bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of the effects of γ-hydroxybutyrate and γ-butyrolactone on cerebral carbohydrate metabolism
Authors: MacMillan V.
Published: April 2011

The metabolic effects of 60-min exposure to 250–2000 mg γ-hydroxybutyrate (GHB) per kilogram or 150–1200 mg γ-butyrolactone (GBL) per kilogram were studied in rats by measurement of the cerebral hemisphere contents of energy phosphates and glycolytic – Krebs' cycle metabolites. A general pattern of increased glycogen and glucose with decreased pyruvate, lactate, α-ketoglutarate, and malate was observed. This pattern in association with unchanged adenylates and decreased energy phosphate utilization was consistent with a metabolic adaptation to a state of cerebral depression.The major qualitative difference between the two drugs was that higher doses of GBL were associated with additional decreases of citrate and glutamate. Since these doses of GBL were also associated with acute increases of arterial CO2 tension, it is proposed that these differences were secondary to hypercapnia and not due to a distinctive primary action of GBL.Derivations of the cytoplasmic NAD(P)H:NAD(P)+ ratios indicated that GHB and GBL were not associated with consistent alterations of the cytoplasmic redox state.
Isolation of cloned Syrian hamster insulinoma cell lines with limited capacity for insulin production
Authors: Rae Patricia A. , Yip Cecil C. , Schimmer Bernard P.
Published: April 2011

Cell lines derived from a Syrian hamster insulinoma have been cloned in agar and maintained continuously in culture in vitro for [Formula: see text] years. The cell lines have average doubling times of 48 h, they have modal chromosome numbers between 38 and 39, and they retain the ability to form tumors when injected into Syrian hamsters. The cells do not produce immunoreactive insulin when grown in vitro (<0.5 ng/mg protein), but do produce immunoreactive insulin when grown in vivo as tumors (mean value from six determinations = 7.1 ± 1.5 ng/mg protein).
The effects of the anticonvulsant valproic acid on cerebral indole amine metabolism
Authors: MacMillan V.
Published: April 2011

The effects of valproic acid (500 mg/kg, ip, 1 h prior to testing) on indole amine metabolism were studied in rats by measurement of the contents of tryptophan, 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebral hemisphere. Tryptophan and 5-HIAA levels were increased, whereas 5-HTP and 5-HT remained unchanged. Furthermore, valproic acid failed to alter the levels of 5-HTP and DOPA, 5-HT and DA, and 5-HIAA in animals pretreated, respectively, with 3-hydroxybenzyl hydrazine (a decarboxylase inhibitor), pargyline (a monoamine oxidase inhibitor), or probenecid (a compound which blocks 5-HIAA transport out of the brain and cerebrospinal fluid). These results militate against the possibility that valproic acid alters the rate of tryptophan hydroxylation or the synthesis of 5-HT. However they do support the concept that valproic acid increases brain 5-HIAA by inhibition of the transport mechanism which removes 5-HIAA from the brain.
Interactions of methylxanthines, nonxanthine phosphodiesterase inhibitors, and calcium with morphine in the guinea pig myenteric plexus
Authors: Sawynok Jana , Jhamandas Khem
Published: April 2011

In an earlier study, theophylline was shown to antagonize the morphine-induced inhibition of electrically induced contractions of the longitudinal muscle – myenteric plexus preparation from the guinea pig ileum. In the present study, acetylcholine (ACh) released from the myenteric plexus was measured directly using a radioenzymatic assay. Theophylline antagonized the morphine-induced inhibition of ACh release. A similar antagonism was also observed with caffeine and 3-isobutyl-1-methylxanthine (IBMX). All three methylxanthines also increased ACh release. The nonxanthine phosphodiesterase (PDE) inhibitors 4-(3-butoxy-4-methoxy)-2-imidazolidinone (Ro 20-1724) and 1-ethyl-4-isopropylidenehydrazino-1H-pyrozolo(3,4-b)-pyridine-5-carboxylate, ethylester, HCl (SQ 20,009) generally did not antagonize the morphine-induced inhibition of ACh release. The PDE inhibitor SQ 20,009, but not Ro 20-1724, enhanced the release of ACh. Both high calcium concentration and the divalent cation ionophore A23187 antagonized the inhibitory action of morphine on ACh release. These observations suggest that alteration in calcium fluxes rather than the inhibition of PDE mediate the methylxanthine-induced antagonism of morphine in this preparation.
Ketamine kinetics: decerebrate vs. intact cats
Authors: Heavner James E. , Bloedow Duane C.
Published: April 2011

Pharmacokinetic parameters of a ketamine (10 mg/kg, iv) bolus in decerebrate and intact cats were compared. A two-compartment open model best described the data in both groups. The apparent volume of distribution of the peripheral compartment, the apparent volume of distribution of the drug in the body, and the half-life of the postdistributive phase were significantly less (p < 0.05) in the decerebrate animals. These results emphasize the importance of correlating behavior and neuronal activity with plasma or blood concentrations of drug in animals rather than assuming that, for a given drug dose, blood (and thus tissue) levels of the agent will be similar regardless of how the animal is prepared for study.
Effects of potassium and ouabain on the vascular reactivity to norepinephrine in the rat mesenteric artery
Authors: Kondo Kazuoki , Okuno Tetsuji , Konishi Konosuke , Saruta Takao , Kato Eiichi
Published: April 2011

