bluuebunny/crossref_metadata_2025 huggingface dataset:
GABA-mediated responses are not selectively depressed by 3-mercaptopropionic acid in the spinal cord
Authors: Davies M. F. , Esplin B. , Čapek R.
Published: April 2011

The competitive inhibitor of glutamic acid decarboxylase (GAD), 3-mercaptopropionic acid (MPA), causes depletion of γ-aminobutyric acid and convulsions. We expected it to be a superior GAB A depleting agent for in vivo experiments to the frequently used semicarbazide. The dorsal root potentials (DRP) and monosynaptic reflex responses (MSR) evoked by adjacent dorsal root and peripheral nerve stimulation, respectively, were recorded in spinal unanaesthetized cats. MPA (100–200 mg/kg) caused a gradual decrease in DRP, reaching a peak in about 40 min after drug administration. This was usually associated with convulsive activity. Postsynaptic direct inhibition was not substantially affected. However, the MSR was consistently decreased, within 10 min after injection of MPA. It is concluded that MPA is not a suitable tool, at least in the spinal cord, for the selective reduction of GABAergic transmission.
Electrophysiological effects of ouabain in 6-hydroxydopamine pretreated dogs
Authors: Godin Diane , Guimond Claude , Nadeau Réginald
Published: April 2011

Chemical sympathectomy and bilateral vagotomy were used to evaluate the contribution of each division of the autonomic nervous system in the electrophysiological actions of ouabain. Intact and chemically sympathectomized dogs were given successive and cumulative doses of ouabain until toxicity became manifest (ventricular extrasystoles and (or) ventricular tachycardia). An additional group of normal and sympathectomized animals was also submitted to bilateral vagotomy in the presence of a therapeutic dose of ouabain. Sinus cycle length, AH interval of the His bundle electrogram, atrioventricular junctional effective and functional refractory periods were increased by ouabain at therapeutic doses. These effects were no different in sympathectomized dogs than in intact dogs, indicating the absence of any significant contribution of efferent sympathetic neural activity. However, our results suggested that vagal enhancement was the main mechanism whereby ouabain produced sinus bradycardia and depression of atrioventricular conduction. Sympathectomy with 6-OHDA did not modify nor abolish ouabain toxicity. However, toxic doses were significantly higher in sympathectomized animals than in normal animals. Considering that increasing heart rate by cardiac pacing or vagotomy significantly lowered toxic doses of ouabain in both intact and sympathectomized dogs, it is possible that sympathectomy could influence ouabain toxicity by altering heart rate alone.
A possible role for somatostatin in depression of insulin and glucagon levels during hemorrhage
Authors: Lautt W. Wayne , Légaré Dallas J. , Martens Elizabeth S.
Published: April 2011

The hypothesis that depression of insulin and glucagon levels during rapid, acute hemorrhage is controlled by somatostatin was supported by hormonal changes measured in the cat. By 5 min of hemorrhage to 50 mmHg (1 mmHg = 133.322 Pa) arterial blood pressure, insulin and glucagon were severely depressed and somatostatin levels rose to 232% of basal levels. Insulin and glucagon suppression was maintained for the 30-min period of hemorrhage. Following return of the blood, somatostatin levels remained high and insulin and glucagon suppression was maintained. The data support, but do not prove, the hypothesis.
Reduced renal vascular response to nerve stimulation and norepinephrine in DOCA–salt hypertensive rats
Authors: Kline R. L.
Published: April 2011

Vascular responses to nerve stimulation and norepinephrine (NE) administration were studied in kidneys perfused in situ at constant flow in uninephrectomized Sprague–Dawley rats made hypertensive by 5–6 weeks of deoxycorticosterone acetate (DOCA) – salt treatment. One- and two-kidney normotensive rats were used as controls. Renal blood flow on a weight basis did not differ significantly between the two control groups. Kidneys of DOCA–salt rats were nearly twice the size of those in one-kidney controls, but blood flow was only half that of controls when perfusion pressure was set at 100 mmHg (1 mmHg = 133.322 Pa). There were no differences in renal vascular responses to nerve stimulation (2–8 Hz) or NE (10–50 ng, ia) between the two control groups; however, in the DOCA–salt rats, responses to nerve stimulation were decreased by 71–87%, while those to NE were decreased by 35–40%. Similar reductions in the response to barium chloride were seen. NE concentration in the perfused kidneys averaged 183 ± 11, 104 ± 16, and 37 ± 3 ng/g in the two-kidney, one-kidney, and DOCA–salt groups, respectively. The decrease in NE concentration in DOCA–salt kidneys was greater than could be accounted for by changes in renal mass alone. In another group of uninephrectomized rats, renal vascular resistance was increased to levels seen in DOCA–salt kidneys by iv infusion of NE. Under these conditions, responses to bolus injections of NE (50 ng) were decreased by 38%. Taken together, the results suggest that renal vascular responses to nerve stimulation in DOCA–salt kidneys are markedly reduced because of (i) a reduced amount of NE available for release, and (ii) a decreased responsiveness of the renal vasculature to NE. The latter response, which may extend to other vasoconstrictors as well, is opposite to what has been shown frequently in isolated, perfused kidneys, and may be explained by the presence of elevated renal vascular tone in DOCA–salt kidneys perfused in situ.
Changes in electrical potential difference and sodium–potassium ATPase of canine mucosa after jejunal–ileal bypass surgery
Authors: Grahame G. R. , Shoenut J. P. , Takeo S. , Sharma G. P.
Published: April 2011

