compounds, whereas apparent synergistically increased hepatic microsomal monooxygenase induction activities were noted at the lower submaximal induction doses. It was concluded that the increased responsiveness of the rats was due to elevated hepatic 2,3,7,8-TCDD receptor levels.
Antagonism of N-methyl-D-aspartate (NMDA) evoked increases in cerebellar cGMP and striatal ACh release by phencyclidine (PCP) receptor agonists; evidence for possible allosteric coupling of NMDA and PCP receptors
Authors: Wood Paul L. , Steel Douglas , McPherson Stephen E. , Cheney Darwin L. , Lehmann John
Published: April 2011

A comparison was made of the actions of phencyclidine receptor agonists and N-methyl-D-aspartate (NMDA) receptor antagonists in two well-defined neurochemical test systems. These included (i) [3H]acetylcholine release from striatal cholinergic interneurons in vitro, a system known to be positively modulated by corticostriatal excitatory amino acid inputs in vivo; and (ii) cerebellar cGMP levels in vivo, an indicator of cerebellar Purkinje cell activity, which is also modulated by excitatory amino acid inputs. Using these neuronal systems, we report that phencyclidine receptor agonists demonstrated a noncompetitive antagonism of NMDA receptor agonist actions.
Vagal inhibition of gastric acid secretion: evidence for cholecystokinin as the inhibitory transmitter in the mouse stomach
Authors: Davison J. S. , Najafi-Farashah A.
Published: April 2011

In the mouse isolated stomach preparation, electrical stimulation of vagal preganglionic fibres activated cholinergic excitatory pathways and noncholinergic inhibitory pathways to the gastric glands. Both were blocked by hexamethonium suggesting that there is at least one nicotinic synapse in each. The inhibitory vagal response was blocked by dibutyryl cyclic GMP, an established cholecystokinin antagonist which abolished cholecystokinin-mediated inhibition of acid secretion. It is suggested that there are direct inhibitory vagal pathways to the gastric glands and that cholecystokinin may be the inhibitory transmitter.
Secretion of 17α-hydroxyprogesterone, androstenedione, and estrogens by porcine granulosa and theca interna cells in culture
Authors: Tsang Benjamin K. , Taheri Arezoo , Ainsworth Louis , Downey Bruce R.
Published: April 2011

The steroid secreting activities of dispersed granulosa and theca interna cells from preovulatory follicles of prepubertal gilts 72 h after pregnant mare's serum gonadotropin treatment (750 IU) were compared. The cells were cultured for 24 h with or without steroid substrate (10−8 to 10−5 M progesterone, 17α-hydroxyprogesterone, or androstenedione), FSH (100 ng/mL), LH (100 ng/mL), and cyanoketone (0.25 μM, an inhibitor of 3β-hydroxysteroid dehydrogenase). Granulosa cells cultured alone secreted mainly progesterone. Theca interna cells secreted mainly 17α-hydroxyprogesterone and androstenedione, with secretion being markedly enhanced by LH. In the presence of cyanoketone, which inhibited endogenous progesterone production, theca interna but not granulosa cells were able to convert exogenous progesterone to 17α-hydroxyprogesterone and androstenedione, and exogenous 17α-hydroxyprogesterone to androstenedione and estradiol-17β in high yield. The secretion of the latter steroids from exogenous substrates was unaffected by LH. Theca interna cells secreted more estradiol-17β than did granulosa cells in the absence of aromatizable substrate, but estradiol-17β secretion by the latter was markedly increased after the addition of androstenedione. These apparent differences in steroid secreting activity between the cell types suggest that the enzymes responsible for conversion of C21 to C19 steroids, i.e., 17α-hydroxylase and C17,20-lyase, reside principally in the theca interna cells. However, aromatase activity appears to be much higher in granulosa cells.
Stimulation of colonic peristalsis by vasopressin: electromyographic study in normal subjects and patients with chronic idiopathic constipation
Authors: Schang Jean-Claude , Dapoigny Michel , Devroede Ghislain
Published: April 2011

