bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of potassium and chloride on the membrane potentials of P815 mastocytoma tumor cells
Authors: Geduldig D. , Jayasinghe D. , Lamb D. , March R.
Published: April 2011

The steady-state transmembrane potentials of P815 mastocytoma cells were recorded when the cells were bathed in salines of different compositions. In the normal growth medium (RPMI 1640 with added fetal calf serum) the mean membrane potential was −8.7 mV (SEM ± 0.4, n = 22). A family of Tris-buffered salines (TBS), modeled from Dulbecco's modified PBS (289 mosmol, 169 milliionic strength units, pH 7.5), having different K+ and different Cl concentrations, were designed and used to bathe the tumor cells. All of the TBS solutions had constant, but reduced levels of ionized Ca2+. In the absence of external Cl, an increase of external K+ from 2 to 20 mM results in a 5.7 mV depolarization. In the presence of external Cl the same increase in external K+ results in a 2.1 mV depolarization. The presence of 145 mM Cl resulted in a steady-state depolarization (for either level of K) of about 50%. One explanation for these results would be the presence of an inward-going active Cl transport.
Assessing environmental toxins by human population effects
Authors: Lees R. E. M.
Published: April 2011

The impact of toxins on the health of human populations can only be accurately assessed by epidemiologic methods. The investigation of toxin–disease associations in human populations and the accurate interpretation of data are often very difficult because of the existence of multiple confounding variables and the unrepresentativeness of sample or study populations.Factors influencing the deduction of cause and effect relationship rather than simple association are discussed, as is the need for continued development of epidemiological surveillance techniques.
Some functional and morphological characteristics of an acutely dispersed purified cell suspension of rat lactotrophs prepared with Percoll
Authors: Milligan John V. , McComb D. J. , Ryan N. , Croxford R.
Published: April 2011

A cell suspension containing more than 90% lactotrophs can be prepared from enzymically dispersed adenohypophyses obtained from male rats pretreated with estradiol. The lactotrophs are separated from the mixed cell population by centrifugation on a discontinuous density gradient prepared from a commercial preparation of colloidal silica (Percoll, Pharmacia). The method allows isopycnic separation of these delicate cells under very mild conditions; normal ionic strength and normal pH were maintained throughout the gradient, centrifugal acceleration did not exceed 1600 × g, and all procedures were done at room temperature. Histological verification that at least 90% of the cells were lactotrophs was done using specific immunoperoxidase staining. The functional capability of the lactotrophs was established by measuring the dose–response to the dopamine agonist bromocriptine and to thyrotropin-releasing hormone (TRH). Bromocriptine decreased spontaneous release in a dose-related way over the concentration range of 10−10 to 10−8 M. TRH, which causes an in vivo release of prolactin (PRL) in estrogen-primed rats, produced a dose-related increase in the release of PRL over the concentration range of 3 × 10−10 to 3 × 10−8 M after the high spontaneous release had been previously reduced by bromocriptine (3 × 10−8 M).
Effect of adrenal denervation on the glucose, insulin, and glucagon responses to exercise in sheep
Authors: Brockman Ronald P.
Published: April 2011

Previous studies suggest that adrenal catecholamines mediate, in part, the glucose and pancreatic hormonal responses to exercise in sheep. This was examined in sheep whose adrenals were denervated to prevent stress-induced changes in catecholamine secretion. The innervation to the right adrenal gland was severed and the left adrenal was removed. Adrenal denervation was associated with a reduction in exercise-induced hyperglycemia and impairment, as measured by [2-3H]glucose, of the increase in glucose appearance during the first 10 min of exercise and increased metabolic clearance rate of glucose after 20 min of exercise. Insulin concentrations were significantly higher during exercise after adrenal denervation than in the controls. Adrenal denervation did not alter the rise in glucagon due to exercise. These effects are consistent with adrenomedullary hormonal stimulation of hepatic and muscular glycogenolysis, either directly or indirectly through the regulation of insulin secretion during exercise in sheep.
Reflex control of arterial compliance in rabbits
Authors: Osberg Catherine , Langille B. Lowell
Published: April 2011

Reflex control of arterial compliance of the hind limb circulation has been assessed in rabbits. Brief interruption of constant flow perfusion of the hind limb produced a pressure decay that was determined by hind limb vascular resistance and arterial compliance; thus independent assessment of resistance was used to derive compliance. Experiments were performed under control conditions, during baroreceptor deactivation and during stimulation of water-sensitive receptors in the upper respiratory airways. Hind limb vascular resistance increased by more than 80% when either reflex was elicited, but parallel changes in the pressure decay curves were not observed. Instead a decrease in arterial compliance compensated for the elevation in vascular resistance. These results indicate that the dynamic elastic properties of the arterial tree can be reflexly controlled such that the time course of adjustments of arterial pressure is relatively independent of vascular resistance.
Plasma parathyroid hormone and divalent cation response to induction of acute metabolic acidosis
Authors: Oster James R. , Perez Guido O. , Canterbury Janet M. , Alpert Helen C. , Vaamonde Carlos A.
Published: April 2011