In the perfused rat mesenteric vascular bed, the effects of potassium and ouabain on the vascular response to norepinephrine were studied. Neither changing the concentration of potassium (1.9 to 7.9 mM) nor adding ouabain (8.6 × 10−7 to 2.2 × 10−4 M) to the perfusate changed the basal pressure. A slight increase in the potassium concentration in the perfusate attenuated the vascular response to norepinephrine, and a slight decrease in the potassium concentration potentiated this response. Ouabain in the perfusate potentiated the vascular response to norepinephrine in a dose-related manner. The effect of potassium on the vascular response was inhibited in the presence of ouabain. In preparations in which vascular reactivity had been abolished by indomethacin and then restored by prostaglandin E2, the effects of potassium and ouabain on the vascular reactivity to norepinephrine were similar to those found in the untreated preparations. These results indicate that a slight change in potassium concentration in the perfusate can affect the vascular response to norepinephrine by changing the activity of a Na+–K+-dependent ATPase. It is also suggested that the potentiating effect of low potassium concentration on the norepinephrine response is, at least in the rat mesenteric vascular bed, not mediated by the synthesis of prostaglandin E2 in the vascular wall.
Theophylline antagonizes flurazepam-induced depression of cerebral cortical neurons
Authors: Phillis J. W. , Edstrom J. P. , Ellis S. W. , Kirkpatrick J. R.
Published: April 2011

Intravenously administered theophylline (50–100 mg/kg) antagonized the depressant actions of adenosine and flurazepam on rat cerebral cortical neurons. When assessed in conjunction with recent reports that theophylline competes with diazepam for binding sites in brain tissue, this finding suggests that one action of the benzodiazepines may be exerted at a purinergic receptor associated with central neurons.
Effects of MK-771 on the isolated amphibian spinal cord: Comparison with thyrotropin-releasing hormone
Authors: Yarbrough G. G. , Singh D. K.
Published: April 2011

Topically applied MK-771 (pyro-2-aminoadipyl-histidyl-thiazolidine-4-carboxamide), a novel thyrotropin-releasing hormone (TRH) analog, was found to be equipotent with TRH in depolarizing the ventral roots of the isolated, hemisected amphibian (Bufo marinus) spinal cord. The 3-methyl-histidyl analog of TRH was approximately 10 times more potent than MK-771 and TRH. MK-771 is known to be equiactive with TRH in their actions on the pituitary gland. Taken together these findings suggest that the previously observed enhanced potency of systemically administered MK-771 over TRH in in vivo central nervous system (CNS) test paradigms is not likely to be due to a difference in the agonist requirements of CNS as compared with pituitary receptors for TRH.
Effects of some divalent cations on motoneurones in cats
Authors: Krnjević K. , Lamour Y. , MacDonald J. F. , Nistri A.
Published: April 2011

In cats under Dial, Co, Mn, La, and Sr were injected extracellularly near lumbosacral motoneurones. All tended to improve intracellular recording, but when the membrane potential was initially stable, Mn, and especially Co, had a moderate and reproducible depolarizing action. Both Mn and Co depressed excitatory postsynaptic potentials evoked by dorsal root stimulation. The prominent after-hyperpolarization (a.h.p.), which normally follows the motoneuronal action potential, was consistently and reversibly depressed by Mn and Co (as well as La), the underlying conductance increase being also diminished, but there was no significant reduction in the after-depolarization. By contrast, Sr tended to potentiate the a.h.p., especially when this was depressed by a previous injection of Co or Mn. Unlike the other cations, Co had a marked depressant effect on the action potential, particularly its rate of rise. Since the action potential could be immediately restored by hyperpolarization or by an injection of Sr (in the absence of depolarization), Co may enhance Na inactivation.
Amino acids and the synaptic pharmacology of granule cells in the dentate gyrus of the rat
Authors: Hicks T. P. , McLennan H.
Published: April 2011

Granule cells of the dentate gyrus in the hippocampi of anaesthetized rats were excited by stimulation of the contralateral hippocampus (the commissural input) and the ipsilateral entorhinal cortex (the perforant path). The cells were also activated by the electrophoretic administration of various amino acids. A selective antagonism of glutamate and perforant path excitations was obtained with glutamic acid diethylester, and of aspartate and other amino acid induced and commissural excitations with D- or DL-α-aminoadipate. An excitatory effect of α-aminoadipate which was sometimes observed was prevented by the γ-aminobutyric acid antagonist bicuculline, and may be a disinhibitory phenomenon. The results lend support to the proposition that the transmitter of the perforant path is glutamate while that of the commissural fibres is aspartate.
Propranolol effects on myocardial ultrastructure and high energy phosphates in anesthetized dogs subjected to ischemia and reperfusion
Authors: Ziegelhoffer A. , Das P. K. , Sharma G. P. , Singal P. K. , Dhalla N. S.
Published: April 2011