The effects of vasopressin on colonic motility were investigated in 6 healthy subjects and 10 patients with chronic idiopathic constipation. Recordings of the colonic myoelectric spiking activity were performed by means of 50-cm long silastic tube, equipped with four bipolar ring electrodes fixed at 10-cm intervals, which was introduced by flexible colonoscopy into the left colon. Tracings were obtained for 1 h in the fasting state and for another hour after an intramuscular injection of a pharmacological dose of vasopressin (0.3 U/kg). The different types of spike bursts generated by the colonic smooth muscle were compared before and after vasopressin injection. In both controls and patients, the tracings showed (i) rhythmic stationary spike bursts (RSB) that were seen at only one electrode site; and (ii) sporadic bursts that were either propagating over all four electrodes (SPB) or nonpropagating (SNPB). Injection of vasopressin in controls was followed for 30 min by a significant increase in the number of propagating bursts from 2.7 ± 0.6 (mean ± SEM) to 5.2 ± 1.4 bursts (p < 0.05); RSB and SNPB were not altered by vasopressin. In the constipated patients, the number of propagating bursts during the control period was significantly lower (0.8 ± 0.2 bursts/30 min) than in the volunteers (p < 0.05). After vasopressin, there was a significant increase to 3.6 ± 0.8 bursts/30 min(p < 0.001); RSB and SNPB also did not show significant alteration after vasopressin. Finally, 4 out of the 10 patients passed stools during the recording session. Since propagating bursts are known to be associated with colonic propulsion, these results indicate that vasopressin at pharmacological doses may stimulate colonic peristalsis and therefore, may be useful in the treatment of some severe idiopathic constipations.
Nutrition and muscle potassium: differential effect in rat slow and fast muscles
Authors: Fong C. N. , Atwood H. L. , Jeejeebhoy K. N. , Charlton M. P.
Published: April 2011

The effects of malnutrition on intracellular K+ activity, (aK)i, and membrane potential, Em, were measured by means of double-barrelled K+ -selective microlectrodes in the soleus and gastrocnemius muscles of the rat. (aK)i and Em were measured in vivo in normal anaesthetized animals and in rats subjected to one of two diet restrictions: a 2-day fast or a long-term hypocaloric diet. In the soleus muscle, (aK)i fell by similar amounts in both 2-day fasted and long-term hypocalorically fed rats, while Em depolarized significantly only in hypocalorically fed rats. In the gastrocnemius muscle, neither the 2-day fast nor the hypocaloric diet affected (aK)i or Em. It is suggested that the selective loss of K+ from the soleus muscle may be related to its activity pattern.
Excitation of rat hippocampal neurones by the stereoisomers of cis- and trans-1-amino-1,3-cyclopentane dicarboxylate
Authors: Curry K. , Magnuson D. S. K. , McLennan H. , Peet M. J.
Published: April 2011

Intracellular recordings were obtained from rat hippocampal neurones during the microiontophoretic ejection of the stereoisomers of cis- and trans-1-amino-1,3-cyclopentane dicarboxylate into the dendritic region (stratum radiatum) of the impaled cells. L-(+)-cis-1-Amino-1,3-cyclopentane dicarboxylate, D-(+)-trans-1-amino-1,3-cyclopentane dicarboxylate, and 1-(−)-trans-1-amino-1,3-cyclopentane dicarboxylate all evoked patterns of excitation resembling that elicited by kainate. All of these responses were unaffected by D-(−)-2-amino-5-phosphonovalerate but were antagonized at comparable currents by kynurenate. The excitation produced by D-(−)-cis-1-amino-1,3-cyclopentane dicarboxylate was similar to that evoked by N-methyl-D-aspartate. At low ejection currents a slow depolarization triggered rhythmic burst firing, each burst consisting of a depolarizing shift in membrane potential upon which were superimposed four to five action potentials. These responses were antagonized both by D-(−)-2-amino-5-phosphonovalerate and by kynurenate. The results are discussed with respect to the conformational requirements considered to be necessary for interaction at the kainate and N-methyl-D-aspartate receptors on CA1 pyramidal neurones. It is important to note that the isopropylene side chain of kainate is absent from the 1-amino-1-3-cyclopentane dicarboxylate molecule.
Effect of diabetes on vascular smooth muscle function in normotensive and spontaneously hypertensive rat mesenteric artery
Authors: Agrawal D. K. , McNeill J. H.
Published: April 2011