Since the effect of acute administration of acid upon blood magnesium and parathyroid hormone (PTH) is unclear we infused anesthetized dogs with saline (controls), HCl, lactic, and methylmalonic acids for 3 h. In all groups but lactic acid, plasma magnesium decreased; ionized calcium levels were increased by all three acids. Nevertheless, PTH increased in each of six dogs following methylmalonic acid and decreased in four of six animals after lactic acid. The decrease in plasma magnesium concentration after methylmalonic acid appeared to be an important factor in explaining the disparate PTH changes in these two groups because concomitant magnesium administration obviated the increases in PTH in four of six additional methylmalonic acid-infused dogs.
Experimental arrhythmia elicited by low K perfusion
Authors: Ruiz-Ceretti E. , Ponce-Zumino A. , Blaney R. , Chartier D.
Published: April 2011

Isolated rabbit hearts undergo ventricular depolarization when exposed to 0.5 mM K – Krebs during 30 to 45 min. A ventricular tachyarrhythmia develops when these hearts are allowed to repolarize in 1.5 mM K – Krebs. Ventricular fibrillation usually follows. These arrhythmias do not cease spontaneously. Initially, perfusion with 0.5 mM K hyperpolarized the membrane to −100 ± 1.2 mV [Formula: see text], decreased the plateau level, greatly increased the action potential duration, and slowed down intraventricular conduction, despite the level of membrane polarization and a high rate of rise of the upstroke. After a delay of 15 to 30 min, a progressive depolarization occurred and a stable potential level of −61 ± 1.9 mV was reached. The arrhythmia elicited by perfusion with 1.5 mM K was of ventricular origin but did not appear when the previous exposure to 0.5 mM K was reduced to 10 min. Addition of verapamil (1.0 μM) to the 1.5 mM K medium did not prevent the early appearance of the arrhythmia, but restored driven electrical activity after variable delays despite the persistence of alterations in the action potential configuration. Verapamil also abolished the slow depolarizing phase of the upstroke. It is proposed that the abnormal electrical activity arose in a partly depolarized Purkinje network and it may have been triggered by the electrical nonhomogeneity created by the repolarization of ventricular cells in an extracellular K+ concentration of 1.5 mM.
The effect of displacement current on the measurement of reversal potential in squid giant axon
Authors: Wodlinger H. , Kunov H. , Atwood H. L.
Published: April 2011

The measurement of the sodium reversal potential (Erev), as that potential where the early current reverses during voltage clamp, was found to exceed the true Erev by 4.1 ± 2.4 mV (mean ± SD) in squid giant axon. This error was found in both intact and internally perfused axons and is due to interference from the displacement current. This was shown by subtraction of the current records obtained before and after treatment with tetrodotoxin (TTX). The error in Erev is proportional to [Formula: see text] where Td is the time constant of the displacement current.
The effect of dietary protein quantity on the activity of UDP-glucuronyltransferase and its physiological significance in drug metabolism
Authors: Merrill Jill C. , Bray Tammy M.
Published: April 2011

Low dietary protein has been shown to induce the activity of rat hepatic UDP-glucuronyltransferase (UDPGTase) as measured in vitro. The assay of UDPGTase in vitro is hampered by the need to solubilize the microsomal membrane, without destroying the physiological significance of the measurements. The present work was to determine the effect of dietary protein on the activity of UDPGTase and on the activity of UDP-glucose dehydrogenase. Chloral hydrate induced sleeping time was used as a bioassay for UDPGTase, confirming the physiological significance of the in vitro analysis. Sixty male rats were maintained on three different protein levels (7.5, 15, and 45%) for 16 days. Fifteen rats from each group were sacrificed and hepatic UDPGTase, cytochrome P-450, UDP-glucose dehydrogenase, and alcohol dehydrogenase were assayed. Five rats from each group were dosed with 7.5% chloral hydrate (4.8 mL/kg body weight) to measure sleeping time. Rats on 7.5% dietary protein had significantly higher UDPGTase activity than rats fed either 15 or 45% protein diets. These differences in enzyme activity in vitro correlated with the differences in chloral hydrate sleeping time. Dietary protein was not found to affect the activity of UDP-glucose dehydrogenase as measured in vitro.
Calculation of the rate of gluconeogenesis from the incorporation of 14C atoms from labelled bicarbonate or acetate
Authors: Hetenyi Jr. G. , Lussier B. , Ferrarotto C. , Radziuk J.
Published: April 2011

The rate of gluconeogenesis in vivo may be estimated by the incorporation of 14C atoms from a labelled precursor into plasma glucose or by introducing 14C atoms into the pathway of gluconeogenesis at known stages by metabolites which in themselves do not contribute to the net synthesis of glucose (e.g., bicarbonate or acetate). The purpose of the investigation was to examine some of the assumptions involved in the calculation of gluconeogenic flux by the second approach. [2- 14C]acetate or NaH 14CO3 was infused to dogs, and the specific activity (SA) of glucose, bicarbonate CO2, urea, and lactate in the plasma was followed. The incorporation of 14C atoms from [2- 14C]acetate into glucose allows the calculation of the degree of underestimation of glucose formation due to "metabolic exchange" in the hepatic oxaloacetate pool. The possible error introduced into this calculation by the incorporation of 14C atoms from 14CO2 (a product of acetate oxidation) was found to be negligible, but the heavy labelling of plasma lactate may possibly affect the estimate of metabolic exchange. It is proposed that in the calculation of the rate of gluconeogenesis from infused NaHCO3 the SA of hepatocellular and not of plasma bicarbonate CO2 should be related to that of plasma glucose. This latter is expected to equal the SA of plasma urea, since the sole precursor of its C atom is hepatocellular CO2. The rate of gluconeogenesis estimated from the SA(glucose)/SA(urea) ratio and a previously estimated correction factor for metabolic exchange was 51% of the glucose production in the postabsorptive state. The nearly identical SA(urea)/SA(CO2) ratios, irrespective of the tracer infused, indicated that plasma CO2 is a major precursor of urea C and that a large fraction of injected acetate is oxidized by extrahepatic tissues.
Fats in nutrition
Authors: Walker Brian L.
Published: April 2011