The effects of propranolol (1–5 mg/kg) on the ultrastructure and high energy phosphate content of dog myocardium were investigated after 2 h of ischemia and 2 h of reperfusion. Two adjoining major ventricular branches of the left circumflex coronary artery were occluded to produce ischemia. Propranolol was administered intravenously just before occlusion of the coronary arteries in all the experiments. Two hours of ischemia caused structural changes and significantly reduced creatine phosphate (CrP) and ATP contents, and increased AMP levels. Propranolol (5 mg/kg) had no effect on these ischemic changes.Propranolol was found to protect the myocardium from structural damage usually observed after 2 h of reperfusion. The size and number of amorphous electron-dense mitochondrial granules, which are considered to contain calcium, observed after reperfusion, were reduced in propranolol-treated animals. Stores of ATP and total nucleotides (ATP + ADP + AMP), and the ATP:AMP ratio were significantly higher in propranolol (5 mg/kg) treated dogs in comparison with the untreated controls after 2 h of reperfusion. There was, however, no difference between the CrP levels of propranolol-treated and untreated preparations. The study shows that propranolol is effective in reducing the reperfusion-dependent changes in ischemic myocardium. Reduction in the intracellular calcium overload as well as maintenance of the structural integrity of the cell, particularly that of mitochondria, may be involved in these protective effects of propranolol.
The development of central nervous system control of the gill withdrawal reflex evoked by siphon stimulation in Aplysia
Authors: Lukowiak Ken
Published: April 2011

In older Aplysia, the central nervous system (CNS) (abdominal ganglion) exerts suppressive and facilitatory control over the peripheral nervous system (PNS) which initially mediates the gill withdrawal reflex and its subsequent habituation evoked by tactile stimulation of the siphon. In young animals, both the suppressive and facilitatory CNS control were found to be absent. In older animals, removal of branchial nerve (Br) input to the gill resulted in a significantly reduced reflex latency and, with ctenidial (Ct) and siphon (Sn) nerves intact, a significantly increased reflex amplitude and an inability of the reflex to habituate with repeated siphon stimulation. In young animals, removal of Br had no effect on reflex latency and with Ct and Sn intact, the reflex amplitude latency was not increased and the reflex habituated. Older animals can easily discriminate between different intensity stimuli applied to the siphon as evidenced by differences in reflex amplitude, rates of habituation, and evoked neural activity. On the other hand, young animals cannot discriminate well between different stimulus intensities. The lack of CNS control in young animals was found to be due to incompletely developed neural processes within the abdominal ganglion and not the PNS. The lack of CNS control in young Aplysia results in gill reflex behaviours being less adaptive in light of changing stimulus conditions, but may be of positive survival value in that the young will not habituate as easily. The fact that CNS control is present in older animals strengthens the idea that in any analysis of the underlying neural mechanisms of habituation the entire integrated CNS–PNS must be taken into account.
The effect of repeated periods of restraint and continued exposure to various ambient temperatures on the core temperature responses of drug-naive rats
Authors: Thornhill J. A. , Cooper K. E. , Veale W. L.
Published: April 2011

Male, Sprague–Dawley rats, maintained at an ambient temperature (Ta = 22 °C) were placed in an environmental room at an Ta of 14, 22, or 32 °C. After 12 h of acclimation to the new Ta (first testing) and 3 and 6 days following (2nd and 3rd test days), colonic temperatures were measured while the rats were restrained (Plexiglas holders or surgical towels) or free moving. Restrained rats kept at an Ta of 22 °C showed transient increases in core temperature (Tc) on the 1st test day, compared with responses of the free-moving group, but little or no differences appeared thereafter. At an Ta of 32 °C, unrestrained rats lay prostrate on their backs and had decreased Tcs on each testing day compared with those of both restrained groups. Tcs on the 1st test day of restrained rats at 4 °C fell markedly and some rats died; the free-moving group maintained normal body temperatures and it was noted that shivering, piloerection, and huddling occurred. By the last test day, temperature responses of all cold-acclimated groups were similar. The results indicate that behavioural thermoregulation is important for the maintenance of normal body temperatures of rats first exposed to extreme Ta and that restraint during the initial exposure disrupts this regulation. Tcs are less affected by restraint on prolonged exposure to the cold as other mechanisms (i.e. nonshivering thermogenesis) appear to have been stimulated to a sufficient degree to offset the increased heat loss of restraint immobilization.
Influence of adrenalectomy and sex on the binding of 3-methylcholanthrene to cytosol macromolecules of rat liver
Authors: Bigger C. A. H. , Short C. R.
Published: April 2011

The retention of 3-methylcholanthrene (3-MC) in rat hepatic cytosol was significantly enhanced by adrenalectomy. In contrast, there was no significant difference in 3-MC retention in females as compared with males. 3-MC present in the cytosol fraction was bound to macromolecules and could be separated into three fractions by ion-exchange column chromatography.
The effects of nitrous oxide on the developing hamster embryos
Authors: Shah Ravindra M. , Burdett David N. , Donaldson David
Published: April 2011

Pregnant hamsters were exposed to different concentrations of nitrous oxide during the period of organogenesis. Teratogenic effects were observed in a small but significant number of fetuses. Types of malformations included cleft palate, limb defects, gut herniation, and fetal edema. A dose–effect relationship was not observed. It is not clear from our observations whether the observed effect on the fetuses was due to the excess of nitrous oxide, hypoxia, or a combination of both. Comparison with published literature indicates that further studies on the effects of nitrous oxide in placental animals are needed.
Pharmacological evaluation of new calcium antagonists: 2-Substituted 3-dimethylamino-5,6-methylenedioxyindenes. Antiarrhythmic effects
Authors: Piascik Mary F. , Piascik Michael T. , Witiak Donald T. , Rahwan Ralf G.
Published: April 2011