Changes in electrical potential difference and sodium–potassium ATPase activity of rectal mucosa in dogs were examined before and after jejunal–ileal bypass surgery. The potential difference in the postoperative period was significantly higher (P < 0.05) than the preoperative value. The potential difference increased by 160% at the 3rd day after the surgery, and then gradually declined with prolonged recovery periods. Ouabain-sensitive sodium–potassium ATPase activity also increased at the 3rd day (160%) and at the 10th day (86%) after the surgery. Fourteen days after the surgery the sodium–potassium ATPase activity returned almost to the preoperative value. These results indicated a close correlation between changes in transmucosal potential difference and sodium–potassium ATPase activity of rectal mucosa, suggesting a significant participation of sodium–potassium ATPase in changes of potential difference induced by jejunal–ileal bypass surgery.
Prevention and reversal of altered myocardial function in diabetic rats by insulin treatment
Authors: Tahiliani Arun G. , Vadlamudi Rao V. S. V. , McNeill John H.
Published: April 2011

Isolated perfused hearts from diabetic rats exhibit a decreased responsiveness to increasing work loads. However, the precise time point at which functional alterations occur is not clearly established. Previous observations in our laboratory have suggested that the alterations in myocardial function are not apparent at 30 days whereas they are clearly seen 100 days after streptozotocin-induced diabetes. We studied the cardiac function of 6-week diabetic rats using the isolated perfused heart preparation. The 6-week time period was found to be sufficient to cause depression of myocardial function in these animals. We also studied the effect of insulin treatment on myocardial performance of diabetic rats. Insulin treatment was initiated 3 days and 6 weeks after injection of streptozotocin (STZ). The treatment was continued for 6 and 4 weeks in the respective groups. Hearts from 6-week diabetic animals exhibited a depressed left ventricular developed pressure (LVDP) and positive and negative dP/dt at higher filling pressures when compared with 6-week control animals. However, the depression was not seen in the 6-week insulin-treated diabetic animals. Ten-week diabetic rat hearts also showed a depression of LVDP and positive and negative dP/dt when compared with 10-week controls. The group of animals that had been diabetic for 6 weeks and then treated for 4 weeks with insulin exhibited a reversal of the depressed myocardial function. These results demonstrate that depression of myocardial performance, which is evident 6 weeks after diabetes is induced, can be prevented if insulin treatment is initiated as the disease is induced. Further, insulin treatment is capable of reversing the abnormalities after they have occurred.
Inhibitory effect of phenelzine on oxidative microsomal enzyme systems of rat liver
Authors: Bélanger P. M. , Atitsé-Gbeassor A.
Published: April 2011

The inhibitory effects of phenelzine on the hepatic microsomal demethylation of aminopyrine, N,N-dimethylaniline, and p-nitroanisole on the hydroxylation of aniline and on the pharmacokinetics of antipyrine were investigated in the rat. Phenelzine produced a competitive and noncompetitive inhibition of the demethylation of p-nitroanisole and N,N-dimethylaniline, respectively, but was a mixed-type inhibitor of the aminopyrine N-demethylase and aniline hydroxylase. The inhibition constant, Ki, varied between 0.06 to 0.25 mM depending on the substrate used. Preincubation of phenelzine for 30 min with the microsomal homogenate prior to substrate addition doubled its inhibitory effect. Phenelzine induced a type II spectral change when combined with oxidized cytochrome P-450 with a Ks value of 0.4 mM. The administration of one dose of 50 mg∙kg−1 of phenelzine sulfate concomitantly with 50 mg∙kg−1 of antipyrine resulted in a significant decrease of the serum elimination of antipyrine. The serum half-life, apparent volume of distribution, and total body clearance of antipyrine were modified to 3.6 h, 294.1 mL∙kg−1, and 56.8 mL∙h−1∙kg−1, respectively, from 1.5 h, 666.7 mL∙kg−1, and 312.5 mL∙h−1∙kg−1 when antipyrine was administered alone. It is concluded that the inhibitory effect of phenelzine on the microsomal oxidative reactions of rat liver is related to its interaction with cytochrome P-450.
Inhibition of antigen and calcium ionophore A23187 induced contractions of guinea pig airways by isoprenaline and forskolin
Authors: Burka John F.
Published: April 2011

Isoprenaline and forskolin both inhibit contractions induced by antigen or by the calcium ionophore A23187 of guinea pig tracheal spirals and parenchymal strips. Antigen-induced airway contraction is considerably more sensitive to the inhibitory effects of isoprenaline than is A23187-induced contraction. In contrast, forskolin is equiactive as an inhibitor of antigenic and ionophoric contractions. Forskolin is a more effective inhibitor of the prolonged phase of antigen-induced tracheal contraction than of the initial peak phase, which may suggest selectivity for the lipoxygenase pathway of arachidonic acid metabolism. Isoprenaline inhibits the mechanisms of the primary peak phase and of the prolonged phase equally. Although there were little, if any, differences between normal and sensitized tissues in the modulation of A23187-induced contractions of parenchyma, distinct differences were observed in trachea. Low concentrations (10−8–10−7 M) of isoprenaline and forskolin enhanced A23187-induced contraction of sensitized, but not normal trachea. Higher concentrations were inhibitory. The results demonstrate that sensitization affects the modulation by isoprenaline and forskolin of A23187-indueed contraction of guinea pig trachea.
The tissue–blood partition coefficient of iodoantipyrine in pig brain and its change with age
Authors: Wootton R. , Flecknell P. A. , Royston J. P. , John M.
Published: April 2011