Investigation of the relationship of diet to blood lipids and atherosclerosis has dominated the field of lipid nutritional biochemistry for the past 25 years. Although this subject has consumed considerable time, effort, and research funds, it has also proved beneficial to other areas of lipid biochemistry by attracting qualified people to the field and by initiating development of sophisticated methodology and instrumentation required for progress in those areas. The development of capillary gas–liquid chromatography and high-performance liquid chromatography, together with more extensive computer control and processing of data, should accelerate progress in all areas of lipid biochemistry. In the next 25 years, I expect to see extensive investigation of dietary hydrogenated fats and their constituent isomeric fatty acids. Specificity of deposition in animal tissues, effects on blood lipids and coronary heart disease, and their relationship to polyunsaturated fatty acids and prostaglandins are among the topics likely to receive attention. The prostaglandins, prostacyclins, thromboxanes, and leukotrienes will continue to receive attention in the near future, and the role of diet in modulating the concentrations of these compounds in blood and other body tissues is a promising area of active research. The discovery of abnormalities in polyunsaturated fatty acid metabolism in pathological conditions in man has renewed interest in these dietary components. Association of neurological abnormalities with lack of linolenic acid metabolites should stimulate further investigation of the role of the n-3 series acids in central nervous system function.
Effect of protein deficiency on endogenous pyrogen-mediated acute phase protein responses
Authors: Bell R. , Hoffman-Goetz L.
Published: April 2011

Endogenous pyrogen (EP) is known to trigger a rise in the plasma concentrations of various acute phase reactant proteins. This study describes the effects of chronic protein deficiency in rabbits on EP-mediated changes in the plasma concentrations of fibrinogen, albumin, and α2-macroglobulm. Injection (i.v.) of EP from healthy donors into protein-deprived rabbits produced a smaller rise in plasma fibrinogen and α2-maeroglobulin, and a smaller fall in plasma albumin than injection of EP into controls. Injection of EP, obtained from malnourished donors, into healthy rabbits also resulted in an attenuation of the acute phase protein response. These data are consistent with the hypothesis that EP activity is influenced by the nutritional status of both the donor and recipient of EP.
Effects of mixed-function oxidase inducers and inhibitors on cytochrome P-450 content, gel electrophoresis profiles, and 3-methylindole-induced lung toxicity in goats
Authors: Leung Cecilia T. , Carlson James R. , Breeze Roger G.
Published: April 2011

Effects of mixed-function oxidase inducers and inhibitors on cytochrome P-450 content, gel electrophoresis profiles, and 3-methylindole-induced lung injury were studied in goats. In the first experiment, goats were pretreated with phenobarbital (PB), 3-methylindole (3MI), 3-methylcholanthrene (3MC), or SKF 525-A. Liver, lung, and kidney microsomes were used for cytochrome P-450 and gel electrophoresis studies. Although pulmonary cytochrome P-450 was not affected by any of the pretreatments, hepatic cytochrome P-450 significantly increased (P < 0.05) after PB and 3MC pretreatment. All pretreatment resulted in changes in liver gel profiles in the 43 000 to 68 000 molecular weight region, but only PB and 3MI pretreatment altered gel profiles in the lung. In the second experiment, pretreated goats were infused with 3MI. The relative severity of lung injury in these animals, based on clinical signs, lung lesions, lung weight, and mean survival time was as follows: SKF 525-A pretreated group > PB-pretreated group = unpretreated group > 3MI-pretreated group ≥ 3MC-pretreated group. The results indicate that changes in 3MI-induced lung injury are accompanied by changes in gel profiles in the molecular weight region of 43 000 to 68 000.
The effects of "dead space" and urine flow changes on measurements of glomerular filtration rate by clearance methods
Authors: Keeler R.
Published: April 2011

The errors inherent in making whole-kidney measurements of glomerular filtration rate or renal plasma flow during periods of changing urine flow are discussed. The quantitative relationships of these errors to the dead space of the collecting system, changes in urine flow, and the duration of the collection period are presented.
Effects of chronic mestranol and (or) norethindrone treatment on ethanol-associated decreases in hepatic benzo[a]pyrene hydroxylase activity and increases in central vein fat accumulation in the female Wistar rat
Authors: Warren B. L. , Bellward G. D.
Published: April 2011