The 2-n-propyl- and 2-n-butyl-3-dimethylamino-5,6-methylenedioxyindene hydrochlorides (MDIs) were previously shown to be calcium antagonists with an intracellular site of action. The present investigation was designed to explore the antiarrhythmic properties of the MDIs using the pathophysiological model of the ouabain-toxic dog. Cardiac arrhythmias in dogs were induced by intravenous administration of a loading dose of 55–60 μg/kg of ouabain, followed by a continuous infusion of a maintenance dose of 0.072 μg/kg per minute of the cardiac glycoside. Intravenous doses of 5–30 mg/kg of either of the MDIs administered to arrhythmic dogs resulted in a dose-dependent conversion to sinus rhythm which was preceded by a dose-dependent drop in diastolic blood pressure. Systolic pressure was unaltered, and the effects of the MDIs on heart rate were variable but generally unimpressive and not dose related. Pretreatment of dogs with single (30 mg/kg) or multiple (six injections of 10 mg/kg each) doses of the MDIs prior to ouabain administration afforded a significant protection of the animals against ouabain-induced arrhythmias, with the "time-to-onset" of arrhythmias being 4.5 to 8 times longer in the presence of the MDI pretreatments as compared with non-protected dogs. These findings indicate that the MDIs possess significant antiarrhythmic properties against ouabain-induced arrhythmias, and may lower blood pressure by direct arteriolar dilation without significant effects on cardiac chronotropy or inotropy.
Effects of PGE2 on electrolyte and fluid excretion in the canine kidney: evidence for a direct tubular effect
Authors: Shea-Donohue P. Terez , Bolger P. Michael , Eisner Gilbert M. , Slotkoff Lawrence M.
Published: April 2011

The effects of prostaglandin (PG) E2 on renal fluid and electrolyte excretion were investigated in pentobarbital anesthetized dogs. PGE2 (0.01 μg/min per kilogram of body weight) increased renal blood flow (RBF), urinary sodium excretion [Formula: see text], and urinary potassium excretion [Formula: see text] and decreased the ratio of the outer to inner cortical blood flows (OC:IC) as measured by radionuclide labelled microspheres. To determine whether these effects are mediated through hemodynamic or direct tubular changes, acetylcholine (ACh, 2 μg/min per kilogram of body weight) was infused before and during the administration of PGE2 (ACh + PGE2) to eliminate the hemodynamic responses to PGE2. Infusion of ACh alone induced renal vasodilatation, a diuresis, natriuresis, and kaliuresis. The infusion of ACh + PGE2 produced an additional 61% increase in the urinary flow rate (V), a 93% rise in [Formula: see text], and a 40% enhancement of [Formula: see text] when compared with ACh alone. There were no changes in RBF, OC:IC, glomerular filtration rate, or filtration fraction between the infusions of ACh and ACh + PGE2. The further increases in V, [Formula: see text], and [Formula: see text] during ACh and PGE2 suggest that PGE2 has a direct inhibitory effect on the tubular transport of electrolytes in the canine kidney.
Conjugated dopamine: peripheral origin, distribution, and response to acute stress in the dog
Authors: Unger Thomas , Buu Nguyen T. , Kuchel Otto , Schürch Walter
Published: April 2011

Conjugated catecholamines in the circulation and in peripheral tissues were measured together with free catecholamines in an attempt to investigate whether there are in vivo correlates to a possible biological role of dopamine sulfate suggested by an in vitro finding of direct conversion of dopamine sulfate to free norepinephrine by dopamine β-hydroxylase.Following the strong sympathoadrenergic stimulus of surgical stress accompanied by an increase in blood pressure and heart rate, conjugated dopamine showed a twofold rise in arterial plasma (p < 0.005) together with increases of all free catecholamines (0.005 < p < 0.02), while conjugates of noreprinephrine and epinephrine decreased in the circulation (0.01 < p < 0.05). Measurements of arteriovenous differences have shown that release of conjugated dopamine occurred from the adrenal gland during operation along with free catecholamines. However, the venous outflow of conjugated dopamine from liver and kidney did not exceed its arterial influx. Conjugated dopamine, in contrast with other conjugates, is present in adrenals, liver, small intestine, and kidney with higher concentrations than free dopamine in the adrenals (p < 0.01). After ultracentrifugation, the chromaffin granule fraction of the adrenal medulla (site of dopamine β-hydroxylase) contains large amounts of conjugated dopamine (apparently sulfate) suggesting a selective accumulation of dopamine sulfate as a readily available free norepinephrine precursor during stress.These findings establish major in vivo differences between peripheral conjugated dopamine and conjugates of norepinephrine and epinephrine. They suggest that there may be biological roles for conjugated dopamine beyond that of a dopamine metabolite.
A relationship between ultrasonic intensity and changes in myocardial mechanics
Authors: Mortimer A. J. , Roy O. Z. , Trollope B. J. , McEwen J. I. , Taichman G. C. , Forester G. V. , Keon W. J.
Published: April 2011

The effects of ultrasound on the mechanical properties of isometrically contracting rat papillary muscle have been studied as a function of the intensity of the ultrasonic irradiation. Each muscle was subjected to irradiation at 1.1, 2.2, and 3.3 W/cm2 at a frequency of 2.3 MHz. Ultrasonic irradiation caused heating in the vicinity of the muscle; thus it was necessary to separate the pure thermal and ultrasonic effects. After irradiation the bath temperature was increased so that the muscle reached the same temperature which occurred during ultrasonic irradiation. The mechanical parameters measured during the equivalent thermal procedure were compared with the parameters during irradiation. There was a significant (p < 0.05) decrease in resting force which was significantly different from the equivalent thermal intervention and could be related to the ultrasonic intensity. Thus the effect of ultrasound on rat papillary consists of two components, a thermal component which affects all parameters studied and a nonthermal component which affects only the diastolic force.
Effect of changes in blood flow, norepinephrine, and pH on oxygen uptake by resting skeletal muscle
Authors: Chapler C. K. , Stainsby W. N. , Gladden L. B.
Published: April 2011