The tissue–blood partition coefficient of 125I-labelled iodoantipyrine was measured in pig brain. The mean coefficient for 11 neonatal piglets (aged 0.5 to 4 days) was 0.718 mL/g (SD 0.083). Measurements in a further 11 animals up to 144 days old (at which time pigs are sexually mature), showed that the partition coefficient increased significantly with age, possibly as a result of the accumulation of brain lipid during growth. The change in partition coefficient with age was curvilinear, rising to unity as the animals reached maturity. There were significant differences between the partition coefficients in grey and in white matter, but these were so small relative to the differences between pigs that they could be neglected for all practical purposes. Since the accuracy of measurement of cerebral blood flow (CBF) by the Kety–Schmidt technique depends directly on the partition coefficient of the tracer, it is important to confirm that apparent changes of CBF do not simply reflect alterations in the partition coefficient rather than real changes in blood flow.
Gas–liquid chromatographic determination of saisolinol in the striatum of rat brain during the calcium carbimide – ethanol interaction
Authors: Brien J. F. , Andrews P. J. , Loomis C. W. , Page J. A.
Published: April 2011

An assay has been developed for the measurement of salsolinol in brain tissue that involves tissue homogenization in dilute hydrochloric acid, purification of the supernatant by cation-exchange chromatography, derivatization of the eluate with heptafluorobutyric anhydride, and analysis by gas–liquid chromatography with electron capture detection using p-tyramine as the internal standard. The lower limit of quantitative sensitivity, using aqueous standards, is 2.5 ng salsolinol per brain sample. This assay was used to study salsolinol formation in rat brain during the calcium carbimide – ethanoi interaction. Rats were administered ethanol (1.0 g/kg) by oral intubation 3 h after intraperitoneal administration of calcium carbimide (7.0 mg/kg). Saisolinol was measured in the striatum over a 270-min period after ethanol administration. Salsolinol concentration appeared to be maximal (275 ng/g) at 90 min and then declined with an apparent elimination half-life of 39.8 min.
Hypobaric hypoxia does not affect lung fluid or protein exchange in awake adult sheep at rest
Authors: Coates G. , Belbeck L. W. , Gray G. W.
Published: April 2011

We measured pulmonary artery [Formula: see text] and left atrial [Formula: see text] pressures, lung lymph flow, and lymph/plasma protein concentrations in four adult sheep at a barometric pressure of 380 Torr (1 Torr = 133.322 Pa) for 22 h. Hypobaric hypoxia caused an immediate increase in [Formula: see text] from 20 to 39 Torr. There was no significant change in [Formula: see text], lymph flow, or lymph protein concentrations. We conclude that hypobaric hypoxia does not affect lung fluid or protein exchange in awake adult sheep at rest.
Nonadditive effects of combined in vivo hepatic microsomal enzyme inducers in the Wistar rat
Authors: Gontovnick Larry S. , Sunahara Geoffrey , Bellward Gail D.
Published: April 2011

Compounds that are known to increase the hepatic microsomal cytochrome P-450 dependent monooxygenases were adminstered to adult female rats, alone or in combination, to determine whether their effects on certain substrate oxidations were additive. 3-Methyleholanthrene (3-MC) and pregnenolone-16α-carbonitrile (PCN), known to induce different forms of cytochrome P-450, when administered together increased benzo[a]pyrene oxidation to the same level as observed following 3-MC treatment alone. Phenobarbital (Pb) and PCN when administered concomitantly increased benzo[a]pyrene, aminopyrine, and ethylmorphine metabolism to the same extent as seen following PCN administration alone. Both compounds are known to induce different forms of cytochrome P-450. Nonadditive effects were also observed with Pb and spironolactone, as well as with Pb and trans-stilbene oxide. Treatment of adult male rats with either PCN or 3-MC resulted in significantly smaller increases in benzo[a]pyrene oxidation than observed in adult female rats. These results suggest that oxidative metabolism in hepatic microsomes is not the sum of activities of a number of cytochrome P-450s, but may represent the activity of a single predominant hemeprotein. In addition, it appears that the oxidation of substrate by a particular cytochrome P-450, in intact microsomes, is greatly influenced by the presence of another form.
Specific binding of [3H]oxytocin in the female rat brain
Authors: Ferrier B. M. , McClorry S.A. , Cochrane A. W.
Published: April 2011

Because of demonstrated effects of oxytocin on some limbic system mediated behaviours, the specific binding of [3H]oxytocin to a plasma membrane containing fraction of rat limbic tissue has been studied. The binding of the microsomal fraction of estrogenized, female rat tissue was time dependent and saturable, with a Bmax of 2.5 × 10−l3 moles per milligram of protein and an apparent KD of 3.53 × 10−8 M, and appeared to show positive cooperativity. The pH optimum of the binding was 6.0, close to the pH optimum for oxytocin – neurophysin binding; however, other results show the two types of binding to be different. The microsomal fraction did not appreciably degrade oxytocin under the conditions used for [3H]oxytocin binding. The distribution in limbic tissue of oxytocin-degrading activity and of individual enzymes capable of degrading oxytocin has been examined and an interplay of enzymes concentrated in different cell types is proposed.
Properties of triiodothyronine-binding proteins in liver cytosol of rat
Authors: Bellabarba D. , Bédard S. , Lehoux J. -G.
Published: April 2011