Wistar rats were fed a liquid diet, Sustacal®, which contained ethanol (40% of calories) or isocaloric sucrose. Mestranol and norethindrone in pharmacological doses were also administered via this diet. Hepatic microsomal benzo[a]pyrene (BP) hydroxylase, epoxide hydrase, aniline hydroxylase, and aminopyrine-N-demethylase activities were measured after 3 and 6 months treatment. In addition, hepatic histology and electron microscopic studies were carried out in an attempt to monitor ethanol-associated fat accumulation in the central vein region. Mestranol or norethindrone alone for 3 months produced an elevation of BP hydroxylase activity which was no longer present after 6 months treatment. When compared with the 3-month time period, BP hydroxylase activity was significantly decreased in livers of animals which had ingested ethanol (group 10 vs. group 2), ethanol plus mestranol (group 12 vs. group 4), and ethanol plus norethindrone (group 14 vs. group 6) for 6 months. However, in the steroid-treated groups, the ethanol associated decreases were not as large as that seen without ethanol over the 3-month time period (group 11 vs. group 3; group 13 vs. group 5). No decrease was observed in the combined steroid plus ethanol-treated groups. Ethanol treatment for 6 months increased hepatic epoxide hydrase activity in both the nonsteroid and mestranol-treated group. Aniline hydroxylase was increased by ethanol in the combined steroid-treated animals. Otherwise there were no significant changes in the enzyme activities measured. Hepatic histology studies carried out on the 6-month ethanol-treated animals provided evidence of fat accumulation in the central vein region of the liver lobule, as expected. However, the steroid- plus ethanol-treated groups exhibited less apparent fat accumulation in the central vein region. These data do not support the hypothesis that mestranol and (or) norethindrone will accentuate the inhibition of liver BP hydroxylase or the central vein fat accumulation produced by chronic ethanol ingestion in the female rat.
Effects of age on muscarinic cholinergic receptors in rat myocardium
Authors: Narayanan Njanoor , Derby Jo-Anne
Published: April 2011

Atrial and ventricular myocardium from young (3–4 months old), young adult (7–8 months old), and aged (24–25 months old) rats were used to study the influence of age on cardiac cholinergic muscarinic receptors. The density of muscarinic receptors (expressed as fmol/mg protein or pmol/g tissue), determined by the specific binding of [3Hjquinuclidinyl benzyl ate ([3H]QNB), was significantly greater (24–29%) in atria of aged rats compared with that in atria of young or young adult rats. The muscarinic receptor density in ventricles was found to be essentially similar in all age groups studied. Antagonist as well as agonist binding characteristics of muscarinic receptor sites were examined in atria and ventricles from young and aged rats. No significant age-related difference was observed in the dissociation constant (KD) of atrial or ventricular receptors for the antagonist ligand [3H]QNB (KD apparent (nM): 1.04 ± 0.16 and 0.91 ± 0.12, respectively, for young and aged atria; 0.75 ± 0.08 and 0.76 ± 0.10, respectively, for young and aged ventricles). Similarly, the concentrations of muscarinic antagonist atropine and agonist carbachol causing 50% inhibition of [3H]QNB binding to the receptor sites (IC50) in atria and ventricles were not altered by age. Age-related difference was also not evident in the Hill coefficients for [3H]QNB, atropine, and carbachol. These results indicate that diminished responsiveness of the aged heart to vagal stimulation and exogenously administered cholinergic agents reported in the literature cannot be attributed to an age-related reduction in the number of cardiac muscarinic receptors or their affinities toward agonist or antagonist ligands.
Studies on canine gastric antrum smooth muscle: preparation and characterization of a plasma membrane enriched fraction
Authors: Grover A. K. , Oakes P. , Sipos S. N. , Kwan C. Y. , Garfield R. E.
Published: April 2011

A method is described for preparation of large amounts of a plasma membrane (PM) enriched fraction from the smooth muscle of dog antrum. It consists of preparing microsomes, treating them with ATP + EGTA + Mg, centrifuging in 30% sucrose and then centrifuging the resulting supernatant in 15% sucrose to yield the plasma membrane enriched fraction P6. The subcellular fractions obtained at various steps during purification were characterized by: 5′-nucleotidase and phosphodiesterase 1 as plasma membrane markers; cytochrome c oxidase as an inner mitochondrial marker; NADPH-cytochrome c reductase as a putative endoplasmic reticulum marker; electron microscopy; polyacrylamide sodium dodecyl sulfate slab gel electrophoresis. The distribution of ATP-dependent and independent Ca uptake in presence and absence of azide and the effect of 5 mM oxalate or 25 mM phosphate on this uptake was also examined. The fraction P6 consists of mostly smooth surface vesicles 164.3 ± 7.2 nm in diameter, has an exclusion volume of 9.7 μL/mg for [3H]inulin and 11.1 μL/mg for [3H]sucrose. P6 is maximally enriched in the ATP-dependent azide-insensitive Ca-uptake capacity and as compared with the postnuclear supernatant (SI) it shows a very small percent stimulation by oxalate and phosphate. The ATP-dependent Ca uptake by the P6 fraction occurs optimally at pH 7.0–7.4 and is much larger than the ATP-independent Ca uptake. At pH 7.1, the ATP-dependent Ca uptake occurs with a Km of 0.27 μM and a Hill coefficient >2 for Ca2+. Half maximum binding of Ca2+ occurred at 300 μM Ca2+. Ca ionophores A23187 and ionomycin inhibited the ATP-dependent Ca uptake, and if added after the uptake, these caused a release of the accumulated Ca2+. From these and other data it is concluded that this PM preparation contains a Ca transport system which can lead to formation of >1000-fold Ca2+ concentration gradient across the vesicle membrane in 1 min when extravesicular Ca2+ concentration is 0.3 μM. Thus this preparation is an extremely useful material for studying the mechanism of action of the Ca pump in smooth muscle plasma membrane.
Evidence for 1,25-dihydroxycholecalciferol (l,25-(OH)2D3) as a proaggregating agent in rat and human platelets
Authors: Agwu D. E. , Holub B. J.
Published: April 2011