The purpose of this study was to examine the effects of norepinephrine infusion alone and during alkalosis on oxygen uptake in the dog gastrocnemius-plantaris muscle group under conditions of constant muscle blood flow. The animals were not cold acclimatized. Blood flow was pump controlled, alkalosis was produced by hyperventilation, and norepinephrine was infused intravenously at a rate of 1–1.5 μg/kg per minute. Alkalosis had no effect either alone or in combination with changes in blood flow. Similarly, changing blood flow from a low (0.10 ± 0.02 mL/g muscle per minute (mean ± SE)) to a high (0.34 ± 0.04 mL/g muscle per minute) rate did not alter resting oxygen uptake. Norepinephrine caused an average increase of about 30% in resting muscle oxygen uptake which was sustained for the 15-min sampling period during low flow - norepinephrine infusion and during the low and high blood flow - norepinephrine - alkalosis sampling periods. Norepinephrine infusion during the period of high muscle blood flow without alkalosis resulted in a transient increase followed by a decrease in muscle oxygen uptake. The data demonstrated that infusion of norepinephrine increased skeletal muscle oxygen uptake in "non-cold-acclimatized" dogs at low constant muscle blood flow. Further, without alkalosis, the norepinephrine effect at high flow was transient.
Studies on the interaction of 5α-androstane-3β,17β-diol with the testicular estrogen receptor
Authors: Moger William H.
Published: April 2011

5α-Androstane-3β,17β-diol (3β-diol) was observed to inhibit [3H]estradiol ([3H]E2) binding to testicular cytosol preparations from both immature and mature rats with a potency of 1% that of diethylstilbestrol. The nature of the inhibition of [3H]E2 binding by 3β-diol was shown to be competitive with a KI of approximately 12 nM. This high competitive potency for a C19 steroid required both 3β- and 17-hydroxyl groups, and a reduced C5 position to inhibit E2 binding. Despite the interaction of 3β-diol with E2 receptor in vitro, injection of immature rats with 25 or 250 μg 3β-diol 1-6 h before autopsy did not occupy or deplete the testicular cytoplasmic E2 receptor. When administered to immature female rats, 3β-diol did not show estrogenic agonistic or antagonistic activity in the uterus. These results suggest that the interaction of 3β-diol with the testicular receptor may be of little physiological significance.
Function of the coronary arterial collateral network le healthy myocardium: studies of peripheral coronary pressure in the dog
Authors: Sherman Igor A. , Grayson John
Published: April 2011

Coronary collateral arterial network function was studied in normal dog myocardium using measurements of peripheral coronary pressure (pressure measured distal to a ligature in a branch of the anterior descending coronary artery). Free communication between all parts of the anastomotic network was demonstrated. Adrenaline infusion raised systolic and diastolic levels of peripheral coronary pressure both when the systemic blood pressure was allowed to rise and in experiments where rise in systemic arterial pressure was prevented by haemorrhage. It is suggested that myocardial contraction pressurizes the subendocardial network thus facilitating perfusion of postnetwork vessels. This effect prolongs the time during which coronary vessels affected by rising intramyocardial pressure in systole can be perfused during the cardiac cycle. Additional evidence is presented to indicate the existence of a critical closing pressure in the coronary circulation at about 1.7 kPa (12.8 mmHg).
The effect of alveolar hypoxia on pulmonary vascular responsiveness in the conscious newborn lamb
Authors: Lock James E. , Hamilton Francis , Olley Peter M. , Coceani Flavio
Published: April 2011

To determine the effect of alveolar hypoxia and consequent increased pulmonary vascular tone on the responsiveness of the neonatal pulmonary circulation, we studied the local pulmonary vascular effects of acetylcholine, bradykinin, and histamine in the normoxic and hypoxic newborn lamb. Right and left pulmonary flows were continuously monitored from chronically implanted electromagnetic flow probes, agents were injected into only one lung, and changes in the proportion of pulmonary blood flow directed to the injected lung (Qinj/QT) provided a measure of active local pulmonary vascular constriction or dilation. At maximally tolerated doses, hypoxia enhanced the dilatory effects of acetylcholine and diminished the constrictor effects of histamine but hypoxia had a minimal effect on the maximal dilatation induced by bradykinin. Hypoxia did appear to lower the threshold dose for bradykinin's effects.These results demonstrate that base-line conditions may qualitatively alter the responsiveness of the neonatal pulmonary circulation to several drugs. In these agents, increased base-line tone generally augmented dilatory effects and diminished constrictor effects. However, the lack of such an effect on the dilator response to a high dose of bradykinin suggests the possibility that hypoxic-induced changes in pulmonary vascular responsiveness may not be entirely passive. Further, these results do not support the hypothesis that hypoxic-induced vasoconstriction is mediated by decreased production of bradykinin.
Preparation and properties of poly(Nα,Nε-L-lysinediylterephthaloyl) microcapsules containing hemolysate in the nanometer range
Authors: Arakawa Masayuki , Kondo Tamotsu
Published: April 2011