The electrophoretic mobility and the sedimentation coefficient were determined in partially purified preparations of both rat liver cytosol and serum triiodothyronine (T3)-binding proteins. Crude cytosol and serum, each labeled with [125I]T3, were filtered through a Sephadex G-100 column. The cytosol yielded a single T3-binding peak, whereas three binding components were recognized in the serum. Protamine sulfate precipitated the cytosol T3-binding protein, but had no effect on the serum T3-binders. The cytosol protein and the three binding proteins from serum were analyzed by polyacrylamide gel electrophoresis and sucrose density gradient centrifugation. The cytosol binder migrated as a single peak on gel electrophoresis with an Rf of 0.53, whereas the serum proteins had Rfs between 0.27–0.33. The sedimentation coefficient of the cytosol protein was 6.3 S, whereas it was 4.1 S for the major binding protein of the serum. These data indicate that: (i) preliminary purification by gel chromatography is a useful step for better characterization of the T3-binding proteins of the cytosol and serum; (ii) the cytosol binder is an acidic protein with completely different properties from those of the serum T3-binding proteins.
Effects of luminal pH and luminal HCO3 on Cl–HCO3 exchange across turtle urinary bladder
Authors: Mahadeva Vidur , Husted Russell F.
Published: April 2011

The Cl–HCO3 exchange rate across turtle urinary bladder was studied by measuring the net flux of 36Cl in paired tissues. Serosal bicarbonate concentration and pH were held constant (10 mM and 7.6, respectively) while luminal composition was altered. The rate of net chloride absorption was the same at a luminal pH of 5 or 7 and at luminal [Formula: see text] concentrations of 0 and 10 mM. These results indicate that the affinity of the exchanger for luminal Cl− is much higher than that for luminal [Formula: see text] or OH−. Vanadate, an inhibitor of a number of ATPases, had no significant effect on chloride absorption.
Gas–liquid chromatographic determination of the distribution of 3,3′,4,4′-tetrachlorobiphenyl in the adult female rat following short-term oral administration
Authors: Clarke D. W. , Brien J. F. , Nakatsu K. , Taub H. , Racz W. J. , Marks G. S.
Published: April 2011

A gas–liquid chromatographic assay using electron-capture detection was developed for the quantitation of 3,3′,4,4′-tetrachlorobiphenyl (TCBP) in the serum, urine, brain, liver, adipose tissue, and feces of the rat. The sample preparation involves extraction of 3,3′,4,4′-TCBP with hexane under neutral or alkaline conditions (and washing with concentrated acid for feces only). Aqueous standards are used for calibration of the assay, except for adipose tissue. The lower limit of quantitative sensitivity of the assay for 3,3′,4,4′-TCBP is 25 ng/mL for serum and urine and 125 ng/g for brain, liver, adipose tissue, and feces, which can be extended to 5 ng/mL and 25 ng/g, respectively, by analyzing a larger aliquot of the hexane extract. The overall accuracy is greater than 95% for serum, urine, brain and feces and 86% for liver, and the within-day coefficient of variation does not exceed 8.6%. 3,3′,4,4′-TCBP was administered orally to adult, female, Sprague–Dawley rats in the dosage regimens: 0.2, 0.5 and 2 mg∙kg−1∙day−1 for 10 days and 5 mg∙k−1∙day−1 for 4 days. 3,3′,4,4′-TCBP distributed preferentially into adipose tissue and liver, where the xenobiotic concentration was greater in adipose tissue. The adipose tissue and hepatic 3,3′,4,4′-TCBP concentrations were dependent on both the absolute dose and dosing schedule of the xenobiotic. Only trace concentrations, usually below the lower limit of quantitation, were detected in the serum, brain and kidney. Fecal excretion of 3,3′,4,4′-TCBP was greater than urinary excretion for the 5 mg∙kg−1∙day−1 × 4-day regimen.
Low-frequency stimulation of the perforant path produces long-term potentiation in the dentate gyrus of unanesthetized rats
Authors: Skelton R. W. , Miller J. J. , Phillips A. G.
Published: April 2011

Brief periods of high-frequency stimulation of hippocampal afferents produce long-term potentiation (LTP) of synaptic transmission, but the minimum frequency capable of inducing this alteration in synaptic efficacy has not been specified. The present study used the repeated measurement of input–output curves in the perforant path – dentate gyrus system of freely moving rats to monitor synaptic efficacy and found that stimulation at 0.2 Hz, but not 0.04 Hz produced LTP. These results suggest that the minimum stimulation frequency capable of producing LTP is lower than previously described. Possible reasons for the discrepancy between the present and previous findings are discussed, along with the implications of low-frequency potentiation.
Evidence that transmitter release in sympathetic nerves is not set by feedback via presynaptic receptors
Authors: Kalsner Stanley
Published: April 2011

The possibility of negative feedback regulation of noradrenaline release was studied in the sympathetically innervated ureters of the guinea pig mounted in vitro. Tissues were transmurally stimulated with 300 pulses at 2 Hz over a range of voltages, from 10 to 60 V. It was determined that the output of transmitter increased with increasing voltage but that the effects of supposed presynaptic antagonism by yohimbine and presynaptic agonism by added noradrenaline did not fulfill the requirements of presynaptic theory governing negative feedback. It is concluded that the presynaptic effects of these drugs is neither linked to the operation of a negative feedback system nor sensitive to the perineuronal concentrations of free and active neurotransmitter.
The 11th J. A. F. Stevenson Memorial Lecture: Blobs and color vision
Authors: Hubel David H. , Livingstone Margaret S.
Published: April 2011