In view of the established biological role for 1,25-dihydroxycholecalciferol (DHCC) in calcium mobilization and the significance of calcium availability in platelet activation, it was of interest to investigate the potential for DHCC to act as a proaggregating agent. The present results provide evidence that DHCC at a concentration of 0.01 μg/µL can both aggregate human platelets and potentiate ADP-induced platelet aggregation. DHCC was also capable of aggregating rat platelets.
The effect of tubular perfusion with PGE2, PGF2α, and PGI2 on the tubuloglomerular feedback control in the rat
Authors: Persson A. Erik G. , Hahne Bengt , Selén Göran
Published: April 2011

The prostaglandins (PG) of the renal medulla might affect the nephron and the cortical arteriolar function via the tubular route. To investigate this question PGE2 (1 μg/mL), PGF2α (10 μg/mL), or PGI2 (1 ng/mL) was added to the tubular perfusion solution when the characteristics of the tubuloglomerular feedback (TGF) control were measured. The experiments were performed on Sprague–Dawley rats. The proximal tubular stop-flow pressure (PSF) was measured upstream to a wax block, while at the same time the distal nephron was perfused with prostaglandin-containing or prostaglandin-free solutions at different flow rates varying from 0 to 50 nL/min. The maximal drop in PSF (ΔPSF) and the tubular flow rate at which 50% of the ΔPSF response was obtained, the turning point (TP), were determined. When PGE2 or PGF2α was added to the tubular perfusion solution in the control animals a significant increase in feedback sensitivity was found. After 10 min of tubular PGI2 perfusion the feedback sensitivity was almost completely abolished, with a ΔPSF of 0.8 mmHg (1 mmHg = 133.322 Pa) (control 8.4 mmHg) and a TP of >40 nL/min (control 22 nL/min). After nephrectomy the feedback sensitivity was reduced, with a ΔPSF of 2.0 mmHg and a TP of >40 nL/min. When PGE2 was added to the tubular perfusion solution in the uninephrectomized animals, the feedback sensitivity was increased to the control level, with a ΔPSF of 8.2 mmHg and a TP of 20.0 nL/min. The results show that PGI2 reduces and PGE2 and PGF2α increase TGF sensitivity when added to the tubular perfusion solution and that the decrease seen after nephrectomy is again reset to the control level by intratubular PGE2 administration.
Effect of thyroid hormone treatment on responses of the isolated working rat heart
Authors: Marriott M. Lynne , McNeill John H.
Published: April 2011

Hearts from rats pretreated either with L-triiodothyronine (T3) or with L-thyroxine (T4) exhibited changed function curve characteristics on the working heart apparatus compared with hearts from vehicle-treated rats. There was no supersensitivity of the hyperthyroid myocardium to the inotropic effect of isoproterenol as estimated by pD2 values. There were significant increases in +dP/dt and −dP/dt in hyperthyroid working hearts over the entire range of the function curve. T3 hearts showed much shorter relaxation times and total contraction times throughout the function curve. T4 hearts showed significantly reduced relaxation times and total contraction times as compared with control at all left atrial filling pressures under 15 cm of water. At high filling pressures T4 heart relaxation times and total contraction times were not different from control, but were however, significantly increased from those of T3 hearts. Area under the left ventricular pressure curve was unchanged by thyroid hormone pretreatment. Heart weight increased about 15% following either T3 or T4 treatment while the increases in (+) or (−) dP/dt and the left ventricular developed pressure (LVDP) were about 20–30%. The increase in cardiac mass certainly played a role in the increased cardiac function. Potency of isoproterenol in hyperthyroid working heart preparations was unchanged from control. The pD2 values, as determined from +dP/dt data, were 8.8 ± 0.15 for T3-treated hearts, 8.25 ± 0.40 for T4-treated hearts, and 8.18 ± 0.12 for euthyroid hearts. While the mechanism(s) for the altered performance of the hyperthyroid working heart are not absolutely known, possible biochemical and physiological changes which may be implicated are discussed.
Oxytocin resistance in Brattleboro rat adipocytes and comparative studies on insulin or oxytocin responsiveness in normal rat adipocytes
Authors: Hanif K. , Goren H. J. , Geonzon R. M. , Lederis K. , Hollenberg M. D.
Published: April 2011

We have evaluated factors, other than genetic, which might be related to the lack of an oxytocin-mediated insulinlike response (glucose oxidation; lipogenesis) in adipocytes from Brattleboro rats, homozygous for the diabetes insipidus trait (HoDI rats). The manoeuvres used in an attempt to restore the glucoregulatory responses to oxytocin in HoDI cells (increased glucose in the fat pad digestion medium; increased calcium concentration in the oxidation assay; estrogen treatment; use of [1-14C]glucose as substrate; inclusion of adenosine in the assay medium; vasopressin replacement therapy) uniformly failed to result in oxytocin activation of HoDI adipocytes, in contrast, the contractile responses of estrogenized HoDI rat uteri were indistinguishable from those of estrogenized normal rats. We conclude that the nonresponsiveness of the Brattleboro adipocytes to the glucoregulatory actions of oxytocin is not due to factors related to the conditions of the bioassay. On the other hand, in normal fat cells (from Sprague–Dawley and Long Evans rats), oxytocin responsiveness was augmented by a number of the manoeuvres mentioned above, most notably by the inclusion of either calcium (10 mM) or adenosine (10 μM) in the assay medium. Nonetheless, the maximum oxytocin responsiveness of adipocytes from Long Evans or Sprague–Dawley rats, under all conditions of assay, was still only a fraction (less than 20%) of the maximal response to insulin. The effect of adenosine on oxytocin action (increased sensitivity, without an effect on the maximum response) is in keeping with the previously observed effects of this nucleoside on the action of insulin; our results thus pointed to a new parallel in the action of insulin and oxytocin.
Regulation of calcium transport in cardiac cells
Authors: Shamoo Adil E. , Ambudkar Indu S.
Published: April 2011