Poly(Nα,Nε-L-lysinediylterephthaloyl) (PPL) microcapsules containing sheep erythrocyte hemolysate (mean diameter, 380 nm) were prepared by an interfacial polymerization technique using electrocapillary emulsification as the means of producing very fine hemolysate droplets to be encapsulated. Measurements of oxygen absorption and resistance to flow were made on the PPL microcapsules. The microcapsules exhibited a myoglobin-like oxygen absorption curve and a resistance to flow higher than that of hemolysate-loaded larger PPL capsules at the same volume concentration.
Relationship of hydrogen ion back-diffusion to histamine liberation from canine oxyntic mucosa
Authors: Tepperman B. L. , Soper B. D.
Published: April 2011

Pharmacological damage to gastric mucosa results in excessive movement of hydrogen out of the lumen and increased movement of sodium and potassium into the lumen. It has been previously reported that one consequence of H+ back-diffusion is the release of intramucosal histamine which probably adds to the damage by increasing capillary permeability and edema formation. In the present study histamine concentration in the solution irrigating an isolated pouch of the gastric fundus was measured following 15% (w/v) ethanol (EtOH) in either 100 mM HCl, 10 mM HCl, or 0.03 M phosphate buffer. All three solutions effectively broke the mucosal barrier as evidenced by increased net fluxes of sodium and potassium. Significant (P < 0.05) increases in the histamine content of the fluid irrigating the pouch were observed after all treatments. The histamine output in response to EtOH in acidic solution was significantly greater than the response to EtOH at neutral pH. Instillation of 150, 200, 225, or 250 mM HCl alone into the pouch resulted in progressive increases in H+ back-diffusion. Application of 250 mM HCl alone resulted in a proportionally greater back-diffusion of H+, increases in Na+ and K+ fluxes indicating barrier damage, and the appearance of histamine. These results indicate that the damaging agent ethanol probably acts at two points: (1) it breaks the mucosal barrier, and (2) it liberates histamine. These results suggest that an increase in H+ back-diffusion per se is not solely responsible for gastric mucosal histamine liberation but that histamine is released as a general consequence of breaking the gastric mucosal barrier.
Interactions between p-tyramine, m-tyramine, or β-phenylethylamine and dopamine on single neurones in the cortex and caudate nucleus of the rat
Authors: Jones R. S. G. , Boulton A. A.
Published: April 2011

p-Tyramine, applied to cortical and caudate neurones with weak iontophoretic currents (0–10 nA), did not usually cause any alteration of base-line firing rate. However, neuronal responses to dopamine (DA) during such weak applications of p-tyramine were greatly enhanced. Cortical neurone responses to noradrenaline (NA) were similarly potentiated, but both cortical and caudate neurone responses to α-aminobutyric acid were unaffected by p-tyramine. In addition, weak background applications of DA which did not affect cell firing rate were also without effect on the neuronal responses to the standard application of DA. The responses of cortical neurones to DA were also potentiated by m-tyramine and β-phenylethylamine applied with weak cationic currents. The results may suggest that trace amines can enhance NA and DA transmission in the central nervous system.
Influence of dietary protein on the disposition and metabolism of phenylbutazone in rats
Authors: Varma Daya R.
Published: April 2011

Influence of dietary protein on the disposition and metabolism of phenylbutazone was investigated in male rats fed ad libitum a 21% (control) or a 5% (low) protein diet for 3 weeks. Phenylbutazone and its metabolites were assayed by high-pressure liquid chromatography. Dietary protein deficiency was associated with a decrease in the conversion of phenylbutazone into oxyphenbutazone by 9000 × g liver supernatant of protein-deficient rats. Also, dietary protein deficiency was associated with a decrease in the urinary excretion of various metabolites of phenylbutazone, namely, oxyphenbutazone γ-hydroxyphenylbutazone, β-hydroxyphenylbutazone, p,γ-dihydroxyphenylbutazone, and an unknown metabolite (not identified). Pretreatment with phenobarbitone or phenylbutazone led to an increase in the hepatic metabolism of phenylbutazone and the urinary excretion of various metabolites in both groups of animals. Within 5 min after an injection of phenylbutazone, plasma contained oxyphenbutazone; the area under the curve of oxyphenbutazone was significantly greater in protein-deficient rats than in controls possibly due to a greater accumulation. It is concluded that dietary protein deficiency is associated with a decrease in the disposition and metabolism of phenylbutazone in rats.
Effects of hexamethonium and methyl-p-tyrosine on normal rats subjected to convulsions induced by oxygen at high pressure
Authors: Banister E. W. , Singh A. K.
Published: April 2011