When the monkey striate cortex is stained for the mitochondrial enzyme cytochrome oxidase a polka-dot pattern of patches or blobs is observed in layers 2 and 3 and more faintly in layers 5 and 6. In the macaque these blobs are aligned along the centers of ocular dominance columns. Cells within blobs lack the orientation selectivity and instead have the simpler concentric center-surround fields common in geniculate cells. Blob cells are specifically concerned with color and in particular with maintaining color constancy despite marked changes in the spectral content of the light source.
Actions of verapamil on the excitability of cultured neurones
Authors: MacDonald J. F. , Schneiderman J. H.
Published: April 2011

Applications of relatively high concentrations of verapamil (0.5–1.0 mM) to cultured spinal cord or dorsal root ganglion neurones blocked both calcium (Ca) and sodium (Na) action potentials. They also depolarized these neurones and caused a voltage-dependent reduction of input conductance (measured under current clamp). The depolarization and apparent reduction of input conductance evoked in spinal cord neurones by L-aspartic acid appeared to be potentiated by coapplications of verapamil. Lower concentrations (maximum 100 μM) of verapamil blocked identified Ca action potentials without depolarizing neurones or changing their input conductance. This Ca antagonist provided only limited selectivity in cultured neurones. Voltage clamp of cultured spinal cord neurones demonstrated that high concentrations of verapamil (0.5–5.0 mM) can reduce outward currents (leakage and rectification). Inward currents evoked with single applications of L-aspartic acid were not potentiated by verapamil and thus potentiations recorded under current clamp can be attributed to depression of outward currents. The reduction of voltage-dependent outward currents (rectification) by verapamil improved resolution of the voltage-dependent inward current activated by L-aspartic acid.
Ventricular fibrillation following canine coronary artery reperfusion: different outcomes with pentobarbital and α-chloralose
Authors: Wenger Thomas L. , Harrell Jr. Frank E. , Brown Kathleen K. , Lederman Samuel , Strauss Harold C.
Published: April 2011

We compared the incidence of ventricular fibrillation after release of a 20 min-proximal left anterior descending coronary artery ligation in dogs anesthetized with either pentobarbital (N = 26) or morphine sulfate plus α-chloralose (N = 26). Results were analyzed using the logistic risk regression model. In each group, outcome correlated with the amount of myocardium perfused by the ligated vessel (myocardium "at risk") as measured by postmortem coronary injection of monastral dyes. At any given myocardium at risk, animals anesthetized with α-chloralose were less likely to fibrillate after release than those anesthetized with pentobarbital (p < 0.01). This difference in outcome can be described by the myocardium at risk at which half the animals are expected to fibrillate (MAR50). MAR50 was 20.9 g for the pentobarbital group and 30.7 g for the α-chloralose group. Myocardium at risk should be taken into account in intervention studies using this coronary reperfusion arrhythmia model. We chose the logistic risk regression model to correct for this variable because it allowed a good fit of the data and offered a concise standard format for expressing the results. Outcome in reperfusion studies may be influenced by the choice of anesthetic agent.
Characterization of contractions in enzymatically isolated rat ventricular myocytes: effects of ouabain and rubidium
Authors: Vornanen Matti
Published: April 2011

The role of sarcolemma and especially sodium pump activity in the control of phasic contractile activity of Ca2+ tolerant myocytes was studied using ouabain and rubidium as sodium pump inhibitors. Initially, ouabain increased both the amplitude of shortening and the frequency of phasic contractions. Later, the amplitude began to decline whereas the frequency of beating continued to rise, often terminating in a steady contracture of the myocyte. Rubidium caused a rapid rise of beating frequency, which reached its full effect within 1–5 min and remained steady after that. The stimulation of contraction frequency and the inhibition of Na+–K+ ATPase were correlated in the case of ouabain but not in the case of rubidium. The results suggest that the stimulation of phasic contractions may be caused by increased uptake of cellular calcium through Na+–Ca+ exchange as a consequence of sodium pump inhibition and (or) depolarization of the sarcolemma by ouabain and rubidium.
Validation of an equation for calculation of glucose appearance during nonsteady state in sheep
Authors: Brockman Ronald P.
Published: April 2011

The purpose of this study was to validate the calculation of the rate of glucose appearance (RA) during nonsteady state for sheep. The RA given by the modified single-compartment model was compared with the actual rate derived from the sum of the infusion of exogenous glucose and endogenous production as determined from hepatic production of glucose. Using a pool fraction of 0.65, the error associated with calculation of RA was about 10%.
Placental drug transfer in near-term ewes: acetylsalicylic and salicylic acid
Authors: Thiessen J. J. , Salama R. B. , Coceani F. , Olley P. M.
Published: April 2011

Radiolabelled acetylsalicylic acid (ASA) and salicylic acid (SA) were given intravenously to four near-term ewes and their occurrence in both maternal and fetal plasma was ascertained using a specific thin-layer chromatographic analysis procedure. Findings proved that ASA and SA cross the placental barrier and reach distribution equilibrium about 40 min after salicylate administration. The equilibrium plasma fetal/maternal ratio for both salicylates averaged 0.4. Plasma concentrations of the two compounds in the mother and the fetus accorded with a two-compartment model having unusually large mean estimates (54 and 39 L) for the tissue distribution space of ASA and SA, respectively. Furthermore, the mean SA clearance in the ewe (358 mL∙min−1) was much greater than that reported in man, while the mean ASA clearance (764 mL∙min−1) was similar. Since ASA is an irreversible inhibitor of arachidonate cyclooxygenase, our findings reassert the need for caution in the use of the drug during pregnancy.
Hypotensive actions of some analogues of platelet-activating factor (PAF) with higher potencies than natural PAF
Authors: Kasuya Yutaka , Masuda Yukinori , Shigenobu Koki
Published: April 2011