Calcium transporting systems and the regulatory events accompanying them are pivotal in the function of the cardiac cell. The concerted involvement of the various membranes achieve cellular calcium homeostasis that can also respond to the physiological exigencies of the cell. Three membrane systems are primarily involved; the sarcolemma, sarcoplasmic reticulum, and the mitochondria. The various Ca2+ transport systems that have been described in these membranes are as follows: the calcium channel, Ca2+-ATPase, Ca2+–Mg2+ ATPase, and sodium–calcium exchanger in the sarcolemma; the Ca2+–Mg2+ ATPase and a possible calcium channel in the sarcoplasmic reticulum; and the sodium–calcium exchanger and electrophoretic calcium uniporter in the mitochondrial inner membrane. These systems mediate calcium fluxes to maintain physiological cytosolic calcium concentrations. β-Adrenergic hormones regulate calcium transport systems in sarcolemma and sarcoplasmic reticulum, while α-adrenergic hormones modulate those in the mitochondria and probably in the sarcolemma. The response to these hormones is initiated at the sarcolemma, which contains the specific receptors. Intracellularly the effects are propagated by secondary messengers, e.g., cAMP, calcium, and lipid changes. Specific proteins are also involved in these events. Phospholamban, a 22 000 dalton protein, is involved in mediating the cAMP-dependent inotropic effects, by activating the Ca2+–Mg2+ ATPase of the sarcoplasmic reticulum. Alterations in any one of the systems involved in the regulation of calcium transport or in the calcium transport systems per se, would then result in drastic alterations in the cellular calcium homeostasis. Such effects could be of significance in cellular dysfunction during cardiac disease.
The effect of vasopressin on fetal oxygenation in sheep
Authors: Rurak D. W. , Gruber N. C.
Published: April 2011

To examine the effects of vasopressin on fetal oxygenation the hormone was infused intravenously for 1 h (1.4–3.5 mU∙min−1∙kg fetal weight−1) to chronically catheterized fetal lambs in utero (113–137 days gestation). Arterial pressure rose (48.3 to 59.6 mmHg) (1 mmHg = 133.322 Pa) and heart rate fell (185.3 to 141.0 beats/min) during the infusion. There was a significant increase in fetal arterial [Formula: see text] (20.0 to 23. 1 mmHg) and significant declines in pH (7.414 to 7.381) and base excess. Umbilical blood flow rose, and the percentage increase in flow (23%) was identical to the proportional rise in arterial pressure. Accompanying the rise in umbilical blood flow was a rise in umbilical oxygen delivery. But as there was no change in fetal oxygen consumption, fractional oxygen extraction by the fetus fell significantly (0.31 to 0.25). These data indicate that the vasopressin-induced rise in fetal vascular [Formula: see text] results from an increase in umbilical oxygen delivery and concomitant fall in fractional extraction. Fetal vasopressin levels are greatly elevated during hypoxia, and under conditions of reduced oxygen supply, the effects of the hormone on umbilical oxygen delivery and vascular [Formula: see text] could have definite survival value.
Effect of leucogenenol, a thymothyroid hormone, on the growth of immature and neonatally thymectomized rats
Authors: Rice F. A. H. , McCurdy J. D. , Newby Mary , Carlyn Cynthia , Stack Jeannette
Published: April 2011

The reports of early investigators that growth is delayed by thymectomy of immature animals have been confirmed. Although growth is delayed by thymectomy, thymectomized animals approach asymptotically with age the same final weight as corresponding intact animals. Treatment with leucogenenol, a thymothyroid hormone, accelerates the rate of growth of immature neonatally thymectomized rats to that of normal rats. However, treatment with leucogenenol does not increase the rate of growth of normal rats. Treatment with leucogenenol does not change levels of growth hormone (GH) or thyroxine (T4) in the serum of either thymectomized or intact immature and adult rats. Neither is the depression in levels of serum leucogenenol that follows thymectomy associated with a change in serum levels of GH or T4. Thus it is apparent that levels of serum leucogenenol do not affect the rate of growth of immature animals by increasing serum levels of GH or T4. By analogy with the finding that treatment with leucogenenol increases the rate at which committed cells of the bone marrow and cells involved in the immune response develop into functional cells, it is suggested that the levels of serum leucogenenol are one of the factors that determine the rate at which types of body cells that make up bone and other body tissues develop from committed precursors.
Hemodynamics of coronary artery stenosis
Authors: Wong Alan Y. K. , Klassen G. A. , Johnstone David E.
Published: April 2011