Hexamethonium infusion (intravenous) does not alter the concentrations of brain catecholamines, ammonia, and amino acids in rats under normal conditions. However, it decreases the concentration of blood adrenaline (A) and nonadrenaline (NA) significantly without affecting blood ammonia and amino acids. Injection of α-methyl-p-tyrosine (α-MPT) (intraperitoneal) decreases brain catecholamines without affecting the concentration of ammonia and amino acids in the brain or catecholamines, ammonia, and amino acids in the blood.In normal, hexamethonium-, and α-MFT-treated rats convulsed by exposure to oxygen at high pressure (OHP), the concentration of ammonia and glutamine plus aspargine increased and glutamate and γ-aminobutyric acid (GABA) (brain only) decreased significantly in both blood and brain. After convulsion, hexamethonium and α-MPT effect the same degree of concentration change for ammonia and amino acids in both blood and brain.When hexamethonium-treated rats are convulsed by OHP, the concentrations of A and NA in blood increased significantly. However, the postconvulsive concentration of A in these rats is significantly less than the preconvulsive control values of normal, undrugged rats. Hexamethonium also prolongs the latency period before convulsions induced by exposure of rats to OHP. This protective action of hexamethonium against oxygen toxicity is probably due to (a) some direct effect of low circulating catecholamines, or (b) delay in the production of toxic levels of ammonia from oxidative deamination of catecholamines, as initial low catecholamine concentration would hinder accumulation of ammonia from such deamination.α-MPT treatment was ineffective in producing an increased latency period before convulsion occurred despite the prevailing low brain catecholamine initially produced by α-MPT treatment. However, the concentration of brain A, NA, and total catecholamines decreased significantly after α-MPT-treated rats were convulsed by OHP exposure. The response of blood catecholamines to OHP-induced convulsions in these α-MPT-treated rats is the same as in normal rats.As α-MPT blocks the synthesis of catecholamines, a further decrease in brain catecholamine values after oxygen-induced convulsions in drugged animals suggests that brain catecholamines are oxidatively deaminated to produce ammonia. These observations suggest that, contrary to earlier reports, brain catecholamines do play an important role in producing ammonia during oxygen toxicity, which, in turn, induces convulsions.
Effects of phentolamine on hepatic in endotoxemia
Authors: Kaelin C. R. , Rink R. D.
Published: April 2011

The effect of phentolamine, an α-adrenergic blocker, on hepatic oxygen supply, plasma glucose, and lactate, and survival in fasted male rats administered Escherichia coli endotoxin (25 mg/kg, ip) has been studied. Survival at 24 h was 8% in untreated endotoxic rats, 83% in rats receiving phentolamine (5 mg/kg, ip) and endotoxin, and 100% in phentolamine controls. Measurements during the initial 8 h postendotoxin recorded transiently lower systemic arterial pressure in the phentolamine–endotoxic rats. Arterial [Formula: see text] and increases of pH and heart rate were similar in both endotoxic groups. Lactacidemia, present by 4 h in untreated endotoxic rats, did not develop in the phentolamine group and plasma glucose was significantly higher at 8 h (98 ± 2.5 vs. 77 ± 5.6 mg%, mean ± SE). Mean hepatic [Formula: see text] at 6 h in phentolamine–endotoxic rats was 9.6 mmHg with 28% of the values below 5 mmHg. By contrast, the mean in untreated endotoxic rats was 1.9 mmHg with 88% of values below 5 mmHg. Phentolamine controls were stable over 8 h; mean hepatic [Formula: see text] was 17.7 mmHg. The differences in plasma glucose and lactate suggest protection of hepatic metabolism in phentolamine-treated endotoxic rats by prevention of excessive hepatic hypoxia.
Influence of nephrectomy on the glucoregulatory response to insulin administration in the rat
Authors: Perez Gavino , Carteni Giacomo , Ungaro Biagio , Saccà Luigi
Published: April 2011

Insulin sensitivity and resistance were examined in vivo in uremic rats by using tracer methods which permit the assessment of "non-steady-state" glucose kinetics. By relating the changes in the rates of glucose output by the liver (Ra), uptake by tissues (Rd), and metabolic clearance (MCR) to immunoreactive glucagon and insulin, it was possible to assess the tissue sensitivity to physiologic and supraphysiologic levels of these two hormones and the site of insulin resistance. The effect of an intravenous injection of insulin (100 mU) on glucose turnover was studied in acutely uremic rats 15 h after bilateral nephrectomy and in sham-operated controls, in the postabsorptive state. Glucose output by the liver and uptake by tissues were determined by the primed constant infusion technique using [3-3H]glucose. Under basal conditions, no significant differences in Ra and Rd between the two groups were observed, while a significant hyperglycemia and a reduced glucose metabolic clearance rate in the face of hyperglucagonemia and normal plasma insulin levels were observed in nephrectomized rats. After insulin injection, the glycemic curves were similar in the two groups, while Ra, Rd, and MCR displayed significantly lower values in nephrectomized rats in the face of higher plasma concentrations of insulin and glucagon. It was concluded that acute uremia in the rat is characterized by a loss of the normal ability of insulin to promote peripheral glucose uptake with retention of hepatic sensitivity to insulin.
α-1,4-Glucosidase–albumin polymers : in vitro properties and advantages for enzyme replacement therapy
Authors: Poznansky Mark J. , Bhardwaj Damyanti
Published: April 2011

Soluble polymers of rat (or human) albumin and α-1,4-glucosidase are prepared using the cross-linking agent glutaraldehyde. The resulting polymer has an average molecular weight of 800 000 indicating an average composition of 12 albumin molecules for each enzyme molecule. Compared with an equivalent amount of free enzyme, the enzyme–albumin polymer has an increased resistance to heat denaturation (half-life of 15 h compared with 1 h for free enzyme at 37 °C) and to proteolysis by trypsin (half-life of 180 min compared with 10 min). The high degree of resistance to bioinactivation of the enzyme–albumin polymer is discussed in relation to requirements for enzyme replacement therapy in a range of metabolic diseases including type II glycogenosis (Pompe's disease) where α-1,4-glucosidase is the defective enzyme.
Effect of diet and drugs on the qualitative and quantitative distribution of cytochromes P-450 in rat liver
Authors: Sitar Daniel S. , Gordon Ellen R.
Published: April 2011