We have examined the functional responses to α-adrenoceptor agonists (α1-selective: methoxamirte and phenylephrine; α2-selective: clonidine and B-HT 920; non-selective: norepinephrine, serotonin and K+ in ring segments of mesenteric artery of control and streptozotocin-induced diabetic spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Systolic blood pressure and contractile responses were examined after 12 weeks of diabetes. There was no significant change in the diabetic WKY rats as compared with the control WKY rats. However, diabetic SHR had significantly less hypertension than control SHR. Responses to serotonin and α2-adrenoceptor agonists were augmented significantly in arteries from control SHR animals as compared with vessels from WKY animals. There was no significant difference in the force of contraction generated by other agonists in both nondiabetic groups. Responses to all agonists in WKY diabetic and to methoxamine and K+ in SHR diabetic arteries were increased as compared with their respective controls. ED50 values for each agonist were similar in all groups. Indomethacin (5 μM) shifted the dose–response curve to norepinephrine to the right in arteries from all groups of animals. However, in the diabetic SHR and WKY, there was a significant reduction in norepinephrine maximum response. Nifedipine was more potent in inhibiting the contraction to K+ and serotonin in WKY diabetic arteries as compared with WKY controls. However, nifedipine inhibited the responses to all agonists with equal potency in the control and diabetic SHR vessels. These results suggest the involvement of α2-adrenoceptors and serotonin receptors in the development and (or) the maintenance of hypertension. Furthermore, the hyperresponsiveness of the diabetic vessels could be due to an alteration in the postreceptor excitation–contraction coupling, possibly involving prostaglandin and an increased activity of calcium channels.
Dependency of lactose absorption on lactase activity in starved rats
Authors: Leichter Joseph , Goda Toshinao , Koldovsky Otakar
Published: April 2011

The effects of starvation on intestinal disaccharidase activities and disaccharide absorption were studied in rats. Adult male rats were starved for either 16 or 72 h and the specific activity of lactase and sucrase was determined together with the absorption of lactose, sucrose, and glucose in vitro by the everted sac technique. The specific activity of lactase was significantly higher and the specific activity of sucrase was lower in the 72-h starved animals when compared with the 16-h starved group. The higher specific lactase activity in the 72-h starved animals was reflected in enhanced absorption of lactose as determined by the transfer of the constituent monosaccharides into the serosal fluid. The transfer of glucose into the serosal fluid by the glucose sac was also higher in the 72-h starved rats but not to the same extent as that of lactose. The absorption of sucrose was not significantly different between the two groups of animals. This study shows that the increase of intestinal lactase activity induced by starvation of adult rats correlates with in vitro increased lactose absorption.
Characteristics of phorbol ester stimulated growth hormone release: inhibition by insulin-like growth factor I, somatostatin, and low calcium medium and comparison with growth hormone releasing factor
Authors: Sheppard M. S. , Eatock B. A. , Bala R. M.
Published: April 2011

TPA (12-O-tetradecanoylphorbol 13-acetate) is one of a class of compounds known as tumor promoters which perturb the inositol phosphate pathway in a number of cells. We have used TPA in a dispersed rat adenohypophysial cell system to probe the characteristics of growth hormone (GH) release. In this system we have found that the cells release GH in response to low concentrations of TPA: the EC50 was 0.23 ± 0.05 nM (n = 6) and the maximal concentration was 5 nM. However, the maximal TPA-induced GH release was only 34 ± 5% (n = 7) of the GH released by maximal growth hormone releasing factor (GRF) suggesting TPA releases a subpool of stored GH. Both somatostatin and insulin-like growth factor I inhibit GH release stimulated by TPA to the same extent as that stimulated by GRF, showing that the normal inhibitory control mechanism of release is not altered. Incubation in a low calcium medium that totally blocks GRF-stimuiated GH release also inhibits TPA-stimulated GH release. The calcium channel blockers nifedipine and diltiazem both partly inhibit GRF- and TPA-stimulated GH release, showing some component of the calcium necessary for GH release arises from influx across the cell membrane.
New insights on the mechanism of the alcohol-induced increase in portal blood flow
Authors: Orrego H. , Carmichael F. J. , Israel Y.
Published: April 2011

Acute administration of ethanol increases portal blood flow by 40–60%. This increase in blood flow compensates for the increase in O2 consumption that follows alcohol intake and may play a protective role against hypoxic hepatocellular necrosis. We have investigated the mechanism of this hemodynamic effect of ethanol in the rat using the labeled microsphere technique. We ruled out a direct role of systemic glucagon and of acetaldehyde in mediating the increase in portal flow. However, the increase in flow is maximal at a blood ethanol concentration of 3.5 mM, corresponding to that required to achieve the Vmax of alcohol dehydrogenase, and is suppressed by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase. Alcohol ingestion results in zonal liver hypoxia and in increases in acetate, both of which have been shown to increase the levels of adenosine, a potent vasodilator, in blood and tissues. Ethanol produces a 400% increase in arterial adenosine. Adenosine infusion leads to a dose-dependent increase in portal blood flow of up to 100%, an effect that is suppressed by administration of 8-phenyltheophylline, an antagonist of adenosine at A1 and A2 receptors. Similarly, the ethanol-induced increase in portal blood flow is fully suppressed by 8-phenyltheophylline. In conclusion, adenosine appears to play an important role in the mechanism by which ethanol increases portal blood flow.