A model is proposed to study the hemodynamics of various types of coronary stenosis. The model coronary artery is assumed to be an elastic tapered tube. A progressive degree of concentric and eccentric stenoses are studied. Measured pulsatile coronary pressure, flow, and intramyocardial pressure are used as input data to calculate the pressure and flow velocities at different locations of the artery. The simulation yields results that agree well with published data in dog experiments, and those from human stenotic coronary arteries. The present model shows that in a cardiac cycle, the overall hydraulic resistance owing to a specific stenosis tends to be flow independent at low flow rate but increases linearly with flow at higher coronary flow. This flow independent resistance increases with progressive stenosis. At low flow, the mean coronary flow in a cardiac cycle is relatively constant with stenoses up to 80%, but decreases dramatically with further increase in the degree of narrowing. At high resting flow rate, this mean flow is markedly reduced at much smaller degrees of constriction. The simulated pressure velocity relation of poststenotic dilatation indicates an additional pressure loss at the distal end of the stenosis, but the calculated resistance to flow is actually lessened. While stenosis length increases pressure loss and resistance to flow, its effect on mean flow appears disproportionally insignificant. Eccentric lesions appear to be more detrimental than concentric ones as they produce additional pressure loss and greater resistance across the coronary artery lesion.
Renal venous pressure and volume natriuresis in the rat
Authors: Rudolph John R. , Ackermann Uwe
Published: April 2011

Anesthetized rats were surgically prepared so that left renal venous pressure could be maintained at its normal level (near 1 mmHg) (1 mmHg = 133.322 Pa) while right renal venous pressure was free to change in response to acute isoncotic blood volume expansion (n = 10). The purpose of the study was to test whether the renal venous pressure changes normally accompanying a 33% blood volume expansion have an effect on inulin clearance (CIn) and on the rates of excretion of water [Formula: see text] or sodium [Formula: see text] by the kidneys. In 10 control rats blood volume was not expanded. The results showed that the volume expansion used resulted in a peak pressure of 5.3 ± 0.5 (SEM) mmHg in the right renal vein. Both kidneys showed significant increases in CIn, [Formula: see text], and [Formula: see text] over their respective preexpansion values. However, there were no significant differences between these parameters measured in the right or in the left kidney even though the differences between the two renal venous pressures were highly significant during the infusion and for the next 20 min. In a further six rats, a caval snare was placed superior to the right renal vein so that both renal venous pressures could be held at normal during blood volume expansion. The ensuing diuresis and natriuresis were not different from those observed in the preceding group. It is concluded that changes in renal venous pressure, of the magnitude associated with volume expansion, have no significant effect on renal excretion rates.
A radiometric assay for debrisoquine 4-hydroxylase in human liver microsomes
Authors: Nakano M. , Inaba T.
Published: April 2011

A radiometric method to assay debrisoquine 4-hydroxylase activity in human liver microsomes was established. Following incubation with 14C-labelled debrisoquine, unreacted debrisoquine was extracted with chloroform; 4-hydroxydcbrisoquine was derivatized with hexafluoroacetylacetone, extracted, and subjected to high performance thin-layer chromatography (HP-TLC) followed by liquid scintillation counting. The Km values for debrisoquine 4-hydroxylase were 70 and 120 μM and the Vmax values were 8 and 24 pmol per milligram microsomal protein per minute. By application of this assay, it was possible to show that 4-hydroxydebrisoquine formation was competitively inhibited by sparteine. Antipyrine up to a concentration of 4 mM had no effect.
Pharmacological studies of smooth muscle from Dahl salt-sensitive and salt-resistant rats
Authors: Laher I. , Triggle C. R.
Published: April 2011

The pharmacological properties of various isolated smooth muscle preparations from the Dahl strain of hypertensive rats were studied. The Dahl salt-sensitive (DS) rat was allowed to develop hypertension by increasing the dietary sodium from 0.4 to 4.0 or 8.0%. The Dahl salt-resistant (DR) rat remained normotensive on the same diet. The preparations studied were the thoracic aorta, tail artery, portal vein, anococcygeus, and the perfused mesenteric bed. The noradrenaline mean effective doses (ED50) either in the absence or presence of cocaine, were similar for tissues obtained from hypertensive DS or normotensive DR. The reactivities of the isolated perfused mesenteric preparation to noradrenaline, serotonin, and phenylephrine were similar in DS and DR. The ED50 for the relaxing effects of papaverine in noradrenaline-precontracted aorta was similar for tissues from DS and DR and the profile for the washout of noradrenaline-precontracted aorta with Krebs (with or without papaverine) was also similar in DS and DR. The results of this study were compared with similar studies performed using other models of hypertension. It is concluded that vascular changes are unlikely to play a major role in the etiology of hypertension in the Dahl rat model of essential hypertension.
Benzodiazepine inhibition of flunitrazepam receptor binding, adenosine uptake, and pentylenetetrazol-induced seizures in mice
Authors: Chweh Andrew Y. , Swinyard Ewart A. , Wolf Harold H.
Published: April 2011

The potencies of seven benzodiazepines (BDZs) were established by three tests: inhibition of [3H]flunitrazepam receptor binding, inhibition of [3H]adenosine uptake, and prevention of pentylenetetrazol-induced seizures in mice. There is a high correlation between the potency for inhibition of [3H]flunitrazepam receptor binding and the antipentylenetetrazol potencies of benzodiazepines (r = 0.941; p < 0.01). The antipentylenetetrazol potencies of benzodiazepines correlate well with their ability to inhibit [3H]adenosine uptake (r = 0.860; p < 0.05 and >0.01). However, there is no significant correlation between the potency for the inhibition of [3H]flunitrazepam receptor binding and the potency for inhibition of [3H]adenosine uptake (r = 0.751; p > 0.05). In addition, there is a marked difference in BDZ potency as measured by these two tests in vitro. The ratios of the Ki values (Ki2/Ki1) range from 98 for BDZ 1 to 64615 for clonazepam. The data presented indicate that antipentylenetetrazol activity of benzodiazepines results from an interaction between BDZ and nanomolar affinity BDZ receptors.
Influence d'un retard de croissance sur la perméabilité de la barrière hémato-encéphalique chez le rat nouveau-né exposé au plomb
Authors: Turnbull John , Brodeur Jules
Published: April 2011