Substituents on the nitrogen atom of the phosphorylcholine moiety of natural C16 platelet-activating factor (PAF) were modified or replaced by more bulky groups, and their hypotensive activities were examined with rats. As a result, it was found that N-methylpiperidine and N-methylpyrrolidine analogues were 3–10 times more potent than natural C16-PAF.
Impedance profiles of peripheral and central neurons
Authors: Gimbarzevsky Boris , Miura Robert M. , Puil Ernest
Published: April 2011

The electrical impedance of trigeminal ganglion cells (in vivo) and hippocampal CA1 neurons (in vitro) of guinea pigs was measured in the frequency range of 5–1250 Hz using intracellular recording techniques with single microelectrodes and computerized methodology. The transfer functions of the electrode and the electrode–neuron system were computed from the ratio of fast Fourier transforms of the output voltage response from the neuron and input current composed of sine waves with rapidly increasing frequency which displaced membrane potential by 2–5 mV. We believe these to be the first measurements of complex impedance and transfer functions in peripheral and central neurons of vertebrates and the first use of such input current functions. The majority of trigeminal ganglion cells did not exhibit electrical behaviour ascribable to a simple resistance-capacitance (RC) circuit but showed a hump at low frequencies (5–250 Hz) in the computed transfer function, probably attributable to resonance. The transfer function in less than 20% of the trigeminal neurons could be fitted approximately to a theoretical transfer function (resistance in series with a parallel RC circuit model) providing values for electrode resistance, effective input resistance, and effective input capacitance. The transfer functions measured in hippocampal CA1 neurons were characterized by a rapid fall-off in the low frequency range (<200 Hz). Impedance locus plots approximate the locus corresponding to a series RC circuit in parallel with a parallel RC circuit.
Effects of digoxin on the chronotropic responses to repetitive vagal stimules bursts in the dog
Authors: Pace Daniel G. , Masuda Yukitaka , Eisenstein Isaac , Levy Matthew N.
Published: April 2011

We studied the effects of digoxin on the chronotropic responses of the heart to repetitive bursts of vagal stimulation in chloralose-anesthetized dogs. The frequency of the stimulus bursts was increased linearly with time. Over a certain range of frequencies, the cardiac pacemaker became synchronized with the vagal stimulation in a 1:1 ratio of heart beats to stimulus bursts. Digoxin increased the range of cardiac cycle lengths over which 1:1 synchronization occurred during repetitive vagal stimulation. This increment in the range of synchronization varied directly with the dose of digoxin. Before digoxin was given, the range of cardiac cycle lengths over which synchronization occurred when the vagus nerve was stimulated with 10 pulses per burst was 272 ± 50 (mean ± SE) ms. However, after a cumulative dose of 120 μg/kg−1 digoxin had been given, the range of 1:1 synchronization increased to 396 ± 32 ms. Digoxin did not appear to have a proportionately greater effect on those processes that take place in the phase of the cardiac cycle during which the pacemaker cells are maximally responsive than on those processes that occur in the phase of the cycle during which the pacemaker cells are minimally responsive. Therefore, we conclude that the augmented entrainment induced by digoxin is ascribable to its tendency to enhance the chronotropic response to vagal stimulation.
After-hyperpolarization and receptor potential attenuation following bursts of action potentials in an insect mechanoreceptor
Authors: French A. S.
Published: April 2011

The receptor potential in the sensory neuron of the cockroach femoral tactile spine was recently observed by raising the axon into an oil bath and measuring the decrementally conducted receptor current. Although action potential discharge in this receptor adapts rapidly, there was no evidence of adaptation in the receptor potential. In the present work we report that bursts of action potentials in the neuron produce a prolonged after-hyperpolarization and attenuate the receptor potential. Both of these effects could be important in receptor adaptation and we sought to identify their origin. It was impossible to control ionic concentrations in the fluid surrounding the sensory neuron because of an effective glial barrier, but it was possible to infuse the tissues with chemical agents which are known to block ionic membrane processes. Cobalt and cadmium, which inhibit calcium influx, eliminated the effects of action potentials, and ouabain had similar effects. These results suggest that both a calcium-activated potassium conductance and an electrogenic sodium pump are involved in these phenomena. However, it is argued that the former is probably more important.
Reconstituted halogenated hydrocarbon pesticide and pollutant mixtures found in human tissues: effects on the immature male Wistar rat after short-term exposure
Authors: Gyorkos J. , Denomme M. A. , Leece B. , Homonko K. , Valli V. E. , Safe S.
Published: April 2011