Male Sprague–Dawley rats were fed either Purina chow or a nutritionally adequate liquid control diet containing either 4 or 38% of the total caloric intake as fat. The hepatic cytochromes P-450 were induced in these animals either by the administration of phenobarbital, β-naphthoflavone, or isocaloric replacement of the carbohydrate of the liquid diets by ethanol at a level of 36% of total calories for 4 or 6 weeks. Three distinct groups of cytochromes P-450 could be efficiently separated by ion-exchange chromatography of microsomal preparations from these rats. The concentration of each group of cytochromes P-450 was markedly affected by variations in lipid and carbohydrate content of the diet as well as by administration of drugs.
An investigation of the negative-reinforcing properties of naloxone and cyclazocine in squirrel monkeys
Authors: Stretch Roger , Pink Catherine , Gervaize Patricia
Published: April 2011

Monkeys were trained to emit 10 responses to terminate a schedule complex consisting of a light and masking noise in the presence of which brief, intravenous injections of naloxone (0.01 mg/kg per injection), dl-cyclazocine (0.003, 0.01 mg/kg per injection), or saline were scheduled to occur over blocks of consecutive daily sessions. Completion of the fixed ratio (FR 10) response requirement terminated the schedule complex, producing a time-out of 60 s in which responses were without consequence and injections did not occur. Sessions lasted for 100 min or ended after 100 injections, whichever came first. When monkeys received an intramuscular injection of morphine (10 mg/kg) 60 min preceding each session, responding to avoid injections of naloxone or cyclazocine was well maintained, though morphine-dependent monkeys tolerated injections of saline or the vehicle in which cyclazocine was dissolved. When the morphine pretreatment regimen was discontinued, monkeys tolerated injections of naloxone and cyclazocine though, at the larger cyclazocine dose (0.01 mg/kg per injection), responding was maintained for at least 30 consecutive sessions in two postdependent animals, but not in two other monkeys treated identically. The capacity of these morphine-antagonist drugs to support responding that avoids their injection depends evidently upon whether monkeys are rendered morphine dependent or not; in the case of cyclazocine, however, an increased sensitivity to the negative-reinforcing effects of the drug appears to persist in some "postdependent" monkeys.
Occurrence of heparin and multisulfated chondroitins in the rat gastrointestinal tract and effect of fat feeding
Authors: Jaques Louis B. , Wice Sandra
Published: April 2011

Rats were fed glucose solution for 3 days and killed without fasting. Examination of the crude polysaccharides extracted from the gastrointestinal tract by electrophoresis on the micro scale and using critical electrolyte concentration and bacterial enzymes showed three types of sulfated mucopolysaccharides were present. These were identified as heparitins, multisulfated chondroitins, and heparins. The heparin resembled a macromolecular heparin of moderate molecular weight. Following oil feeding, only the heparitins and muitisulfated chondroitins were present in the small intestine, and no heparin was found. With fasting for 12 h after glucose feeding, the amount of the heparin fraction in the small intestine was reduced. The results obtained demonstrate the presence of a heparin in the rat small intestine which is responsive to changes in diet.
Effect of heat exposure on in vitro intestinal transport and utilization of glucose in the rat
Authors: Toraason M. A. , Knecht E. A. , Wright G. L.
Published: April 2011

Intestinal transport and utilization of glucose were studied in vitro in chronically heat-exposed (Ta = 34 °C) rats. Despite mucosal tissue per centimetre being significantly reduced following 7 and 14 days of exposure, no differences from control values were noted in final serosal to mucosal (S/M) fluid glucose concentrations ratios obtained from everted sac preparations. Measurements on 40-cm jejunal segments perfused in vitro at days 13–15 showed a reduction in the rate of glucose absorption per centimetre of intestine, while glucose absorption per gram of tissue was unaltered in heat-exposed rats. At the same time, glucose secretion at the serosal surface was unchanged as calculated per centimetre of intestine and increased when calculated per gram of dry tissue. The utilization of glucose by the intestine was found to be significantly reduced whether expressed for intestinal length or for intestinal weight. In addition, the glucose concentration of the tissue water was elevated in intestinal segments of heat-exposed rats after 60 min of perfusion. The decrease in glucose uptake per centimetre of intestine was attributed to the decrease in mucosal tissue. Elevated tissue glucose concentration and enhanced translocation of glucose to the serosal surface were attributed, at least in part, to the decreased rate of glucose metabolism observed in intestines of heat-exposed rats.
Development of membrane conductance of chick skeletal muscle in culture. II. Effect of aminopyridines
Authors: Thomson C. M. , Dryden W. F.
Published: April 2011

The effects of 4-aminopyridine and 3,4-diaminopyridine on membrane parameters during differentiation of embryonic chick skeletal muscle in culture have been studied. Both agents caused depolarization of fibres at all stages of development. In older cultures (day 6 onward), membrane conductance was suppressed by 0.1 mS cm−2. The addition of a maximal blocking concentration of tetraethylammonium to aminopyridine-treated fibres caused no further change in membrane conductance. In older cultures, it is concluded that the aminopyridines block resting potassium conductance. However in young fibres (day 3 to day 5), the aminopyridines caused an increase in membrane conductance. It is postulated that the aminopyridines increase membrane conductance to sodium or calcium or a combination of the two ions in immature muscle fibres.