Postnatal administration of lead to young rats via maternal milk increases the permeability of the blood–brain barrier to trypan blue. However, since this regimen delays postnatal maturation, the question arises whether growth retardation per se could explain the altered permeability to the dye. The present investigation was undertaken to examine this possibility. A first group of newborn rats were fed by dams having free access to normal food; a second group was fed by dams receiving 3% lead as the acetate salt in their food; a third group was fed by dams whose normal diet was restricted to the amount taken daily by dams of the second group. Signs of encephalopathy as shown by urinary incompetence and hind-limb paralysis were observed only in young pups exposed to lead; similarly, only the latter showed increased brain permeability to trypan blue. These results suggest that the altered permeability of the blood–brain barrier in young rats is the direct consequence of lead toxicity and not of growth retardation secondary to a nutritional effect of lead.
Release of 3,4-dihydroxyphenylglycol from the rat tail artery induced by veratridine
Authors: Palatý Vladimír
Published: April 2011

The overflow of endogenous 3,4-dihydroxyphenylethylene glycol and noradrenaline from the isolated rat tail artery was measured by high pressure liquid chromatography with amperometric detection. Veratridine, but not elevated external K, caused a significant increase in the overflow of the glycol under conditions when formation of the latter from released noradrenaline was prevented by blockade of neuronal uptake1 with desipramine. The results support the hypothesis that, in addition to evoking exocytotic release of noradrenaline into Ca-containing solution, the alkaloid also increases leakage of noradrenaline from storage vesicles. The latter process seems responsible for veratridine-induced release of noradrenaline into Ca2+-free solution.
Intracellular potential changes following coronary occlusion in isolated perfused rat hearts
Authors: Inoue F. , MacLeod B. A. , Walker M. J. A.
Published: April 2011

A method of perfusing rat ventricles has been developed which permits the recording of intracellular potentials from up to 10 cell layers below the endocardial surface. Intracellular potentials from all layers remained the same for up to 1.5 h before occlusion. Regional occlusion of flow was produced by occluding the left anterior descending coronary artery and then intracellular potentials were recorded from normal and occluded cells for up to 2 h after occlusion. Immediately after occlusion, marked changes in potentials were recorded from occluded tissue. The greatest change was in the duration of the action potential which showed a marked shortening. There was also a reduction in the maximum rise rate and action potential height with smaller falls in resting membrane potential. Changes were greatest in the deeper cells (layers 6 – 10) and least in superficial subendocardial cells which were always superfused with perfusion fluid. Occlusion increased the number of quiescent cells (no action potential) as well as the number of cells showing aberrant action potential configurations (e.g., double peaks). Similar changes in intracellular potentials following occlusion were also recorded from the subepicardial surface of anaesthetized rats in situ. Arrhythmias induced by occlusion were similar to those seen in conscious rats following occlusion of a coronary artery.
Mechanisms of intestinal adaptation: unstirred layer resistance and membrane transport
Authors: Thomson A. B. R.
Published: April 2011

The effect of the resistance of unstirred water layers (UWL) on the kinetic parameters of active and passive intestinal transport processes is well established, but the possibility of adaptive changes in the resistance of this diffusion barrier in health and disease has only recently been appreciated. The rate of uptake (Jd) of a homologous series of saturated fatty alcohols into the jejunum is limited by diffusion through the UWL. The Jd of lauryl alcohol has been determined at different rates of stirring of the bulk phase and at different sites along the intestine, in animals of different ages, in varying species, in rats with streptozotocin-induced diabetes mellitus, following abdominal irradiation, after acute and chronic exposure to ethanol and after the feeding of various diets. The UWL varies in response to most of these experimental manipulations. After correcting for unstirred layer effects, the incremental change in free energy (∫ΔFW → l) of the uptake of medium chain-length fatty acids and the maximal transport rate ([Formula: see text]) and Michaelis constant (Km) for glucose uptake were determined. These kinetic parameters changed in many of these experimental manipulations. However, there was no correlation between changes in UWL, ∫ΔFw → l, [Formula: see text], Km or [Formula: see text]/Km. It is concluded that (1) the intestine is capable of adapting to a variety of physiological and pathological challenges; and (2) the major kinetic changes included UWL, ∫ΔFW → l[Formula: see text] and Km. The molecular mechanisms responsible for these changes in the dimensions and characteristics of the barriers to intestinal transport must now be defined.
How toxic are propoxyphene and ethanol in combination?
Authors: Reiffenstein R. J. , Mah Manuel
Published: April 2011

Ethanol has been claimed to potentiate greatly the lethality of propoxyphene, although published clinical data suggest only an additive effect. Mice were treated intraperitoneally with various doses of propoxyphene hydrochloride and ethanol. Isobolograms of the data show the combination to be less-than-additive for lethality and loss of motor coordination and, at worst, simply additive for sedation.