Halogenated hydrocarbon insecticides and polychlorinated biphenyl (PCB) mixtures are routinely detected as residues in human adipose tissue, serum, and milk. Based on average values observed in analytical studies, reconstituted halogenated hydrocarbon pesticide mixtures and PCB mixtures were prepared and administered to immature male Wistar rats. The mixtures were administered at dose levels which approximate the concentrations which would be absorbed by an infant suckling for 180 days (low dose, L), and at three higher dose levels (2 × L, 10 × L, and 100 × L). The pesticide mixture contained isomeric hexachlorocyclohexanes, dieldrin, heptachlor epoxide, oxychlordane, trans-nonachlor, hexachlorobenzene, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane, and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene; the reconstituted PCB mixture contained 13 of the major congeners which have been identified in human milk samples. Administration of the L dose level of the pesticide (0.95 mg/kg), PCB (0.45 mg/kg), and pesticide plus PCB mixture (0.95 + 0.45 mg/kg, respectively) in corn oil on days 1 and 3 did not significantly alter hepatic drug-metabolizing enzyme activities or elicit any observable pathological damage 6 days after the first exposure. In contrast, administration of the higher dose levels of this mixture elicited a dose-dependent induction of several hepatic drug-metabolizing enzymes. Moreover, despite the short duration of exposure to these chemicals, the rats treated with the higher doses (10 × L and 100 × L) of these mixtures exhibited mild alterations in thyroid architecture, changes in hepatocellular nuclei including variations in chromatin distribution, vesiculation of larger nuclei, and frequent appearance of pyknotic shrunken nuclei. In addition there were changes in hepatocellular cytoplasm organization including vacuolations and mild zonal variations in volume. The results clearly indicate that relatively low doses of the pesticides and pollutant mixtures commonly found in human breast milk can elicit significant biologic and toxic effects in the immature male Wistar rat.
Effects of amino and ammonio derivatives of adenosine on smooth muscle preparations and mouse neuroblastoma adenylate cyclase
Authors: Baer H. P. , Morr M.
Published: April 2011

Several amino- and ammonio-substituted derivatives of adenosine were tested as effectors of adenosine receptors in different smooth muscle preparations and mouse neuroblastoma adenylate cyclase. The compounds did not affect adenosine receptors in smooth muscles. N6-[3-(trimethylammonio)propyl]adenosine was a weak stimulator of adenylate cyclase, and 3′-amino-3′-deoxyadenosine and 3′-rnonomethylamino-3′-deoxyadenosine antagonized the stimulation of adenylate cyclase by 2-chloroadenosine.
Metabolic and cyclic nucleotide enzyme activities in muscle and nonmuscle cells of rat heart during perinatal development
Authors: Dowell Russell T.
Published: April 2011

Enzyme activities related to aerobic metabolism and cyclic nucleotides were evaluated in muscle and nonmuscle cells of rat heart. The perinatal period from weaning to adult was studied. Malate dehydrogenase, citrate synthase, and 3-hydroxyacyl-CoA dehydrogenase activities of nonmuscle cells equal or exceed muscle cell activities in the weanling heart. Aerobic enzymes remain unchanged in nonmuscle cells during growth; however, muscle cell activities are enhanced. Adenylate cyclase and guanylate cyclase activities are higher in heart homogenates of weanling than adult rats. Despite elevated adenylate cyclase activity, cyclic AMP levels are identical in weanling and adult rats. Cyclic GMP levels are twofold higher in weanling than in adult rats. Muscle cell metabolism and cyclic nucleotide levels are associated with growth-related changes in heart function and cellularity, respectively.
Benzodiazepine receptors and seizure susceptibility in epileptic fowl
Authors: Fisher T. E. , Davis L. G. , Tuchek J. M. , Johnson D. D. , Crawford R. D.
Published: April 2011

Benzodiazepine binding to brain membrane preparations obtained from epileptic and nonepileptic carrier fowl was compared. [3H]Flunitrazepam binding to whole brain homogenates from 2-day-old chicks and [3H]diazepam binding to synaptosomal membranes and homogenates from adult chickens were determined. Scatchard analysis revealed no differences in either the number of receptors or their affinity for the ligands when the epileptics were sacrificed in the interictal state. Evoked seizures in adult epileptics had no effect on the number or affinity of binding sites using [3H]diazepam as the ligand. Moreover, the ability of gamma-aminobutyric acid to facilitate benzodiazepine binding was not different in epileptic fowl when compared with carriers.
Levels of hippocampal calcium and zinc following kindling-induced epilepsy
Authors: Mody I. , Miller J. J.
Published: April 2011

Hippocampal calcium and zinc content was determined using atomic absorption spectrophotometry in control and commissural-kindled rats. In animals exhibiting 5–10 consecutive motor seizures hippocampal calcium was slightly elevated (356.7 parts per million (ppm), dry weight) but not significantly different from controls (329.8 ppm), whereas the amount of zinc was significantly higher (101.6 ppm) than in nonstimulated animals (88.3 ppm). These results are indicative of certain pathophysiological changes in kindled hippocampi, most likely localized to the granule cells of the dentate gyrus where the bulk of hippocampal zinc is confined.
Inhibition of monoamine oxidase by metaiodobenzylguanidine, a new radiodiagnostic agent
Authors: Burba J. V.
Published: April 2011

Metaiodobenzylguanidine, which is used in the diagnosis and treatment of pheochromocytoma, produced 50% inhibition of monoamine oxidase at a concentration of 8 × 10−6 M in vitro. These results suggest that a careful study of the structure of a new radiodiagnostic agent should be done to anticipate and prepare for possible unwanted biological effects when administering the preparation to patients.
Hindlimb vascular responses to sympathetic augmentation during acute anemia
Authors: Cain Stephen M. , Chapler C. K.
Published: April 2011

The effect of increased sympathetic activity on skeletal muscle blood flow during acute anemic hypoxia was studied in 16 anesthetized dogs. Sympathetic activity was altered by clamping the carotid arteries bilaterally below the carotid sinus. One group (n = 8) was beta blocked by administration of propranolol (1 mg/kg); a second group (n = 8) was untreated. Venous outflow from the left hindlimb was isolated for measurement of blood flow and O2 uptake [Formula: see text]. After a 20-min control period, both carotid arteries were clamped (CC) for 20 min followed by a 20-min recovery period. The sequence was repeated after hematocrit was lowered to about 15% by dextran exchange for blood. Prior to anemia, CC did not alter cardiac output or limb blood flow in either group. After induction of anemia, hindlimb resistance was higher with CC in the beta block than in the no block group. Both limb blood flow and [Formula: see text] fell in the β-block group with CC during anemia. Beta block also prevented the additive increases in whole body [Formula: see text] seen with CC and induction of anemia. The data showed that the increased vasoconstrictor tone that was obtained with beta block during anemia was successful in redistributing the lower viscosity blood away from resting skeletal muscle, even to the point that muscle [Formula: see text] was decreased.
Effects of L-canavanine on immune function in normal and autoimmune mice: disordered B-cell function by a dietary amino acid in the immunoregulation of autoimmune disease
Authors: Prete Pamela E.
Published: April 2011

This study reports the effects in vitro and in vivo of L-canavanine (LCN), an amino acid found in commonly consumed legumes, on immune function in normal and autoimmune mice. L-Canavanine in high doses effectively blocks all DNA synthesis in vitro within 24 h. At lower doses, LCN affects B-cell function of autoimmune New Zealand Black/New Zealand White (NZB/NZW)F1 mice, inhibiting [3H]thymidine incorporation in response to B-cell mitogens, and pokeweed-induced intracytoplasmic immunoglobulin synthesis. LCN stimulates intracytoplasmic immunoglobulin (IgG > IgM). T-cell functions such as lymphoproliferation in response to concanavalin A or phytohemagglutinin and T-cell cytotoxicity are not affected. Suppression of the lipopolysaccharide response by LCN is removed by the addition of fresh B cells. Addition of the amino acid to mouse diet resulted in a decrease in the life-span of the autoimmune NZB and (NZB × NZW)F1 mice and abolished the protective effect of male sex on their survival. The decrease in survival in LCN-treated autoimmune mice correlated with an increase in spontaneous immnunoglobulin-secreting cells (IgG > IgM) and antinuclear and double-stranded DNA antibodies. The histopathological analyses revealed increased glomerular damage and immunoglobulin deposition in the kidneys of the LCN-treated autoimmune and normal (DBA/2) mice. Ten percent of normal mice developed high titers of autoantibodies after 24 weeks of the diet. These data suggest a dietary amino acid, L-canavanine, affects B-cell function resulting in autoimmune phenomena and providing a new animal model of autoimmunity, a diet-induced systemic lupus erythematosus.
Inhibitory processes of hippocampal CA1 pyramidal neurons following kindling-induced epilepsy in the rat
Authors: Oliver M. W. , Miller J. J.
Published: April 2011

To determine the alterations in cellular function which may contribute to the chronic predisposition of neuronal tissue to epileptiform activity, the membrane properties and inhibitory processes of hippocampal CA1 pyramidal cells were investigated using in vitro slices prepared from commissural-kindled rats. No changes were observed in resting membrane potential, input resistance, spike amplitude, and membrane time constant of "kindled" CA1 pyramidal neurons when compared with controls. There were also no differences between control and kindled preparations in the amplitude of recurrent inhibitory postsynaptic potentials (IPSP) and in the duration of inhibition produced by either alvear (Alv) or stratum radiatum (SR) stimulation. Irrespective of group, repetitive stimulation of the Alv reduced the amplitude of the recurrent IPSP but failed to induce seizurelike activity. On the other hand, repetitive stimulation of SR frequently produced a neuronal burst discharge even though the duration and to some extent the amplitude of orthodromic inhibition was increased. On the basis of these data, it may be suggested that chronic changes in CA1 pyramidal cell membrane properties and transient reductions of inhibitory processes do not underlie the enhanced sensitivity of these neurons to seizure activity associated with kindling.
Excitation–contraction coupling in crab muscle fibers with swollen T tubules
Authors: Leal-Cardoso J. H. , Suarez-Kurtz G.
Published: April 2011

Single crab (Callinectes danae) fibers were equilibrated with isotonic, high KC1 solutions and were subsequently returned to the control saline. This caused marked swelling of the T tubules. Fibers treated with 100 mM KCl had a 2.5-mV residual depolarization, a 50% decrease in effective membrane resistance (Reff) and a 75% reduction in membrane time constant (τm). These fibers exhibited large increases in membrane conductance upon depolarization and were inexcitable; membrane depolarization with current pulses elicited no contraction. The effects of the KCl treatment on membrane properties were not reproduced by treatment with high potassium gluconate solutions, which did not cause tubular swelling. Tetrabutylammonium (10 mM) or Ba ions (10–20 mM), but not tetraethylammonium (40–100 mM), Sr ions (15–70 mM), or procaine (1–8 mM) reversed the effects of the KCl treatment on Reff, τm, membrane excitability, and excitation–contraction coupling. The time course of the Ba effects was consistent with the suggestion that the KCl treatment increases the K conductance of the tubular membranes, which in turn prevents the activation of voltage-dependent Ca channels located in the membranes of the T system. This results in inhibition of the Ca-dependent electrogenesis and consequently, the absence of contraction upon depolarization of the plasma membrane.